Maternal and Child Nutrition · June, 2013 www.thelancet.com

“The Series identifi es a set of ten proven nutrition-specifi c interventions, which if scaled up from present population coverage to cover 90% of the need, would eliminate about 900 000 deaths of children younger than 5 years in the 34 high nutrition-burden countries —where 90% of the world’s stunted children live.”

Maternal and Child Nutrition The Lancet—London 32 Jamestown Road, London NW1 7BY, UK T +44 (0)20 7424 4910 Maternal and Child Nutrition · June, 2013 F +44 (0)20 7424 4911 The Lancet—New York 360 Park Avenue South, New York, NY 10010–1710, USA T +1 212 633 3810 F +1 212 633 3853 The Lancet—Beijing Unit 1–6, 7F, Tower W1, Oriental Plaza, Beijing 100738, China T + 86 10 85208872 Comment F + 86 10 85189297 1 Nutrition: a quintessential sustainable development goal [email protected] R Horton, S Lo 2 Maternal and child nutrition: building momentum for impact Maternal and Child Nutrition Study Group 5 Delivery platforms for sustained nutrition in Ethiopia Editor F Lemma, J Matji Richard Horton Deputy Editor 7 Only collective action will end undernutrition Astrid James A Taylor and others Senior Executive Editors 9 Nutrition-sensitive food systems: from rhetoric to action Pam Das P Pinstrup-Andersen Sabine Kleinert William Summerskill 10 Global child and maternal nutrition—the SUN rises Executive Editors D Nabarro Stephanie Clark Justine Davies 12 Early nutrition and adult outcomes: pieces of the puzzle Joanna Palmer Z A Bhutta Pia Pini Stuart Spencer Richard Turner Series Managing Editor Hannah Jones 15 Maternal and child undernutrition and overweight in low-income and Web Editors middle-income countries Richard Lane R E Black and others Erika Niesner 40 Evidence-based interventions for improvement of maternal and child nutrition: Senior Assistant Web Editor Katherine Rolfe what can be done and at what cost? Z A Bhutta and others Senior Editors Niall Boyce 66 Nutrition-sensitive interventions and programmes: how can they help to accelerate Audrey Ceschia Lin Guo progress in improving maternal and child nutrition? Selina Lo M T Ruel and others Udani Samarasekera Onisillos Sekkides 82 The politics of reducing malnutrition: building commitment and accelerating progress S Gillespie and others Asia Editor Helena Hui Wang (Beijing) North America Editor Articles Rebecca Cooney (New York) Conference Editors 100 Mortality risk in preterm and small-for-gestational-age infants in low-income and Laura Hart middle-income countries: a pooled country analysis Nicolai Humphreys J Katz and others Deputy Managing Editor Laura Benham 109 Associations of linear growth and relative weight gain during early life with adult Senior Assistant Editors health and human capital in countries of low and middle income: findings from five Olaya Astudillo birth cohort studies Stephanie Bartlett L S Adair and others Abi Cantor Sean Cleghorn Tim Dehnel Dara Mohammadi Odhran O’Donoghue Helen Penny Frances Whinder Farhat Yaqub Assistant Editors Neil Bennet Hannah Cagney Stephanie Clague Katherine Gourd Natalie Harrison Rebecca Heald Zena Nyakoojo Cover image © Betty Press/Panos Louise Rishton Previously published online Media Relations Manager See www.thelancet/com for WebExtra content Daisy Barton Editorial Assistants Version verified by CrossMark Holly Baker Nawsheen Boodhun International Advisory Board Nicolas Dolan Karen Antman (Boston) Karen Gelmon (Vancouver) Alwyn Mwinga (Lusaka) Caroline Savage (Birmingham) Francesca Towey Valerie Beral (Oxford) David Grimes (Durham) Marie-Louise Newell (Somkhele) Ken Schulz (Chapel Hill) Robert Beaglehole (Auckland) Ana Langer (Cambridge, MA) Magne Nylenna (Oslo) Frank Shann (Melbourne) The Lancet® is a registered Anthony Costello (London) Judith Lumley (Melbourne) Peter Piot (London) Jan Vandenbroucke (Leiden) trademark of Reed Elsevier Robert Fletcher (Boston) Elizabeth Molyneux (Blantyre) Stuart Pocock (London) Cesar Victora (Pelotas) Properties SA, used under licence. Suzanne Fletcher (Boston) Christopher Murray (Seattle) Giuseppe Remuzzi (Bergamo) Nick White (Bangkok) Comment

Nutrition: a quintessential sustainable development goal

In the final paper of our 2008 Lancet Series on maternal the first 1000 days from conception to 2 years. What Published Online and child undernutrition, Saul Morris and colleagues goes right and what goes wrong for fetal and child June 6, 2013 http://dx.doi.org/10.1016/ wrote that, “The international nutrition system—made nutrition during this period has lasting and irreversible S0140-6736(13)61100-9 up of international and donor organisations, academia, consequences for later life. See Online/Series http://dx.doi.org/10.1016/ civil society, and the private sector—is fragmented There are several entirely new findings in this Series. S0140-6736(13)60937-X, and dysfunctional”.1 They concluded that, incredibly, First, the adolescent girl is identified as especially http://dx.doi.org/10.1016/ S0140-6736(13)60996-4, no evidence base existed to prioritise actions to vulnerable to the effects of undernutrition. But that very http://dx.doi.org/10.1016/ improve nutrition. And they argued that the voice of predicament also makes adolescent girls a group with a S0140-6736(13)60843-0, and http://dx.doi.org/10.1016/ countries must be better heard, felt, and reflected in special opportunity too. S0140-6736(13)60842-9 global decision making. Too often country priorities Second, the importance of fetal growth restriction See Online/Articles to strengthen nutrition were ignored by donors and or being born small for gestational age is highlighted. http://dx.doi.org/10.1016/ S0140-6736(13)60993-9 and agencies alike. 5 years on, thanks to the work of a According to new estimates, fetal growth restriction http://dx.doi.org/10.1016/ consortium of scientists led by Robert E Black from causes more than 800 000 neonatal deaths and 20% of S0140-6736(13)60103-8 Johns Hopkins Bloomberg School of Public Health stunting in children younger than 5 years worldwide. (the Maternal and Child Nutrition Study Group), we These findings are presented by Robert E Black and review the progress made against these findings and colleagues,2 and Joanne Katz and colleagues7 in the recommendations.2–6 Although some news is better companion Article. Third, the Series is not only concerned than 5 years ago, there is still a deeply worrying gulf with interventions. It also identifies delivery platforms between country needs and global actions. But what is for the implementation of those interventions, most most different—an extraordinary opportunity as well as promisingly in the community and in schools. Fourth, a severe challenge—is the political urgency of nutrition. the Series costs these interventions and explains why This latest Lancet Series updates, with extensive those costs—an additional Int$9·6 billion annually for new data, the contribution undernutrition in its the 34 countries identified—are much less prohibitive various forms makes to child mortality and morbidity. than they might at first seem. And finally, the Series Compared with 2008, the result is a radically different identifies a further threat to maternal and child picture of the relation between nutritional deficiencies nutritional status: overweight and obesity. and child health. The overall finding is that 3·1 million On June 8, 2013, the Governments of Brazil and the children younger than 5 years die every year from UK will co-host a Nutrition for Growth event. There is undernutrition; that is a staggering 45% of total child therefore an immediate opportunity to foster political deaths in 2011. To address this enormous and too often hidden cause of child mortality, the Maternal and Child Nutrition Study Group propose a new framework to optimise the delivery of priority evidence-based interventions to prevent and treat undernutrition across the whole life course. Unique to this Series is the systematic approach to both the timing of the interventions and to creating an enabling environment for nutrition. The Maternal and Child Nutrition Study Group emphasises ten interventions targeted to women of reproductive age, during pregnancy, and to infants and children. They calculate the effects of these interventions in 34 countries across Africa, Asia, and the Middle East, where 90% of the global burden of undernutrition

resides. In doing so, they reinforce the importance of Corbis

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support for the interventions that can be quickly scaled and policy makers to do something—or worse, simply up or linked to nutrition programmes—such as early hoping that political commitment will appear like a child development initiatives. It is equally important to rabbit out of a hat—they set out a practical guide about take note of the message of Marie Ruel and colleagues4— how to seize the agenda for nutrition, how to create that in certain sectors, such as agriculture, the evidence political momentum, and how to turn that momentum of the effect of targeted programmes on maternal and into results. This is the prize we have to grasp in the next child nutrition is largely inconclusive and requires new 18 months. approaches to field evaluation. Since 2008, there have been only limited increases in Richard Horton, Selina Lo donor aid for nutrition. It is true that nutrition is not The Lancet, London NW1 7BY, UK so readily attractive to politicians as an international We thank the Maternal and Child Nutrition Study Group, led by Robert E Black, for leading the conception and design of this Series. We also acknowledge the development priority. Undernutrition has a complex generosity of the Bill & Melinda Gates Foundation for providing financial support. set of political, social, and economic causes, none of 1 Morris S, Cogill B, Uauy R, et al. Effective international action against undernutrition: why has it proven so difficult and what can be done to which are amenable to easy solutions that fit within accelerate progress? Lancet 2008; 371: 608–21. the timeframe of a single political cycle. For this reason, 2 Black RE, Victora CG, Walker SP, et al, and the Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in low- the outlook today for nutrition is not wholly good. The income and middle-income countries. Lancet 2013; published online target endorsed only a year ago at the World Health June 6. http://dx.doi.org/10.1016/S0140-6736(13)60937-X. 3 Bhutta ZA, Das JK, Rizvi A, et al, The Lancet Nutrition Interventions Review Assembly—to reduce by 40% the number of children Group, and the Maternal and Child Nutrition Study Group. Evidence-based interventions for improvement of maternal and child nutrition: what can stunted by 2025—is already on course to be missed. be done and at what cost? Lancet 2013; published online June 6. http://dx. As the endpoint of the Millennium Development doi.org/10.1016/S0140-6736(13)60996-4. 4 Ruel MT, Alderman H, and the Maternal and Child Nutrition Study Group. Goals approaches, countries and the international Nutrition-sensitive interventions and programmes: how can they help to community may agree that nutrition was one of the accelerate progress in improving maternal and child nutrition? Lancet 2013; published online June 6. http://dx.doi.org/10.1016/ great missed opportunities of the past 15 years. But this S0140-6736(13)60843-0. neglect can be turned around quickly. As sustainable 5 Gillespie S, Haddad L, Mannar V, Menon P, Nisbett N, and the Maternal and Child Nutrition Study Group. The politics of reducing malnutrition: development becomes the dominant idea post-2015, building commitment and accelerating progress. Lancet 2013; published online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60842-9. nutrition emerges as the quintessential example of a 6 Maternal and Child Nutrition Study Group. Maternal and child nutrition: sustainable development objective. If maternal and building momentum for impact. Lancet 2013; published online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60988-5. child nutrition is optimised, the benefits will accrue 7 Katz J, Lee ACC, Kozuki N, et al, and the CHERG Small-for-Gestational-Age- and extend over several generations. This remarkable Preterm Birth Working Group. Mortality risk in preterm and small-for- gestational-age infants in low-income and middle-income countries: opportunity is why Stuart Gillespie and colleagues5 take a pooled country analysis. Lancet 2013; published online June 6. http:// a very different approach to implementation than in any dx.doi.org/10.1016/S0140-6736(13)60993-9. previous Lancet Series. Instead of exhorting politicians

Maternal and child nutrition: building momentum for impact

Published Online In the 5 years since the Maternal and Child Under­ and middle-income countries (LMICs) is growing, June 6, 2013 nutrition Series1–5 was published in The Lancet there donor funding is rising, and civil society and the http://dx.doi.org/10.1016/ S0140-6736(13)60988-5 has been a substantial increase in commitment to private sector are increasingly engaged. reduction of malnutrition at global and national Despite this progress, improvements in nutrition levels. Most development agencies have developed still represent a massive unfinished agenda. The or revised their strategies to address undernutrition 165 million children with stunted growth in 2011 have focused on the first 1000 days of life—the period from compromised cognitive development and physical pregnancy to a child’s second birthday—as called for in capa­bilities, making yet another generation less pro­ the 2008 Series. One of the main drivers of this new ductive than they would otherwise be.8 Countries will international momentum is the Scaling Up Nutrition not be able to break out of poverty or sustain economic movement.6,7 National commit­ment in low-income advances when so much of their population is unable

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to achieve the nutritional security that is needed for a Panel: Global nutrition targets for 2025, endorsed by the healthy and productive life. Undernutrition­ is estimated World Health Assembly to reduce a nation’s economic advancement by at • 40% reduction of the global number of children least 8% (direct productivity losses, losses via poorer younger than 5 years who are stunted 9,10 cognition, and losses via reduced schooling). • 50% reduction of anaemia in women of Although preventable child mortality continues to reproductive age decrease, undernutrition is responsible for 45% of • 30% reduction of low birthweight deaths of children younger than 5 years, amounting • No increase in childhood overweight • Increase the rate of exclusive breastfeeding in the to more than 3 million deaths each year.8 Deficiencies first 6 months to at least 50% of essential vitamins and minerals are widespread and • Reduce and maintain childhood wasting to less than 5% have important adverse effects on child survival and development. Additionally, overweight in adults and increasingly in children constitutes an emerging burden and zinc supplementation. It is, however, important that that is quickly establishing itself globally, affecting both interventions that have so far contributed to reductions poor and rich populations.8 in child mortality, such as vitamin A supplementation, Evidence presented in the accompanying Series on be continued where the need still exists. The cost of Mater­nal and Child Nutrition8,10–12 shows the importance scaling up this set of needed nutrition interventions to of adolescent and maternal nutrition for the health 90% coverage is estimated at Int$9·6 billion per year.10 of the mother and for ensuring healthy fetal growth Additionally, nutrition-sensitive activities should be and development. Fetal growth restriction is a cause pursued in sectors that address the underlying deter­ of 800 000 deaths in the first month of life each year, minants of nutrition. Some, but not all, programmes more than a quarter of all neonatal deaths.8 Newborn in agriculture, cash transfers, early child development, babies with fetal growth restriction have a substantially and schooling have been shown to improve nutrition increased risk of developing stunting by 24 months and broader developmental outcomes for children.11 of age. Furthermore, these adverse nutritional insults The studies with the most positive effects had strong early in life, when coupled with rapid weight gain later designs (including nutrition goals and actions), reached in childhood, are important determinants of obesity mothers and children early (and for longer durations), and non-communicable diseases in adulthood. Thus, and targeted the poorest and most undernourished it is imperative to act as early as possible in the crucial groups. Many also included actions to empower women window of opportunity of pregnancy and the first and enhance their social status. More evidence is needed 2 years of life.8 The emerging platforms for adolescent from programmes that have good designs, strong health and nutrition might offer opportunities for imple­mentation,­ and rigorous evaluation. enhanced benefits.10 An enabling environment for nutrition requires According to our conservative estimates, we identify empirically sound, timely data about the nature of a set of ten proven nutrition-specific inter­ven­tions, the problem, evidence for what works and how, good which if scaled up from present population coverage coherence between sectors, good coordination between to cover 90% of the need, would eliminate about national and subnational levels, sufficient capacity to 900 000 deaths of children younger than 5 years in build commitment, implementation of programmes the 34 high nutrition-burden countries—where 90% at scale, and sustainable public and private means to of the world’s stunted children live—and reduce the finance interventions.12 prevalence of stunting by a fifth, reducing the number Countries that have managed to improve nutritional of children with stunted growth and development status in these contexts have adopted an approach that by 33 million.10 The interventions with the largest targets the whole of society.13 This approach requires a predicted effects on child mortality are treatment good understanding of the political economy of nutri­ of severe acute malnutrition throughout childhood; tion. Governments and other stakeholders in success­ promotion of infant and young child feeding, including ful countries have built alliances, managed tensions, breastfeeding and appropriate complementary foods; identified win-win outcomes, established strong

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account­ability mechanisms, and innovated in the Many nutrition gains have been made, but they need mobilisation of resources for nutrition.11 to be protected in the face of new stressors such as The private sector is an important force in shaping climate change, humanitarian crises, and food price nutrition outcomes and has the potential to do more. volatility. We need to encourage innovation in design Much more needs to be known about how different and delivery of nutrition-specific interventions, to make forms of public policy, regulation, and financial incen­ them even more affordable at scale. New incentives need tives can support private organisations to do the right to be established that support innovations in nutrition- things to improve nutrition. Knowledge in this area is sensitive pro­gramme design and implementation—to scarce and must be expanded rapidly. unleash their potential to achieve their own goals by The impetus for improving nutrition is stronger today providing crucial additional support to efforts to reduce than 5 years ago. The World Health Assembly nutrition malnutrition. This Series strengthens the evidence that targets14 for reduction of stunting, wasting, low birth­ good nutrition is a fundamental driver of a wide range weight, anaemia, and overweight, and increasing exclu­ of development goals. sive breastfeeding in the first 6 months of life (panel), Investments need to be directed not only to inter­ can be achieved by 2025 with sufficient support. The ventions, but also to the creation of environments costs of inaction are enormous. As economies grow that enable them. This approach requires strategic and the rate of population growth slows, the returns investment in commitment building, capacity, and to improved cognitive performance and psychological leadership; timely data describing the nature of the functioning in the workforce will expand substantially. malnutrition problem and its causes; evidence for Benefits will be greater where strategies integrate the what works; accountability mechanisms; resource promotion of nutrition and child development.15 mobilisation; and building of institutions required The new evidence provided in the Maternal and Child for sustainable implementation. A political economy Nutrition Series strengthens the case for a continued approach to prioritisation of such investments is crucial focus on the first 1000 days. Investments within this if viable enabling environments are to be created. window can help meet crucial goals: the prevention of More research is needed to develop scalable inter­ undernutrition, overweight, and poor child development ventions­ or improve the effectiveness of existing ones outcomes with longlasting effects on human capital to have greater effects, especially by preventing fetal formation. Because many women do not access growth restriction and growth faltering in infancy. nutrition-promoting services until month 5 or 6 of Although promising service delivery platforms exist in pregnancy, we draw attention to the need to ensure communities, evidence is needed about how to ensure women enter pregnancy in a state of optimum nutrition. that nutrition interventions reach the populations Nutrition is foundational to both individual and with greatest need. More research is needed into the national development. The post-Millennium Develop­ barriers to effective implementation and into the costs ment Goals agenda must put the resolution of all forms and logistics of scaling up: into the crucial elements of of malnutrition at the top of its aims. An increase capacity at different levels, into the development and in donor spending is crucial if nutrition targets are assessment of financing mechanisms for nutrition, to be met or surpassed. Government spending in and into ways to reduce the costs of implementation. LMICs needs to match or exceed this rate of increase. Rigorous evidence is needed to show how the private Nutrition budget lines need to be established in all sector can best support optimum nutrition. Research is high-burden countries. Governments need to be also needed into the drivers of country success, how to supported to raise public resources for nutrition. create enabling environments, and into the features of The increased mobilisation of private resources from nutrition-sensitive programmes that improve nutrition. individuals, businesses, and new philanthropies needs This year, 2013, represents the best opportunity yet to be incentivised towards the most effective ways of to make these proposed actions a reality. National and improving nutrition. Scaling Up Nutrition is a crucial international momentum to address human nutrition driver of these needed actions and support for it must and related food security and health needs is at a high remain strong. level. Nutrition is now more prominent on the agendas

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of the UN, G8, and G20, and supporting civil society, 4 Bryce J, Coitinho D, Darnton-Hill I, et al, for the Maternal and Child Undernutrition Study Group. Maternal and child undernutrition: effective business, and academic organisations. We must work action at national level. Lancet 2008; 371: 510–26. together to seize this opportunity. 5 Morris SS, Cogill B, Uauy R. Effective international action against undernutrition: why has it proven so difficult and what can be done to accelerate progress? Lancet 2008; 371: 608–21. Maternal and Child Nutrition Study Group 6 Scaling Up Nutrition. A framework for action. 2010. http://unscn.org/files/ Activities/SUN/PolicyBriefNutritionScalingUpApril.pdf (accessed April 2, Group members: *Robert E Black (Johns Hopkins Bloomberg School 2013). of Public Health, USA), Harold Alderman (International Food Policy 7 Bezanson K, Isenman P. Scaling up nutrition: a framework for action. Research Institute, USA), Zulfiqar A Bhutta (Aga Khan University, Food Nutr Bull 2010; 31: 178–86. Pakistan), Stuart Gillespie (International Food Policy Research 8 Black RE, Victora CG, Walker SP, et al, and the Maternal and Child Nutrition Study Group. Maternal and child undernutrition and overweight in Institute, USA), Lawrence Haddad (Institute of Development low-income and middle-income countries. Lancet 2013; published online Studies, UK), Susan Horton (University of Waterloo, Canada), June 6. http://dx.doi.org/10.1016/S0140-6736(13)60937-X. Anna Lartey (University of Ghana, Ghana), Venkatesh Mannar 9 Horton S, Steckel RH. Global economic losses attributable to malnutrition 1990–2000 and projections to 2050. In: Lombard B, ed. How much have (The Micronutrient Initiative, Canada), Marie Ruel (International global problems cost the world? A scorecard from 1900 to 2050. Food Policy Research Institute, USA), Cesar G Victora (Universidade Cambridge: Cambridge University Press, 2013 (in press). Federal de Pelotas, Brazil), Susan P Walker (The University of the 10 Bhutta ZA, Das JK, Rizvi A, et al, The Lancet Nutrition Interventions Review Group, and the Maternal and Child Nutrition Study Group. Evidence-based West Indies, Jamaica), Patrick Webb (Tufts University, USA) interventions for improvement of maternal and child nutrition: what can [email protected] be done and at what cost? Lancet 2013; published online June 6. http://dx. doi.org/10.1016/S0140-6736(13)60996-4. REB serves on the Boards of the Micronutrient Initiative, Vitamin Angels, the 11 Ruel MT, Alderman H, and the Maternal and Child Nutrition Study Group. Child Health and Nutrition Research Initiative, and the Nestlé Creating Shared Nutrition-sensitive interventions and programmes: how can they help to Value Advisory Committee. VM serves on the Nestlé Creating Shared Value accelerate progress in improving maternal and child nutrition? Advisory Committee. HA, ZAB, SG, LH, SH, AL, MR, CGV, SPW, and PW declare Lancet 2013; published online June 6. http://dx.doi.org/10.1016/ that they have no conflicts of interest. S0140-6736(13)60843-0. 1 Black RE, Allen LH, Bhutta ZA, et al, for the Maternal and Child 12 Gillespie S, Haddad L, Mannar V, Menon P, Nisbett N, and the Maternal and Undernutrition Study Group. Maternal and child undernutrition: global Child Nutrition Study Group. The politics of reducing malnutrition: and regional exposures and health consequences. Lancet 2008; building commitment and accelerating progress. Lancet 2013; published 371: 243–60. online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60842-9. 2 Bhutta ZA, Ahmed T, Black RE, et al, for the Maternal and Child 13 Dube L, Pingali P, Webb P. Paths of convergence for agriculture, health, and Undernutrition Study Group. What works? Interventions for maternal and wealth. Proc Natl Acad Sci USA 2012; 109: 12294–301. child undernutrition and survival. Lancet 2008; 371: 417–40. 14 WHO. Discussion paper. Proposed global targets for maternal, infant and 3 Victora CG, Adair L, Fall C, et al, for the Maternal and Child Undernutrition young child nutrition. Geneva: World Health Organization, 2012. Study Group. Maternal and child undernutrition: consequences for adult 15 Grantham-McGregor S, Cheung YB, Cueto S, et al. Developmental potential in health and human capital. Lancet 2008; 371: 340–57. the first 5 years for children in developing countries. Lancet 2007; 369: 60–70.

Delivery platforms for sustained nutrition in Ethiopia

The 2013 Lancet Series on Maternal and Child strengthening to take place, a system or platform for Published Online June 6, 2013 Nutrition emphasises the crucial importance of service delivery should be country led and owned to http://dx.doi.org/10.1016/ scale-up of effective nutrition interventions through ensure sustainability and effectiveness. S0140-6736(13)61054-5 health and community delivery platforms. The Series acknowledges that strong health systems are central to achievement of this goal, and for progress towards the 2015 Millennium Development Goals (MDGs).1 A broad consensus exists about the need for strengthening of health systems to meet the goals of the health- related MDGs by 2015.1 Because disease-control programmes and general health services often share common service-delivery platforms, they are necessary and complementary in countries with a high disease burden, especially in sub-Saharan Africa.2,3 Some findings have suggested that health and nutrition programmes can strengthen health systems and, similarly, that health systems can strengthen 4–7 programme implementation. Furthermore, for such Corbis

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In the past few years, many countries have worked The Health Extension Programme plays a crucial part to develop systems and infrastructure at the most in the success of the national nutrition programme and decentralised level of services, and these investments strategy that was introduced in Ethiopia in 2008. The have enabled populations to access essential services community-based management of acute malnutrition in sectors such as health, agriculture, education, and approach of the Health Extension Programme manages social welfare. Ethiopia is exemplary in this regard in more than 300 000 children in more than 10 000 health view of the country’s progress towards some of the posts annually, has provided vita­min A supplementation key MDGs, which is mainly attributable to a decentral­ and deworming tablets to 11 million children and ised service delivery platform—the Health Extension 700 000 pregnant and lactating women every 6 months Programme.8 Launched in 2003, this programme was since 2005–06, and distributes iron-folate supplemen­ ­ organised to provide uni­versal access to primary health tation targeted to reach 80% of pregnant women every care, mainly preventive services,6,7 through more than year.13 Interventions of the community-based nutrition 38 000 government-salaried female health extension programme include infant and young child nutrition,­ workers. Two workers were placed in a health post and growth monitoring and promotion via the Triple A to serve each kebele (the smallest administrative cycle (assess the problem, analyse its causes and possible unit) of about 5000 people nationwide. Through solutions, and take appropriate action). The community- this programme new vaccines were introduced and based nutrition pro­gramme is currently being supported health services expanded, which improved health in more than 300 food-insecure woredas (districts), and nutrition care practices, and invest­ments were reaching 1 500 185 (80%) children younger than 2 years. made in education and social economic development, Efforts of the community-based nutrition programme contributing to a reduction in the number of child have resulted in more than 50% of children in Ethiopia deaths by nearly half.9,10 being exclusively breastfed (EDHS, 2011).10 However, the The present estimate (supported by the Central proportion of children receiving a minimum acceptable Statis­tical Agency) for the mortality rate in children diet is only 4% in Ethiopia, show­ing the urgent need to younger than 5 years in Ethopia is 77 per 1000 livebirths finalise a national strategy for improvement of quantity (com­pared with 166 in 2000 and 123 in 2005).11 On the and quality of complementary feeding. basis of the present trend, Ethiopia is predicted to meet The revised national nutrition programme spanning MDG 4, to reduce child mortality, by 2015, by having 2013–15 will address these challenges by emphasising a mortality rate in children younger than 5 years of the first 1000 days of life, with a focus on children 68 per 1000 livebirths.12 Furthermore, a comparison of younger than 2 years, pregnant and lactating women, national levels of malnutrition in the 2000 and 2011 and adolescent­ girls, to break the intergenerational Ethiopia Demographic and Health Surveys (EDHS) cycle of malnutrition. Furthermore, the revised pro­ shows that stunting has declined from 58% to 44%, gramme will emphasise actions for acceleration of underweight from 41% to 29%, and prevalence of stunting reduction by focusing on nutrition-sensitive wasting from 12% to 10%.10 Globally, the prevalence of interventions in other development sectors such as stunting in children younger than 5 years has fallen by education, agriculture, social protection and women’s 36% in the past two decades, from an estimated 40% affairs, and civil society organisations and the private in 1990, to 26% in 2011.9 sector. The role of health extension workers and the To consolidate the gains and enhance the effectiveness health development army will continue to be central of the Health Extension Programme, the Government to achievement of equitable access of all vulnerable of Ethiopia has designed a scaling-up strategy, in the women and children to both curative and preventive form of a so-called health development army, which will services, and to ensure that targets specified in the scale up documented best practices and use families as health sector development plan IV of Ethiopia are met.13 role models. Such a strategy is based on social learning Ethiopia’s actions have enabled development workers theory whereby peer-to-peer modelling can dissemin­ to engage people at risk in an integrated manner ate emerging information and instil improved health- using a unified Health Extension Programme, enabling seeking behaviours at community level. achievement of great gains in child survival and

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nutrition. The Government of Ethiopia, on the basis of 2 WHO. Everybody’s business. Strengthening health systems to improve health outcomes: WHO’s framework for action. Geneva: World Health experiences in the past 10 years of this programme and Organization, 2007. the substantial improvements in nutritional status, 3 WHO. The Global Fund strategic approach to health systems strengthening: report from WHO to the Global Fund Secretariat. Geneva: World Health believes that even greater efforts can be made to reduce Organization, 2007. stunting. The government­ will continue to optimise the 4 Atun R, Bennett S, Duran A. When do vertical (stand-alone) programmes have a place in health systems? Copenhagen: World Health Organization revised national nutrition programme and the global Regional Office for Europe and the European Observatory on Health Systems and Policies, 2008. efforts on nutrition such as Scaling Up Nutrition (SUN) For more on the SUN initiative 5 Atun R, de Jongh T, Secci F, Ohiri K, Adeyi O. A systematic review of the see http://scalingupnutrition. and Renewed Efforts Against Child Hunger (REACH),14 evidence on integration of targeted health interventions into health systems. Health Policy Plan 2010; 25: 1–14. org/resources-archive which are mechanisms to catalyse further multisectoral 6 Atun R, de Jongh T, Secci F, Ohiri K, Adeyi O. Integration of targeted health nutrition-sensitive actions beyond the health sector. interventions into health systems: a conceptual framework for analysis. Health Policy Plan 2010; 25: 104–11. Nutrition, as one of many crucial indicators of health 7 Atun R, Menabde N. Health systems and systems thinking: In: Coker R, status, should be used for close programmatic link­ Atun R, McKee M, eds. Health systems and the challenge of communicable diseases: experiences from Europe and Latin America. Berkshire, UK: Open ages and synergies between targeted social protection University Press, 2009: 121–40. 8 Wakabi W. Extension workers drive Ethiopia’s primary health. Lancet 2008; interventions. These synergistic actions across social 372: 880. services will contribute towards increased resource 9 UN Children’s Fund. Improving child nutrition: the achievable imperative allocation for the national nutrition programme, and for global progress. New York: UNICEF, 2013. 10 Central Statistical Agency, ICF International. Ethiopia Demographic and ensure that sustainable interventions are scaled up to Health Survey 2011. March, 2012. http://measuredhs.com/pubs/pdf/ FR255/FR255.pdf (accessed May 22, 2013). improve food and nutrition security. 11 WHO. Ethiopia: health profile. May, 2013. http://www.who.int/gho/ countries/eth.pdf (accessed May 22, 2013). 12 Ministry of Finance and Economic Development, UN Ethiopia. Child survival, *Ferew Lemma, Joan Matji health and nutrition. In: Nebede A, Pearson R, eds. Investing in boys and girls Ethiopian Federal Ministry of Health, PO Box 1234, Addis Ababa, in Ethiopia: past, present and future, 2012. Ethiopia: UNICEF, 2012: 35–53. Ethiopia (FL); and UNICEF Ethiopia, Addis Ababa, Ethiopia (JM) 13 Federal Democratic Republic of Ethiopia, Ministry of Health. Health Sector Development Program IV, 2010/11–2014/15. Addis Ababa: Federal [email protected] Democratic Republic of Ethiopia Ministry of Health, 2010. We declare that we have no conflicts of interest. 14 REACH Partnership. Annual report 2012. 2012. http://www. reachpartnership.org/documents/312104/315126/REACH+Annual+Report+ 1 Singh A. Strengthening health systems to meet MDGs. Health Policy Plan 2012?version=1.0 (accessed May 22, 2013). 2006; 21: 326–28.

Only collective action will end undernutrition

We are in a race against time to eradicate the global Women and girls are at the heart of this message. Published Online scourge of undernutrition. Undernutrition cripples global As the bearers and carers of children, their health and June 6, 2013 http://dx.doi.org/10.1016/ economic growth and development, and future global economic potential is entwined with that of future S0140-6736(13)61084-3 prosperity and security are intimately linked with our ability to respond adequately to this urgent challenge. The new Series in The Lancet shows that undernutrition contributes to the deaths of about 3 million children each year—45% of the total.1 Its results stunt the physical growth and life chances of millions of people, and for Africa and Asia estimates suggest that up to 11% of national economic productivity is lost to undernutrition.2 The evidence provided in this Series should act as a turning point to galvanise global action. The solution lies largely in the early years of life, when the foundations for human potential are laid—getting the right nutrients at the right time prevents undernutrition. The result is heightened educational attainment, adult wages, and

economic productivity. Corbis

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generations. Unless girls grow well in early childhood agriculture and food system. As the global population and adolescence and enter into motherhood well rises, our food system needs to keep pace with the nourished, are lent support during pregnancy, demand for both dietary energy and the essential protected from heavy physical labour, and empowered vitamins and minerals needed for human health. Our to breastfeed and provide good food for their agriculture and food system needs to be profitable for babies and toddlers, the intergenerational cycle of farmers and the wider food sector, environmentally undernutrition will not be broken. This Series shows sustainable, and directly supportive of the health and that poor maternal nutrition at conception and during nutritional needs of populations. pregnancy is a major contributor to undernutrition in Everyone is part of the solution. Governments childhood.1 Empowering women to make the right need to lead; businesses need to identify how to choices for their health, and that of their children, is improve nutrition through their business models crucial to solving this challenge. and employment practice; civil society organisations Why is this such an urgent issue? Important demo­ need to help citizens to drive transparency and graphic changes are occurring in many countries with accountability; and the scientific community needs to high levels of undernutrition. The ratio of the work­ keep us focused on evidence about what works. Policy ing age to non-working age population is rising and commitments, capacity strengthening, and targeted will peak in the next 20 years, and this increase in financing are all essential. the available workforce has substantially boosted Global efforts on food and nutrition will likewise economic growth in many parts of the world.3 Any be substantially boosted by a clear signal of nutrition such demographic dividend will be even greater in well- priorities in the post-2015 development agenda. This nourished populations. Additionally, rapid urbanisation, agenda will do more than steer aid; it should provide increased sedentary behaviour, and a transition in direction on global investment, buy in support from the dietary patterns has resulted in a fast rise of obesity in private sector, and encourage a coherent approach from middle-income and even low-income countries. This international institutions. Nutrition should be centrally Series emphasises that undernourished children are at positioned in that agenda to ensure energy and nutrient increased risk of becoming overweight and developing needs are met at each stage of life. For the first Lancet Series on non-communicable diseases such as diabetes in later The first Lancet Series on maternal and child under­ maternal and child life.1 Acting now brings a triple benefit: it saves lives nutrition, published in 2008, helped to start the race undernutrition see http://www. thelancet.com/series/maternal- today, maximises economic opportunity, and helps to to eradicate poor nutrition. In the past 5 years the and-child-undernutrition reduce obesity and chronic disease in the future. governments of 35 countries have committed to do This Series shows that there are simple and more to tackle undernutrition, and have joined the For Scaling Up Nutrition see proven interventions that can substantially reduce Scaling Up Nutrition movement. On the last day of the http://scalingupnutrition.org undernutrition and mortality in children. Many of 2012 Olympics, the governments of the UK and Brazil these interventions deliver an excellent return on co-hosted an event in London, UK, to generate political investment and should be delivered at scale without momentum in the fight against undernutrition. On delay. However, making a lasting effect on the root June 8, 2013, the Nutrition for Growth high level event causes of undernutrition will need more effort. Brazil’s in London will help to secure a global response that remarkable experience during the past 20 years shows will include financial, business, scientific, and political us that the right programmes need to be matched with commitments matched to the scale of the challenge. strong political leadership and determination. Brazil’s Progress will be reviewed annually and again at the success resulted from a whole-government response, Olympics in Rio de Janeiro, Brazil, in 2016. We cannot a clear focus on groups at greatest risk, strong civil afford to miss this opportunity to act together to society engagement, and investments to track progress beat undernutrition. and use data to strengthen accountability and inform policy choices.4 *Anna Taylor, Alan D Dangour, K Srinath Reddy In addition to strong national action on under­ UK Department for International Development, London nutrition, we need to take a hard look at our global SW1A 2EG, UK (AT, ADD); Faculty of Epidemiology and Population

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Health and Leverhulme Centre for Integrative Research in 2 Horton S, Steckel RH. Malnutrition: Global economic losses attributable to Agriculture and Health, London School of Hygiene & Tropical malnutrition 1900–2000 and projections to 2050. In: Lomborg B, ed. How much have global problems cost the world? A scorecard from 1900 to Medicine, London, UK (ADD); and Public Health Foundation of 2050. Cambridge: Cambridge University Press, 2013 (in press). India, New Delhi, India (KSR) 3 Eastwood R, Lipton M. Demographic transition in sub-Saharan Africa: [email protected] how big will the economic dividend be? Popul Stud (Camb) 2011; 65: 9–35. 4 Monteiro CA, Benicio MH, Conde WL, et al. Narrowing socioeconomic We declare that we have no conflicts of interest. inequality in child stunting: the Brazilian experience, 1974–2007. 1 Black RE, Victora CG, Walker SP, et al, and the Maternal and Child Nutrition Bull World Health Organ 2010; 88: 305–11. Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; published online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60937-X.

Nutrition-sensitive food systems: from rhetoric to action

Action to improve the nutrition sensitivity of food as treatment of chronic diseases and micronutrient Published Online June 6, 2013 systems—and thereby increase the nutritional value of supplementation, are introduced­ to remedy problems http://dx.doi.org/10.1016/ food for people around the world—​offers substantial that could have been avoided. S0140-6736(13)61053-3 but underused opportunities.1,2 The rhetoric about such The appropriate policy interventions to change opportunities brought about by the global food crisis behaviour will be context specific and might include in 2007–08 has not resulted in much new action, for agricultural research to increase productivity of fruit at least two reasons. First, goals other than improved and vegetable cultivation and reduce micronutrient nutrition are pursued by strong economic and political deficiency; taxes on sugar, sweeteners, and fat to reduce interests in both the agricultural sector and the post- the prevalence of obesity; regulations for advertising harvest value chain.3 Farmers and other economic and promotion; and education about nutrition.5 In high- agents in food systems aim to make money subject income and rapidly growing low-income countries, the to reasonable levels of risk, and governments pursue agricultural sector has become or is rapidly becoming policies that are compatible with the interests of a supplier of raw materials for the food processing politically powerful stakeholder groups.4 Malnourished industry, rather than a provider of food for direct populations are rarely among these interests. consumption. As this transition proceeds, the potential The very high value of improved nutrition to for improvements to nutrition through nutrition- societies should be supported by alignments to create sensitive food systems moves from agriculture to the compatibility between nutrition and economic goals post-harvest value chain. The transition amplifies health for farmers and processors, and political momentum3 and nutrition risks by promotion of what Monteiro has to be created to foster policy interventions that make food systems nutrition sensitive. Governments could pursue two kinds of policy action: they could either change the behaviour of farmers, consumers, food processors, and other economic agents in the system through incentives, regulations, and knowledge; or they could accept present behaviours and introduce health-specific and nutrition-specific interventions to compensate for any nutritional damage done or improvements forgone. Although changing of behaviour is likely to be more cost-effective and sustainable, the second option is the most common. For example, food-system policies and the private sector promote inexpensive calories and expensive nutrients, resulting in overweight and micronutrient deficiencies.

Health and nutrition-specific interventions, such Getty Images Bloomberg via

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and colleagues call “ultra-processed” foods,6,7 resulting programmes such as kitchen garden projects, whereas in unhealthy dietary patterns. However, policy action the really important changes for nutrition, such as to regulate and incentivise the food industry to avoid prioritisation of agricultural research to enhance pro­ such negative health and nutrition effects and change duc­tivity in fruit and vegetable cultivation so as to consumer preferences is very scarce. reduce prices and improve micronutrient status, and A second reason for lack of action to improve nutrition various policies to change women’s time allocation or is the fixation of the health and nutrition community prices of various foods, will be ignored because they on randomised controlled trials (RCTs) as the only cannot be studied in RCTs.1,10 legitimate source of evidence.8,9 Unfortunately, RCTs— the gold standard in health research—are generally Per Pinstrup-Andersen impossible to apply to the food system except in small, Division of Nutritional Sciences, Cornell University, Ithaca, usually unimportant, projects. Health and nutrition NY 14853, USA [email protected] effects resulting from agricultural and other food- I declare that I have no conflicts of interest. system policies and programmes are very difficult to 1 Ruel MT, Alderman H, and the Maternal and Child Nutrition Study Group. assess with RCTs, partly because treatments cannot be Nutrition-sensitive interventions and programmes: how can they help to accelerate progress in improving maternal and child nutrition? randomised and because the effect pathway is long. Yet Lancet 2013; published online June 6. http://dx.doi.org/10.1016/ the most promising opportunities for improvement S0140-6736(13)60843-0. 2 Pinstrup-Andersen P. Food systems and human health and nutrition: of health and nutrition are undoubtedly found in such an economic policy perspective with a focus on Africa. Oct 11, 2012. http:// policies, and not in home gardens and other minor iis-db.stanford.edu/evnts/6697/Pinstrup-Andersen_10_11_12.pdf (accessed May 2, 2013). projects which are amenable to study within the 3 Gillespie S, Haddad L, Mannar V, Menon P, Nisbett N, and the Maternal and Child Nutrition Study Group. The politics of reducing malnutrition: building framework of randomised trials. commitment and accelerating progress. Lancet 2013; published online Although existing evidence obtained by other June 6. http://dx.doi.org/10.1016/S0140-6736(13)60842-9. 1 4 Pinstrup-Andersen P, Watson DD II. Food policy for developing countries: approaches is deemed inconclusive and does not the role of government in global, national, and local food systems. Ithaca, support policy intervention, the pathways through NY: Cornell University Press, 2011. 5 Herforth A, Jones A, Pinstrup-Andersen P. Prioritizing nutrition in which food systems can affect nutrition (positively agriculture and rural development: guiding principles for operational or negatively) are well known. Furthermore, key investments. Washington, DC: World Bank, 2012. 6 Monteiro CA, Levy RB, Claro RM, deCastro IRR, Cannon G. Increasing components making up these pathways, such as consumption of ultra-processed foods and likely impact on human health: incomes, prices, women’s time allocation, dietary evidence from Brazil. Public Health Nutr 2011; 14: 5–13. 7 Monteiro CA. Nutrition and health. The issue is not food, nor nutrients, so diversity, advertising and promotion,­ and household much as processing. Public Health Nutr 2009; 12: 729–31. 8 Bhutta ZA, Ahmed T, Black RE, et al, for the Maternal and Child and individual behaviour have a substantial effect Undernutrition Study Group. What works? Interventions for maternal and on nutrition. Thus, if pathway analysis shows that child undernutrition and survival. Lancet 2008; 371: 417–40. 9 Bhutta ZA, Das JK, Rizvi A, et al, The Lancet Nutrition Interventions Review changes in the food system improve one or more of Group, and the Maternal and Child Nutrition Study Group. Evidence-based these components—eg, dietary diversity or women’s interventions for improvement of maternal and child nutrition: what can be done and at what cost? Lancet 2013; published online June 6. http://dx. time allocation—and such improvements reduce micro­ doi.org/10.1016/S0140-6736(13)60996-4. 10 Masset E, Haddad L, Cornelius A, Isaza-Castro J. A systematic review of nutrient deficiencies, is such evidence really acceptable agricultural interventions that aim to improve nutritional status of for policy guidance only if it is derived from RCTs? If children. London: EPPI-Centre, Social Science Research Unit, Institute of Education, University of London, 2011. so, the evidence will be limited to small food-systems

Global child and maternal nutrition—the SUN rises

Published Online In April, 2010, a policy brief—Scaling Up Nutrition: an emphasis on the 1000 day window from the June 6, 2012 A Framework for Action—was released at the spring start of pregnancy to a child’s second birthday, with http://dx.doi.org/10.1016/ S0140-6736(13)61086-7 meetings of the World Bank and International interventions that are both cost-effective and yield For the Scaling Up Nutrition Monetary Fund. It was a collective effort stimulated high returns for cognitive development, individual policy brief see http:// scalingupnutrition.org/ by the publication in January, 2008, of The Lancet’s adult earnings, and economic growth. A second Series wp-content/uploads/pdf/ Series on undernutrition. The Lancet Series encouraged on nutrition, published in The Lancet,1–4 now explicitly SUN_Framework.pdf

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shows that the solution to malnutrition relies on a collective effort in which all stakeholders—governments, academia, civil society, UN system organisations, foundations, development banks, and businesses—carry out specific roles in ensuring that interventions are delivered equitably and at scale. The policy brief, which quickly became known as the SUN Framework, set the stage for the transformation that is now happening in global nutrition. It called for country-owned nutrition strategies and programmes; urgent scaling up of evidence-based and cost-effective interventions; integration of nutrition within national strategies for gender equality, agriculture, food security, social protection, education, water supply, sanitation, and health care; and a substantial increase in domestic support and external assistance for nutrition within the Getty Images Bloomberg via food security, social protection, and health sectors. The SUN Road Map, prepared later in 2010 and revised in Series by bringing additional evidence to support the For the Lancet’s 2008 Series 2012, set out ways for a wide range of groups to work focus on ensuring that all women, girls, and young on maternal and child undernutrition see http://www. together in sharpening, scaling up, and aligning their children are able to access specific interventions of thelancet.com/series/maternal- responses to people’s nutritional needs—and achieving good quality; they should be included in mainstream and-child-undernutrition For the SUN Movement Revised results. efforts for public health, family planning, and water Roadmap see http:// Alongside the 1000 days advocacy partnership, and sanitation. The third paper3 sets the foundation scalingupnutrition.org/wp- content/uploads/2012/10/SUN- the SUN Movement was launched at the UN General for evidence-based research into achieving outcomes Movement-Road-Map- Assembly in September, 2010. It takes forward the SUN through nutrition-sensitive strategies in four key Septemeber-2012_en.pdf Road Map by encouraging coherence and effectiveness areas: agriculture and food, social security, early child For the 1000 days partnership see http://www.thousanddays. among all groups working for better nutrition; it is not development, and class­room education. It draws on org an initiative, project, or programme. By April, 2013, the experience of countries that have made great 35 countries had joined the SUN Movement with progress when stressing that gender and social commitments that are in line with the SUN Framework equality are the cornerstones of nutritional success. and Road Map. These countries’ nutrition solutions By focusing on the political context for effective show the commitments of political leaders, whole-of- action, the fourth paper4 recalls that the realisation of society responses, careful tracking of progress, and the human rights, a commitment to equity, and gender benefits of shared experience. equality should be properly prioritised. It includes The second Lancet nutrition Series provides a range important proposals for ways in which business can of valuable insights as the SUN Movement moves best be engaged (and the challenges of doing so), and through 2013, a year dense with events that will encourages increased involvement of civil society at all move nutrition to the heart of the development levels. It likewise underlines the need for governments agenda. It calls for a substantial increase of political to increase their own accountability for ensuring commitment in responding to the complex causes of that people are able to achieve good nutrition and undernutrition. It recognises that the SUN Movement to ensure the existence of a fair and transparent has the potential to harness such change and yield framework for regulating any entity that might—even durable results. unwittingly—undermine nutritional justice. The first paper1 of the Series leaves no doubt as to At the May, 2012, World Health Assembly, why nutrition is key for sustainable development government representatives agreed ambitious and the wellbeing of entire populations. The second goals for reduction of all forms of malnutrition, paper2 strengthens the arguments of the 2008 Lancet including obesity. This Lancet Series points out that

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these goals can only be achieved through improved David Nabarro nutrition governance, more human resources, better SUN Movement Secretariat, Villa La Pelouse (2nd Floor), Palais Des demonstration of results, and increased investments Nations, 1201 Geneva, Switzerland [email protected] from domestic and international sources. In the past I declare that I have no conflicts of interest. 3 years the SUN Movement has provided a platform 1 Black RE, Victora CG, Walker SP, et al, and the Maternal and Child Nutrition to enable leaders to pledge to intensify efforts for Study Group. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013; published online improved nutrition. 2013 provides a once-in-a-lifetime June 6. http://dx.doi.org/10.1016/S0140-6736(13)60937-X. opportunity to strengthen worldwide resolve for 2 Bhutta ZA, Das JK, Rizvi A, et al, The Lancet Nutrition Interventions Review Group, and the Maternal and Child Nutrition Study Group. Evidence-based improved nutrition, through commitments being made interventions for improvement of maternal and child nutrition: what can in a series of international and regional events. be done and at what cost? Lancet 2013; published online June 6. http:// dx.doi.org/10.1016/S0140-6736(13)60996-4. The publication of the second Lancet Series is 3 Ruel MT, Alderman H, and the Maternal and Child Nutrition Study Group. Nutrition-sensitive interventions and programmes: how can they help to timely and reinforces the urgency for transformation accelerate progress in improving maternal and child nutrition? of political commitment into actions that lead to Lancet 2013; published online June 6. http://dx.doi.org/10.1016/ S0140-6736(13)60843-0. improvements in nutrition. The Series brings scientific 4 Gillespie S, Haddad L, Mannar V, Menon P, Nisbett N, and the Maternal and rigour to the challenge of equitable delivery of effective Child Nutrition Study Group. The politics of reducing malnutrition: building commitment and accelerating progress. Lancet 2013; published services at scale—both now and in the years to come. online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60842-9.

Early nutrition and adult outcomes: pieces of the puzzle

Published Online The association between nutrition in early life and after exposure to suboptimum nutrition during crucial March 28, 2013 long-term health has been of interest for decades. periods of development.1 The importance of these http://dx.doi.org/10.1016/ S0140-6736(13)60716-3 Since the articulation of the fetal origins hypothesis by findings greatly increased after reports about the global See Online/Articles David Barker and colleagues,1 there has been debate burden of non-communicable diseases and risk factors http://dx.doi.org/10.1016/ 2 S0140-6736(13)60103-8 about the implications of fetal undernutrition and were published in December, 2012. early childhood growth on outcomes of importance Evidence for the importance of early nutrition for in adult health and risks of chronic diseases. Both adult outcomes was derived initially from obser­ epidemiological and animal studies have shown that vational cohort studies3 and was reaffirmed by analysis the risk of metabolic syndrome is significantly increased of outcome data from several cohort studies in 2008.4 This analysis4 was focused on a meta-analysis of coefficients from different sites: birthweight, weight and length Z scores, and stunting at age 2 years. In The Lancet, Linda Adair and colleagues5 report findings from a study in which they pooled data from five birth cohorts and investigated how linear growth and relative weight gain in several age ranges affected adult outcomes. They report that higher birthweight was associated with an adult body- mass index of greater than 25 kg/m² (odds ratio 1·28, 95% CI 1·21–1·35) and a reduced likelihood of short stature (0·49, 0·44–0·54) and of not completing secondary school (0·82, 0·78–0·87). Faster linear growth was also strongly associated with reduced likelihood of short adult stature (age 2 years: 0·23, 0·20–0·52; mid-childhood 0·39, 0·36–0·43) and of

Andrew Aitchison/In Pictures/Corbis not completing secondary school (age 2 years: 0·74,

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0·67–0·78; mid-childhood 0·87, 0·83–0·92). Faster However, this tenet could be too simplistic, because relative weight gain was associated with an increased it focuses on care during pregnancy and ignores the risk of adult overweight (age 2 years: 1·51, 1·43–1·60; vital contribution of maternal health and nutrition mid-childhood 1·76, 1·69–1·91) and elevated blood in the periods before and just after conception to pressure (age 2 years: 1·07, 1·01–1·13; mid-childhood: intrauterine and postnatal growth. Evidence supports 1·22, 1·15–1·30). an association between micronutrient supple­men­ Notwithstanding the key findings, several limitations tation around the time of conception and DNA of this pooled analysis should be recognised. The methylation13 and increased methylation of the IGF2 authors had to make do with disparate information genes in childhood,14 indicating that these factors about socio­economic status and income, and impute could affect linear growth postnatally. Although some information that was missing. Although they Adair and colleagues’ analysis of birth outcomes in adjusted for maternal education and socioeconomic the international cohorts does not shed light on the status (largely assets rather than income), other importance of maternal health and nutrition before potential confounding factors (eg, household and conception, these factors might be just as important learning environment) could not be assessed in relation as postnatal factors and should be investigated. to attained schooling. Several additional limitations What is the way forward? Although the evidence preclude firm conclusions.­ Little or no information was emerging from observational studies such as Adair available about maternal nutrition and micronutrient and colleagues’ is important for policy, well designed status. Additionally, Adair and colleagues do not prospective studies with appropriate interventions and report any outcomes related to intrauterine growth follow-up are clearly needed. The outcomes should retardation or gestational age at birth, and merely include elements of child development, education, report association with birthweight, which might employment, and earnings, which would allow be oversimplified. Being small for gestational age at improved estimation of effect on human capital. term, and especially preterm, has now been recognised Although expensive and difficult to organise and as a major risk factor for excess newborn and infant implement, such cohort studies are a crucial investment mortality6 and accounts for a substantial proportion for the future and, in view of the interest in human of child stunting.7 Prematurity is associated with development in the post-2015 era, should be prioritised increased risks of metabolic syndromes in later life.8 for funding. Potential variations in body composition of newborn babies might not be captured by mere measurement of Zulfiqar A Bhutta birthweight or size. So-called thin-fat infants—ie, small Division of Women and Child Health, Aga Khan University, Karachi newborn babies that have elevated body fat content— 74800, Pakistan [email protected] have been described9 and could be associated with I declare that I have no conflicts of interest. increased risks of insulin resistance in childhood.10 1 Barker DJ. Sir Richard Doll lecture: developmental origins of chronic disease. These limitations aside, Adair and colleagues’ find­ Public Health 2012; 126: 185–89. 5 2 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden ings are some of the most important from existing of disease and injury attributable to 67 risk factors and risk factor clusters cohorts linking early childhood nutrition—especially in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2224–60. birthweight and improved patterns of linear growth— 3 Barker DJP, Godfrey KM, Gluckman PD, Harding JE, Owens JA, Robinson JS. with long-term outcomes. They have clear implications Fetal nutrition and cardiovascular disease in adult life. Lancet 1993; 341: 938–41. for public health policy and nutrition interventions. As 4 Victora CG, Adair L, Fall C, et al, for the Maternal and Child Undernutrition shown by an analysis of evidence-based interventions,11 Study Group. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 2008; 371: 340–57. a focus on improvements in nutrition in pregnancy 5 Adair LS, Fall CHD, Osmond C, et al, for the COHORTS group. Associations of linear growth and relative weight gain during early life with adult health and linear growth in the first 2 years of life could lead and human capital in countries of low and middle income: findings from to substantial reductions in stunting and improved five birth cohort studies. Lancet 2013; published online March 28. http:// dx.doi.org/10.1016/S0140-6736(13)60103-8. survival. These improvements form the basis for the 6 Marchant T, Willey B, Katz J, et al. Neonatal mortality risk associated with emphasis on the first 1000 days of life, which has preterm birth in East Africa, adjusted by weight for gestational age: individual participant level meta-analysis. PLoS Med 2012; 9: e1001292. been used effectively to scale up nutrition activities.12

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7 Black RE, Victora CG, Walker SP, et al, and the Maternal and Child Nutrition 11 Bhutta ZA, Ahmed T, Black RE, et al, for the Maternal and Child Study Group. Maternal and child undernutrition and overweight in Undernutrition Study Group. What works? Interventions for maternal and low-income and middle-income countries. Lancet 2013; published online child undernutrition and survival. Lancet 2008; 371: 417–40. June 6. http://dx.doi.org/10.1016/S0140-6736(13)60937-X. 12 Save The Children. Nutrition in the first 1000 days: state of the world’s 8 Parkinson JRC, Hyde M J, Gale C, Santhakumaran S, Modi N. Preterm birth mothers 2012. May, 2012. http://www.savethechildren.ca/document. and the metabolic syndrome in adult life: a systematic review and doc?id=195 (accessed March 21, 2013). meta-analysis. Pediatrics 2013; published online March 18. DOI:10.1542/ 13 Cooper WN, Khulan B, Owens S, et al. DNA methylation profiling at peds.2012-2177. imprinted loci after periconceptional micronutrient supplementation in 9 Yajnik CS, Fall CH, Coyaji KJ, et al. Neonatal anthropometry: humans: results of a pilot randomized controlled trial. FASEB J 2012; the thin-fat Indian baby—the Pune Maternal Nutrition Study. 26: 1782–90. Int J Obes Relat Metab Disord 2003; 27: 173–80. 14 Steegers-Theunissen RP, Obermann-Borst SA, Kremer D, et al. 10 Lakshmi S, Metcalf B, Joglekar C, Yajnik CS, Fall CH, Wilkin TJ. Differences in Periconceptional maternal folic acid use of 400 microg per day is related to body composition and metabolic status between white UK and Asian increased methylation of the IGF2 gene in the very young child. PLoS One Indian children (EarlyBird 24 and the Pune Maternal Nutrition Study). 2009; 4: e7845. Pediatr Obes 2012; 7: 347–54.

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Maternal and Child Nutrition 1 Maternal and child undernutrition and overweight in low-income and middle-income countries

Robert E Black, Cesar G Victora, Susan P Walker, Zulfiqar A Bhutta*, Parul Christian*, Mercedes de Onis*, Majid Ezzati*, Sally Grantham-McGregor*, Joanne Katz*, Reynaldo Martorell*, Ricardo Uauy*, and the Maternal and Child Nutrition Study Group†

Maternal and child malnutrition in low-income and middle-income countries encompasses both under­nutrition and Published Online a growing problem with overweight and obesity. Low body-mass index, indicative of maternal undernutrition, has June 6, 2013 declined somewhat in the past two decades but continues to be prevalent in Asia and Africa. Prevalence of maternal http://dx.doi.org/10.1016/ S0140-6736(13)60937-X overweight has had a steady increase since 1980 and exceeds that of underweight in all regions. Prevalence of stunting This is the first in a Series of of linear growth of children younger than 5 years has decreased during the past two decades, but is higher in south four papers about maternal and Asia and sub-Saharan Africa than elsewhere and globally affected at least 165 million children in 2011; wasting child nutrition affected at least 52 million children. Deficiencies of vitamin A and zinc result in deaths; deficiencies of iodine and *Members listed alphabetically iron, together with stunting, can contribute to children not reaching their developmental potential. Maternal †Members listed at end of paper undernutrition contributes to fetal growth restriction, which increases the risk of neonatal deaths and, for survivors, Johns Hopkins University, of stunting by 2 years of age. Suboptimum breastfeeding results in an increased risk for mortality in the first 2 years Bloomberg School of Public of life. We estimate that undernutrition in the aggregate—including fetal growth restriction, stunting, wasting, and Health, Baltimore, MD, USA (Prof R E Black MD, deficiencies of vitamin A and zinc along with suboptimum breastfeeding—is a cause of 3·1 million child deaths Prof P Christian DrPH, annually or 45% of all child deaths in 2011. Maternal overweight and obesity result in increased maternal morbidity Prof J Katz ScD); Universidade and infant mortality. Childhood overweight is becoming an in­creasingly important contributor to adult obesity, Federal de Pelotas, Pelotas, diabetes, and non-communicable diseases. The high present and future disease burden caused by malnutrition­ in Rio Grande do Sol, Brazil (Prof C G Victora MD); The women of reproductive age, pregnancy, and children in the first 2 years of life should lead to interventions focused on University of the West Indies, these groups. Tropical Medicine Research Institute, Mona Campus, Introduction continuing stunting of growth and deficiencies of essential Kingston, Jamaica (Prof S P Walker PhD); Maternal and child malnutrition, encompassing both nutrients along with obesity in national populations­ and The Aga Khan University and undernutrition and overweight, are global problems with within families. We also want to assess national progress Medical Center, Department of important consequences for survival, incidence of acute in nutrition programmes and inter­national actions con­ Pediatrics, Karachi, Pakistan and chronic diseases, healthy development, and the sistent with our previous recommendations. (Prof Z A Bhutta PhD); World economic productivity of individuals and societies. Maternal and child undernutrition, including stunting, wasting, and deficiencies of essential vitamins and Key messages 1–5 minerals, was the subject of a Series in The Lancet in • Iron and calcium deficiencies contribute substantially to maternal deaths 2008, which quantified their prevalence, short-term and • Maternal iron deficiency is associated with babies with low weight (<2500 g) at birth long-term consequences, and potential for reduction • Maternal and child undernutrition, and unstimulating household environments, through high and equitable coverage of proven nutrition contribute to deficits in children’s development and health and productivity in adulthood interventions. The Series identified the need to focus on • Maternal overweight and obesity are associated with maternal morbidity, preterm the crucial period of pregnancy and the first 2 years of birth, and increased infant mortality life—the 1000 days from conception to a child’s second • Fetal growth restriction is associated with maternal short stature and underweight birthday during which good nutrition and healthy growth and causes 12% of neonatal deaths have lasting benefits throughout life. The 2008 Series also • Stunting prevalence is slowly decreasing globally, but affected at least 165 million called for greater national priority for nutrition pro­ children younger than 5 years in 2011; wasting affected at least 52 million children grammes, more integration­ with health programmes, • Suboptimum breastfeeding results in more than 800 000 child deaths annually enhanced intersectoral­ approaches, and more focus • Undernutrition, including fetal growth restriction, suboptimum breastfeeding, and coordination in the global nutrition system of inter­ stunting, wasting, and deficiencies of vitamin A and zinc, cause 45% of child deaths, national agencies, donors, academia, civil society, and the resulting in 3·1 million deaths annually private sector. 5 years after that series, we intend not • Prevalence of overweight and obesity is increasing in children younger than 5 years only to reassess the problems of maternal and child globally and is an important contributor to diabetes and other chronic diseases undernutrition, but also to examine the growing problems­ in adulthood of overweight and obesity for women and children and • Undernutrition during pregnancy, affecting fetal growth, and the first 2 years of life is their consequences in low-income and middle-income a major determinant of both stunting of linear growth and subsequent obesity and countries (LMICs). Many of these countries are said to non-communicable diseases in adulthood suffer the so-called double burden of malnutrition, with www.thelancet.com 15 Series

Health Organization, The present Series is guided by a framework (figure 1) undernutrition in childhood and obesity and related Department of Nutrition for that shows the means to optimum fetal and child growth diseases in adulthood. Thus, we organise this paper to Health and Development, and development, rather than the determinants of consider prevalence and con­sequences of nutritional Geneva, Switzerland (M de Onis MD); Imperial College undernutrition as shown in the conceptual model conditions during the life course from adolescence to of London, St Mary’s Campus, developed by UNICEF and used in the 2008 Series.1 This pregnancy to childhood and discuss the implications for School of Public Health, new framework shows the dietary, behavioural, and adult health. In the second paper, we describe evidence MRC-HPA Centre for Environment and Health, health determinants of optimum nutrition, growth, and supporting nutrition-specific interventions and the health Department of Epidemiology development and how they are affected by underlying effects and costs of increasing their population coverage. and Biostatistics, London, UK food security, caregiving resources, and environmental In the third paper we examine nutrition-sensitive inter­ (Prof M Ezzati PhD); Institute of conditions,­ which are in turn shaped by economic and ventions and approaches and their potential to improve Child Health, University College London, London, UK (Prof social conditions, national and global contexts, resources, nutrition. In the fourth paper we examine the features of S Grantham-McGregor FRCP); The and governance. This Series examines how these an enabling environment that are needed to provide University of the West Indies, determinants can be changed to enhance growth and support for nutrition programmes and how they can be Mona, Jamaica development. These changes include nutrition-specific favourably changed. Finally, in a Comment6 we will (Prof S Grantham-McGregor); Emory University, Atlanta, GA, interventions that address the immediate causes of examine the desired national and global response to USA (Prof R Martorell PhD); and suboptimum growth and development. The framework address nutritional and developmental needs of women London School of Hygiene and shows the potential effects of nutrition-sensitive inter­ and children in LMICs. Tropical Medicine, London, UK ventions that address the underlying determinants of (Prof R Uauy PhD) malnutrition and incorporate specific nutrition goals Prevalence and consequences of nutritional Correspondence to: Prof Robert Black, Johns Hopkins and actions. It also shows the ways that an enabling conditions University, Bloomberg School of environment can be built to support interventions and Adolescent nutrition Public Health, Baltimore, programmes to enhance growth and development and Adolescent nutrition is important to the health of girls MD 21205, USA their health consequences. In the first paper we assess and is relevant to maternal nutrition. There are 1·2 billion [email protected] the prevalence of nutritional conditions and their health adolescents (aged 10–19 years) in the world, 90% of whom and development consequences. We deem a life-course live in LMICs. Adolescents make up 12% of the population perspective to be essential to conceptualise the nutritional in industrialised countries, compared­ with 19% in LMICs See Online for appendix effects and benefits of interventions. The nutritional (appendix p 2 shows values for ten countries studied in status of women at the time of conception and during depth).7 Adolescence is a period of rapid growth and pregnancy is important for fetal growth and development, maturation from childhood to adulthood. Indeed, some and these factors, along with nutritional status in the first researchers have argued that adolescence is a period 2 years of life, are important determinants of both with some potential for height catch-up in children with

Benefits during the life course Morbidity and Cognitive, motor, School performance Adult stature Work capacity mortality in childhood socioemotional development and learning capacity and productivity Obesity and NCDs

Nutrition specific Optimum fetal and child nutrition and development Nutrition sensitive interventions programmes and approaches and programmes • Agriculture and food security • Adolescent health and Breastfeeding, nutrient- Feeding and caregiving Low burden of • Social safety nets preconception nutrition rich foods, and eating practices, parenting, infectious diseases • Early child development • Maternal dietary routine stimulation • Maternal mental health supplementation • Women’s empowerment • Micronutrient • Child protection supplementation or Food security, including Feeding and caregiving Access to and use of • Classroom education fortification availability, economic resources (maternal, health services, a safe and • Water and sanitation • Breastfeeding and access, and use of food household, and hygienic environment • Health and family planning services complementary feeding community levels) • Dietary supplementation for children • Dietary diversification Building an enabling environment Knowledge and evidence • Feeding behaviours and • Rigorous evaluations Politics and governance stimulation • Advocacy strategies Leadership, capacity, and financial resources • Treatment of severe acute • Horizontal and vertical coordination Social, economic, political, and environmental context (national and global) malnutrition • Accountability, incentives regulation, • Disease prevention and legislation management • Leadership programmes • Nutrition interventions in • Capacity investments emergencies • Domestic resource mobilisation

Figure 1: Framework for actions to achieve optimum fetal and child nutrition and development

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stunting from early childhood.8 Adolescent fertility is In India, for example, 55·8% of adolescents aged three times higher in LMICs than in high-income coun­ 15–19 years and 56·7% of women aged 20–24 years were tries. Preg­nancies in adolescents have a higher risk of anaemic;14 corresponding values for Guatemala were complications and mortality in mothers9 and children10 21·0% and 20·4 %, respectively.15 and poorer birth outcomes than pregnancies in older women.10,11 Furthermore,­ pregnancy in adolescence will Maternal nutrition slow and stunt a girl’s growth.12,13 In some countries, as Prevalence of low BMI (<18·5 kg/m²) in adult women many as half of adolescents are stunted (height-for-age has decreased in Africa and Asia since 1980, but remains Z score [HAZ] <–2), increasing the risk of poor perinatal higher than 10% in these two large developing regions outcomes in their offspring (appendix p 2). We used (figure 2). During the same period, prevalence of age-specific, low body-mass index (BMI) cutoffs (BMI over­weight (BMI ≥25 kg/m²) and obesity (BMI ≥30 kg/m²) Z score [BMIZ] <–2) from the WHO reference for has been rising in all regions, together reaching more children aged 5–19 years to examine ten selected than 70% in the Americas and the Caribbean and more countries; in these locations as many as 11% (India) of than 40% in Africa by 2008.16,17 adolescent girls are thin. In these countries, prevalence of Few studies have examined the risk of maternal high BMI for age, defined as BMIZ >2 (obesity), is as mortality in relation to maternal anthropometry with a high as 5% (Brazil; appendix p 2). Adolescents have as prospective design. In one study in Nepal18 of about high a prevalence of anaemia as women aged 20–24 years. 22 000 women, mid upper arm circumference during

Africa Americas and the Caribbean 60·0 1980 2000 1985 2005 50·0 1990 2008 1995 40·0

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Figure 2: Trends in thinness (BMI <18·5 kg/m²), overweight (BMI ≥25 kg/m²), and obesity (BMI ≥30 kg/m²), using population weighted average prevalences for women aged 20–49 years UN regions and globally, 1980–2008 Error bars are 95% CIs. BMI=body-mass index. www.thelancet.com 17 Series

pregnancy was inversely associated with all-cause mater­ Maternal vitamin deficiencies nal mortality up to 42 days post-partum after adjust­ing Anaemia and iron for numerous factors. An inverse association exists Anaemia (haemoglobin <110 g/L), which might be between maternal height and the risk of dystocia (difficult attributable to low consumption or absorption in the diet labour), as measured by cephalopelvic dispro­portion or or to blood loss, such as from intestinal worms, is highly assisted or caesarean deliveries.19–23 prevalent during pregnancy. This Series focuses on Figure 2 also shows trends for overweight and obesity anaemia amenable to correction with iron supple­men­ in women aged 20–49 years in different UN regions. tation.42 To establish the importance of iron deficiency as Oceania, Europe, and the Americas had the highest a cause of maternal anaemia we used the results of trials proportion of overweight and obese women; however of iron supplementation to work out the shift in the northern and southern Africa, and central and west Asia popu­lation haemoglobin distribution. A meta-analysis of also had high prevalences (appendix p 3). the effects of iron supplementation­ trials showed that, Maternal obesity leads to several adverse maternal and among pregnant women with anaemia at baseline, iron fetal complications during pregnancy, delivery, and supple­mentation led to a 10·2 g/L increase in haemo­ post-partum.24 Obese pregnant women (pre-pregnant globin.43 The corresponding figure for children was BMI ≥30 kg/m²) are four times more likely to develop 8·0 g/L.44 We applied these shifts to the present dis­tri­ gestational diabetes mellitus and two times more likely to butions of haemoglobin estimated by Stevens and develop pre-eclampsia compared with women with a colleagues42 and calculated the proportion of pregnant BMI 18·5–24·9 kg/m2).25–28 During labour and delivery, women with anaemia whose blood haemoglobin would maternal obesity is associated with maternal death, increase to at least 110 g/L. We likewise calculated the haemor­rhage, caesarean delivery, or infection;29–31 and a proportion of severe anaemia that would increase to at higher risk of neonatal and infant death,32 birth trauma, least 70 g/L. These results constitute the prevalence of and macrosomic infants.33–37 In the post-partum period, iron amenable or iron deficiency anaemia (IDA) or severe obese women are more likely to delay or fail to lactate and IDA, defined as the proportion of anaemia or severe to have more weight retention than women of normal anaemia that would be reduced if only iron was provided, weight.38 Obese women with a history of gestational holding other determinants of anaemia unchanged. With diabetes have an increased risk of subsequent type this approach in 2011, Africa had the highest proportion two diabetes, metabolic syndrome, and cardio­vascular of IDA for pregnant women followed closely by Asia disease.39 The early intrauterine­ environment has a role in (table 1,45–47 appendix p 4). Likewise, Africa had the highest programming pheno­type, affecting health in later life. prevalence of severe IDA, but in all regions prevalence Maternal overweight and obesity at the time of pregnancy was less than 1%. increases the risk for childhood obesity that continues Our previous analyses48 showed that anaemia in preg­ into adoles­cence and early adulthood, potentiating the nancy increased the risk of maternal mortality. An transgenerational­ trans­mission of obesity.40,41 updated analysis49 with ten studies (four more than the

Vitamin A deficiency45 Iodine Zinc deficiency47 Iron deficiency anaemia (haemoglobin deficiency46 (weighted <110 g/L) (UIC <100 µg/L) average of country means) Children <5 years Pregnant women Children <5 years Pregnant women Night Serum retinol Night Serum retinol blindess <0·70 µmol/L blindness <0·70 µmol/L Global 0·9% 33·3% 7·8% 15·3% 28·5% 17·3% 18·1% 19·2% (0·1–1·8) (29·4–37·1) (6·5–9·1) (6·0–24·6) (28·2–28·9) (15·9–18·8) (15·6–20·8) (17·1–21·5) Africa 2·1% 41·6% 9·4% 14·3% 40·0% 23·9% 20·2% 20·3% (1·0–3·1) (34·4–44·9) (8·1–10·7) (9·7–19·0) (39·4–40·6) (21·1–26·8) (18·6–21·7) (18·3–22·4) Americas 0·6% 15·6% 4·4% 2·0% 13·7% 9·6% 12·7% 15·2% and the (0·0–1·3) (6·6–24·5) (2·7–6·2) (0·4–3·6) (12·5–14·8) (6·8–12·4) (9·8–16·0) (11·7–18·6) Carribean Asia 0·5% 33·5% 7·8% 18·4% 31·6% 19·4% 19·0% 19·8% (0·0–1·3) (30·7–36·3) (6·6–9·0) (5·4–31·4) (30·7–32·5) (16·9–22·0) (14·5–23·4) (15·8–23·5) Europe 0·7% 14·9% 2·9% 2·2% 44·2% 7·6% 12·1% 16·2% (0·0–1·5) (0·1–29·7) (1·1–4·6) (0·0–4·3) (43·5–45·0) (6·2–9·1) (7·8–16·2) (12·6–19·7) Oceania 0·5% 12·6% 9·2% 1·4% 17·3% 5·7% 15·4% 17·2% (0·1–1·0) (6·0–19·2) (0·3–18·2) (0·0–4·0) (16·6–18·1) (1·0–10·3) (7·0–25·2) (9·7–25·6)

Data are % (95% CI). UIC=urine iodine concentration.

Table 1: Prevalence of vitamin A deficiency (1995–2005), iodine deficiency (2013), inadequate zinc intake (2005), and iron deficiency anaemia (2011)

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previous analysis) showed that the odds ratio (OR) for suggesting that benefits can be detected in later childhood maternal deaths was 0·71 (95% CI 0·60–0·85) for a when more complex tasks can be measured.62 10 g/L greater mean haemoglobin in late pregnancy. Only two of the ten studies adjusted for socioeconomic Vitamin A con­founding variables; one showed no attenuation and Maternal vitamin A deficiency can cause visual impair­ the other a 20% attenuation of the effect. ment and possibly other health consequences. Deficiency There is strong biological plausibility for a causal link is assessed in pregnant women as either a history of night between maternal IDA and adverse birth outcomes includ­ blindness or serum or plasma retinol concentrations of ing low birthweight and increased perinatal mortality.50–52 A less than 0·70 µmol/L (subclinical vitamin A deficiency). meta-analysis53 that included 11 trials indentified­ a WHO provides prevalence estimates for 1995–2005 from significant 20% reduction in the risk of low birthweight 64 countries, which we used for estimates for the UN associated with antenatal supplementation with iron alone world regions (table 1).45 Globally, the prevalence of night or combined with folic acid (relative risk [RR] 0·80, 95% CI blindness in pregnant women is estimated to be 7·8% 0·71–0·90). A previous Cochrane review54 had much the (95% CI 7·0–8·7), affecting 9·7 million women. An same findings. Dibley and colleagues55 pooled data from estimated 15·3% (7·4–23·2) of pregnant women globally demographic and health surveys from Indonesia for 1994, (19·1 million women) have deficient serum retinol con­ 1997, 2002–03, and 2007 and showed that risk of death of centrations. The degree to which night blindness and low children younger than 5 years was reduced by 34% when serum retinol overlap is not accounted for in this esti­ the mother consumed any iron-folic acid supplements mation, but night blindness is known to be associated (hazard ratio [HR] 0·66; 95% CI 0·53–0·81). Dibley and with a four-times higher odds of low serum retinol colleagues further showed that the protective effect was (OR 4·02, 95% CI 2·2–7·4).63 Night blindness is reduced greatest for deaths on the first day of life (0·40; 0·21–0·77), by vitamin A supplementation in pregnancy.63,64 Maternal but the protective effect was also shown for neonatal night blindness has been associated with increased low deaths (0·69; 95% CI 0·49–0·97) and post-neonatal deaths birthweight64 and infant mortality,65 yet trials of vitamin A (0·74; 0·56–0·99). A randomised controlled trial56 from in pregnancy have not showed significant effects on China showed a significant 54% (RR 0·46, 95% CI these outcomes.66–69 0·21–0·98) reduction in neonatal mortality with antenatal iron and folic acid supplementation compared with folic Zinc acid alone as control. In Nepal, mortality from birth to Zinc is a key micronutrient with a ubiquitous role in 7 years was reduced by 31% (HR 0·69, 95% CI 0·49–0·99) biological functions, including protein synthesis, cellular in the offspring of mothers who had received iron and folic division, and nucleic acid metabolism. Estimates­ revised acid during pregnancy compared with controls who in 2012 suggest that 17% of the world’s population is at received vitamin A only.57 risk of zinc deficiency, on the basis of an analysis of Randomised controlled trials from high-income national diets.47 Excess losses of zinc during diarrhoea coun­­­tries have shown benefits of iron supplementation also contribute to zinc deficiency. The effect of subclinical for improved maternal mental health and reduced zinc deficiency (defined as low plasma zinc concentration fatigue.58 Evidence from LMICs for the effect of mater­ without obvious signs of zinc deficiency) in women of nal IDA on mothers’ mental health and mother-child reproductive age and during pregnancy on health and interactions is scarce. In a small South African trial,59 development outcomes is poorly understood, although iron supplemen­tation of women with IDA from zinc deficiency has been suggested as a risk factor with 10 weeks post-partum to 9 months led to lower maternal adverse long-term effects on growth, immunity, and depression and perceived stress at 9 months compared metabolic status of surviving offspring.70 Zinc deficiency with placebo. At 9 months, iron supplemented mothers due to a rare genetic abnormality—acrodermatitis entero­ had better maternal-child interactions.60 By contrast, in ­pathica—in pregnancy results in a high risk of preterm Bangladesh higher levels of maternal iron supple­ and prolonged labour, post-partum haemorrhage,­ and mentation decreased the quality of maternal-child fetal growth restriction.70,71 A review of supple­mentation interaction at age 3–4 months and had no effect on trials with zinc in pregnancy showed a significant 14% maternal distress (anxiety and depression).61 reduction in preterm births in women in low-income There is some evidence for whether maternal IDA settings, but no significant effect on low birthweight.72 affects child development. Infants of mothers identified as having IDA at 6–8 weeks post-partum had lower Iodine developmental levels at 10 weeks and 9 months compared Maternal iodine deficiency is of concern in regard to with infants of control mothers without IDA.60 In Nepal, adverse effects on fetal development, yet few countries children whose mothers received iron and folate supple­ have nationally representative data from large-scale mentation during pregnancy had better general intelli­ surveys of urinary iodine concentration in pregnant gence and cognitive functioning at age 7–9 years women. Because of the correlation between urinary compared with children of mothers receiving placebo, iodine concentration in pregnant women and children www.thelancet.com 19 Series

aged 6–12 years (r² 0·69),73 status assessment in school- Substantial evidence suggests that calcium supple­ age children is used to estimate country, regional, and mentation in pregnancy is associated with a reduction global prevalence of iodine deficiency. Global estimates in gestational hypertensive disorders and preterm of iodine deficiency suggest that 28·5% of the world’s birth.89,90 However, the effect varies according to the population or 1·9 billion individuals are iodine- baseline calcium intake of the population and pre- deficient (table 1).46,74 This figure represents largely mild existing risk factors. A review of 1591 randomised con­ deficiency (defined as urinary iodine concentration of trolled trials suggested that calcium supplementation 50–99 ug/L). during preg­nancy was associated with a reduction in the Severe iodine deficiency in pregnancy causes cretin­ risk of gestational hypertension and a 52% reduction ism, which can be eliminated with iodine supple­men­ in the incidence of pre-eclampsia, along with a tation before conception or in the first trimester of 24% reduction in preterm birth and an increase in birth­ preg­nancy.75 Furthermore, two meta-analyses showed weight of 85 g. There was no effect on low birthweight average deficits of 12·5–13·5 intelligence quotient (IQ) or perinatal or neonatal mortality. The effect was mainly points in children associated with iodine deficiency of noted in populations with low calcium intake.92 The their mothers in pregnancy; however, they controlled effects of calcium supplementation interventions are for only a limited number of socioeconomic con­ described in the accompanying report by Zulfiqar A founders.76,77 A review of the effects of iodine supple­ Bhutta and colleagues.93 mentation in deficient populations showed a small The US Institute of Medicine has defined adequate increase in birth­weight.78 Effects of mild or moderate vitamin D status as having serum 25-hydroxyvitamin D iodine deficiency on brain development are not well ([OH]D) concentrations greater than 50 nmol/L in both estab­lished.78,79 The index of iodine deficiency (urinary the general population and pregnant women;94 serum iodine concentration) is a population measure and not concentrations of less than 25 nmol/L denote vita­ an individual one,80 therefore some individuals in min D deficiency whereas concentrations of less than regions of mild to moderate deficiency might have more 50 nmol/L denote vitamin D insufficiency.95 Although severe deficiency. few nationally representative surveys exist for vitamin D status, an estimated 1 billion people globally residing in Folate diverse geographies, many in LMICs, might be vitamin D The global prevalence of folate deficiency has not been insufficient or deficient.96–103 estimated because of the scarcity of suitable population- Vitamin D has an essential role in fetal development, based data.81 A substantial proportion of neural tube ensuring fetal supply of calcium for bone development, defects (congenital malformations of the spinal cord and enabling immunological adaptation required to main­ brain) are related to inadequate consumption of folic tain normal pregnancy, preventing miscarriage, and acid around the time of conception, in some populations promot­ing normal brain development.99,104–108 Poor associated with genetic factors that increase the need for maternal vitamin D status has been associated with dietary folic acid. A Cochrane review82 in 2010 included severe pre-eclampsia (new-onset gestational hyper­ five trials of folic acid (a synthetic form of folate) tension and protein­uria after 20 weeks of gestation) in supplementation and identified a 72% (RR 0·28; 95% CI turn leading to an increased risk of perinatal morbidity 0·15–0·52) reduction in the risk of neural tube defects. and mor­tality.99,109,110 Maternal vitamin D deficiency, A more recent systematic review had much the same especially in early pregnancy, has been associated findings and estimated that in 2005 56 000 deaths were with risk of pre-eclampsia (OR 2·09, 95% CI attributable to insufficient dietary folic acid.83 These 1·50–2·90), preterm birth (1·58, 1·08–2·31), and small- deaths were not added to the total deaths associated with for-gestational age (SGA; 1·52, 1·08–2·25).109,111 A undernutrition in the present analysis, because of the systematic review of three trials of vitamin D in uncertainty about this estimate. pregnancy showed an overall reduction of low birthweight of border­line significance(relative risk Calcium and vitamin D [RR] 0·48; 95% CI 0·23–1·01).111 These asso­ciations Calcium is an essential nutrient for several body func­ need to be better quantified before they can be included tions, including enzymatic and hormonal homoeostasis.­ in the global disease burden related to undernutrition. Evidence for the association between maternal dietary calcium intake and maternal bone density and fetal Effect of maternal stature or BMI on fetal mineralisation is inconsistent.84 Epidemiological evi­ growth restriction or postnatal growth dence does show an inverse association between calcium Maternal characteristics intake and development of hypertension in pregnancy.85,86 The 2008 Maternal and Child Undernutrition Series Gestational hypertensive disorders are the second examined the association of maternal nutritional status leading cause of maternal morbidity and mortality and (BMI and short stature) and fetal growth restriction, are associated with increased risk of preterm birth and defined as low birthweight at term. Here, we use data fetal growth restriction.87,88 from nine (height) and seven (BMI) population-based

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cohort studies and WHO perinatal facility-based data for studies that use different reference populations for SGA. 24 countries to examine associations separately for term Previous studies have also not separated SGA into term and preterm SGA in LMICs.112–121 Maternal stunting and preterm. In a pooled-analysis130 of 22 population- (height <145 cm) put infants at risk of term and preterm based cohort studies in LMICs in Asia, sub-Saharan SGA (appendix p 5). Low maternal BMI in early pregnancy Africa, and Latin America, the RR for neonatal (1–28 day) also put infants at higher risk of SGA (appendix p 5). BMI mortality associated with SGA (<10th centile) of 25 or greater was somewhat protective against term and was 1·83 (95% CI 1·34–2·50) and for post-neonatal preterm SGA (appendix p 5). Notably, most women in the (29–365 day) mortality was 1·90 (1·32–2·73), compared BMI category of greater than 25 kg/m² were very mildly with appropriate-for-gestational-age (AGA) infants. The overweight with very few obese women, which might RR for term SGA was 3·06 (95% CI 2·21–4·23) for explain the protective effect. neonatal mortality and 1·98 (1·39–2·81) for post-neonatal Maternal stature is a composite indicator representing genetic and environmental effects on the growing period 35·0 Prevalence preterm SGA of childhood. In a study122 involving 109 Demographic Prevalence term SGA Health Surveys, analyses adjusted for wealth, education, 30·0 and urban or rural residence showed that the absolute risk of dying among children younger than 5 years born 25·0 to the tallest mothers (≥160 cm) was 0·073 (95% CI 20·0 0·072–0·074) and to those born to the shortest mothers

(<145 cm) was 0·128 (0·126–0·130). The correspond­ 15·0 ing absolute risk for a child being stunted was Proportion (%) 0·194 (0·192–0·196) for the tallest mothers and 10·0 0·682 (0·673–0·690) for the shortest. The association with wasting was significant but much weaker.122 5·0

0 Fetal growth restriction Africa Asia Latin America Oceania Previous global and regional estimates of fetal growth and the Caribbean restriction used the term low birthweight as a proxy for being SGA in the absence of population-based birthweight Figure 3: Prevalence of small-for-gestational-age births, by UN regions and gestational age data at that time.1 Through recent analyses,­ we now have estimates of SGA prevalence from Attributable Proportion of Attributable Proportion of deaths with UN total deaths deaths with NIMS total deaths 22 population-based cohort studies and 23 countries with prevalences* of children prevalences† of children facility-based data,114 which were used to model SGA as a younger than younger than function of low birthweight and other covariates (neonatal 5 years 5 years mortality rate, representativeness of facility delivery) to Fetal growth restriction 817 000 11·8% 817 000 11·8% obtain country-specific SGA prevalence for 2010.123 The (<1 month) numbers on which the model is based include all livebirths, Stunting (1–59 months) 1 017 000* 14·7% 1 179 000† 17·0% but exclude babies who died so soon after birth that they Underweight (1–59 months) 999 000* 14·4% 1 180 000† 17·0% were not weighed. Imputing birthweight for these infants Wasting (1–59 months) 875 000* 12·6% 800 000† 11·5% did not change the estimation of SGA prevalence, although Severe wasting 516 000* 7·4% 540 000† 7·8% it did increase the mortality risk associated with being (1–59 months) born SGA. Figure 3 shows prevalence­ of SGA separated Zinc deficiency 116 000 1·7% 116 000 1·7% (12–59 months) into term and preterm SGA. By our estimate, in 2010 Vitamin A deficiency 157 000 2·3% 157 000 2·3% 32·4 million babies were born SGA, 27% of all births in (6–59 months) LMICs regions. When comparing­ the estimated numbers Suboptimum breastfeeding 804 000 11·6% 804 000 11·6% of children with SGA with those affected by stunting or (0–23 months) wasting, it is important to note that the cutoff for SGA is Joint effects of fetal growth 1 348 000 19·4% 1 348 000 19·4% the 10th centile of a reference population, whereas the restriction and suboptimum cutoffs for wasting or stunting are two Z scores below the breastfeeding in neonates median, or the 2·3rd centile. Appendix p 8 shows prevalence Joint effects of fetal growth 3 097 000 44·7% 3 149 000 45·4% restriction, suboptimum with 95% CIs of term and preterm SGA by UN subregions. breastfeeding, stunting, Notably, only 20% of preterm births in LMICs were also wasting, and vitamin A and SGA. Appendix p 8 show the ten countries with the highest zinc deficiencies (<5 years) number of SGA births in 2010. Data are to the nearest thousand. *Prevalence estimates from the UN. †Prevalence estimates from Nutrition Impact Associations between fetal growth restriction and Model Study (NIMS). infant survival have been previously reported,124–129 Table 2: Global deaths in children younger than 5 years attributed to nutritional disorders although it is difficult to compare associations across www.thelancet.com 21 Series

mortality, relative to term AGA infants. Infants born Causes of childhood growth faltering are multifactorial, preterm and SGA were at highest risk with RR of 15·42 but fetal growth restriction might be an important (9·11–26·12) for neo­natal mortality and 5·22 (2·83–9·64) contributor to stunting and wasting in children. To for post-neonatal mortality, relative to term AGA. quantify the association between fetal growth restriction By applying the attributable fractions of deaths to the and child undernutrition, we did a systematic scientific total neonatal and post-neonatal deaths for 2011 obtained literature search to identify longitudinal studies that had from the UN Interagency Group on Mortality Esti­ taken measurements of birthweight, gestational age, and mation,131 we estimated that the number of deaths child anthropometry. Data could be obtained from 19 birth attributed to SGA in 2011 was 817 000 in neonates and cohort studies which were submitted to a meta-analysis to 418 000 in infants aged 1–11 months using standard examine the odds of stunting, wasting, and underweight methods.1 The largest number of attributed deaths were in children 12–60 months of age associated with SGA and in Asia (appendix p 22). For the calculation in the group preterm birth.132 Four mutually exclusive exposure cate­ who were both SGA and preterm, the counterfactual was gories were created: AGA and preterm; SGA and term; AGA and preterm so that the SGA effect was separated SGA and preterm; and term AGA (as the reference group). from that of being preterm. In the estimation of the The meta-analysis showed that SGA alone and preterm deaths attributed to several nutritional conditions, we alone were associated with increased overall ORs of 2·43 attributed only the neonatal deaths to SGA; for children (95% CI 2·22–2·66) and 1·93 (1·71–2·18), respectively, aged 1–59 months, we attributed deaths to wasting and whereas both SGA and preterm increased the OR to 4·51 stunting, to which SGA contributed (table 2). (3·42–5·93) for stunting (appendix p 23). These raised

Panel 1: Determinants of childhood stunting and overweight The determinants of optimum growth and development proportion of stunting attributed to five previous episodes of (figure 1) consist of factors operating at different levels of diarrhoea was 25% (95% CI 8–38). causation, ranging from the most distal socioeconomic and Environmental (or tropical) enteropathy is an acquired political determinants to the proximate level where food, disorder, characterised by reduced intestinal absorptive disease, and care have a crucial role. A mirror image of figure 1 capacity, altered barrier integrity, and mucosal inflammation, would show the determinants of linear growth failure—the occurring in young children living in unsanitary settings.148 process leading to child stunting—and overweight. The large These children also have high rates of symptomatic and socioeconomic inequalities in stunting prevalence in almost all asymptomatic infections with enteric pathogens, but the exact low-income and middle-income countries (LMICs) show the association of these infections or of other possible toxic enteric great importance of distal determinants. In particular, maternal exposures with enteropathy is unclear. Some researchers have education is associated with improved child-care practices suggested that these functional changes and the associated related to health and nutrition and reduced odds of stunting, inflammation have significant adverse effects on the growth of and better ability to access and benefit from interventions. children. Alternatively, these changes might be a consequence Almost all stunting takes place in the first 1000 days after of nutritional deficits very early in life, including in utero, that conception. The few randomised controlled trials of lead to intestinal microbial colonisation. 145 breastfeeding promotion that included nutritional status Optimum growth in the first 1000 days of life is also essential for outcomes did not show any effects on the weight or length of prevention of overweight. Whereas attained weight at any age in infants. By contrast, there is strong evidence that the early life is positively associated with adult body-mass index in promotion of appropriate complementary feeding practices LMIC cohorts,2,149,150 rapid weight gains in the first 1000 days are 93 reduces the incidence of stunting. A meta-analysis of zinc strongly associated with adult lean mass, whereas weight gains 146 supplementation trials has shown a significant protective later in childhood lead mainly to adult fat mass. In particular, effect against stunting. evidence suggests that infants whose growth faltered in early life, Severe infectious diseases in early childhood—such as and who gained weight rapidly later in childhood, might be at measles, diarrhoea, pneumonia, meningitis, and malaria—​ particular risk of adult obesity and non-communicable diseases.2 can cause acute wasting and have long-term effects on linear Child overweight is also related to growing up in an obesogenic growth. However, studies have consistently shown that environment, in which population changes in physical activity diarrhoea is the most important infectious disease and diet are the main drivers. Modifiable risk factors for determinant of stunting of linear growth. In a pooled childhood obesity are maternal gestational diabetes; high levels 147 analysis of nine community-based studies in low-income of television viewing; low levels of physical activity; parents’ countries with daily diarrhoea household morbidity and inactivity; and high consumption of dietary fat, carbohydrate, longitudinal anthropometry, the odds of stunting at and sweetened drinks, yet few interventions have been 24 months of age increased multiplicatively with each rigorously tested.151–153 diarrhoea episode or day of diarrhoea before that age. The

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ORs were also noted in the Asian, African, and Latin that is attributable to birth size, independent of that American UN regions (data not shown). attributable to poor postnatal growth.137 We estimated population attributable risk for childhood Evidence for effects of fetal growth restriction on stunting for the risk categories of SGA and preterm cognition and behaviour after early childhood is less birth. Because risk estimates were derived as ORs using consistent. Birthweight was associated with attained logistic regression analysis, we used a method to schooling in the COHORTS analyses;138 however, this approximate the risk ratio proposed by Zhang and Yu133 was unadjusted for gestational age. Size at birth was for estimation of the population attributable risk. Using not related to women’s educational achievement in the approximated RR estimates across all 19 cohorts, Guatemala139 and term low birthweight was not associated­ population attributable risk for SGA-term for stunting with IQ and behaviour in school-aged chil­dren in Brazil140 was 0·16 (0·12–0·19), that for SGA-preterm was 0·04 and Jamaica,141 or behaviour in South Africa.142 In Taiwan, (0·02–0·05), and that for AGA-preterm was 0·04 term infants of low birthweight had lower academic (0·02–0·06). The combined population attributable risk achievement at age 15 years than did infants of normal related to SGA for stunting was 0·20 and that for preterm birthweight,143 and in Thailand birthlength­ was associated birth was 0·08. Thus, overall we estimate that about a with IQ at age 9 years independent of postnatal growth to fifth of childhood stunting could have its origins in the age 1 year;144 however, in both cases effect sizes were small. fetal period, as shown by being born SGA. Most studies of fetal growth restriction and childhood Childhood nutrition cognitive and motor development in LMICs involve term Stunting, underweight, and wasting infants of low birthweight or examine birthweight Panel 12,145–153 describes the determinants of stunting and adjusted for gestational age. Consistent evidence exists overweight in children. Estimates of the prevalence of for associations of fetal growth restriction with lower stunting, underweight, and wasting worldwide and for psychomotor development levels in early childhood (up UN subregions are based on analyses jointly done by to age 36 months) with small to moderate effect sizes UNICEF, WHO, and the World Bank154 of 639 national compared with infants of normal birthweight.134,135 A surveys from 142 countries in the WHO database, using study136 from Bangladesh showed much the same standard methods.1,155,156 In 2011, globally, 165 million associations for both mental and motor development. children younger than 5 years had a height-for-age Evidence suggests that there is an effect on development Z score (HAZ) of –2 or lower (stunted) on the basis of

Stunt­ing (HAZ <–2) Wast­ing (WHZ <–2) Severe wast­ing (WHZ <–3) Under­weight (WAZ <–2) UN155 NIMS158 UN NIMS UN NIMS UN NIMS Pro­ Number Pro­­ Number Pro­ Number Pro­ Number Pro­­ Number Pro­ Number Pro­ Number Pro­ Number portion (millions) portion (millions) portion (millions) portion (millions) portion (millions) portion (millions) portion (millions) portion (millions) Africa 35·6% 56·3 35·5% 56·6 8·5% 13·4 7·9% 12·5 3·5% 5·5 2·8% 4·4 17·7% 27·9 18·4% 29·0 (33·3– (52·5– (34·4– (54·3– (7·4– (11·6– (7·3– (11·5– (2·9– (4·5–6·4) (2·5– (4·0–5·2) (15·7– (24·7– (17·4– (27·5– 38·0) 60·0) 36·6) 57·8) 9·6) 15·2) 8·6) 13·6) 4·1) 3·3) 19·7) 31·1) 19·1) 30·1) Asia 26·8% 95·8 29·5% 103·5 10·1% 36·1 10·0% 5·2 3·6% 12·9 3·6% 12·7 19·3% 69·1 21·9% 76·6 (23·2– (82·8– (26·4– (92·5– (7·9– (28·2– (8·2– (4·3–5·9) (2·4– (8·4– (2·7– (9·4– (14·6– (52·1– (18·8– (65·9– 30·5) 108·8) 31·3) 109·8) 12·3) 44·0) 11·4) 4·8) 17·3) 4·7) 16·4) 24·1) 86·1) 24·0) 84·1) Latin 13·4% 7·1 14·6% 7·8 1·4% 0·7 1·5% 0·8 0·3% 0·2 0·4% 0·2 3·4% 1·8 3·7% 2·0 America (9·4– (4·8–9·4) (13·6– (7·3–8·2) (0·9– (0·5–1·0) (1·3– (0·7–1·0) (0·2– (0·1–0·2) (0·4– (0·2–0·3) (2·3–4·5) (1·2–2·4) (3·5– (1·8–2·2) and the 17·7) 15·5) 1·9) 1·8) 0·4) 0·6) 4·1) Carib­ bean Oceania 35·5% 0·5 34·7% 0·4 4·3% 0·1 5·1% 0·1 0·7% 0·0 1·5% 0·0 14·0% 0·2 13·9% 0·2 (16·0– (0·2–0·8) (27·8– (0·3–0·5) (3·0– (0·0–0·1) (3·3– (0·0–0·1) (0·5– (0·0–0·0) (0·9– (0·0–0·0) (8·0– (0·1–0·3) (10·7– (0·1–0·2) 61·4) 39·5) 6·2) 6·8) 1·1) 2·4) 23·2) 16·8) LMICs 28% 159·7 29·9% 168·3 8·8% 50·3 9·3% 52·6 3·3% 18·5 3·1% 17·3 17·4% 99·0 19·4% 109·1 (25·6– (145·9– (27·9– (157·3– (7·4– (42·1– (8·4– (47·4– (2·5– (14·0– (2·6– (14·4– (14·3– (81·7– (17·3– (97·2– 30·4) 173·4) 31·0) 174·6) 10·3) 58·4) 10·4) 58·5) 4·0) 23·1) 3·8) 21·5) 20·4) 116·3) 20·5) 115·4) High- 7·2% 5·1 ·· ·· 1·7% 1·2 ·· ·· 0·3% 0·2 ·· ·· 2·4% 1·7 ·· ·· income (4·1– (2·9–8·9) (0·8– (0·6–2·5) (0·0– (0·0–0·9) (1·7–3·4) (1·2–2·4) countries 12·6) 3·5) 1·3) Global 25·7% 164·8 ·· ·· 8·0% 51·5 ·· ·· 2·9% 18·7 ·· ·· 15·7% 100·7 ·· ·· (23·5– (150·8– (6·8– (43·3– (2·2– (14·2– (13·0– (83·3– 27·9) 178·8) 9·3) 59·6) 3·6) 23·2) 18·4) 118·0)

Data are % (95% CI). HAZ=height-for-age Z score. WHZ=weight-for-height Z score. WAZ=weight-for-age Z score. LMICs=low-income and middle-income countries.

Table 3: Prevalence and numbers of children younger than 5 years with stunting, wasting, severe wasting, and underweight using estimates from UN and NIMS, by UN regions for 2011

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the WHO Child Growth Standards (table 3)—a However, with the increase in population in Africa, this is 35% decline from an estimated 253 million in 1990. The the only major world region with an increase in the prevalence decreased from an estimated 40% in 1990, to number of stunted children in the past decade. an estimated 26% in 2011—an average annual rate of The complex interplay of social, economic, and reduction of 2·1% per year (figure 1544 ). East and west political determinants of undernutrition (figure 1) Africa, and south-central Asia have the highest preva­ results in substantial inequalities between population lence estimates in UN subregions with 42% (east subgroups. In our analysis, using previously described Africa) and 36% (west Africa and south-central Asia); methods,158 of 79 countries with population-based the largest number of children affected by stunting, surveys since the year 2000 (figure 5), stunting 69 million, live in south-central Asia (appendix p 9). prevalence among children younger than 5 years was The surveys in the WHO database and other population- 2·47 times (range 1·00–7·64) higher in the poorest representative data were also analysed with a Bayesian quintile of households than in the richest quintile. Sex hierarchical mixture model to estimate Z-score distri­ inequalities in child nutrition tend to be substantially butions of anthropometric indices by the Nutrition smaller than economic inequalities (appendix p 24). In Impact Model Study (NIMS).157 These distributions were 81 countries with data, stunting prevalence is slightly used to assess trends in stunting and underweight in higher (1·14 times, range 0·83–1·53) in boys than in children, the present prevalence of these measures, and girls. This finding is consistent with the higher the present prevalence of wasting. These methods have mortality in children younger than 5 years in boys than the advantage of esti­mating the full distribution of in girls in most countries in the world. Place of anthropometric variables and therefore measure the full residence is also an important correlate of the risk of extent of mild-to-severe undernutrition without restrictive stunting (appendix p 24). In 81 countries with data, assumptions. They also allow for non-linear time trends. stunting was 1·45 times higher (range 0·94 to 2·94) in NIMS analyses resulted in much the same estimates of rural than in urban areas. the prevalence of stunting, underweight, and wasting According to UN estimates, globally in 2011, more than as those of the UN in 2011 (table 3, appendix p 10). 100 million children younger than 5 years, or 16%, were The complete trend analysis showed that the largest underweight (weight-for-age Z score [WAZ] <–2 on the reductions in stunting since 1985 have been in Asia, basis of the WHO Child Growth Standards), a 36% whereas Africa had an increase until the mid-1990s and decrease from an estimated 159 million in 1990.154 subsequently a modest reduction in the prevalence.157 Estimated prevalences in NIMS were slightly higher at

Global Asia 300 Numbers Prevalence 60 300 60 270 253·1 55 270 55 50 50 240 226·3 Global target 240 =100 million 45 45 210 201·0 Prevalence (%) 210 Prevalence (%) 181·2 40 188·7 40 167·1 180 153·5 35 180 161·5 98·4 35 140·2 135·6 83·3 150 127·4 30 150 69·2 30 120 25 120 113·9 56·5 25 20 20 90 90 Numbers (millions) 15 Numbers (millions) 15 60 60 10 10 30 5 30 5 0 0 0 0

Africa Latin America and the Caribbean 300 60 300 60 270 55 270 55 50 50 240 240 45 45 210 Prevalence (%) 210 Prevalence (%) 40 40 180 35 180 35 150 30 150 30 120 25 120 25 20 20 90 90 Numbers (millions) 53·3 55·8 58·1 59·9 60·6 15 Numbers (millions) 15 60 45·7 47·9 50·2 60 10 10 30 30 13·7 5 12·1 10·4 9·0 7·4 6·2 5·1 4·2 5 0 0 0 0 1990 1995 2000 2005 2010 2015 2020 2025 1990 1995 2000 2005 2010 2015 2020 2025 Year Year

Figure 4: Trends in prevalence and numbers of children with stunted growth (HAZ <–2), by selected UN regions and globally, 1990–2010, and projected to 2025 on the basis of UN prevalence estimates HAZ=height-for-age Z score. Data from UNICEF, WHO, World Bank.154

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110 million (19·4%).155 Prevalences were highest in south- Standards) was 8% (52 million) globally in 2011, an 11% central Asia and western Africa where 30% and 22%, decrease from an estimated 58 million in 1990.154 70% of respectively, were underweight (appendix p 9). the world’s children with wasting live in Asia, most in The UN estimate for wasting (weight-for-height Z south-central Asia, where an estimated 15% (28 million) score [WHZ] <–2 on the basis of WHO Child Growth are affected. Much the same regional pattern occurs for

Stunting (HAZ <–2) Overweight (HAZ >2) Guatemala (DHS 1998) Timor-Leste (DHS 2009) India (DHS 2005) Madagascar (DHS 2005) Laos (MICS 2006) Niger (DHS 2006) Nepal (DHS 2011) Malawi (DHS 2010) Peru (DHS 2004) Bangladesh (DHS 2007) Rwanda (DHS 2010) Chad (DHS 2004) Nigeria (DHS 2008) Somalia (MICS 2006) Cameroon (MICS 2006) Mozambique (MICS 2006) Honduras (DHS 2005) Benin (DHS 2006) Cambodia (DHS 2010) Central African Republic (MICS 2006) Ethiopia (DHS 2011) Guinea Bissau (MICS 2006) Tanzania (DHS 2010) Zambia (DHS 2007) Burkina Faso (MICS 2006) Côte d’Ivoire (MICS 2006) Democratic Republic of the Congo (DHS 2007) Bolivia (DHS 2008) Lesotho (DHS 2009) Guinea (DHS 2005) Mali (DHS 2006) Kenya (DHS 2008) Liberia (DHS 2007) Uganda (DHS 2006) Nicaragua (DHS 2001) Gabon (DHS 2000) Haiti (DHS 2005) Tajikistan (MICS 2005) Namibia (DHS 2006) Belize (MICS 2006) São Tomé and Príncipe (DHS 2008) Togo (MICS 2006) Congo (Brazzaville) (DHS 2005) Swaziland (DHS 2006) The Gambia (MICS 2005) Syria (MICS 2006) Morocco (DHS 2003) Zimbabwe (DHS 2010) Senegal (DHS 2010) Sierra Leone (DHS 2008) Mauritania (MICS 2007) Ghana (DHS 2008) Azerbaijan (DHS 2006) Mongolia (MICS 2005) Guyana (DHS 2009) Turkey (DHS 2003) Egypt (DHS 2008) Vanuatu (MICS 2007) Palestinians in Lebanon (MICS 2006) Albania (DHS 2008) Armenia (DHS 2010) Georgia (MICS 2005) Maldives (DHS 2009) Uzbekistan (MICS 2006) Figure 5: Prevalence of Kazakhstan (MICS 2006) Thailand (MICS 2005) stunting (HAZ <–2 Z scores Kyrgyzstan (MICS 2005) below median) and Colombia (DHS 2010) overweight (BMI for age >2 Bosnia and Herzegovina (MICS 2006) Jordan (DHS 2007) Z scores above median) for Suriname (MICS 2006) highest and lowest wealth Dominican Republic (DHS 2007) quintiles in selected countries Macedonia (MICS 2005) Moldova (DHS 2005) Blue circles are lowest wealth Montenegro (MICS 2005) quintiles, red circles are Serbia (MICS 2005) highest wealth quintiles. Belarus (MICS 2005) Brazil (DHS 2006) HAZ=height-for-age Z score. BMI=body-mass index. 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100 DHS=Demographic and Health Prevalence (%) Survey. MICS=Multiple Indicator Cluster Survey. www.thelancet.com 25 Series

severe wasting (WHZ <–3), with a global prevalence in 2 years of life are a crucial period linking growth and 2011 of 3% or 19 million children. The highest percen­ development; growth from birth to 24 months but not tages of children with severe wasting are in south-central from 24 to 36 months was associated with child develop­ Asia (5·1%) and central Africa (5·6%). ment in Guatemala,167 and weight gain in the first Suboptimum growth, according to anthropometric 2 years predicted school outcomes in five cohorts.138 measures indicative of stunting, wasting, and under­ Analyses from the COHORTS group that are presented weight, has been shown to increase the risk of death from here suggest that growth in the first 2 years of life, but infectious diseases in childhood.159,160 This association not at later ages, is associated with achieved school has been recently re-examined with the pooled analysis grades in adults.168 However, some evidence suggests of individual-level data from ten longi­tudinal studies that growth after 24 months of age might also be involving more than 55 000 child-years of follow-up and associated with lower cognitive ability, but with a 1315 deaths in children younger than 5 years.161 As with smaller effect size than for early growth.169 In a Malawi previous analyses, all degrees of stunting, wasting, and cohort, height gain from 18 to 60 months predicted under­weight had higher mortality and the risk increased mathematics ability at 12 years. Height gain at 1 month as Z scores decreased (appen­dix p 11). Undernutrition and change from 1 to 6 months and 6 to 18 months can be deemed the cause of death in a synergistic were not significant predictors.170 association with infectious diseases; if the undernutrition We analysed changes in stunting prevalence between did not exist, the deaths would not have occurred.1 All 1996 and 2008 in Bangladesh, Brazil, and Nigeria, anthropo­metric measures of under­nutrition were asso­ according to wealth and urban or rural status (panel 2, ciated with increased hazards of death from diarrhoea, figure 6). pneumonia, and measles; the association was also noted for other infectious diseases, but not malaria. We Overweight and obesity calculated the population attributable fractions for stunt­ The prevalence of overweight worldwide and for UN ing, under­weight, wasting, and its subset of severe regions is based on the joint analyses done by UNICEF, wasting using the UN and NIMS prevalence data with WHO, and the World Bank.154 In 2011, globally, an standard methods.1 These fractions were multiplied by estimated 43 million children younger than 5 years, or the corresponding age-specific and cause-specific deaths162 7%, were overweight (ie, WHZ greater than two Z scores to estimate the number of deaths attributable to each above the median WHO standard), on the basis of the anthropometric measure (table 2).162 For the percentage of WHO Child Growth Standards (appendix p 9)—a 54% total deaths the denominator was 6·934 million.131 Details increase from an estimated 28 million in 1990. This of these estimates for UN subregions and causes of death trend is expected to continue and reach a prevalence of are in appendix pp 12–13. Stunting and underweight have 9·9% in 2025 or 64 million children (figure 7). Increasing the highest proportions of attributed child deaths, about trends in child overweight are taking place in most world 14% for both; wasting accounts for 12·6% (severe wasting regions, not only in high-income countries, where preva­ 7·4%) of child deaths. Table 2 and appendix pp 14–15 lence is the highest (15% in 2011). However, most show estimations using the NIMS prevalence data. In overweight children younger than 5 years (32 million in these estimates stunting and underweight each account 2011) live in LMICs. In Africa, the estimated prevalence for 17% of child deaths and wasting for 11·5% (severe increased from 4% in 1990 to 7% in 2011, and is expected wasting 7·8%). to reach 11% in 2025 (figure 7). Prevalence of over­ Stunting is a well established risk factor for poor child weight is lower in Asia (5% in 2011), but the number of development with numerous cross-sectional studies affected children is higher compared with Africa (17 and showing associations between stunting and motor and 12 million, respectively). cognitive development. Several longitudinal studies Differences in childhood overweight prevalence show stunting before age 2–3 years predicts poorer cog­ between the richest and poorest quintiles are small in nitive and educational outcomes in later childhood and most countries (figure 5), and in general prevalence adolescence.135,163 Effect sizes for the longitudinal studies tends to be higher in the richest quintile than in the comparing children with HAZ of –2 or lower with non- poorest. In 78 countries with data, prevalence in the stunted children (HAZ ≥1) are moderate to large.163 richest quintile was on average 1·31 (range 0·55–3·60) Length-for-age Z score (LAZ) at age 2 years was con­ times higher than in the poorest quintile. Overweight is sistently associated with higher cognitive Z scores in much the same between the sexes (appendix p 24) and children aged 4–9 years (0·17–0·19 per unit change LAZ) slightly more prevalent in urban than in rural areas across four cohorts with moderate (24–32%) or high (appen­dix p 25). In 81 countries with data, urban preva­ (67–86%) stunting prevalence.164 Associations with lence was 1·08 times higher on average (range 0·44–1·46) underweight have also been reported.163 than rural prevalence. Stunted children show behavioural differences in Childhood overweight results in both immediate and early childhood including apathy, more negative affect, longer-term risks to health. Among the immediate risks and reduced activity, play, and exploration.165,166 The first are metabolic abnormalities including raised cholesterol,

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triglycerides, and glucose, type 2 diabetes, and high blood pressure.171 Childhood overweight is also a strong Panel 2: How do inequalities in stunting evolve with time? risk factor for adult obesity and its consequences.2,172 Increased availability of survey data, including several surveys from different years, allowed the analyses of time trends in nutritional indicators according to population subgroups. Childhood vitamin deficiencies Figure 6A compares trends in stunting by wealth quintile in three countries. In Nigeria, Anaemia and iron there was almost no change in stunting prevalence from 2003 to 2008, and the degree of The percentages of children with anaemia (haemoglobin inequality remained almost unchanged. In Bangladesh, stunting prevalence decreased in all <110 g/L) and severe anaemia (haemoglobin <70 g/L) due subgroups, but inequality also remained at the same magnitude. In Brazil, where prevalence to inadequate iron, (ie, anaemia that is correctable by oral of stunting is much lower, equity improved because of a substantial decrease in stunting iron supplements, calculated as described earlier) are the poorest populations. 18·1% and 1·5%, respectively. The prevalence is highest Figure 6B shows the corresponding results for urban and rural differences over time. In in Africa and Asia for all IDA and in Africa for severe Nigeria, rural prevalence was higher than urban prevalence in 2003, and both remained at IDA (table 1). However, the proportion of all childhood similar levels by 2008. In Bangladesh, both urban and rural rates decreased, but the gap anaemia corrected by iron supplementation ranges from was reduced over time. In Brazil, where there was a two-times rural-urban gap in 1996, 63% in Europe to 34% in Africa where there are other full equality had been reached by 2006. major causes of anaemia; the proportion of severe anaemia corrected by iron supplementation in Africa is Increased data availability has led to the ability to study trends over time for subnational 57% (appendix p 4). groups. Such data should be used for advocacy purposes, showing which population Iron supplementation in children aged 5 years and groups require closer attention, and also as a means to assess the effect of older with IDA generally benefits their cognition, but nutrition-specific and nutrition-sensitive interventions, as well as of broader studies of children younger than 3 years have had developmental programmes and initiatives. mostly negative findings.135,173–175 Most cohort and cross- sectional studies of children younger than 3 years with IDA find developmental deficits and studies from the past 15 years provide evidence of neurophysiological A 135 100 Wealth quintiles changes suggestive of delayed brain maturation. Q1: poorest 20% Q2 Q3 Q4 Q5: richest 20% However, IDA is associated with many social dis­ 90 advantages that also affectchild development and, thus, 80 randomised controlled trials are necessary to establish 70 a causal association. A previous systematic review 60 showed that iron supplementation resulted in a small 50 improvement in mental development scores in children 40 with IDA aged older than 7 years, but had no effect in 30 173 Stunting prevalence (%) children younger than 27 months. To further assess 20 this scientific literature, we identified seven double- 10 blind randomised controlled trials176–182 of iron lasting at 0 least 8 weeks in children younger than 4 years. Five trials177–180,181,182 showed benefits in motor develop­ment B and two did not.176,180 Only one showed benefits in 100 Area of residence Rural Urban language,178 and a small study showed benefits in 90 mental develop­ment.177 In an eighth randomised 80 183 controlled trial, children given iron in infancy showed 70 no cognitive benefit when followed up at age 9 years. 60 184–187 Four additional ran­domised controlled trials 50 examined the combined effects of iron and folate 40 supplementation in children younger than 36 months 184 30 of age. One showed benefits to motor milestones, Stunting prevalence (%) others showed no benefits to motor185,186 or language186 20 milestones, and one showed no benefit to cognitive 10 function.187 Thus, there is some evidence that iron 0 deficiency affects motor development in children 1996 1999 2004 2007 1996 2006 2003 2008 younger than 4 years, but no consistent evidence for an Bangladesh Brazil Nigeria effect on mental development. However, many of the supplementation trials produced only small differences in iron status between the treated and control groups, Figure 6: Changes in stunting over time, in Bangladesh, Brazil, and Nigeria (A) Stunting prevalence by wealth quintile. The longer the line between possibly limiting their ability to affect development. It two groups, the greater the inequality. (B) Stunting prevalence by urban or is also possible that mental develop­ment takes longer to rural location. www.thelancet.com 27 Series

Global Africa 65 Numbers Prevalence 63·7 14 65 14 60 60 55·2 55 12 55 12 50 47·8 50 10 10 45 45 41·2 Prevalence (%) 40 Prevalence (%) 40 35·3 8 8 35 31·7 35 29·6 30 28·4 30 6 6 25 25 21·4 Numbers (millions) Numbers (millions) 20 20 4 17·3 4 15 15 13·8 11·0 8·7 10 2 10 6·9 2 4·6 5·6 5 5 0 0 0 0

Asia Latin America and the Caribbean 65 14 65 14 60 60 55 12 55 12 50 50 10 10 45 45 Prevalence (%) 40 Prevalence (%) 40 8 8 35 35 30 30 6 6 25 14·7 23·1 25 Numbers (millions) Numbers (millions) 14·4 14·1 14·3 20·5 20 18·4 20 16·5 4 4 15 15

10 2 10 2 5 5 3·6 3·7 3·8 3·9 3·8 3·8 3·8 3·8 0 0 0 0 1990 1995 2000 2005 2010 2015 2020 2025 1990 1995 2000 2005 2010 2015 2020 2025 Year Year

Figure 7: Trends in prevalence and numbers of overweight (WHZ >2) children, by selected UN regions and globally, 1990–2010, and projected to 2025, on the basis of UN prevalence estimates WHZ=weight-for-height Z score.

improve than the duration of the trials or that the has declined, probably because of large-scale vitamin A effects of iron deficiency early in life are irreversible. supplementation programmes in many countries, sub­ clinical vitamin A deficiency affects high proportions of Vitamin A children in Africa and southeast Asia (table 2). Clinical assessment of ocular symptoms and signs of Many randomised controlled trials have been done xerophthalmia and biochemical assessment of serum to examine the effect of supplementation every concentration of retinol are the two common methods 4–6 months and fortification on survival of children in population surveys for estimation of prevalence of aged 6 months and older; these studies provide the vitamin A deficiency. WHO provides prevalence esti­ best evidence for deaths attributable to vitamin A mates of vitamin A deficiency in preschool children deficiency.188–191 Meta-analyses of these trials show a (<5 years) for 1995–2005 from 99 countries.45 Globally, mortality reduction of 23%,188 30%,189 and 24%190 in 0·9% (95% CI 0·3–1·5) or 5·17 million preschool age children aged 6–59 months. With publication of a large children are estimated to have night blindness and programme effectiveness study from India, a revised 33·3% (31·1–35·4) or 90 million to have subclinical meta-analysis shows a mortality effect of 11%, still a vitamin A deficiency, defined as serum retinol concen­ statistically significant­ benefit.192 In our calcu­lations we tration of less than 0·70 µmol/L. Vita­min A deficiency use only the effects in the trials on particular causes of using night blindness prevalence can be defined as a death, not the effects on overall deaths because the global problem of mild public health importance,45 causes of death at the time of the trials and nowadays are although the prevalence in Africa (2%) is higher than probably different (eg, diarrhoea and measles account for elsewhere. Although prevalence of clinical symptoms a much smaller proportion of child deaths now than

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10–20 years ago).162 To derive the risk of vitamin A intake in countries to estimate the attributable deaths. deficiency the inverse (1/risk reduction) of the cause- The population attributable fractions for diarrhoea and specific mortality reduction identified in the trials was pneumonia were multiplied by the number of these deemed to be the risk of deficiency and adjusted with the deaths in 2011.162 The number of child deaths attributed to assumption that all the effect was in the subset of the zinc deficiency in 2011 is 116 000 (table 2). trial population with low serum retinol (appendix p 16). Zinc deficiency also has a small negative effect on Much the same adjust­ment was done for the effect growth. A meta-analysis of randomised controlled trials of of vitamin A deficiency on diarrhoea incidence zinc supplementation showed a significant benefit for (appen­dix p 17). This allows the adjusted RR to be applied linear growth in children aged 0–5 years.201 The effect was a to the present prevalence of low serum retinol to estimate gain of 0·37 cm in zinc-supplemented children. Trials that the attributable deaths or disease episodes. Although used a dose of zinc of 10 mg per day for 24 weeks, rather results of trials193–195 in south Asia show a newborn than lower doses, showed a larger benefit of 0·46 cm. supplementation effect on mortality in the first 6 months of life, the evidence from Africa is less clear, and further Breastfeeding practices studies are underway. Therefore, we do not estimate Present recommendations are that babies should be deaths attributable to vitamin A deficiency in the first put on the breast within 1 h after birth, be exclusively 6 months of life. Child deaths attributable to vitamin A breastfed for the first 6 months, and for an additional deficiency for 2011 are estimated to be 157 000 (table 2). 18 months or longer, be breastfed along with comple­ mentary foods. There are no recently published system­ Zinc atic com­pilations of data for breastfeeding patterns so Zinc deficiency in populations could be assessed by a we analysed data from 78 countries with surveys done shift of the population distribution of serum zinc concen­ ­ in LMICs during 2000–10 (appen­dix p 20). Early trations to lower values as recommended by the Inter­ initiation of breastfeeding (within 1 h) is highest in national Zinc Nutrition Consultative Group;196 how­ever, Latin America (mean 58%, 95% CI 50–67), intermediate insufficient data exist to classify countries or subnational­ in Africa (50%, 45–55) and Asia (50%, 42–58), and populations. Instead the proportion of the national lowest in eastern Europe (36%, 23–50). Except for population estimated to have an inadequate zinc intake eastern Europe, where the lowest rates of breastfeeding on the basis of national food availability and dietary are recorded, globally about half of children younger requirements is used.70 According to this method, an than 1 month, and three in every ten children aged estimated 17% of the world’s population has an inadequate 1–5 months are exclusively breastfed. Breastfeeding in zinc intake; substantial regional variation exists, with 6–23 month olds is most frequent in Africa (mean 77%, Asia and Africa having the highest prevalences­ (table 1). A 95% CI 73–81) followed by Asia (62%, 54–71) and Latin systematic review197 showed that zinc supplementation America (60%, 50–69), with lower occurrence in eastern resulted in a 9% reduction (RR 0·91, 95% CI 0·82–1·01) Europe (33%, 24–42). of borderline significance in all-cause child mortality. A The risks of increased mortality and morbidity due to separate analysis of available trials showed a significant deviation from present breastfeeding recommendations 18% reduction (RR 0·82, 0·70–0·96) in all-cause mortality are well documented.1 Updated systematic reviews of in children aged 1–4 years.198 There were suggestive these risks have results that are much the same as our benefits on diarrhoea-specific (RR 0·82, 95% CI previous estimates (appendix p 21).1,202,203 The number of 0·64–1·05) and pneumonia-specific (0·85, 0·65–1·11) child deaths attributed to suboptimum breastfeeding in mortality.197 This and previous analyses have included 2011 is 804 000 or 11·6% of all deaths (table 2). cause-specific mortality effects even when they were not Three prospective case-cohort studies provide data for statistically significant when the effect on all-cause the association of early breastfeeding initiation (within mortality was statistically significant.199,200 These trials 24 h) with neonatal mortality.204 Although early initiation were not powered for cause-specific mortality effects. was associated with lower neonatal mortality (RR 0·56, Supporting evidence for the cause-specific mortality 95% CI 0·46–0·79), in babies who were exclusively effects comes from randomised controlled trials that breastfed the mortality risk was not significantly showed significant reductions in diarrhoea incidence reduced (0·69, 0·27–1·75). The possible benefit of early (RR 0·87, 95% CI 0·81–0·94) and pneumonia incidence initiation of breastfeeding was therefore not deemed to (0·81, 0·73–0·90).197 To derive the risk of zinc deficiency, be additive to the effects of exclusive breastfeeding in we adjusted the inverse of the cause-specific mortality our analyses. (appendix p 18) and incidence (appen­dix p 19) reductions A systematic review shows that breastfeeding is con­ noted in the trials with the assumption that all the effect sistently associated with an increase in IQ of about three was in the subset of the trial population at risk of zinc points,205 even after adjustment for several con­founding deficiency, as estimated from the availability of food in factors including maternal IQ. Evidence for the pro­ national diets.70 This method allows the adjusted RRs to tection afforded by breastfeeding against risk factors for be applied to the present prevalence of inadequate zinc non-communicable diseases is less consistent. A series www.thelancet.com 29 Series

of meta-analyses,205 based mainly on studies in adults attributed jointly to fetal growth restriction, suboptimum from high-income settings, showed no evidence of breastfeeding, stunting, wasting, and deficiencies of protection against total cholesterol levels or diastolic vitamin A and zinc. The overall results were the same blood pressure. When the meta-analysis was restricted to using UN or NIMS prevalence estimates. As part of this high-quality studies, breastfeeding was associated on total, the joint distribution of suboptimum breastfeeding average with a 1 mm reduction in systolic blood pressure, and fetal growth restriction in the neonatal period and with a 12% reduction in the risk of overweight or contributes 1·3 million deaths or 19% of all deaths of obesity. Studies of diabetes or glucose levels were too few children younger than 5 years. to allow a firm conclusion. Effects of fetal and early childhood Joint effects of nutritional conditions on child undernutrition on adult health mortality In The Lancet’s 2008 Series on maternal and child To estimate the population attributable fraction and the undernutrition,2 consequences of early childhood number of deaths attributable to several risk factors, we nutrition on adult health and body composition were used Comparative Risk Assessment methods.206 We assessed by reviewing the scientific literature and doing calculated attributable deaths from four specific causes meta-analyses of five birth cohorts from LMICs (India, of mortality (diarrhoea; measles; pneumonia; and other the Philippines, South Africa, Guatemala, Brazil), an infections, excluding malaria) associated with different effort that gave rise to the COHORTS collaboration.208 On nutritional status measures. In the neonatal period all the one hand, the conclusions were that small size at deaths were deemed to be associated only with sub­ birth and at 2 years of age (particularly height) were optimum breastfeeding and fetal growth restriction. The associated with reduced human capital: shorter adult Comparative Risk Assessment methods allow the height, less schooling, reduced economic productivity, estimation of the reduction in death that would take and for women, lower offspring birthweight. On the place if the risk factors were reduced to a minimum other hand, larger child size at 24 months of age was a theoretical level or counterfactual level of exposure.206 For risk factor for high glucose concentrations, blood the assessment the following formula was used: pressure, and harmful lipid levels once adjustment for adult BMI was made, suggesting that rapid weight gain, n especially after infancy, is linked to these conditions. ∑ PRii()R–1 The COHORTS group later did pooled analyses that use i=1 PAF= n conditional growth variables that remove the correlation ∑PRii()R–1+1 between growth measures across ages, allowing inferences i=1 to be made about the relative asso­ciation between growth during specific age intervals and outcomes.149 Also,

For the purpose of this analysis, RRi equals the RR of because gains in height and weight are correlated, these mortality for the ith exposure category, associated with analyses use conditionals that separate linear growth from

specific UN regions. iP equals the proportion of children weight gain. The conclusions were that heavier birthweight in the ith exposure in theoretical or counterfactual and faster linear growth from 0 to 2 years lead to large category. P equals the population weighted mean of gains in human capital, but have little association with countries’ prevalence estimates for different levels of adult cardiovascular risk factors. Also, faster weight gain fetal growth restriction, stunting, wasting, deficiencies of independent of linear growth has little benefit for human vitamin A and zinc, and suboptimum breastfeeding capital. After the age of 2 years, and particularly after the practices in their relevant age groups. age of 4 years, rapid weight gains show adverse effects on Because specific causes of deaths could potentially be adult cardiovascular risk. The COHORTS analyses control caused by more than one factor, the population for confounding and the findings are broadly much the attributable fractions for multiple risk factors that affect same across the five cohorts. the same disease outcome overlap and cannot be Additional longitudinal studies report effects on later combined by simple addition. For this reason, the joint mental health with higher levels of depression and population attributable fraction was estimated with the anxiety and lower self-esteem in adolescents who were 209 formula: Joint PAFi=1–product (1–PAFi), where PAFi stunted by age 2 years compared with non-stunted; equals the population attributable fraction of the different increased depression in adolescents who had severe risk factors.207 All analyses were done for relevant age acute malnutrition in infancy;210 increased risk of suicidal groups of that risk factor and then the results from the ideation associated with lower HAZ at 24 months,211 and age groups were aggregated. For stunting and wasting higher levels of hyperactivity in late adolescence and we did calculations separately with UN and NIMS attention deficit in adults.209,212 Although observational, prevalence estimates. the findings are persuasive and consistent with the little The resulting 3·1 million deaths constitute 45% of quasi-experimental evidence available. Follow-up studies global deaths in children younger than 5 years in 2011, of a community randomised nutrition trial in Guatemala

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have shown long-term effects of exposure to improved fetal growth restriction and maternal nutritional con­ nutrition during the first 2–3 years, but not after 3 years, ditions, short stature, and low BMI, should lead to more on education,213 and wages.214 Effects of improved nutri­ emphasis on nutritional interventions before and during tion in the first several years of life on risk factors for pregnancy. These interventions would have benefits for chronic diseases were minor but in some cases bene­ health of adolescents and women, could reduce compli­ ficial.215 Exposure to improved nutrition during child­ cations of pregnancy and delivery for the mother, and hood affected the growth of the next generation in girls enhance fetal growth and development. and their future children.2 Stunted linear growth has become the main indicator Famines are another source of information about long- of childhood undernutrition, because it is highly term effects of poor nutrition in early life. The Dutch prevalent in all developing regions of the world, and has famine of 1944–45 (brief, intense, but affecting a pre­ important consequences for health and development. It viously well-nourished population) suggests effects of should replace underweight as the main anthropometric prenatal exposure on schizophrenia, no effects on human indicator for children. Underweight indices include chil­ capital (height, cognitive function), and weak and in­ dren who are short, but who can have an increased consistent effects on cardiovascular risk factors.216 The WHZ, being therefore at increased risk of long-term 1959–61 Chinese famine (prolonged, severe, and affecting adverse health outcomes. Linear growth assessment in an already malnourished population) suggests effects of primary care is an essential component of country efforts exposure during pregnancy and the first 2 years of life to reduce childhood stunting. More experience is needed on height, wealth, income, mental health, and inter­ in the operational aspects of the assessment and inter­ generational effects on birthweight.217–220 Sur­prisingly, pretation of linear growth by health workers and in the some findings suggest protective effects of famine expo­ effective intervention responses. sure, which might be explained by high mortality and Prevalence of stunting in children younger than 5 years intense selection of the hardiest.219–221 in developing countries in 2011 was about 28%, a decrease from 40% or more in 1990 and the 32% estimate Discussion in our 2008 nutrition Series for 2004.1 The number of Nutrition has profound effects on health throughout the stunted children globally has decreased from 253 million human life course and is inextricably linked with cog­ in 1990 to 165 million in 2011. Another reported estimate nitive and social development, especially in early child­ was 167 million in developing countries for 2010.157 The hood. In settings with insufficient material and social 13-year Comprehensive Implementation Plan (2012–25) resources, children are not able to achieve their full on Maternal, Infant and Young Child Nutrition, endorsed growth and developmental potential. Consequences at the 2012 World Health Assembly, includes six global range broadly from raised rates of death from infectious nutrition targets, the first of which calls for a 40% diseases and decreased learning capacity in childhood to reduction of the global number of children younger than increased non-communicable diseases in adulthood. 5 years who are stunted by 2025 (compared with the Nutrition and growth in adolescence is important for a baseline of 2010).222 This goal would translate into a 3·9% girl’s health and adult stature. Women with short stature relative reduction per year and imply reducing the are at risk of complications in delivery, such as obstructed number of stunted children from the 171 million in 2010 labour. Nutritional status at the time of conception and to about 100 million. However, at the present rate of during pregnancy is crucial for fetal growth. Babies with decline, prevalence of stunting is expected to reach 20%, fetal growth restriction, as shown by being SGA, are at or 127 million, in 2025. In Africa, only small reductions increased risk of death throughout infancy. We estimate in prevalence are anticipated on the basis of present that 32 million babies are born SGA, 27% of births trends. However, in view of the rising number of births, in LMICs, and about 800 000 neonatal deaths and the actual number of stunted children will increase from 400 000 post-neonatal infant deaths can be attributed to 56 to 61 million. By contrast, Asia is projected to show a the increased risk associated with having fetal growth substantial decrease in stunting prevalence and in the restriction. The use of more appropriate methods than absolute number of children affected. those in our previous review1 to understand the preva­ Stunted, underweight, and wasted children have an lence and risk of SGA presented here resulted in increased risk of death from diarrhoea, pneumonia, estimates that are more than double our previous measles, and other infectious diseases. Recalculated estimate of attributable neonatal deaths related to term risks of cause-specific mortality161 confirmed previous low birthweight. This new finding contradicts the esti­mates1,159,160 and were used in estimation of the deaths widespread assumption that SGA infants, by contrast attributable to these conditions. The attributable fraction with preterm babies, are not at a substantially increased of deaths for these nutritional status measures has risk of mortality. Additionally, babies who are SGA have remained nearly the same as in previous calculations, an increased risk of growth faltering in the first 2 years of but the number of attributed deaths has declined because life; our estimates suggest that 20% of stunting might be of the decrease in the prevalence of these measures and a attributable to fetal growth restriction. The links between decline in the affected causes of death. By our estimates www.thelancet.com 31 Series

more than 1 million deaths can be attributed to stunting is highly beneficial. Data from developing regions show and about 800 000 to wasting, about 60% of which are that present practices are far from optimum, despite attributable to severe wasting. These attributable deaths improvements in some countries. Our previous estimates cannot be added because of the overlap of these and suggested that 1·4 million deaths were attributed to other nutritional conditions, but are instead included in suboptimum breastfeeding, especially related to non- the calculation of the deaths attributed to the joint exclusive breastfeeding in the first 6 months of life. Our effects of all nutritional conditions. Our estimate of new estimates are 804 000 deaths, a substantial reduction about 1 million child deaths due to underweight is higher since our estimate for the year 2004. Although present than the recently published 860 000 deaths in the Global estimates of the risks associated with suboptimum Burden of Disease (GBD).200 The GBD Study did not breast­­feeding practices are almost unchanged from what estimate deaths attributed to stunting or wasting. was used previously, the reduction in infectious disease Deficiencies of vitamins and minerals have important deaths in the past 10 years results in a lower number of health consequences, both through their direct effects, preventable deaths.173 Our number is higher than the such as iron deficiency anaemia, xerophthalmia due to estimated 545 000 deaths attributed to suboptimum vitamin A deficiency, and iodine deficiency disorders, breastfeeding in the GBD Study.200 Insufficient methods and because they increase the risk of serious infectious are provided by GBD to understand the reasons for diseases. In the latter category, vitamin A and zinc differences, but one reason is probably the lower deficiencies have been shown to have the greatest effects estimates of affected diarrhoea and pneumonia deaths among the micronutrients. Our estimate of the nearly than the UN estimates we used.223 157 000 child deaths attributed to vitamin A deficiency is To work out the total deaths attributed to nutritional smaller than our previous estimate (668 000).1 Notably, conditions, we calculated the joint distribution of we did not include the risk of mortality in the first stunting, wasting, fetal growth restriction, deficiencies of 6 months of life, as we did last time for Asia, because of vitamin A and zinc, and suboptimum breastfeeding. The more uncertainty about this risk; several trials of neonatal resulting 3·1 million deaths constitute 45% of the vitamin A supplementation are underway in Asia and 6·9 million global child deaths in 2011. The total number Africa to assess the benefits. Likewise, our estimate of of attributed deaths is reduced from the 3·5 million we 116 000 child deaths attributed to zinc deficiency is much estimated for 2004, despite the population attributable smaller than the 450 000 in our previous estimates, partly fraction increasing from 35% to 45%. In this period the because we now estimate the risk of pneumonia and mortality in children younger than 5 years decreased diarrheal mortality beginning at 12 rather than 6 months from 10 million to 6·9 million deaths and there were of age. In both cases there have also been changes in our even larger decreases in the causes of death—such as methods of estimating the prevalence of the conditions measles, diarrhoea, and pneumonia162—that are most and the risk associations, and combining these factors to affected by nutritional conditions. The increase in the get attributed fractions of deaths. These methods are percentage of attributed deaths compared with the much the same as those reported by the GBD Study.200 previous series is largely because of the more appropriate Our estimates are 20% higher for zinc and 30% higher inclusion of the effects of SGA (about 800 000 deaths) for vitamin A, than the GBD estimates. The reduction instead of term low birthweight (337 000 deaths) and the from our estimates for the year 2004 is partly explained inclusion of all wasting (WHZ <–2) instead of severe by decreases in the prevalences of these deficiencies—for wasting (WHZ <–3) in the joint calculations. vitamin A mostly because of large-scale implementation The number of children affected by excessive body­ of high-dose supplementation programmes, and a weight relative to length or height is increasing globally. reduction in deaths from diarrhoea and measles affected Although the prevalence of overweight in high-income by vitamin A deficiency and in deaths from diarrhoea countries is more than double that in LMICs, three and pneumonia affected by zinc deficiency. Some of quarters of the global total live in LMICs. The recorded this mortality reduction (eg, for diarrhoea) could be trends in the prevalence of early childhood overweight are attributable to the vitamin A supplementation, but might probably a consequence of changes in dietary and physical be also related to improvement in nutritional status activity patterns over time. These behavioural changes measures (eg, stunt­ing), water and sanitation, and illness are affected by many social and environmental factors, treatment, and for measles is largely attributable to including interpersonal (family, peers, and social net­ improved coverage with measles vaccine. Although the works), community­ (school, work­place, and institu­tions), number of deaths attributed to the present prevalence of and govern­mental (local, state, and national policies).224 vitamin A deficiency is relatively small, importantly, a Studies show that the trend toward childhood obesity can reduction in present coverage of vitamin A interventions start as early as age 6 months.225,226 In LMICs, rapid weight would probably result in an increase in mortality, because gain after 2 years of age is particularly associated with in most LMICs dietary intake is still inadequate. adult fat mass.2,168 Intrauterine, infant, and preschool Breastfeeding exclusively for the first 6 months and periods are deemed to be possible crucial periods for then along with complementary food to 24 months of age programming long-term regulation of energy balance.227–229

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If trends are not reversed, increasing rates of childhood health con­sequences, with a high child mortality overweight and obesity will have vast impli­cations not burden related to both stunting and wasting. New only for future health-care expenditures but also for the evidence in this paper supports the focus on pregnancy overall development of nations. These find­ings confirm and the first 2 years of life, the crucial 1000 days, which the need for effective interventions and programmes to we called for in the previous series, but adds more reverse anticipated trends. The early recognition of exces­ emphasis to the nutritional conditions in adolescence, sive weight gain relative to linear growth is essential. at the time of conception, and during pregnancy, as Routine assessment of both weight and length in all important for mater­nal health and survival, fetal growth children needs to become standard clinical practice from and sub­sequent early childhood survival, growth, and very early childhood. develop­ment. Fetal growth restriction­ and poor growth We have reported previously and confirmed in a new early in infancy are now recognised as important analysis that anaemia that is reduced by supplemental determinants of neonatal and infant mortality, stunting, iron in pregnancy is a risk factor for more than a and overweight and obesity in older children and quarter of maternal deaths. Anaemia is probably a adults. Preventive efforts should continue to focus on particularly important risk factor for haemorrhage, the the 1000 days, while therapeutic efforts continue to leading cause of maternal deaths (23% of total deaths).223 target severe wasting. Additionally, there is now sound evidence that calcium deficiency increases the risk of pre-eclampsia, now the second most important cause of maternal death (19% of Panel 3: Research priorities 223 total deaths). Thus, addressing deficiencies of these • How much of the effect of the underlying economic and social determinants of two minerals could result in substantial reduction of optimum growth and development is mediated through known, measurable maternal deaths. proximate determinants? Nutrition is crucial for optimum child development • What are the consequences of calcium or vitamin D deficiencies for maternal health, throughout the first 1000 days of life and beyond. fetal growth, birth outcomes, and infant health? Maternal nutrition affects fetal growth and brain develop­ • What is the importance of zinc deficiency or other micronutrient deficiencies in the ment with clear evidence for the need to continue and risk of preterm delivery? strengthen programmes to prevent maternal iodine • What is the role of nutrition in adolescence, at the time of conception, and in deficiency. Fetal growth restriction and postnatal growth pregnancy in healthy fetal growth and development? affect motor and cognitive development, with the largest • What factors are associated with regional variation in fetal growth restriction and do effects from stunting before age 2–3 years. Growth later its consequences on growth and mortality vary by setting? in childhood might also affect development though with • What is the interaction of fetal growth restriction and post-partum infections and diet a smaller effect size. Iron deficiency anaemia affects in contributing to stunting? motor development; effects on cognitive development • What is the role of vitamin A deficiency in newborn babies or the first 6 months of life have been more clearly shown in children older than in neonatal and infant mortality? 5 years than in younger children. • Are there benefits from iron supplementation for mental development in children Promotion of good early nutrition is essential for younger than 5 years with iron deficiency anaemia? children to attain their developmental potential; however, • Do deficiencies of any micronutrients other than vitamin A and zinc increase the risk poor nutrition occurs with other risks for development, of mortality from infectious diseases? in particular inadequate stimulation during early child­ • Can the risk of stunting be explained by specific dietary factors, micronutrient hood. Interventions to promote home stimulation and deficiencies, and clinical or subclinical infections? learning opportunities in addition to good nutrition will • How can the rapid decreases in stunting noted in selected countries be explained by be needed to ensure good early development and longer- changes in intervention coverage and in distal determinants? term gains in human capital, with integration and coord­ • Are there benefits of early initiation of breastfeeding that are independent of the ination of programmes and policies across sectors. practice of exclusive breastfeeding? Panel 3 lists research priorities. Additionally, there is a • How can developmental differences associated with nutritional deficiencies at general need for better data on micronutrient deficiencies various ages of childhood be best quantified and related to functioning and and other nutritional conditions at national and sub­ productivity in adulthood? national levels. This work should involve the development • What are the optimum physical growth rates in the first year of life to avoid both and use of improved biomarkers that could be used to undernutrition and obesity? describe nutritional conditions and increase knowledge • What are the effects of physical growth rates and stunting on cognitive abilities and about how they affect health and development. uchS psychological functioning? information is needed to guide intervention programmes • Can health workers effectively and efficiently assess and interpret height-for-age in countries and priorities for support globally. measures of linear growth in health and nutrition programmes? In the 5 years since our last series there have • How important is optimum growth and nutritional status in the fetal and early been some improvements in nutritional conditions, childhood period (first 1000 days of life) in the development of adult obesity and especially for child growth. Nonetheless, the extent of non-communicable diseases? these conditions remains high with serious detrimental www.thelancet.com 33 Series

Contributors Nestle Creating Shared Value Advisory Committee. VM serves on the REB conceptualised and coordinated the analyses, did the first draft of the Nestle Creating Shared Value Advisory Committee. MdO is a staff paper, responded to reviewer comments and incorporated all revisions member of the World Health Organization. MdO alone is responsible until publication. CGV contributed with analyses of inequalities, for the views expressed in this publication; they do not necessarily breastfeeding patterns, and long-term consequences of early nutrition, represent the decisions or policies of the World Health Organization. and served as a coordinator for this paper. SPW contributed sections on The other authors declare that they have no conflicts of interest. As the effect on child development of maternal IDA, fetal growth restriction, corresponding author Robert E Black states that he had full access to all and childhood undernutrition, maternal IDA, and mental health and data and final responsibility for the decision to submit for publication. served as a coordinator for this paper. ZAB assisted with conceptualising Acknowledgments the paper and contributed sections on micronutrients and adolescent Funding for the preparation of the Series was provided to the Johns nutrition. PC contributed to writing the sections on maternal and Hopkins Bloomberg School of Public Health through a grant from the childhood micronutrient deficiencies (vitamin A and iodine), mortality Bill & Melinda Gates Foundation. The sponsor had no role in the and morbidity effects of maternal low BMI and short stature, and analysis and interpretation of the evidence or in writing the paper and micronutrient deficiencies and effects of fetal growth restriction on the decision to submit for publication. childhood stunting. MdO contributed global and regional analyses on childhood stunting, wasting, underweight, and overweight. ME References contributed to exposures for various child and maternal nutritional 1 Black RE, Allen LH, Bhutta ZA, et al, for the Maternal and Child indicators, to selected aetiological effect sizes for childhood exposures, Undernutrition Group. Maternal and child undernutrition: global and provided advice on methods for calculation of attributable burden. and regional exposures and health consequences. Lancet 2008; SG-MG reviewed the scientific literature on iron and iodine deficiency 371: 243–60. and contributed to these sections. JK contributed analyses and text on 2 Victora CG, Adair L, Fall C, et al, for the Maternal and Child maternal risk factors for, prevalence of, and mortality consequences of Undernutrition Group. Maternal and child undernutrition: consequences for adult health and human capital. Lancet 2008; fetal growth restriction and the mortality effect of vitamin A 371: 340–57. supplementation. RM contributed the sections on adolescent nutrition, 3 Bhutta ZA, Ahmed T, Black RE, et al, for the Maternal and Child the consequences of short maternal stature, and long-term consequences Undernutrition Group. What works? Interventions for maternal of early nutrition. RU contributed to sections on maternal obesity, and child undernutrition and survival. Lancet 2008; 371: 417–40. considering causes and short-term and long-term consequences to 4 Bryce J, Coitinho D, Darnton-Hill I, et al, for the Maternal and mothers, neonates, and infants. All authors contributed to the final paper. Child Undernutrition Group. Maternal and child undernutrition: Maternal and Child Nutrition Study Group effective action at national level. Lancet 2008; 371: 510–26. Robert E Black (Johns Hopkins Bloomberg School of Public Health, 5 Morris SS, Cogill B, Uauy R. Effective international action against USA), Harold Alderman (International Food Policy Research Institute, undernutrition: why has it proven so difficult and what can be done USA), Zulfiqar A Bhutta (Aga Khan University, Pakistan), to accelerate progress? Lancet 2008; 371: 608–21. Stuart Gillespie (International Food Policy Research Institute, USA), 6 Maternal and Child Nutrition Study Group. Maternal and child Lawrence Haddad (Institute of Development Studies, UK), nutrition: building momentum for impact. Lancet 2013; published online June 6. http://dx.doi.org/10.1016/S0140-6736(13)60988-5. Susan Horton (University of Waterloo, Canada), Anna Lartey (University of Ghana, Ghana), Venkatesh Mannar (The Micronutrient 7 Cappa C, Wardlaw T, Langevin-Falcon C, et al. Progress for children: a report card on adolescents. Lancet 2012; 379: 2323–25. Initiative, Canada), Marie Ruel (International Food Policy Research Institute, USA), Cesar Victora (Universidade Federal de Pelotas, Brazil), 8 Prentice AM, Ward KA, Goldberg GR, et al. Critical windows for nutritional interventions against stunting. Am J Clin Nutr 2013; Susan Walker (The University of the West Indies, Jamaica), 93: 911–18. Patrick Webb (Tufts University, USA) 9 UNICEF. Progress for children: a report card on maternal mortality. Series Advisory Committee New York: United Nations Children’s Fund, 2008. Marc Van Ameringen (Gain Health Organization, Switzerland), 10 Kozuki N, Lee AC, Vogel J, et al. The association of parity and Mandana Arabi (New York Academy of Sciences, USA), Shawn Baker maternal age with small-for-gestational age, preterm and neonatal (Helen Keller International, USA), Martin Bloem (United Nations and infant mortality: a meta-analysis. BMC Public Health (in press). World Food Programme, Italy), Francesco Branca (WHO, Switzerland), 11 Gibbs CM, Wendt A, Peters S, et al. The impact of early age at first Leslie Elder (The World Bank, USA), Erin McLean (Canadian childbirth on maternal and infant health. Paediatr Perinat Epidemiol International Development Agency, Canada), Carlos Monteiro 2012; 26 (suppl 1): 259–84. (University of São Paulo, Brazil), Robert Mwadime (Makerere School of 12 Gigante DP, Rasmussen KM, Victora CG. Pregnancy increases BMI Public Health, Uganda), Ellen Piwoz (Bill & Melinda Gates Foundation, in adolescents of a population-based birth cohort. J Nutr 2005; USA), Werner Schultink (UNICEF, USA), Lucy Sullivan (1000 Days, 135: 74–80. USA), Anna Taylor (Department for International Development, UK), 13 Rah JH, Christian P, Shamim AA, et al. Pregnancy and lactation Derek Yach (The Vitality Group, USA). The Advisory Committee hinder growth and nutritional status of adolescent girls in rural Bangladesh. J Nutr 2008; 138: 1505–11. provided advice in a meeting with Series Coordinators for each paper at the beginning of the process to prepare the Series and in a meeting to 14 Ministy of Health and Family Welfare Government of India. International Institute for Population Sciences, Macro International. review and critique the draft reports. National family health survey (NFHS-3), 2005–06: India: Volume I. Other contributors Mumbai: IIPS, 2007. http://www.measuredhs.com/pubs/pdf/ Tanya Malpica-Llanos, Li Liu, and Jamie Perin assisted with analyses of FRIND3/FRIND3-Vol1AndVol2.pdf (accessed May 20, 2013). attributable deaths and Rachel White provided administrative support 15 Ministerio de Salud Pública y Asistencia Social, Instituto Nacional for this paper and the series. Aluisio Barros, Giovanny França, and de Estadística, Centros de Control y Prevención de Enfermedades., Maria Clara Restrepo contributed to the analyses of inequalities and of Encuesta Nacional de Salud Materno-infantil 2008 breastfeeding patterns. Anne CC Lee and Naoko Kozuki contributed to (ENSMI-2008/2009). Guatemala, 2010. analyses on fetal growth restriction. Monika Blössner and Elaine Borghi 16 Finucane MM, Stevens GA, Cowan MJ, et al, on behalf of the contributed to the analyses of global and regional estimates of stunting, Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose). National, regional, and global wasting, underweight, and overweight. Gretchen Stevens and Yuan Lu trends in body-mass index since 1980: systematic analysis of health conducted analysis of maternal BMI; Yuan Lu analysed the studies on examination surveys and epidemiological studies with 960 the effects of vitamin A and zinc deficiencies. country-years and 9·1 million participants. Lancet 2011; 377: 557–67. Conflicts of interest 17 Stevens GA, Singh GM, Lu Y, et al. National, regional, and global REB serves on the Boards of the Micronutrient Initiative, Vitamin trends in adult overweight and obesity prevalences. Angels, the Child Health and Nutrition Research Initiative, and the Popul Health Metr 2012; 10: 22.

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Levels and trends in child Children’s Fund, 2011. malnutrition. Joint child malnutrition estimates. New York, NY: 132 Christian P, Lee S, Donahue M and the CHERG Working Group. United Nations International Children’s Fund; Geneva: World Risk of childhood undernutrition related to small-for-gestational Health Organization; Washington, DC: World Bank, 2012. age and preterm birth in developing countries. Int J Epidemiol 155 de Onis M, Blössner M, Borghi E, et al. Methodology for estimating (in press). regional and global trends of child malnutrition. Int J Epidemiol 133 Zhang J, Yu KF. What’s the relative risk? A method of correcting 2004; 33: 1260–70. the odds ratio in cohort studies of common outcomes. JAMA 1998; 156 de Onis M, Blössner M, Borghi E. Prevalence and trends of stunting 280: 1690–91. among pre-school children, 1990–2020. Pub Health Nutr 2011; 134 Walker SP, Wachs TD, Gardner JM, et al. Child development: risk 15: 142–48. factors for adverse outcomes in developing countries. Lancet 2007; 157 Stevens GA, Finucane MM, Paciorek CJ, et al. Trends in mild, 369: 145–57. moderate, and severe stunting and underweight, and progress 135 Walker SP, Wachs TD, Grantham-McGregor S, et al. Inequality in towards MDG 1 in 141 developing countries: a systematic analysis of early childhood: risk and protective factors for early child population representative data. Lancet 2012; 380: 824–34. development. Lancet 2011; 378: 1325–38.

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158 Barros AJ, Victora C. Measuring coverage in MNCH: determining 179 Lind T, Lönnerdal B, Stenlund H, et al. A community-based and interpreting inequalities in coverage of maternal, newborn, and randomized controlled trial of iron and zinc supplementation in child health interventions. PLoS Med 2013; 10: e1001390. Indonesian infants: interactions between iron and zinc. 159 Pelletier DL, Frongillo EA Jr, Schroeder DG, et al. The effects of Am J Clin Nutr 2003; 77: 883–90. malnutrition on child mortality in developing countries. 180 Black MM, Baqui AH, Zaman K, et al. Iron and zinc Bull World Health Organ 1995; 73: 443–48. supplementation promote motor development and exploratory 160 Caulfield LE, de Onis M, Blossner M, et al. Undernutrition as an behavior among Bangladeshi infants. Am J Clin Nutr 2004; underlying cause of child deaths associated with diarrhea, 80: 903–10. pneumonia, malaria, and measles. Am J Clin Nutr 2004; 80: 193–98. 181 Friel JK, Aziz K, Andrews WL, et al. 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Long-term effects of iron and zinc supplementation during infancy 163 Grantham-McGregor S, Cheung YB, Cueto S, et al. Developmental on cognitive function at 9 y of age in northeast Thai children: potential in the first 5 years for children in developing countries. a follow-up study. Am J Clin Nutr 2011; 93: 636–43. Lancet 2007; 369: 60–70. 184 Olney DK, Pollitt E, Kariger PK, et al. Combined iron and folic acid 164 Walker CLF, Lamberti L, Adair L, et al. Does childhood diarrhea supplementation with or without zinc reduces time to walking influence cognition beyond the diarrhea-stunting pathway? unassisted among Zanzibari infants 5- to 11-mo old. J Nutr 2006; PloS One 2012; 7: e47908. 136: 2427–34. 165 Aburto NJ, Ramirez-Zea M, Neufeld LM, et al. Some indicators of 185 Katz J, Khatry SK, Leclerq SC, et al. Daily supplementation with nutritional status are associated with activity and exploration in iron plus folic acid, zinc, and their combination is not associated infants at risk for vitamin and mineral deficiencies. J Nutr 2009; with younger age at first walking unassisted in malnourished 139: 1751–57. preschool children from a deficient population in rural epal.N 166 Gardner JM, Grantham-McGregor SM, Himes J, et al. Behaviour J Nutr 2010; 140: 1317–21. and development of stunted and nonstunted Jamaican children. 186 Surkan PJ, Siegel EH, Patel SA, et al. Effects of zinc and iron J Child Psychol Psychiatry 1999; 40: 819–27. supplementation fail to improve motor and language milestone 167 Kuklina EV, Ramakrishnan U, Stein AD, et al. Early childhood scores of infants and toddlers. Nutrition 2013; 29: 542–48. growth and development in rural Guatemala. Early Hum Dev 2006; 187 Siegel EH, Kordas K, Stoltzfus RJ, et al. Inconsistent effects of 82: 425–33. iron-folic acid and/or zinc supplementation on the cognitive 168 Adair LS, Fall CH, Osmond C, et al, for the COHORTS group. development of infants. J Health Popul Nutr 2011; 29: 593–604. Associations of linear growth and relative weight gain during early 188 Beaton GH, Martorell R, Aronson K, et al. Effectiveness of life with adult health and human capital in countries of low and vitamin A supplementation in the control of young child middle income: findings from five birth cohort studies. Lancet 2013; morbidity and mortality in developing countries—nutrition policy published online March 28. http://dx.doi.org.10.1016/S0140- discussion paper no 13. Toronto, ON: International Nutrition 6736(13)60103-8. Program, 1993. 169 Cheung YB, Ashorn P. Continuation of linear growth failure and its 189 Fawzi WW, Chalmers TC, Herrera MG, et al. Vitamin A association with cognitive ability are not dependent on initial supplementation and child mortality. JAMA 1993; 269: 898–903. length-for-age: a longitudinal study from 6 months to 11 years of 190 Mayo-Wilson E, Imdad A, Herzer K, et al. Vitamin A supplements age. Acta Paediatr 2010; 99: 1719–23. for preventing mortality, illness, and blindness in children aged 170 Gandhi M, Ashorn P, Maleta K, et al. Height gain during early under 5: systematic review and meta-analysis. BMJ 2011; childhood is an important predictor of schooling and mathematics 343: d5094. ability outcomes. Acta Paediatr 2011; 100: 1113–18. 191 Imdad A, Yakoob MY, Sudfeld C, et al. Impact of vitamin A 171 Koplan JP, Liverman CT, Kraak VI, Committee on Prevention of supplementation on infant and childhood mortality. Obesity in Children and Youth. Preventing childhood obesity: BMC Public Health 2011; 11 (suppl 3): S20 health in the balance: executive summary. J Am Diet Assoc 2005; 192 Awasthi S, Peto R, Read S, et al. Population deworming every 105: 131–38. 6 months with albendazole in 1 million pre-school children in 172 Lloyd LJ, Langley-Evans SC, McMullen S. Childhood obesity and north India: DEVTA, a cluster-randomised trial. Lancet 2013; risk of the adult metabolic syndrome: a systematic review. 381: 1478–86. Int J Obes (Lond) 2012; 36: 1–11. 193 Rahmathullah L, Tielsch JM, Thulasiraj RD, et al. Impact of 173 Sachdev H, Gera T, Nestel P. Effect of iron supplementation on supplementing newborn infants with vitamin A on early infant mental and motor development in children: systematic review of mortality: community based randomised trial in southern India. randomised controlled trials. Public Health Nutr 2005; 8: 117–32. BMJ 2003; 327: 254. 174 Szajewska H, Ruszczynski M, Chmielewska A. Effects of iron 194 Klemm RD, Labrique AB, Christian P, et al. Newborn vitamin A supplementation in nonanemic pregnant women, infants, and supplementation reduced infant mortality in rural Bangladesh. young children on the mental performance and psychomotor Pediatrics 2008; 122: e242–50. development of children: a systematic review of randomized 195 Humphrey JH, Agoestina T, Wu L, et al. Impact of neonatal vitamin controlled trials. Am J Clin Nutr 2010; 91: 1684–90. A supplementation on infant morbidity and mortality. J Pediatr 175 Grantham-McGregor S, Baker-Henningham H. Iron deficiency in 1996; 128: 489–96. childhood: causes and consequences for child development. 196 International Zinc Nutrition Consultative Group, Brown KH, Ann Nestlé 2010; 68: 105–19. Rivera JA, et al. International Zinc Nutrition Consultative Group 176 Aukett M, Parks Y, Scott P, et al. Treatment with iron increases (IZiNCG) technical document #1. Assessment of the risk of zinc weight gain and psychomotor development. Arch Dis Child 1986; deficiency in populations and options for its control. 61: 849–57. Food Nutr Bull 2004; 25 (1 suppl 2): S99–203. 177 Idjradinata P, Pollitt E. Reversal of developmental delays in 197 Yakoob MY, Theodoratou E, Jabeen A, et al. Preventive zinc iron-deficient anaemic infants treated with iron. Lancet 1993; supplementation in developing countries: impact on mortality and 341: 1–4. morbidity due to diarrhea, pneumonia and malaria. 178 Stoltzfus RJ, Kvalsvig JD, Chwaya HM, et al. Effects of iron BMC Public Health 2011; 11 (suppl 3): S23. supplementation and anthelmintic treatment on motor and 198 Brown KH, Peerson JM, Baker SK, et al. Preventive zinc language development of preschool children in Zanzibar: double supplementation among infants, preschoolers, and older blind, placebo controlled study. BMJ 2001; 323: 1389–93. prepubertal children. Food Nutr Bull 2009; 30 (suppl 1): S12–40.

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199 Rice AL, West KP Jr, Black RE. Vitamin A deficiency. In: WHO. 214 Hoddinott J, Maluccio JA, Behrman JR, et al. Effect of a nutrition Comparative quantification of health risks: global and regional intervention during early childhood on economic productivity in burden of disease attributes to selected major risk factors. Geneva: Guatemalan adults. Lancet 2008; 371: 411–16. World Health Organization, 2004: 211–56. 215 Stein AD, Wang M, Ramirez-Zea M, et al. Exposure to a nutrition 200 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment supplementation intervention in early childhood and risk factors for of burden of disease and injury attributable to 67 risk factors and cardiovascular disease in adulthood: evidence from Guatemala. risk factor clusters in 21 regions, 1990–2010: a systematic analysis Am J Epidemiol 2006; 164: 1160–70. for the Global Burden of Disease Study 2010. Lancet 2013; 216 Lumey LH, Stein AD, Susser E. Prenatal famine and adult health. 380: 2224–60. Ann Rev Public Health 2011; 32: 237–62. 201 Imdad A, Bhutta ZA. Effect of preventive zinc supplementation on 217 Chen Y, Zhou L-A. The long-term health and economic linear growth in children under 5 years of age in developing consequences of the 1959–1961 famine in China. J Health Econ countries: a meta-analysis of studies for input to the lives saved tool. 2007; 26: 659–81. 218 Huang C, Li Z, Wang M, et al. Early BMC Public Health 2011; 11 (suppl 3): S22. life exposure to the 1959–1961 Chinese famine has long-term health 202 Lamberti LM, Fischer Walker CL, Noiman A, et al. Breastfeeding consequences. J Nutr 2010; 140: 1874–78. and the risk for diarrhea morbidity and mortality. 219 Song S, Wang W, Hu P. Famine, death, and madness: BMC Public Health 2011; 11 (suppl 3): S15. schizophrenia in early adulthood after prenatal exposure to the 203 Lamberti LM, Zakarija-Grkovic I, Fischer Walker CL, et al. Chinese great leap forward famine. Soc Sci Med 2009; 68: 1315–21. Breastfeeding for reducing the risk of pneumonia morbidity and 220 Huang C, Phillips MR, Zhang Y, et al. Malnutrition in early life and mortality in children under two: a systematic literature review and adult mental health: evidence from a natural experiment. Soc Sci Med meta-analysis. BMC Public Health (in press). 2012; published online Dec 20. DOI:10.1016/j.socscimed.2012.09.051. 204 Debes AK, Kohli A, Walker N, et al. Time to initation of 221 Huang C, Li Z, Venkat Narayan KM, et al. Bigger babies born to breastfeeding and neonatal mortality and morbidity: a systematic women survivors of the 1959–1961 Chinese famine: a puzzle due to review. BMC Public Health (in press). survival selection? J Dev Orig Health Dis 2010; 1: 412–18. 205 Horta BL, Victora C. Long-term effects of breastfeeding: a series of 222 WHO. Discussion paper. Proposed global targets for maternal, systematic reviews. Geneva: World Health Organization, 2013. infant and young child nutrition. Geneva: World Health 206 Ezzati M, Lopez AD, Rodgers A, et al, and the Comparative Risk Organization, 2012. Assessment Collaborating Group. Selected major risk factors and 223 Lozano R, Naghavi M, Foreman K, et al. Global and regional global and regional burden of disease. Lancet 2002; 360: 1347–60. mortality from 235 causes of death for 20 age groups in 1990 and 207 Ezzati M, Hoorn SV, Rodgers A, et al, and the Comparative Risk 2010: a systematic analysis for the Global Burden of Disease Study Assessment Collaborating Group. Estimates of global and regional 2010. Lancet 2013; 380: 2095–128. potential health gains from reducing multiple major risk factors. 224 de Onis M, Blössner M, Borghi E. Global prevalence and trends of Lancet 2003; 362: 271–80. overweight and obesity among preschool children. Am J Clin Nutr 208 Richter LM, Victora CG, Hallal PC, et al. Cohort profile: the 2010; 92: 1257–64. consortium of health-orientated research in transitioning societies. 225 McCormick DP, Sarpong K, Jordan L, et al. Infant obesity: are we Int J Epidemiol 2012; 41: 621–26. ready to make this diagnosis? J Pediatr 2010; 157: 15–19. 209 Walker SP, Chang SM, Powell CA, et al. Early childhood stunting is 226 Evellen vanDijk C, Innis SM. Growth-curve standards and the associated with poor psychological functioning in late adolescence assessment of early excess weight gain in infancy. Pediatrics 2009; and effects are reduced by psychosocial stimulation. J Nutr 2007; 123: 102–08. 137: 2464–69. 227 Bruce KD, Hanson MA. The developmental origins, mechanisms, 210 Galler JR, Bryce CP, Waber D, et al. Early childhood malnutrition and implications of metabolic syndrome. J Nutr 2010; 140: 648–52. predicts depressive symptoms at ages 11–17. 228 Gewa CA. Childhood overweight and obesity among Kenyan J Child Psychol Psychiatry 2010; 51: 789–98. pre-school children: association with maternal and early child 211 Cheung YB, Ashorn P. Linear growth in early life is associated with nutritional factors—erratum. Pub Health Nutr 2009; 13: 496–503. suicidal ideation in 18-year-old Filipinos. Paediatr Perinat Epidemiol 229 Griffiths L, Hawkins S, Cole T, et al. Risk factors for rapid weight 2009; 23: 463–71. gain in preschool children: findings from a UK-wide prospective 212 Galler JR, Bryce CP, Zichlin ML, et al. Infant malnutrition is study. Int J Obes (Lond) 2010; 34: 624–32. associated with persisting attention deficits in middle adulthood. J Nutr 2012; 142: 788–94. 213 Maluccio JA, Hoddinott J, Behrman JR, et al. The impact of improving nutrition during early childhood on education among Guatemalan adults. Econ J 2009; 119: 734–63.

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Maternal and Child Nutrition 2 Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

Zulfiqar A Bhutta, Jai K Das, Arjumand Rizvi, Michelle F Gaffey, Neff Walker, Susan Horton, Patrick Webb, Anna Lartey, Robert E Black, The Lancet Nutrition Interventions Review Group, and the Maternal and Child Nutrition Study Group

Published Online Maternal undernutrition contributes to 800 000 neonatal deaths annually; stunting, wasting, and micronutrient June 6, 2013 deficiencies are estimated to underlie nearly 3·1 million child deaths annually. Progress has been made with many http://dx.doi.org/10.1016/ interventions implemented at scale and the evidence for effectiveness of nutrition interventions and delivery strategies S0140-6736(13)60996-4 has grown since The Lancet Series on Maternal and Child Undernutrition in 2008. We did a comprehensive update of This is the second in a Series of four papers about maternal and interventions to address undernutrition and micronutrient deficiencies in women and children and used standard child nutrition methods to assess emerging new evidence for delivery platforms. We modelled the effect on lives saved and cost of Aga Khan University, Karachi, these interventions in the 34 countries that have 90% of the world’s children with stunted growth. We also examined Pakistan (Prof Z A Bhutta PhD, the effect of various delivery platforms and delivery options using community health workers to engage poor J K Das MBA, A Rizvi MSc); populations and promote behaviour change, access and uptake of interventions. Our analysis suggests the current Hospital for Sick Children, Toronto, ON, Canada total of deaths in children younger than 5 years can be reduced by 15% if populations can access ten evidence-based (M F Gaffey MSc); Johns nutrition interventions at 90% coverage. Accelerated gains are possible and about a fifth of the existing burden of Hopkins University, Bloomberg stunting can be averted using these approaches, if access is improved in this way. The estimated total additional School of Public Health, annual cost involved for scaling up access to these ten direct nutrition interventions in the 34 focus countries is Baltimore, MD, USA (N Walker PhD, Int$9·6 billion per year. Continued investments in nutrition-specific interventions to avert maternal and child Prof R E Black PhD); University undernutrition and micronutrient deficiencies through community engagement and delivery strategies that can of Waterloo, Waterloo, ON, reach poor segments of the population at greatest risk can make a great difference. If this improved access is linked Canada (Prof S Horton PhD); to nutrition-sensitive approaches—ie, women’s empowerment, agriculture, food systems, education, employment, Tufts University, Medford, MA, USA (Prof P Webb PhD); and social protection, and safety nets—they can greatly accelerate progress in countries with the highest burden of University of Ghana, Accra, maternal and child undernutrition and mortality. Ghana (Prof A Lartey PhD) Correspondence to: Introduction Selection of interventions for review Prof Zulfiqar A Bhutta, Center of Stunting prevalence has been decreasing slowly and We selected several nutrition-specific interventions Excellence in Women and Child 1 Health, The Aga Khan University, 165 million children were stunted in 2011. Under­ across the lifecycle for assessment of evidence of benefit Karachi 74800, Pakistan nutrition, consisting of fetal growth restriction, stunt­ (figure 1); these interventions included those affect­ [email protected] ing, wasting, and deficiencies of vitamin A and zinc, ing adolescents, women of reproductive age, pregnant along with sub­optimum breastfeeding, underlies nearly women, newborn babies, infants, and children. We also 3·1 million deaths of children younger than 5 years reviewed the evidence for delivery platforms for nutri­ annually world­wide, representing about 45% of all tion interventions and other emerging interventions of deaths in this group.2 Maternal and child obesity interest for nutrition of women and children. have also increased in many low-income and middle- We identified and relied on the most recent reviews income countries.3 with good quality methods for all interventions and In a comprehensive review of nutrition interven­ updated the evidence by incorporating newer studies, tions, we previously assessed 43 nutrition-related inter­ when available. For other identified interventions, when ventions in detail and reported estimates of efficacy and we did not find any relevant review, we did a de-novo effect for 11 core interventions.4 Much progress has review using the methodology described in panel 1.5 been made since with many interventions implemented Additionally, we consulted the electronic library on at scale, assessments of promising new interventions, nutrition actions (eLENA) for existing evidence used by and new delivery strategies. We used standard methods WHO for development of guidelines and policies for See Online for appendix to do a comprehensive review of potential nutrition- action (appendix p 2). specific inter­ventions to address undernutrition and micro­nutrient deficiencies in women and children. Interventions to address adolescent health We modelled the potential effect of delivery of these and nutrition inter­ventions on lives saved in the 34 countries with There is growing interest in adolescent health as an entry 90% of the global burden of stunted children, and point to improve the health of women and children,­ estimated the effect of various delivery platforms especially because an estimated 10 million girls younger that could enhance equitable scaling up of nutrition- than 18 years are married each year.6 A range of inter­ specific interventions. ventions exist in relation to adolescent health and

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Key messages • Globally, 165 million children are stunted; undernutrition is needed for prevention and management strategies for underlies 3·1 million deaths in children younger than 5 years. moderate acute malnutrition in population settings, • A clear need exists to introduce promising evidence-based especially in infants younger than 6 months. interventions in the preconception period and in • Data for the effect of various nutritional interventions on adolescents in countries with a high burden of neurodevelopmental outcomes are scarce; future studies undernutrition and young age at first pregnancies; should focus on these aspects with consistency in however, targeting and reaching a sufficient number of measurement and reporting of outcomes. those in need will be challenging. • Conditional cash transfers and related safety nets can address • Promising interventions exist to improve maternal nutrition the removal of financial barriers and promotion of access of and reduce fetal growth restriction and small-for-gestational- families to health care and appropriate foods and nutritional age (SGA) births in appropriate settings in developing commodities. Assessments of the feasibility and effects of countries, if scaled up before and during pregnancy. These such approaches are urgently needed to address maternal interventions include balanced energy protein, calcium, and and child nutrition in well supported health systems. multiple micronutrient supplementation and preventive • Innovative delivery strategies, especially community-based strategies for malaria in pregnancy. delivery platforms, are promising for scaling up coverage • Replacement of iron-folate with multiple micronutrient of nutrition interventions and have the potential to reach supplements in pregnancy might have additional benefits for poor populations through demand creation and household reduction of SGA in at-risk populations, although further service delivery. evidence from effectiveness assessments might be needed to • Nearly 15% of deaths of children younger than 5 years can guide a universal policy change. be reduced (ie, 1 million lives saved), if the ten core • Strategies to promote breastfeeding in community and facility nutrition interventions we identified are scaled up. settings have shown promising benefits on enhancing • The maximum effect on lives saved is noted with exclusive breastfeeding rates; however, evidence for long-term management of acute malnutrition (435 000 benefits on nutritional and developmental outcomes is scarce. [range 285 000–482 000] lives saved); 221 000 • Evidence for the effectiveness of complementary feeding (135 000–293 000) lives would be saved with delivery of an strategies is insufficient, with much the same benefits infant and young child nutrition package, including noted from dietary diversification and education and food breastfeeding promotion and promotion of complementary supplementation in food secure populations and slightly feeding; micronutrient supplementation could save greater effects in food insecure populations. Further 145 000 (30 000–216 000) lives. effectiveness trials are needed in food insecure populations • These interventions, if scaled up to 90% coverage, could with standardised foods (pre-fortified or non-fortified), reduce stunting by 20·3% (33·5 million fewer stunted duration of intervention, outcome definition, and cost children) and can reduce prevalence of severe wasting effectiveness. by 61·4%. • Treatment strategies for severe acute malnutrition with • The additional cost of achieving 90% coverage of these recommended packages of care and ready-to-use proposed interventions would be Int$9·6 billion per year. therapeutic foods are well established, but further evidence

nutrition, which could also affect the period before first Interventions in women of reproductive age and pregnancy or between pregnancies. Evi­dence supporting during pregnancy reproductive health and family planning interventions in Folic acid supplementation this age group suggests that it might be possible to Neural tube defects can be effectively prevented with reduce unwanted pregnancies and optimise age at first periconceptional­ folic acid supplementation. A review19 pregnancy. These aims might be important to reduce of five trials of periconceptional folic acid supplemen­ the risk of small-for-gestational age (SGA) births in tation suggested a 72% reduction in risk of development­ populations in which a substantial proportion of births of neural tube defects and a 68% reduction in risk of occur in adolescents. Opportunities might also exist to recur­rence compared with either no intervention, address micronutrient deficiencies and emerging issues placebo, or micro­nutrient intake without folic acid of overweight and obesity in adolescents­ through com­ (table 119–26). A review20 of folic acid supplementation munity and school-based education­ platforms. Although during preg­nancy showed that folic acid supple­mentation evidence from robust randomised controlled trials is improved mean birthweight, with a 79% reduction in the scarce, we identified a range of interventions in the adol­ incidence of megaloblastic anaemia (table 119–26). Further­ es­­cent period affecting maternal, newborn, and child more no evi­dence of adverse effects was noted from folic health and nutrition outcomes (panel 27–18). acid supplementation­ in pro­gramme settings. Despite www.thelancet.com 41 Series

Preconception care: family • Folic acid supplementation • Delayed cord clamping • Exclusive breast feeding planning, delayed age at first • Multiple micronutrient • Early initiation of breast • Complementary feeding pregnancy, prolonging of supplementation feeding • Vitamin A supplementation inter-pregnancy interval, • Calcium supplementation • Vitamin K administration (6–59 months) abortion care, psychosocial care • Balanced energy protein • Neonatal vitamin A • Preventive zinc supplementation supplementation supplementation • Iron or iron plus folate • Kangaroo mother care • Multiple micronutrient • Iodine supplementation supplementations • Tobacco cessation • Iron supplementation Decreased maternal and childhood morbidity and mortality Adolescent WRA and pregnancy Neonates Infants and children Improved cognitive growth and neurodevelopmental outcomes Disease prevention and Disease prevention and treatment treatment

• Malaria prevention in Management of SAM Increased work women Management of MAM capacity • Maternal deworming • Therapeutic zinc for and productivity • Obesity prevention diarrhoea • WASH Economic • Feeding in diarrhoea development • Malaria prevention in children • Deworming in children • Obesity prevention

Delivery platforms: Community delivery platforms, integrated management of childhood illnesses, child health days, school-based delivery platforms, financial platforms, fortification strategies, nutrition in emergencies

Bold=Interventions modelled Italics=Other interventions reviewed

Figure 1: Conceptual framework WRA=women of reproductive age. WASH=water, sanitation, and hygiene. SAM=severe acute malnutrition. MAM=moderate AM.

other foods might be a feasible way to reach the Panel 1: Methods, search strategy, and selection criteria population in need. As per the Child Health Epidemiology Reference Group (CHERG) systematic review guidelines,5 we searched PubMed, Cochrane libraries, electronic library on evidence on Iron or iron and folic acid supplementation nutrition actions (eLENA), and WHO regional databases and included publications in A review21 of iron supplementation in non-pregnant every language available in these databases. We used Medical Subject Heading Terms women of reproductive age showed that intermittent iron (MeSH) and keyword search strategies with various combinations of relevant terms. We supplementation (alone or with any other vitamins and made every effort to gather unpublished data when reports were available for full minerals) reduced the risk of anaemia by 27% (table 119–26). A abstraction. Inclusion and exclusion criteria were established for each area of review, and Cochrane review22 of daily iron supplementation to women studies meeting these criteria were double data extracted and categorised according to during pregnancy reported a 70% reduction in anaemia at outcome. Evidence was then summarised by outcome and study design, including study term, a 67% reduction in iron deficiency anaemia (IDA), quality, generalisability, and summary outcome measures. We did meta-analyses for each and 19% reduction in the incidence of low birthweight. outcome containing more than one study, using either the Mantel-Haenszel or the Another review27 further suggests that the effects were Der Simonian-Laird pooled relative risks (RR, with 95% CIs), when there was unexplained much the same in women receiving intermittent iron heterogeneity of effect. Heterogeneity was assessed by visual inspection of forest plots supplementation, or daily iron, or iron and folic acid and by the χ2 p value (p<0·10). The binary measure for individual studies and pooled supplementation. Although some evidence suggests that statistics was reported as the RR between the experimental and control groups with side-effects are fewer with intermittent iron therapy in non- 95% CIs. For the outcome of interest for each intervention, we applied the CHERG Rules anaemic populations, WHO recommends daily iron for Evidence Review5 to generate a final estimate. supplementation during pregnancy as part of the standard of care in populations at risk of iron deficiency.28

strong evidence of benefit, reaching women of reproduc­ Maternal multiple micronutrient supplementation tive age in the periconceptual­ period to provide folic Multiple-micronutrient deficiencies often coexist in low- acid supplements­ through existing delivery platforms income and-middle-income countries (LMICs) and can remains a logistical challenge. Fortification of cereals and be exacerbated in pregnancy with potentially adverse

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maternal outcomes. A Cochrane review23 of multiple micronutrient­­ supplementation in pregnant women Panel 2: Interventions to address adolescent nutrition and preconception care assessed 23 trials and reported an 11–13% reduction in low Women of lower socioeconomic status and young age are at risk of being undernourished birthweight and SGA births, whereas effects on anaemia and underweight. Ronnenberg and colleagues7 assessed the association between and IDA were much the same when compared with iron preconception anaemia and poor fetal and neonatal outcomes. They showed that the risk and folic acid supplements (table 1). Despite earlier of being born low birthweight was significantly greater with moderate preconception concerns about potential excess neonatal mortal­ity with anaemia (odds ratio [OR] 6·5, 95% CI 1·6–26·7) and fetal growth restriction (4·6, 1·5–13·5). multiple micronutrient­ use,29 present analyses suggest no Important factors indirectly related to maternal, fetal, and neonatal nutritional status adverse effects on maternal mortality, still­births, perinatal, and pregnancy outcomes include young age at first pregnancy and repeated and neonatal mortality with insuf­fi cient data for neuro­ pregnancies. Young girls who are not physically mature might enter pregnancy with developmental outcomes. Although scarce, there are depleted nutrition reserves and anaemia.8 Adolescent pregnancy is associated with a interesting data for benefits of maternal multiple micro­ 50% increased risk of stillbirths and neonatal deaths, and increased risk of preterm nutrient supplementation­ on growth in early childhood.30 birth, low birthweight, and asphyxia.9–11 Adolescents are especially prone to Preliminary data from a large trial31 comparing multiple complications of labour and delivery, such as obstructed and prolonged labour, micronutrient with iron-folate supplementation in preg­ vesico-vaginal fistulae, and infectious morbidity.11 In societies in which most births are nancy in Bangladesh show a significant reduction in pre­ within a marital relationship, interventions to increase the age at marriage and first term births with no adverse effects. Inclusion of this study pregnancy are important.12 Evidence suggests that programmes for adolescent in our meta-analysis confirms the reduction in low birth­ mothers can reduce repeat adolescent pregnancies by 37% (95% CI 12–51%) when they weight (relative risk [RR] 0·88, 95% CI 0·85–0·91) and teach parenting skills through home visitation and provide young mothers with SGA (0·89, 0·83–0·96) and is also indicative of a small education and vocational or job support. effect on preterm births (0·97, 0·94–0·99). These find­ ings support the potential replacement of iron-folate Two reviews by Conde-Agudelo and colleagues13,14 assessed the association between supplements in pregnancy with multiple micronutrient inter-pregnancy intervals with maternal, newborn, and child health outcomes and supplements in populations at risk. found a J-shaped dose-response association for perinatal outcomes. Short inter- pregnancy intervals (<6 months) were associated with a higher probability of maternal Maternal calcium supplementation anaemia (32%) and stillbirths (40%) whereas longer intervals (>60 months) were Gestational hypertensive disorders are the second associated with an increased risk of pre-eclampsia.15 Both short and long birth intervals leading cause of maternal morbidity and mortality and increase the risk for preterm births (OR 1·45 [95% CI 1·30–1·61] for short term; OR 1·21 are associated with increased risk of preterm birth and [95% CI 1·12–1·30] for long intervals), low birthweight (OR 1·65 [95% CI 1·27–2·14] for fetal growth restriction.32,33 Calcium supplementation short intervals; relative risk [RR] 1·37 [95% CI 1·21–1·55] for long intervals), and during pregnancy in women at risk of low calcium intake neonatal mortality (OR 1·31 [95% CI 0·96–1·79] for short interval; RR 1·15 [95% CI has been shown to reduce maternal hypertensive dis­ 1·06–1·25] for long intervals). With repeated pregnancies and advanced maternal age orders and preterm birth. A Cochrane review by Hofmeyr there is increased risk of chromosomal abnormalities, and increased risks of gestational and colleagues34 assessed 13 trials and showed that diabetes and hypertension, stillbirths (RR 1·62, 95% CI 1·50–1·76), perinatal mortality calcium supplementation during pregnancy reduced the (RR 1·44, 95% CI 1·10–1·89), and low birthweight (RR 1·61, 95% CI 1·16–2·24).16,17 incidence of gestational hypertension by 35%, pre- These findings support the need to optimise age at first pregnancy and family size and eclampsia by 55%, and preterm births by 24% (table 1). inter-pregnancy intervals. A global unmet need exists for family planning with more These estimates have been updated in a review24 of than 100 million unmarried women in developing countries not using contraception.18 15 randomised controlled trials, which also showed a Optimisation of age at first pregnancy must be coupled with promotion of effective 52% reduction in the incidence of pre-eclampsia and contraceptive use and exclusive breastfeeding, so that women can ideally space their confirmed that these effects were only noted in popu­ pregnancies 18–24 months apart. lations at risk of low calcium intake.

Maternal iodine supplementation or fortification developmental scores in children. Existing evidence In nearly all regions affected by iodine deficiency, use of supports continued focus on effective universal salt iodised salt is the most cost-effective way to avert deficiency. iodisation for women of reproductive age and those who A Cochrane review35 suggests that although iodised salt is are pregnant. Further high-quality controlled studies are an effective means to improve iodine status, no conclusions needed to address dosage and alternative strategies for can be drawn about physical and mental development in iodine supplementation in different population groups children and mortality. In some regions of the world with and settings. severe iodine deficiency, salt iodisation alone might not be sufficient for control of iodine deficiency in pregnancy; in Addressing maternal wasting and food insecurity with these circumstances iodised oil supplementation during balanced energy and protein supplementation pregnancy can be a viable option (table 1). A review25 of Maternal undernutrition is a risk factor for fetal growth five randomised trials of iodised oil supplementation in restriction and adverse perinatal outcomes.1 Several pregnancy in iodine-deficient populations showed a nutritional interventions have been assessed in such 73% reduction in cretinism and a 10–20% increase in situations, including dietary advice to pregnant women, www.thelancet.com 43 Series

Evidence reviewed Setting Estimates Folic acid supplementation Women of reproductive age Systematic review of five Developing and developed Significant effects: NTDs (RR 0·28, 95% CI 0·15–0·52), recurrence of NTDs (RR 0·32, 95% CI trials19 of periconceptual folic countries 0·17–0·60) acid supplementation Non-significant effects: other congenital abnormalities, miscarriages, still births Pregnant women Systematic review of Mostly developed countries Significant effects: mean birthweight (MD 135·75, 95% CI 47·85–223·68), incidence of 31 trials20 megaloblastic anaemia (RR 0·21, 95% CI 0·11–0·38) Non-significant effects: preterm birth, still births, mean predelivery haemoglobin, serum folate, red cell folate Iron and Iron-folate supplementation Women of reproductive age Systematic review of 21 RCTs Developing and developed Intermittent iron supplementation and quasi-experimental countries. Intervention mostly Significant effects: anaemia (RR 0·73, 95% CI 0·56–0·95), serum haemoglobin concentration studies21 given in school settings. Mostly (MD 4·58 g/L, 95% CI 2·56–6·59), serum ferritin concentration (MD 8·32, 95% CI 4·97–11·66) effectiveness studies Non-significant effects: iron deficiency, adverse events, depression Pregnant women Systematic review of 43 RCTs Developed and developing Daily iron-alone supplementation and quasi-experimental countries. Intervention Significant effects: low birthweight (RR 0·81, 95% CI 0·68–0·97), birthweight (MD 30·81 g, 95% CI studies22 (34 iron alone, delivered in community or at 5·94–55·68), serum haemoglobin concentration at term (MD 8·88 g/L, 95% CI 6·96–10·80), eight iron-folate) facility antenatal clinic. Mostly anaemia at term (RR 0·30, 95% CI 0·19–0·46), iron deficiency (RR 0·43, 95% CI 0·27–0·66), iron effectiveness studies deficiency anaemia (RR 0·33, 95% CI 0·16–0·69), side-effects (RR 2·36, 95% CI 0·96–5·82) Non-significant effects: premature delivery, neonatal death, congenital anomalies Iron-folate supplementation Significant effects: birthweight (MD 57·7 g, 95% CI 7·66–107·79), anaemia at term (RR 0·34, 95% CI 0·21–0·54), serum haemoglobin concentration at term (MD 16·13 g/L, 95% CI 12·74–19·52) Non-significant effects: low birthweight, premature birth, neonatal death, congenital anomalies MMN supplementation Pregnant women Systematic review of Developed and developing Significant effects: low birthweight (RR 0·88, 95% CI 0·85–0·91), SGA (RR 0·89, 95% CI 21 RCTs23 countries. Studies compared 0·83–0·96), preterm birth (RR 0·97, 95% CI 0·94–0·99) MMN with two or fewer Non-significant effects: miscarriage, maternal mortality, perinatal mortality, stillbirths, and micronutrients neonatal mortality Insufficient data for neurodevelopmental outcomes Calcium supplementation Pregnant women Systematic review of Developed and developing Significant effects: pre-eclampsia (RR 0·48, 95% CI 0·34–0·67), birthweight 85 g (95% CI 15 RCTs24 countries. Mostly effectiveness 37–133), preterm birth (RR 0·76, 95% CI 0·60–0·97) trials Non-significant effects: perinatal mortality, low birthweight, neonatal mortality Iodine through iodisation of salt Pregnant women Systematic review of five Mostly developing countries. Significant effects: cretinism at 4 years of age (RR 0·27, 95% CI 0·12–0·60), developmental scores RCTs25 Mostly effectiveness trials 10–20% higher in young children, birthweight 3·82–6·30% higher Maternal supplementation with balanced energy protein Pregnant women Systematic review of 16 RCTs Developing and developed Significant effects: SGA (RR 0·66, 95% CI 0·49–0·89), stillbirths (RR 0·62, 95% CI 0·40–0·98, and quasi-experimental countries birthweight (MD 73g, 95% CI 30–117) studies26 Non-significant effects: Bayley mental scores at 1 year

NTD=neural tube defects. RR=relative risk. MD=mean difference. RCT=randomised controlled trial. MMN=multiple micronutrient. SGA=small-for-gestational age.

Table 1: Review of nutrition interventions for women of reproductive age and during pregnancy

provision of balanced energy protein supplements, and Nutrition interventions in neonates high protein or isocaloric protein supplementation. In Delayed cord clamping other contexts, prescription and promotion of low energy Early clamping of the umbilical cord after birth is a diets to pregnant women who are either overweight or common practice and permits immediate transfer of the exhibit high weight gain in early gestation have been baby for care as required, whereas delaying of clamping assessed.36 Balanced energy protein supplementation, allows continued blood flow between the placenta and the providing about 25% of the total energy supplement as baby for a longer duration. A Cochrane review39 suggested protein, is deemed an important intervention for preven­ that delayed cord clamping in term neonates led to tion of adverse perinatal outcomes in mal­nourished significant increase in newborn haemoglobin and higher women.26,37 A Cochrane review38 con­cluded that balanced serum ferritin concentration at 6 months of age (table 239–45). energy protein supplementation reduced the incidence of Another review40 of studies in preterm neonates concluded SGA by 32% and risk of stillbirths by 45% (table 1). An that delayed cord clamping was associated with 39% updated meta-analysis showed that balanced energy reduction in need for blood transfusion and a lower risk of protein supplementation increased birthweight by 73 g complications after birth. Although promising, these (95% CI 30–117) and reduced risk of SGA by 34%, with strategies have as yet not been assessed for effect or more pronounced effects in malnourished­ women.26 feasibility of implementation at scale in health systems.

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Evidence reviewed Setting Estimates Delayed cord clamping Term neonates Systematic review of Developing and Significant effects: increased newborn haemoglobin conentration (MD 2·17 g/dL, 95% CI 0·28–4·06) 11 RCTs39 developed countries. Non-significant effects: postpartum haemorrhage, severe postpartum haemorrhage 24 and 36 weeks’ Delayed cord clamping was associated with an increased requirement for phototherapy for jaundice gestation at birth Preterm neonates Systematic review of Developing and Significant effects: reduced need for blood transfusion (RR 0·61, 95% CI 0·46–0·81), decrease in intraventricular 15 RCTs40 developed countries haemorrhage (RR 0·59, 95% CI 0·41–0·85), reduced risk of necrotising enterocolitis (RR 0·62, 95% CI 0·43–0·90) Peak bilirubin concentration was higher for delayed cord clamping group (MD 15·01 mmol/L, 95% CI 5·62–24·40) Neonatal vitamin K administration Neonates Systematic review of two Developing and Significant effects: One dose of intramuscular vitamin K reduced clinical bleeding at 1–7 days and improved RCTs for intramuscular developed countries biochemical indices of coagulation status. Oral vitamin K also improved coagulation status vitamin K and 11 RCTs for oral vitamin K41 Vitamin A supplementation Very low birthweight Systematic review of Developed countries Significant effects: reduced number of deaths and oxygen requirement at 1 month of age. infants nine RCTs42 Non-significant effects: one large trial showed no significant effect on neurodevelopment assessment at 18–22 months of age Term neonates Systematic review of five Developing countries Significant effects: reduction in infant mortality at 6 months (RR 0·86, 95% CI 0·77–0·97) RCTs and quasi- Non-significant effects: infant mortality at 12 months (RR 1·03, 95% CI 0·87–1·23) experimental studies43 Little data available for cause specific mortality, morbidity, vitamin A deficiency, anaemia, and adverse events Kangaroo mother care for promotion of breastfeeding and care of preterm and SGA infants Healthy neonates Systematic review of Developing and Significant effects: increase in breastfeeding at 1–4 months after birth (RR 1·27, 95% CI 1·06–1·53), increased 34 RCTs44 developed countries breastfeeding duration (MD 42·55 days, 95% CI 1·69–86·79) Preterm neonates Systematic review of Developing and Significant effects: reduction in the risk of mortality (RR 0·60, 95% CI 0·39–0·93), reduction in nosocomial 16 RCTs45 developed countries infection and sepsis (RR 0·42, 95% CI 0·24–0·73), reduction in hypothermia (RR 0·23, 95% CI 0·10–0·55), reduced length of hospital stay (MD 2·4 days, 95% CI 0·7–4·1)

RCT=randomised controlled trial. MD=mean difference. RR=relative risk. SGA=small-for-gestational age.

Table 2: Review of nutrition interventions in neonates

Neonatal vitamin K administration review43 did report a 14% reduction in the risk of infant Vitamin K deficiency can result in bleeding in the first mortality at 6 months of age, four more trials are weeks of life and vitamin K is commonly given currently underway in Asia and Africa, and researchers prophylactically after birth for prevention of bleeding. agree that these additional data will be needed before In the absence of vitamin K prophylaxis there is a development of recommendations for neonatal vitamin A 0·4–1·7% risk of development of clinically significant supplementation. bleeding. A Cochrane review41 suggested that one dose of intra­muscular vitamin K, when compared with Kangaroo mother care placebo, reduced clinical bleeding at 1–7 days of life, Kangaroo mother care denotes early skin-to-skin contact including bleeding after circumcision (table 2). Oral between mother and baby at birth or soon thereafter, plus and intra­muscular vitamin K had much the same early and continued breastfeeding, parental support, and effects on improved biochemical indices of coagulation early discharge from hospital. A Cochrane review44 of status at 1–7 days. Currently, vitamin K administration 34 randomised controlled trials of early skin-to-skin care after birth is largely restricted to births in health in healthy neonates showed a significant 27% increase in facilities; no information is available on the public breastfeeding at 1–4 months of age and increased dura­ health significance of vitamin K deficiency-related tion of breastfeeding (table 2). In a Cochrane review45 of bleeding in LMICs or population-based programmes 16 randomised trials, kangaroo mother care in preterm for prevention. neonates was associated with a 40% reduction in the risk of mortality, a 58% reduction in nosocomial infection or Neonatal vitamin A supplementation sepsis, and a 77% reduction in prevalence of hypothermia. A Cochrane review42 of oral or intramuscular vitamin A The trials included in these analyses were done in health supplementation to very low birthweight infants showed facilities; although kangaroo mother care might also be reduced mortality and oxygen requirement at 1 month of useful for home deliveries, there is not yet evidence of age compared with placebo (table 2).42 Although neonatal effectiveness in community settings. Kangaroo mother vitamin A supplementation has also been shown to be care was also shown to increase some measures of infant effective in reduction of all-cause mortality by 6 months growth, breastfeeding, and mother-infant attachment,45 of age, evidence is conflicting, and might be related to but few studies provide objective evidence of any effect maternal vitamin A status.46 Although a Cochrane on early child development. www.thelancet.com 45 Series

Nutrition interventions in infants and children In an update of a previous review of complemen­ Promotion of breastfeeding and supportive strategies tary feeding,68 we assessed 16 randomised and non- WHO recommends initiation of breastfeeding within 1 h randomised controlled trials and programmes of birth, exclusive breastfeeding of infants till 6 months of of moderate quality (table 3).54 We identified ten studies age, and continued breastfeeding until 2 years of age or that assessed the effect of nutrition education and seven older.47 However, global progress on this intervention is studies that assessed the effect of provision of additional both uneven and suboptimum.48 The exact scientific basis complementary foods (one trial with three intervention for the absolute early time window of feeding within the groups was in both these categories). Studies of nutrition first hour after birth is weak.49,50 A systematic review51 education in food secure populations showed a significant suggests that breast­feeding initiation within 24 h of birth increase in height (standard mean difference [SMD] is associated with a 44–45% reduction in all-cause and 0·35, 95% CI 0·08–0·62, four studies), and HAZ (0·22, infection-related neonatal mortality, and is thought to 0·01–0·43, four studies), whereas the effect on stunting mainly operate through the effects of exclusive breast­ was not statistically significant (RR 0·70, 95% CI feeding. We updated the previous review by Imdad and 0·49–1·01, four studies). We identified a significant effect colleagues,52 which assessed the effect of promotion on weight gain (SMD 0·40, 95% CI 0·02–0·78, four interventions on occurrence of breastfeeding, and con­ studies), whereas no effects were noted for weight-for- cluded that counselling or educational inter­ventions age Z scores (WAZ; 0·12; 95% CI –0·02 to 0·26, four increased exclusive breastfeeding by 43% at day 1, by 30% studies). Studies of nutrition education in food insecure till 1 month, and by 90% from 1–5 months. Significant populations (with an average daily per person income of reductions in occurrence of mothers not breast­feeding less than US$1·25) showed significant effects on HAZ were also noted; 32% reduction at day 1, 30% till 1 month, (SMD 0·25, 95% CI 0·09–0·42, one study), stunting (RR and 18% for 1–5 months53 (table 353–62). Com­bined 0·68, 95% CI 0·60–0·76, one study), and WAZ (SMD individual and group counselling seemed to be better 0·26, 95% CI 0·12–0·41, two studies). The review54 did than individual or group counselling alone. Although not find any eligible study that provided complementary these results show the potential for scaling up, none of feeding (with or without education) in a food secure these trials address the issues of barriers around work population. Overall, the provision of complementary environments and supportive strategies such as maternity foods in food insecure populations was associated with leave provision. A Cochrane review63 of interventions in significant gains in HAZ (SMD 0·39; 95% CI 0·05–0·73, the workplace to support breast­feeding for women found seven studies) and WAZ (SMD 0·26, 95% CI 0·04–0·48, no trials. Although some trials are underway, much more three studies), whereas the effect on stunting did not needs to be done to assess innovations and strategies to reach statistical significance (RR 0·33, 95% CI 0·11–1·00, promote breast­feeding in working women, especially in seven studies). under­privileged communities. Vitamin A supplementation in children Promotion of dietary diversity and complementary A Cochrane review55 of 43 randomised trials showed feeding that vitamin A supplementation reduced all-cause Complementary feeding for infants refers to the timely mortality by 24% and diarrhoea-related mortality by introduction of safe and nutritionally rich foods in 28% in children aged 6–59 months (table 3). Vitamin A addition to breast-feeding at about 6 months of age and supplementation­ also reduced the incidence of typically provided from 6 to 23 months of age.64 Different diarrhoea and measles in this age group but there was approaches have been used to create indicators of no effect on mortality and morbidity related to dietary diversity and to study its association with child respiratory infections. Although a large effectiveness mal­nutrition. In seven Latin American surveys, Ruel study69 from India assessing the effect of vitamin A and Menon65 noted significant associations between supplementation and deworming over several years comple­mentary feeding practices and height-for-age did not show a significant effect on mortality from Z scores (HAZ). Similarly, analysis of Demographic vitamin A supplementation (mortality ratio 0·96, Health Survey data to create a dietary diversity score 95% CI 0·89–1·03), inclusion of these data with based on seven food groups showed that increased previous results still shows a significant, albeit lower, dietary diversity was positively associated with height- effect on mortality (RR 0·88, 95% CI 0·84–0·94).55 We for-age HAZ in nine of 11 countries.66 More recently, believe that vitamin A supplementation continues to be WHO infant and young child feeding indicators were an effective intervention in children aged 6–59 months studied in 14 Demographic Health Survey datasets from in populations at risk of vitamin A deficiency. low-income countries;67 consumption of a minimum acceptable diet with dietary diversity reduced the risk of Iron supplementation in infants and children both stunting and under­weight whereas minimum A Cochrane review56 of 33 studies showed that inter­ meal frequency was associated with lower risk of mittent iron supplementation to children younger than underweight only. 2 years reduced the risk of anaemia by 49% and iron

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Setting Estimates Breast feeding promotion in infants Systematic review of Developing and developed Significant effects: educational or counselling interventions increased EBF by 43% (95% CI 9–87) at day 1, by 30% (19–42) till 110 RCTs and countries 1 month, and by 90% (54–134) from 1–6 months. Significant reductions in rates of no breastfeeding also noted; 32% (13–46) at quasi-experimental studies53 day 1, 30% (20–38) 0–1 month, and 18% (11–23) for 1–6 months. Non-significant effects: predominant and partial breastfeeding Complementary feeding promotion in children 6–24 months of age 16 RCTs and Mostly from food secure Nutrition education in food secure populations quasi-experimental studies54 populations. Various foods Significant effects: increased height gain (SMD 0·35; 95% CI 0·08–0·62), HAZ (SMD 0·22; 95% CI 0·01–0·43), weight gain (SMD 0·40, used 95% CI 0·02–0·78) Non-significant effects: stunting, WAZ Nutrition education in food insecure populations Significant effects: HAZ (SMD 0·25, 95% CI 0·09–0·42), stunting (RR 0·68, 95% CI 0·60–0·76), WAZ (SMD 0·26, 95% CI 0·12–0·41) Complementary food provision with or without education in food insecure populations Significant effects: HAZ (SMD 0·39, 95% CI 0·05–0·73), WAZ (SMD 0·26, 95% CI 0·04–0·48) Non-significant effects: stunting (RR 0·33, 95% CI 0·11–1·00) Preventive vitamin A supplementation in children 6 months to 5 years of age Systematic review of Developing and developed Significant effects: reduced all-cause mortality (RR 0·76, 95% CI 0·69–0·83), reduced diarrhoea-related mortality (RR 0·72, 95% CI 43 RCTs55 countries 0·57–0·91), reduced incidence of diarrhoea (RR 0·85, 95% CI 0·82–0·87), reduced incidence of measles (RR 0·50, 95% CI 0·37–0·67) Non-significant effects: measles-related and ARI-related mortality Iron supplementation in children Systematic review of LMICs. Participant’s ages Intermittent iron supplementation 33 RCTs and ranged from neonates to Significant effects: decreased anaemia (RR 0·51, 95% CI 0·37–0·72), decreased iron deficiency (RR 0·24, 95% CI 0·06–0·91), increased quasi-experimental studies56 19 years haemoglobin concentration (MD 5·20 g/L, 95% CI 2·51–7·88), increased ferritin concentration (MD 14·17 mcg/L, 95% CI 3·53–24·81) Non-significant effects: HAZ, WAZ Evidence for mental development, motor skill development, school performance, and physical capacity was assessed by very few studies and showed no clear effect Systematic review of Developing and developed Significant effects: increased mental development score (SMD 0·30, 95% CI 0·15–0·46), increased intelligence quotient scores 17 RCTs57 countries. In children aged (≥8 years age; SMD 0·41, 95% CI 0·20–0·62) 6 months to 15 years Non-significant effects: Bayley mental development index in younger children (≤27 months old), motor development MMN supplementation including iron in children Systematic review of Mostly developing MMN supplementation 18 trials58 countries. In children aged Significant effects: increased length (MD 0·13, 95% CI 0·06–0·21), increased weight (MD 0·14, 95% CI 0·03–0·25) 6 months to 16 years MMN might be associated with marginal increase in fluid intelligence and academic performance in healthy school children Systematic review of Developing countries. Micronutrient powders 17 RCTs59 Mostly effectiveness Significant effects: Reduced anaemia (RR 0·66, 95% CI 0·57–0·77), reduced iron deficiency anaemia (RR 0·43, 95% CI 0·35–0·52), studies. In children aged reduced retinol deficiency (RR 0·79, 95% CI 0·64–0·98). Improved haemoglobin concentrations (SMD 0·98, 95% CI 0·55–1·40). 6 months to 11 years MNP was associated with a significant increase in diarrhoea (RR 1·04, 95% CI 1·01–1·06) Non-significant effects: serum ferritin, zinc deficiency, stunting, wasting, underweight, HAZ, WAZ, WHZ, fever, URI Zinc supplementation in children Systematic review of Mostly developing Preventive zinc supplementation 18 RCTs60,61 countries. In children Significant effects: mean height improved by 0·37 cm (SD 0·25) in children supplemented for 24 weeks, diarrhoea reduced by younger than 5 years 13% (95% CI 6–19), pneumonia reduced by 19% (95% CI 10–27) Non-significant effects: mortality (cause specific and all-cause) Systematic review of Developing and developed Non-significant effects: Mental developmental index, psychomotor development index 13 trials62 countries. In children younger than 5 years

RCT=randomised controlled trial. EBF=exclusive breastfeeding. HAZ=height-for-age Z score. WAZ=weight-for-age Z score. WHZ=weight-for-height Z score. MMN=multiple micronutrient. ARI=acute respiratory infection. URI=upper-respiratory infection. SMD=standard mean difference. MD=mean difference. RR=relative risk.

Table 3: Review of evidence for nutrition interventions for infants and children

deficiency by 76% (table 3). The findings also suggested treatment had an effect on mental development in that intermittent­ iron supplementation could be a children younger than 27 months. viable public health intervention in settings in which Since the demonstration of increased risk of admis­ daily supple­mentation had not been implemented or sion to hospital and serious illnesses with iron was not feasible. A review57 of the effect of iron supplementation,70 there has been concern about supplementation in children on mental and motor adminis­­tration of iron supplements in malaria endemic development showed only small gains in mental areas. WHO currently recommends administration of development and intelligence scores in supplemented iron supple­ments in malaria endemic areas on the school-age children who were initially anaemic or iron- stipulation that malaria prevention and treatment is deficient. There was no con­vincing evidence that iron made available.71 www.thelancet.com 47 Series

Multiple micronutrient supplementation in children zinc-supplemented children compared with placebo.60 Although the theoretical benefits of strategies to improve There is no convincing evidence that zinc supple­ diet quality and micronutrient density of foods consumed mentation in infants or children results in improved by small children are well recognised, few resource-poor motor or mental development.62 countries have clear policies in support of integrated strategies to control micronutrient deficiencies in Disease prevention and management young children.72 Available options include the provision Several interventions have the potential to affect health and of multiple micronutrients via supplements, micro­ nutrition outcomes through reduction in the burden of nutrient powders, or fortified ready-to-use foods includ­ infectious diseases. Table 477–88 summarises the evidence ing lipid-based nutrient supplements. A compre­hensive for interventions for disease prevention and management. review of the effects of multiple micronutrients compared with two or fewer micronutrients showed small benefits Prevention and treatment of severe acute on linear growth (mean difference [MD] 0·13, 95% CI malnutrition 0·06–0·21) and weight gain (0·14, 0·03–0·25) but with A substantial global burden of wasting exists, especially little evidence of effect on morbidity outcomes as severe acute malnutrition (SAM; weight-for-height Z score suggested by individual studies (table 3).58 Another [WHZ] <–3), which coexists with moderate acute mal­ review73 of the effect of multiple micronutrient supple­ nutrition (MAM; WHZ <–2). In stable non-emer­gency mentation on improvement of cognitive perfor­mance in situations with endemic malnutrition, MAM can often children concluded that multiple micro­nutrient supple­ present in combination with stunting. Most of the inter­ mentation might be associated with a marginal increase ventions previously discussed should be implemented­ to in reasoning abilities but not with acquired skills prevent the development of SAM in food insecure popu­ and knowledge. lations. Several approaches for prevention and treatment Micronutrient powders are increasingly in use at are in use. Although the provision of comple­mentary and scale in programmes to address iron and multiple supplementary foods could be considered in targeted food micronutrient deficiencies in children. We reviewed distribution pro­grammes, other ways to stimulate access 16 randomised controlled trials to assess the effectiveness and purchasing power can be conceived. Where markets of micronutrient powders and estimated that they are fragmented or food access is constrained, appropriate significantly improved haemoglobin concentration and food supple­ments might be considered as in-kind reduced IDA by 57% and retinol deficiency by 21%.59 We transfers. WHO recommends inpatient treatment for noted no evidence of benefit on linear growth. However, children with complicated SAM, with stabilisation and in-line with findings from an earlier review of liquid iron appro­priate treatment of infections, fluid management, supplementation trials,74 use of micronutrient powders and dietary therapy and also supports community-based was shown to be associated with a significant increase in care for uncomplicated SAM.89 Although facility-based the incidence of diarrhoea (RR 1·04, 95% CI 1·01–1·06), treatment of SAM remains important, community largely because of results from a recent large cluster- manage­ment of SAM continues to grow rapidly globally. randomised controlled trial of micronutrient powders This shift in treatment norms from centralised, inpatient in Pakistan in malnourished children.75 These find­ care towards community-based models allows more ings underscore the need for further assessment of affected children to be reached and is cost effective. Up to micronutrient powder programmes in varying contexts an estimated 15% of cases of SAM will need initial facility- for safety and benefits. based care, whereas the rest can receive only community- based treatment.90 Preventive zinc supplementation in children Preventive zinc supplementation in populations at risk Facility-based management of SAM according to the of zinc deficiency reduces the risk of morbidity from WHO protocol child­hood diarrhoea and acute lower respiratory infec­ A scientific literature review by Schofield and Ashworth91 tions and might increase linear growth and weight gain showed that between the 1950s and 1990s, case fatality in infants and young children.60,76 A review by Yakoob rates were typically 20–30% in children with SAM treated and colleagues61 assessed 18 studies from developing in hospitals or rehabilitation units, and rates were higher coun­tries and showed that preventive zinc supple­ (50–60%) for oedematous malnutrition. A previous mentation reduced the incidence of diarrhoea by 13% review4 of existing studies had estimated that following and pneumonia by 19%, with a non-significant 9% the WHO protocol, as opposed to standard care, would reduction in all-cause mortality (table 3). However, lead to a 55% reduction in deaths (RR 0·45, 95% CI subgroup analysis showed that there was a significant 0·32–0·62; random effects). 18% reduction in all-cause mortality in children aged In view of the limitations of analysis and variable quality 12–59 months. A daily dose of 10 mg zinc per day over of studies in the previous review, we updated the review to 24 weeks in children younger than 5 years could lead to assess the effect of the WHO protocol or adaptations an estimated net gain of 0·37 cm (SD 0·25) in height in thereof on recovery and case fatality of children with SAM.

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Case fatality rates ranged from 3·4% to 35%. The highest Community-based management of SAM case fatality rate stemmed from a cohort of children with The products used to deliver nutrients for management HIV infection.92,93 Only two studies provided information of SAM and MAM, and the approaches used to target on recovery rates, which were 79·7% and 83·3%.94,95 In and deliver these products, evolved rapidly during the summary, the WHO protocol is substantiated through past decade. Innovations include new formulations and much evidence, based both on research and expert packaging and a shift from institutional to community- opinion. However, a clear need exists for continued work based management. to improve staff training and quality96 to achieve high rates We reviewed interventions to treat SAM in community of survival across various resource-constrained settings. settings, and were largely able to pool studies comparing

Settings Estimates WASH interventions Overview of three Developing Significant effects: reduced risk of diarrhoea with hand washing with soap (RR 0·52, 95% CI 0·34–0·65), with systematic reviews77 countries improved water quality, and with excreta disposal DHS data from 65 countries78 Developing Significant effects: a recent World Bank report78 based on analysis of trends in DHS data suggests that open countries defecation explained 54% of international variation in child height by contrast with GDP, which only explained 29%. A 20 percentage point reduction in open defecation was associated with a 0·1 SD increase in child height A Cochrane review of the effect of WASH interventions on nutrition outcomes is underway87 Maternal deworming Systematic review of Developing Non-significant effects: one dose of anthelminthic in second trimester of pregnancy had a non-significant five RCTs79 countries effect on maternal anaemia, low birthweight, preterm births, and perinatal mortality Deworming in children (for soil-transmitted intestinal worms) Systematic review of Developing Non-significant effects: one-dose deworming had a non-significant effect on haemoglobin and weight gain. 34 RCTs80 countries For multiple doses at 1 year follow up, there was a non-significant effect on weight, haemoglobin, cognition, and school attendance Treatment after confirmed infection Significant effects: one-dose of deworming drugs increased weight (0·58 kg, 95% CI 0·40–0·76) and haemoglobin (0·37 g/dL, 95% CI 0·1–0·64). Evidence on cognition was inconclusive These analyses are corroborated by the large-scale DEVTA trial88 of regular deworming and VAS over 5 years, which also did not show any benefits on weight gain or mortality Feeding practices in diarrhoea Review of 29 RCTs81 Developing Significant effects: in acute diarrhoea, lactose-free diets, when compared with lactose-containing diets, countries significantly reduced incidence of diarrhoea (SMD –0·36, 95% CI –0·62 to –0·10) and treatment failure (RR 0·53, 95% CI 0·40–0·70) Non-significant effects: weight gain Zinc therapy for diarrhoea Systematic review of Mostly Asia Significant effects: reduced all-cause mortality reduced by 46% (95% CI 12–68), diarrhoea-related 13 studies82 admissions to hospital by 23% (95% CI 15–31) Non-significant effects: diarrhoea-specific mortality, diarrhoea-prevalence Zinc reduced duration of acute diarrhoea by 0·50 days and persistent diarrhoea by 0·68 days IPTp/ITN for malaria in pregnancy Systematic review of Mostly Africa Significant effects: Anti-malarials to prevent malaria in all pregnant women reduced antenatal parasitemia 16 RCTs83 (RR 0·53, 95% CI 0·33–0·86), increased birthweight (MD 126·7 g, 95% CI 88·64–164·75), reduced low birthweight by 43% (RR 0·57, 95% CI 0·46–0·72) and severe antenatal anaemia 38% (RR 0·62, 95% CI 0·50–0·78) Non-significant effects: perinatal deaths Systematic review of Developing Significant effects: ITNs in pregnancy reduced low birthweight (RR 0·77, 95% CI 0·61–0·98) and reduced fetal six RCTs84 countries loss (first to fourth pregnancy; RR 0·67, 95% CI 0·47–0·97) Non-significant effects: anaemia and clinical malaria Malaria prophylaxis in children Systematic review of Developing Significant effects: Reduced clinical malaria episodes (RR 0·26; 95% CI 0·17–0·38), reduced severe malaria seven RCTs85 countries of episodes (RR 0·27, 95% CI 0·10–0·76). IPTc also reduced risk of moderately severe anaemia (RR 0·71, 95% CI West Africa 0·52–0·98) Non-significant effects: all-cause mortality Systematic review of Developing Significant effects: ITNs improved packed cell volume of children by 1·7 absolute packed cell volume percent. 22 RCTs86 countries in When the control group used untreated nets, the difference was 0·4 absolute packed cell volume percent. Africa ITNs and IRS reduced malaria-attributable mortality in children (1–59 months) by 55% (95% CI 49–61) in Plasmodium falciparum settings

WASH=water, sanitation, and hygiene. RCT=randomised controlled trial. DHS=Demographic and Health Survey. GDP=gross domestic product. RR=relative risk. MD=mean difference. SMD=standard mean difference. WAZ=weight-for-age Z score. HAZ=height-for-age Z score. DEVTA=de-worming and enhanced vitamin A. IPTp=intermittent preventive treatment of malaria in pregnancy. IPTc=IPT in children. ITN=insecticide-treated bednets. IRS=indoor residual spraying.

Table 4: Review of evidence for disease prevention and management

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ready-to-use therapeutic foods (RUTF) with standard adulthood.102–107 All studies suggested a small protective care, as opposed to rigorous evaluation of effectiveness of effect of breastfeeding on obesity later in life, although the approach in programme settings.97 We identified no the magnitude of the effect varied between reviews and significant differences in mortality; however, children the strength of the affect of confounding was unclear. who received RUTF had faster rates of weight gain and The largest prospective follow up study in healthy term had 51% greater likelihood to recover (defined as attaining infants in Belarus showed that improving the duration WHZ ≥ –2) than did those receiving standard care. and exclusivity of breastfeeding did not prevent over­ Notably, a new randomised controlled trial98 compared weight or obesity in children, nor did it affect insulin- standard RUTF with RUTF and additional 7 day course like growth factor I concentrations at age 11·5 years.108 of antibiotics, either amoxicillin or cefdinir, in children These findings suggest that despite the myriad with uncomplicated SAM. This trial showed that the advantages of breastfeeding, population strategies to children receiving an antibiotic had a lower mortality increase the duration and exclusivity of breastfeeding rate, faster recovery rate, and higher weight gain com­ are unlikely to curb the obesity epidemic. pared with children receiving placebo. Although further A Cochrane review107 examined the effects of obesity research on this topic is needed, especially in children prevention interventions delivered for more than 12 weeks with HIV infection, this study shows that effective on changes in BMI and BMI Z scores in children and community management of SAM might require an suggested a significant beneficial effect across age groups approach that goes beyond merely the choice of specially with a SMD of –0·15 kg/m (95% CI –0·21 to –0·09). The formulated foods to the entire package of care. subgroup analysis showed significant­ effects for children Substantial programmatic evidence supports use of aged 6–12 years with non-significant effects in younger RUTF for community-based treatment,99 which has sub­ children and adoles­cents. Interventions that combined stantially changed the approach to treatment of SAM. Yet physical activity and diet were more effective than either because of the nature of the evidence, establishing effect delivered alone. Findings suggested that short-term inter­ estimates for the overall approach to community manage­ ventions (<12 months duration) were more effective than ment has proved challenging. Available evidence shows were those delivered over a longer duration (SMD –0·17, some positive effects with the use of RUTF compared 95% CI –0·25 to –0·09 and SMD –0·12, 95% CI with standard care for the treatment of SAM in –0·21 to –0·03, respectively); however, there was sub­stan­ community settings, yet the differences were for the tial heterogeneity in all pooled estimates. Another most part small and several outcomes had substantial review109 of interventions to treat obesity in children hetero­geneity. An emphasis not only on the choice of showed that combined behavioural and lifestyle­ inter­ commodities, but also on the quality of programme ventions or self-help could benefit overweight­ children design and implementation is crucial to improvement of and adolescents. Overall the evidence of effectiveness of outcomes for children with SAM, as is research to fill all obesity prevention and therapeutic interventions is information gaps, such as optimum­ treatment methods weak, underscoring the need for high-quality research in and approaches for treat­ment of breastfed infants this discipline. younger than 6 months. Delivery platforms and strategies for Interventions for prevention and management implementation of nutrition-specific of obesity interventions Obesity is increasing in many populations and is one of Delivery strategies are crucial to achieve coverage the most important challenges of the 21st century. with nutrition-specific interventions and to reach popu­ Obese women are at an increased risk of adverse lations in need. A range of channels can provide oppor­ pregnancy outcomes. A Cochrane review100 assessed tunities for scaling up and reaching large segments of the effectiveness of interventions (eating, exercise, the population. behaviour modification, or counselling) that reduce weight in obese pregnant women and identified no Fortification of staple foods and specific foods evaluable trials. Some studies assessed the effect of diet, A detailed discussion of fortification strategies is exercise, or both for weight reduction in women after beyond the scope of this review. As supported by the childbirth, and showed that women who exercised did Copenhagen consensus,110 fortification is one the most not lose significantly more weight, but women who took cost-effective strategies to reach populations at large. part in a diet (MD –1·70 kg, 95% CI –2·08 to –1·32), or Further discussion of fortification as a means for delivery diet plus exercise programme (–2·89 kg; –4·83 to –0·95), of key micronutrients is provided in panel 3111–118 and the did so. These interventions did not seem to adversely accom­panying report by Stuart Gillespie and colleagues.119 effect breastfeeding performance in any setting.101 We identified six reviews that examined breastfeeding Cash transfer programmes in infancy and its association with obesity prevalence Financial incentives are widely used as policy strategies to or average body-mass index (BMI) in childhood or ameliorate poverty, reduce financial barriers, and improve

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Panel 3: Effect of fortification strategies Food fortification is safe and cost effective in the prevention of significant benefits on serum micronutrient concentrations, micronutrient deficiencies and has been widely practised in which could indirectly be used to work out the population-level developed countries for more than a century.111 Foods can be effect. A meta-analysis of multiple micronutrient fortification in fortified at three levels: mass or universal, targeted, and children shows an increase in haemoglobin concentrations by household. Mass or universal fortification—ideally legislated to 0·87 g/dL (95% CI 0·57–1·16) and reduced risk of anaemia by be mandatory for industries—has the potential to produce 57% (relative risk [RR] 0·43; 95% CI 0·26–0·71). The mean ferritin foods and food products that are widely consumed by the increase with fortification was 11·3 μg/L (95% CI 3·3–19·2) general population (eg, salt iodisation and flour fortification compared with control groups. Fortification also increased with iron and folate). Mass fortification is by far the most vitamin A serum concentrations compared with control groups cost-effective nutrition intervention, particularly when (four studies, mean retinol increase 3·7 μg/dL, 95% CI 1·3–6·1).113 produced by medium-to-large scale industries.111 Targeted A meta-analysis of 60 trials showed that iron fortification of fortification (eg, nutrient-fortified complementary foods for foods resulted in 41% reduction in the risks of anaemia (RR 0·59, children aged 6–24 months) is important for subgroups of 95% CI 0·48–0·71, p< 0·001) and a 52% reduction in iron nutritionally vulnerable populations and populations in deficiency (0·48, 0·38–0·62, p<0·001).114 Other studies have also emergency situations whose nutrient intake is insufficient shown that use of vitamin D fortified bread increased serum through available diets. Targeted fortification is also effective in 25-hydroxyvitamin D concentration as effectively as the resource poor settings where family foods do not include cholecalciferol supplement in women.115 Zinc fortification has animal-source foods that are typically necessary to meet also shown significantly higher zinc concentrations in serum and nutrient requirements of young children. Home fortification erythrocytes and lower serum copper concentrations compared involves addition of nutrients directly to food consumed by with a placebo group in preterm infants.116 women or children, or both, in the form of micronutrient Fortification has the greatest potential to improve the nutritional powders or small quantities of food-based fortified lipid status of a population when implemented within a spreads (eg, lipid-based nutrient supplement). Such direct comprehensive nutrition strategy. Key issues to ensure a addition of micronutrients to foods is different from foods sustainable programme include: identification of the right food fortified in the preparatory processes, has the advantage that it (accounting for bioavailability, interaction with food, availability, does not require changing dietary practices, and has little effect acceptability, and cost) and target population, ensuring quality of on the taste of food. However, addition of micronutrient product, and consumption of sufficient quantity of the fortified powders to prepared foods has characteristics akin to foods.117 To accomplish these aims, there needs to be demand that supplementation as opposed to foods fortified at source. is sustained through behaviour change communication at the Biofortification of food crops (fortification of food at source) is consumer level and ready access to a sufficient supply of products an alternative to more common fortification interventions and that maintain standards set through legislative process from is rapidly advancing in technology with much success, production to point-of-consumption. Government monitoring of particularly with regard to increasing iron, provitamin A, zinc, compliance to standards and public-private partnerships are 112 and folate contents in staple foods. essential to ensure a competitive market for fortified products.118 Despite many limitations to establishing causality during Fortification seems to be a potentially effective strategy but assessment of food fortification programmes, several studies evidence of benefits on morbidity and functional outcomes from have reported outcomes. Fortification for children shows large-scale programmes in developing countries is scarce. population health. We reviewed relevant studies reporting information on the benefit of such programmes for health the effect of financial incentives on coverage of health and and nutrition outcomes is provided in the accompanying nutrition interventions and behaviours targeting children report by Stuart Gillespie and colleagues.119 younger than 5 years.120 The affect of financial incentive programmes on five categories of interventions (breast­ Community-based platforms for nutrition education feeding practices, immunisation coverage, diarrhoea man­ and promotion age­ment, healthcare use, and other preventive strategies) Community-based interventions to improve maternal, was assessed. The review concluded that financial incen­ newborn, and child health are now widely recognised as tives have the potential to promote increased coverage of important strategies to deliver key maternal and child several important child health interventions, but the survival interventions121 and have been shown to reduce quality of evidence available was low. The more pronounced inequities in childhood pneumonia and diarrhoea effects seemed to be achieved by programmes that directly deaths.122 These interventions are delivered by health-care removed user fees for access to health services.120 Some personnel or lay individuals, and implemented locally in indication of effect was also noted for programmes that homes, villages, or any defined community group. A full conditioned financial­ incentives on participation in health spectrum of promotive, preventive, and curative inter­ education and attendance to health-care visits. 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including provision of basic antenatal, natal, and crucial importance of community engagement and buy- postnatal care; preventive essential newborn care; in to ensure effective community outreach programmes, breastfeeding counselling; man­age­ment and referral behaviour change, and access. of sick neonates; development of skills in behaviour change communication; and com­munity mobilisation Integrated management of childhood illnesses strategies to promote birth and newborn­ care prepared­ WHO, in collaboration with UNICEF and other agencies, ness. For example, a review123 of community-based developed the Integrated Management of Childhood packages of care suggested that these inter­ventions can Illness (IMCI) strategy in the 1990s.126 IMCI includes improve rates of facility births by 28% (RR 1·28, 95% CI both curative and preventive interventions targeted at 1·04–1·59) and result in a doubling of the rate of improve­ment of health practices at health facilities and at initiation of breastfeeding within 1 h (RR 2·25, 95% CI home. The strategy includes three components: improve­ 1·70–2·97). Lewin and colleagues124 reviewed 82 studies ments in case management; improvements in health with lay health workers and showed moderate quality systems; and improvements in family and com­munity evidence of effect on initiation of breastfeeding (RR 1·36, practices. Assessments of IMCI in Uganda, Tanzania, 95% CI 1·14–1·61), any breastfeeding (1·24, 1·10–1·39), Bangladesh, Brazil, Peru, South Africa, China, Armenia, and exclusive breastfeeding (2·78, 1·74–4·44) when Nigeria, and Morocco have shown various benefits in compared with usual care. Although much of the health service quality, mortality reduction, and health- evidence from large-scale programmes using community care cost savings.127 In Tanzania, implemen­tation of IMCI health workers is of poor quality, process indicators and was associated with significant improvements­ in equity assessments do suggest that community health workers differentials for six child health indicators, with the are able to implement many of these projects at scale, largest improvements noted for stunting in children and have substantial potential to improve the uptake of between 24 and 59 months of age.128 Much the same child health and nutrition outcomes among difficult to findings were reported from Bangladesh, where imple­ reach populations.125 It is important to underscore the mentation­ of IMCI was associated­ with a significant

Panel 4: Nutrition in emergencies Irrespective of the underlying cause, humanitarian emergencies undernutrition are not dangerously high, alternatives or are often characterised by high and rising rates of severe acute complements to food-based rations might be viable and malnutrition (SAM), moderate acute malnutrition (MAM), and potentially cost-effective.138,139 micronutrient deficiencies in children (and sometimes adults). Concern has also grown about the potential trade-offs between The foremost intent of nutrition-specific interventions in such long-term versus short-term objectives of emergency nutrition situations is to prevent mortality, and involves management of interventions. Although life-saving actions are justifiably wasting and resolution of specific nutrient deficiencies, and prioritised over the prevention of chronic diseases, food ensuring adequate food consumption. The humanitarian assistance programmes suitable for acute emergencies might be community largely agrees that emergency nutrition less appropriate for protracted situations.140 This has important interventions have improved in the past 10–15 years in terms of implications when thinking through seasonal blanket distribution coverage, scale of operations, reporting standards, and of ready-to-use foods to prevent a worsening of levels of acute 133 effectiveness (assessed by Sphere and other standards of malnutrition. As a result of the difficulty of generating practice). Until the early 2000s, nutrition programming in experimental data specific to programming in emergencies,141 the emergencies was dominated by facility-based therapeutic care, discipline has evolved relying less on randomised controlled trials targeted or blanket supplementary feeding, and provision of and more on the sharing of lessons learned, which are used to 134–136 micronutrient supplements. More recently, the focus has inform technical or operational guidelines disseminated by WHO widened, with attention being given to both short-term and and UN bodies.142–144 Although practice must still be improved in longer-term concerns, and to a choice of actions from a more many areas, and outcomes better documented, it remains 137 comprehensive range of interventions. The options for crucially important to secure appropriate resources to support effective management for both SAM and MAM in emergencies nutrition actions in this most challenging of disciplines and to have improved in the past 10–15 years as products used have assess outcomes for future learning. The nutritional status of been improved and coverage has increased through individuals assessed and treated in emergency contexts overlaps community-based treatment. Potential alternatives to the use substantially with non-emergency settings. Although of food to address seasonal or emergency-driven peaks in high-quality programmatic research can and must help improve wasting are being explored, including combinations of food the design and outcome of effective emergency nutrition plus cash, cash alone, or vouchers; however, cost-effectiveness interventions, these interventions should be seen as entry points studies of various strategies are scarce. There is evidence that in that support, rather than supplant, longer-term actions seeking contexts in which markets have not been seriously disrupted, to address underlying causes of poor nutrition. appropriate foods are readily accessible, and rates of

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increase in exclusive breastfeeding and com­paratively survival interventions. There are few robust assessments faster reduction in the prevalence of stunting in children or reported experiences with child health days, which aged 24–59 months.129 commonly include delivery of vitamin A supplements, immunisations, insecticide-treated nets, and deworming School-based delivery platforms drugs. Available evidence suggests that these days can Many countries have school feeding programmes achieve greater coverage than stand-alone campaigns targeting children who are older than 5 years. The main in previously low-coverage countries.131 A descriptive purpose of such programmes is to provide incentives review132 of scale-up of child health days from 1999 to for school enrolment and evidence of nutrition benefits 2009 suggests that these days were more effective than is scarce. A Cochrane review130 of 18 relevant studies of stand-alone campaigns, provided that the number of the effectiveness of school feeding programmes in interventions did not exceed four. The overall equity improving physical and psychosocial health for effect of these approaches are uncertain and further disadvantaged school pupils reported an increase in studies are needed to establish how best to integrate this school attendance by 4–6 days annually and weight approach within routine health-care services. gains averaging 0·39 kg (95% CI 0·11–0·67) over 11 months and 0·71 kg (0·48–0·95) over 19 months. The Delivery of nutrition interventions in results were inconclusive for height gain, so there must humanitarian emergency settings be caution that these programmes do not lead to obesity. Delivery strategies for nutrition interventions in human­ A detailed discussion of school feeding programmes is i­tarian emergencies necessitate a different approach to provided in the accompanying report by Stuart Gillespie what might be deemed optimum in stable circumstances. and colleagues.119 Notwithstanding the scarce evidence, In view of variability in the characteristics of emergencies schools offer an enormous opportunity for promotion of and protracted population displace­ment, humanitarian health and nutrition for older children and adolescents emergencies might closely mirror situations­ of endemic and could have an important role in future. malnutrition in food insecure settings. Hence prevention and health promotion strategies, such as breastfeeding Child health days and complementary feeding education and support, Child health days have been introduced in weak health should also become essential parts of the packages of systems to rapidly enhance coverage of essential child interventions in emergency contexts (panel 4133–144).

Panel 5: Evidence for emerging interventions Household air pollution Maternal vitamin D supplementation Household air pollution (HAP) from solid fuels used in simple Vitamin D is an essential requirement of the body at any age. stoves for cooking and heating, is recognised as a risk factor for Vitamin D can be acquired through three main channels: several health outcomes with important consequences for child through the skin via exposure to sunlight, from the diet, and survival, including pneumonia,146 low birthweight, and from supplements or fortified foods. However, natural low-cost stillbirths.147 A review of observational studies148 shows sources of dietary sources of vitamin D are very scarce. A significant risk reduction estimates for HAP for low birthweight systematic review151 assessing the association of vitamin D (29%), stillbirth (34%), stunting (21%), and all-cause mortality status in pregnancy, suggests that women with circulating (27%). Reduction of exposure to HAP could substantially reduce 25-hydroxyvitamin D (25[OH]D) concentrations of less than risk of several important outcomes for child survival. One 50 nmol/L in pregnancy have an increased risk of preeclampsia randomised controlled trial in rural Guatemala,149 with an (odds ratio [OR] 2·09, 95% CI 1·50–2·90), gestational diabetes improved stove intervention, reduced average exposure to mellitus (1·38, 1·12–1·70), preterm birth (1·58, 1·08–2·31) and indoor air pollution by 50% and resulted in a reduction in small-for-gestation age ([SGA] 1·52, 1·08–2·15). A long-term physician-diagnosed pneumonia (relative risk [RR] 0·84, 95% CI cohort study152 did not find any association of low maternal 0·63–1·13) although this difference was not statistically vitamin D concentrations with bone mineral content in late significant. However, this finding was supported by the results childhood. Similarly, a Cochrane review153 assessed the of an exposure-response analysis which showed a statistically effectiveness of vitamin D supplementation in pregnancy and significant reduction in the same outcome (0·82, 0·70–0·98). revealed little evidence of benefits on functional pregnancy This intervention also resulted in a reduction in low birthweight outcomes, although significant increase in serum vitamin D (0·74, 95% CI 0·33–1·66), with babies weighing 89 g more concentrations at term were noted and borderline reduction in (95% CI –27 to 204) than those in the control group.150 A range low birthweight was reported in three trials (RR 0·48, 95% CI of interventions, including both clean fuels and improved solid 0·23–1·01). The number of high-quality trials with maternal fuel stoves are available, but substantial challenges remain in vitamin D supplementation is too small to draw conclusions on achieving sustained use of low-cost low-emission technologies its usefulness and safety. at scale in low-income households. (Continues on next page)

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(Continued from previous page) Role of massage for promoting growth in preterm Infants Preterm infants have been noted to benefit from massage Maternal zinc supplementation therapy and the suggested mechanisms include increased vagal A Cochrane review154 suggests that zinc supplementation in activity and gastric motility, which leads to increased pregnancy results in a 14% reduction in preterm birth (RR 0·86, concentrations of insulin and Insulin-like growth factor 1.168 A 95% CI 0·76–0·97). This decrease was not accompanied by a Cochrane review169 of the effect of massage in preterm infants similar reduction in stillbirths, neonatal death, SGA, or low showed that massage increased daily weight gain by 5 g, birthweight. No subgroup differences were identified in women reduced the length of hospital stay by 4·5 days, and had a slight with low versus normal zinc nutrition levels or in women who effect on development and weight gain at 4–6 months, complied with their treatment versus those who did not. We although the evidence was of weak quality. A more recent conclude that there is presently insufficient evidence for a review170 of the effects of massage therapy for preterm infants beneficial role of isolated zinc supplementation in pregnancy. showed that 5–10 days of moderate pressure massage, typically Omega-3 fatty acid supplementation 15 min three-times daily, resulted in improved weight gain Several reviews155–162 have been done to assess the effectiveness (mean for studies 28–48%) and bone density, and reduced of maternal supplementation with omega-3 fatty acids during length of hospital stay. Related evidence from studies of pregnancy and its effects on various outcomes including emollient therapy in preterm infants from the developing world nutritional, morbidity, mortality, cognitive, and suggest potential synergistic benefits of skin barrier protection, neurodevelopmental measures. Findings from these reviews, thermoregulation, and light massage. consisting of studies done in developed countries and of Vitamin D supplementation in children variable quality, suggest that marine omega-3 fatty acids In view of the widespread deficiency of vitamin D and administered in pregnancy reduce the rate of preterm birth and associated health consequences and rickets, preventive vitamin increase birthweight. However, a Cochrane review155 suggests D supplementation to high-risk populations, including infants that there is not enough evidence to support the routine use of and toddlers, might be a useful strategy. A Cochrane review of marine oil supplements or other prostaglandin precursors vitamin D supplementation in children in at-risk populations is during pregnancy to reduce the risk of pre-eclampsia, preterm underway, and an existing review171 of postnatal birth, low birthweight, or SGA. A review163 of the intake of supplementation shows relatively few studies assessing effects omega-3 and omega-6 fatty acids in low-income countries on bone density, growth, and other functional outcomes. showed that the total omega-3 fatty acid supply was below the recommended intake range for infants and young children, and Zinc supplementation for treatment of newborn infections below the minimum recommended level for pregnant and and childhood pneumonia lactating women, in the nine countries with the lowest gross A Cochrane review172 suggests that zinc supplementation in domestic product. The review noted that supply of omega-3 addition to antibiotics in children with severe and non-severe fatty acids could be increased by using vegetable oils with pneumonia did not have a significant effect on clinical higher alpha-linolenic acid and by increasing fish production recovery or duration of hospital stay. Other recent studies through fish farming. Another review164 on the effect of fatty show mixed effects across a range of severity of disease,173–176 acid status on immune function of children in low-income showing the need for larger well-powered studies for the countries suggested that fatty acid interventions could yield treatment of severe pneumonia with zinc in populations immune benefits in children in poor settings, especially in at-risk of deficiency. Two trials177,178 of adjunctive zinc non-breastfed children and in relation to inflammatory supplementation in presumed serious infections in neonates disorders, such as persistent enteropathy, although more trials and young infants show disparate findings, underscoring the are needed for a conclusive association. need for further well-designed and adequately powered studies of zinc as an adjunct to the treatment of serious Antenatal psychosocial assessment and mental health support infections in infancy. Stable maternal mental health during pregnancy is crucial for the development of the early mother–child relationship and for Lipid-based nutrient supplementation health. Although there is ample evidence of the link between Lipid-based nutrient supplements (LNS, in the form of maternal mental health and child health and growth,165 there is vegetable oil, peanut butter, milk powder, sugar, vitamins, and insufficient evidence to support routine psycho-social screening minerals) are used in small quantities (20 g) to meet for all pregnant women.166 There is promising evidence that micronutrient requirements in children, in combination with a cognitive-behaviour therapy-based interventions provided by normal diet. Randomised controlled trials in Malawi179,180 and community health workers to pregnant women, can effectively Ghana181,182 have shown significant benefits on iron status and reduce depression at 3 months post-partum (adjusted OR 0·22, linear growth. Further evidence of benefits and absence of 95% CI 0·14–0·36) and at 1-year follow-up (0·23, 0·15–0·36).167 adverse effects are needed to assess the feasibility of use of LNS However, there was no effect on weight gain or linear growth in in programme settings and randomised controlled trials are infancy. There is a need for further robust trials of maternal underway—three in Africa and one in Asia—which should mental health interventions with longer term follow up. provide more information.

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Panel 6: Overview of the Lives Saved Tool (LiST) To model the effect of scaling up the ten proven nutrition- Figure 2 shows the linkages in LiST between risk factors, specific interventions on the health of children we used the interventions, and mortality. For example, the input of multiple Lives Saved Tool (LiST). This model has been developed under micronutrients consumed by pregnant women has an effect on the auspices of the Child Health Epidemiology Reference Group birth outcomes. It directly affects the probability of a child being (CHERG) to allow users to estimate the effect of scaling up born small-for-gestational-age (SGA). A child born SGA will in interventions on maternal and child health. The present version turn have an increased risk of dying during the neonatal period of the model is based on previous modelling exercises, and those who survive through the first month of life then have including The Lancet’s 2008 Maternal and Child Undernutrition an increased risk of being stunted. Stunted children have higher series.4,122,145,184 A more detailed description of the LiST model is risks of mortality from 1 to 59 months of age. provided in appendix pp 3–7 and at the LiST website. A second example is promotion of breastfeeding. Scaling up The LiST has been characterised as a linear, mathematical breastfeeding promotion will affect breastfeeding practice, model that is deterministic.185 It describes fixed associations shifting the distribution of mothers who exclusively, between inputs and outputs that will produce the same outputs predominately, or partly breastfeed their child or do not each time the model is run. In LiST the primary inputs are breastfeed. Within the model, this intervention is examined coverage of interventions and the outputs are changes in separately for the first month of life and for the period of population level of risk factors (such as wasting or stunting 1–5 months. Within each of the two time periods there is a rates, or birth outcomes such as prematurity or size at birth) different relative risk of dying of pneumonia and diarrhoea and cause-specific mortality (neonatal, mortality in children associated with each breastfeeding practice and an effect on aged 1–59 months, maternal mortality, and stillbirths). The diarrhoea incidence. So within the model, breastfeeding association between an input (change in intervention promotion has an effect on breastfeeding practices, which in turn coverage) with one or more outputs is specified in terms of the has a direct effect on mortality in the neonatal and 1–23 month effectiveness of the intervention for reduction of the probability period. Additionally, there is an effect on diarrhoea incidence, of that outcome. The outcome can be cause-specific mortality which then has an effect on stunting rates and mortality. or a risk factor. The overarching assumption in LiST is that The assumptions of the effects of the ten nutrition interventions mortality rates and cause of death structure will not change we used in the modelling are shown in appendix pp 13–16. For except in response to changes in coverage of interventions. The each of the interventions we have also shown the 95% CIs around model assumes that changes in distal variables, such as increase the estimates, which were used in the sensitivity analyses. The in income per person or mothers’ education, will affect source and methods used to develop these assumptions and mortality by increasing coverage of interventions or reducing others used in the model are described in a series of reports.186–188 risk factors.

Emerging interventions that need further Folic acid MMN, BEP Breastfeeding Complementary Vitamin A Zinc fortification promotion feeding, supplementation supplementation evidence education, and We also reviewed interventions that are not currently supplementation recommended but that have potential and future prospects for inclusion in regular programmes. These interventions, Neonatal Breastfeeding mortality practices Diarrhoea incidence which have possible effects on nutritional outcomes in by cause women and children, include strategies to reduce house­ hold air pollution, maternal vitamin D supple­mentation, Birth risk defined Birth outcomes Stunting maternal zinc supplementation, omega 3 fatty acids by maternal age, (SGA and preterm) parity, and spacing Mortality by cause supplementation­ in pregnancy, antenatal psychosocial­ 1–59 months assessment and cognitive behaviour therapy for depres­ Wasting sion, emollient and massage therapy for preterm infants, Risk factors Interventions vitamin D supplementation in children, zinc therapy for Management of SAM Management of MAM Mortality pneumonia, and lipid-based nutrient supplements.­ Some of the existing evidence around these interventions is Figure 2: Linkages between risk factors, interventions, and mortality in LiST summarised in panel 5.146–182 LiST=Lives Saved Tool. MMN=multiple micronutrients. BEP=balanced energy protein. SGA=small-for-gestational-age. SAM=severe acute malnutrition. MAM=moderate AM. Modelling the effect of scaling up coverage of nutrition interventions in countries with the scaling up a set of ten nutrition-specific interven­­­ highest burden tions that could affect stunting and severe wasting183 We used the Lives Saved Tool (LiST) to model the (panel 6,4,122,145,184–188 figure 2). For modelling, we selected potential effect on child health and mortality in 2012 of 34 countries with more than 90% of the burden of www.thelancet.com 55 Series

Afghanistan Pakistan Iraq Bangladesh Egypt Chad Nepal Myanmar

Burkina Faso India Mali Niger Philippines Sudan Yemen Guatemala Vietnam C te d’Ivoire Ethiopia Ghana Nigeria Kenya Uganda Cameroon Tanzania Rwanda Indonesia Congo Angola Madagascar Zambia Malawi Mozambique South Africa High burden countries Other countries

Figure 3: Countries with the highest burden of malnutrition These 34 countries account for 90% of the global burden of malnutrition.

1 400 000 Baseline higher than 90%). Appendix pp 13–16 list the estimates Nutrition interventions scaled up of effect considered for each intervention. The con­ 1 200 000 version of intervention effects of preventive zinc supple­mentation and complementary feeding strategies 1 000 000 from linear growth to stunting effects in LiST is detailed in appendix pp 17–22. We assessed the effect of this 800 000 scale up scenario on mortality in children younger than 600 000 5 years, rates of breastfeeding, stunting, and wasting. Our model suggested that if these ten nutrition Number of deaths of Number 400 000 interventions were scaled up to 90% coverage, mortality in children younger than 5 years could be reduced by 200 000 15% (range 9–19), with a 35% (19–43) reduction in

0 diarrhoea-specific mortality, a 29% (16–37) reduction in Diarrhoea Pneumonia Measles Neonatal Neonatal Neonatal Neonatal pneumonia-specific mortality, and a 39% (23–47) deaths deaths deaths in diarrhoea pneumonia congenital asphyxia children <5 years deaths deaths anomalies reduction in measles-specific mortality (figure 4). The Cause-specific deaths in children <5 years and neonates analysis also showed fewer deaths attributable to congenital anomalies and birth asphyxia related to Figure 4: Effect of scale up of interventions on cause-specific deaths periconceptual folic acid use and a reduction in SGA Error bars are ranges. (figure 4; appendix pp 23–24). This scale up had a little effect on maternal mortality (data not shown). Scaling stunt­ing (figure 3; appendix pp 8–12) and took 2011 as up of all ten interventions to 90% coverage was also the base year. The present coverage level for each associated with a mean 20·3% (range 11·1–28·9) reduc­ intervention was taken from the latest available esti­ tion in stunting and a 61·4% (35·7–72) reduction in mates from large-scale surveys and effective­ness of severe wasting. The maximum effect for severe wasting For more on the Lives Saved interventions (see LiST for details). We modelled the was noted in children in the 12–23 months age group Tool see http://www.jhsph.edu/ effect of scaling up the follow­ing ten nutrition inter­ (appendix p 25). iip/LiST ventions: periconceptional folic acid supplementation The analysis suggested that the interventions with the or fortifi­ca­tion, maternal balanced energy protein largest potential affect on mortality in children younger supple­­men­tation, maternal cal­cium supple­­men­tation, than 5 years are management of SAM, preventive multiple micro­­nutrient supple­­men­tation in pregnancy, zinc supplementation, and promotion of breastfeeding promotion of breast­feeding, appro­priate complementary (figure 5). Analysis of community support strategies for feeding, vitamin A and preven­ ­tive zinc supplementation breastfeeding suggested that achieving 90% coverage of in chil­dren 6–59 months of age, management of SAM, breastfeeding promotion could increase exclusive breast­ and management of MAM, from their present level of feeding by 15% (7–22) in children younger than 1 month coverage to 90% (or retention of present coverage when and by 20% (13–26) in children aged 1–5 months.

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Management of SAM Preventive zinc supplementation Promotion of breastfeeding Appropriate complementary feeding Management of MAM Periconceptual folic acid supplementation or fortification Maternal balanced energy protein supplementation Interventions Maternal multiple micronutrient supplementation Vitamin A supplementation Maternal calcium supplementation 0 50 000 100 000 150 000 200 000 250 000 300 000 350 000 400 000 Number of deaths of children <5 years averted

Figure 5: Effect of scale up of interventions on deaths in children younger than 5 years Error bars are ranges. SAM=severe actute malnutriton. MAM=moderate AM.

Implementation of nutrition-specific packages Number of lives Cost per life- of care saved* year saved† We also assessed the potential effect of nutrition-specific Optimum maternal nutrition during pregnancy packages of care by scaling up these interventions to Maternal multiple micronutrient supplements to all 102 000 $571 (398–1191) 90% coverage. Four packages were assessed for effect on Calcium supplementation to mothers at risk of low intake‡ (49 000–146 000) child survival: optimum maternal nutrition during preg­ Maternal balanced energy protein supplements as needed nancy (maternal multiple micronutrients, use of iodised Universal salt iodisation‡ salt, calcium, and balanced energy protein supple­men­ Infant and young child feeding tation), an infant and young child nutrition package Promotion of early and exclusive breastfeeding for 6 months 221 000 $175 (132–286) and continued breastfeeding for up to 24 months (135 000–293 000) (breast­feeding promotion and appropriate comple­ Appropriate complementary feeding education in food secure mentary feeding education or provision), micronutrient populations and additional complementary food supplements supplemen­tation (preventive zinc and vitamin A supple­ in food insecure populations mentation), and management of acute malnutrition Micronutrient supplementation in children at risk (management of MAM, management of SAM). Analysis Vitamin A supplementation between 6 and 59 months age 145 000 $159 (106–766) of these nutrition-specific packages showed that the most Preventive zinc supplements between 12 and 59 months of age (30 000–216 000) lives could be saved by the therapeutic feeding for severe Management of acute malnutrition acute mal­nutrition, followed by the infant and young child Management of moderate acute malnutrition 435 000 $125 (119–152)§ Management of severe acute malnutrition (285 000–482 000) nutrition package (table 5189). Data are number (95% CI) or cost in 2010 international dollars (95% CI). *Effect of each of package when all four packages Can these interventions promote equitable are scaled up at once. †Cost per life-year saved assumes that a life saved of a child younger than 5 years saves on average 59 life-years, based on WHO data (2011189) that life expectancy at birth on average in low-income countries is 60, and access? that most deaths of children younger than 5 years occur in the first year of life. To convert to cost per discounted life-year To assess the potential benefit of community-based saved multiply these estimates by 59/32 (ie, 1·84). ‡Intervention has effect on maternal or child morbidity, but no direct delivery strategies on reaching and engaging poor and effect on lives saved. §Cost per life-year saved by management of severe acute malnutrition only, costs for supplementary marginalised populations, we assessed the effect of feeding for moderate acute malnutrition are currently unavailable. community-based promotion and delivery of seven Table 5: Effect of packages of nutrition interventions at 90% coverage nutrition-specific interventions (multiple micronutrient supple­ment­ation in pregnancy, promotion­ of breast­ feeding, appropriate complementary feeding, manage­ by asset quintiles from a recent analysis.192 As shown in ment of SAM, vitamin A supple­men­taton, preventive­­ zinc figure 6 and appendix p 26, the effect of this scale up is supple­mentation, and treatment of diarrhoea with zinc) greatest in the poorest quintiles, suggesting that scal­ across various wealth quintiles in three target countries— ing up these interventions through community-based Pakistan, Bangladesh, and Ethiopia (figure 6). Baseline approaches would not only reduce the overall burden of data were stratified by wealth quin­tiles by reanalysing childhood mortality but also substantially reduce the most recently available Demographic Health Survey existing disparities in access and mortality. for each country. Since no recent estimates existed for cause-specific mortality across wealth quintiles for Cost analysis Bangladesh and Ethiopia, we used LiST to recompute We used a so-called ingredients approach to work out the the cause of death structure using the procedures cost of nutrition interventions, based on the UN One described by Amouzou and colleagues.190 For Pakistan, Health Tool,193 which allows for regional variation due to we used the recent national verbal autopsy study191 for personnel costs. We constructed cost estimates as add- the cause of death structure and distribution of deaths ons to existing antenatal, postnatal, and standard infant www.thelancet.com 57 Series

A Pakistan Cost Salt iodisation $68 Richest Multiple micronutrient supplementation in pregnancy $472 Richer (includes iron-folate) Calcium supplementation in pregnancy $1914 Middle Energy-protein supplementation in pregnancy $972 Vitamin A supplementation in childhood $106 Poorer Zinc supplementation in childhood $1182 Poorest Breastfeeding promotion $653 Complementary feeding education $269 0 5·0 15·0 20·0 20·0 25·0 Complementary food supplementation $1359 B Bangladesh SAM management $2563 Total $9559 Richest Data are 2010 international dollars, millions. Richer Table 6: Total additional annual cost of achieving 90% coverage Middle with nutrition interventions, in 34 countries with more than 90% of the burden Poorer

Poorest pregnancy, and six after birth; intervention definitions

0 2·0 4·0 6·0 8·0 10·0 12·0 and assumptions are provide in appendix pp 29–30). We calculated unit costs separately for WHO sub­ C Ethiopia regions (appendix p 31).195 Unit costs were higher in Africa compared with elsewhere, because of higher Richest labour costs and the extra travel time required for delivery Richer using outreach (associated with lower population density in many areas, and also the lower coverage of primary Middle care facilities). The unit costs for interventions were much the same between the ingredients and SUN Poorer approaches, allowing for some difference in interventions Poorest based on updated recommendations. Our analysis shows that the estimated total additional 0 5·0 10·0 15·0 20·0 cost involved to achieve 90% coverage of the population Proportion of deaths in children <5 years averted (%) in need in the 34 focus countries with the selected set of Figure 6: Equity analysis showing effect of scale up of nutrition interventions ten nutrition interventions is Int$9·6 billion per annum on proportion of deaths of children younger than 5 years averted in (table 6). Of this $9·6 billion, $3·7 billion (39%) is for Pakistan, Bangladesh, and Ethiopia Error bars are ranges. micronutrient interventions, $0·9 billion (9%) for educational interventions, and $2·6 billion (27%) for SAM management. The amount required for provision of visits as part of WHO’s Expanded Program on Immuni­ supplementary food for pregnant women and for chil­ sation, plus five stand-alone nutrition visits between dren aged 6–23 months in poor households (those with 6 and 35 months of age. The few interventions targeted <$1·25 per person per day) constitutes the remaining at children between 36 and 59 months of age were $2·3 billion (24%). When these costs are broken down by assumed to be delivered opportunistically (at clinic visits, region, $3·4 billion is needed in the 20 countries included or during outreach visits for younger siblings). The base from sub-Saharan Africa, $4·8 billion in the four in south delivery platform assumed was outreach pro­grammes Asia plus Myanmar (Burma), $1·0 billion for the six in for sub-Saharan Africa, and primary health-care clinics eastern Mediterranean, and $0·5 billion for the three elsewhere (appendix pp 27–28 provides details). We remaining countries (Vietnam and the Philippines in compared the unit costs from the ingredients method western Pacific region, plus Guatemala; appendix p 32). with actual costs as used in the Scaling up Nutrition The $9·6 billion estimate for the nutrition interventions (SUN) costing.194 Although the ingredients method is lower than the 2008 SUN estimate of $11·8 billion.194 allows greater detail than an actual costs method such as The SUN figure included $1·2 billion for capacity- SUN for planning purposes, the comparison to actual building and monitoring and assessment, which we costs serves as a useful check on the appropriateness of excluded from the present analysis because we do not assumptions made. Costs were estimated for ten have a mechanism to allocate this cost by region or nutrition interventions (one population-wide, three in country and category.

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There are differences in the details of our results inferences that can be drawn on neuro­development and compared with the earlier SUN estimates. Unit costs are long-term outcomes from nutrition interventions. similar but not identical. The list of focus countries is Notwithstanding these limitations, our estimates of the likewise similar but not identical (using 2005 data, Turkey, effect of nutrition-specific interventions, though more Peru, Cambodia, and Burundi were included in the list of conservative than previous findings, still suggest great countries with 90% of the world’s stunted children, but not benefits from a core set of interventions delivered ante­ with 2010 data; Rwanda and Chad entered this list with natally or postnatally. Our assessments of benefits from 2010 data). Some interventions are excluded from the new interventions to reduce SGA are hindered by the limited total (deworming, therapeutic zinc for diarrhoea), whereas range of interventions in pregnancy. Even though ante­ some new ones are included (calcium supplements­ and natal care services offer a unique opportunity for maternal balanced energy protein supplements in preg­nancy). screening and interventions, the difficulty of reaching Complementary food supple­mentation is targeted only to women early enough in pregnancy is a major limitation in the 6–23 month age group in this new analysis. Population ensuring adequate uptake of interventions for a reasonable in need has changed since the SUN estimates were length of time. In parts of the world with high rates of calculated, with changes in coverage of some inter­ventions maternal malnutrition, micronutrient deficiencies, and (notably, management of SAM has begun to scale up). SGA births, these factors remain major determinants of stunting in early childhood. This finding underscores the Discussion need to address determinants of under­nutrition early in This update of nutrition interventions differs from past the lifecycle through appropriate strategies, such as exercises in several ways. First, we included a wider range enhancing adolescent nutrition and family planning to of nutrition-specific interventions and applied more delay the age of first pregnancy or increase spacing stringent assessment criteria, using the Grades of Recom­ between births.196 Achieving high coverage­ of multiple mendation Assessment, Development and Evalu­ation micronutrient supplementation in pregnancy­ offers a new system and Child Health Epidemiology Reference Group avenue to reduce SGA births and their consequences for criteria for most inverventions.5 Second, in view of mortality and growth in early childhood. The absence of emerging evidence of the importance of maternal appreciation of the crucial links of maternal and fetal nutrition, SGA, and early stunting,1 we specifically focused nutrition to fertility and repeated pregnancies­ has been a on interventions that might affect prevalence and out­ major barrier in targeting of interventions­ to address comes in SGA births and early stunting. We also reviewed these factors appropriately. and modelled a range of delivery strategies and platforms Although the overall effect on stunting alleviation seems and specifically explored the potential of reaching poor and modest, the rate of decline suggested from the package of disadvantaged popu­lations through community platforms nutrition-specific interventions is plausible and within the and outreach services, an approach used to assess the broad range of observed effects across countries. A review effect of interventions to address childhood diarrhoea and of global stunting trends by Stevens and colleagues197 pneumonia.122 Finally, the LiST model was substantially showed average rates of reduction in stunting in the best updated to include age-specific effects and the inter- performing countries ranging from 21–42% over the past relationship of new interventions and their effect on decade, broadly consistent with what our model predicts maternal and child undernutrition, a much more complex from scaling up a core set of nutrition-specific inter­ exercise than what was undertaken previously­ .4 To under­ ventions. Importantly, the countries that have made take this exercise we substantively updated LiST in a way tremendous strides in improving nutrition and health that more accurately captures the role of undernutrition outcomes (such as Brazil, China, Saudi Arabia, Kuwait, and the effect of proven interventions on maternal and and Chile) have implemented nutrition-specific inter­ child health. ventions, but also have been settings with exceptional Several limitations should be recognised in considering economic growth, and investments in nutrition-sensitive our findings. A large proportion of the evidence on inter­ interventions to address population health, education, and ventions is still derived from efficacy trials as opposed to social sector development. Much the same conclusions effectiveness studies and hence variations exist in esti­ were drawn by UNICEF in a report on undernutrition.198 mates of effect size for various interventions. Few robust A major advance on our previous review of inter­ assessments have been done in programme settings and ventions is the addition of delivery platforms that allow available data from observational studies do not permit us to assess strategies to reach populations who are not ready assessment of intervention effective­ness. There are being reached currently. Our findings suggest that com­ also very few studies that report morbidity and neuro­ munity platforms offer a unique opportunity to engage developmental outcomes. We reviewed the available and reach poor and difficult to access populations evidence of effects on neurodevelopmental outcomes through com­munication and outreach strategies. These from studies of maternal and child nutrition interventions strategies could also lead to potential integration of and identified little data with evaluation methodologies nutrition with maternal, newborn, and child health for assessment. We are therefore greatly limited in the interventions. Since several countries are investing in www.thelancet.com 59 Series

community health worker programmes to address Much funding for nutrition-relevant programmes prob­ maternal, newborn, and child health,125 much potential ably overlaps with existing programmes for maternal, exists for scaling up nutri­tion promotion and therapeutic newborn, and child health and health systems strengthen­ interventions through such platforms and hence ing and there might also be potential synergies, making it integrating the two at point-of -service delivery. This possible to share costs. integration could also help achieve reductions in The evidence from carefully conducted cohort inequities in the short term as has been noted by studies202 of benefits of higher birthweight and early universal scaling up of selected maternal and child linear growth on education and improved health survival interventions.199 However, importantly, imple­ outcomes is con­vincing and consistent with the overall mentation of such programmes involves unique message from our review and modelling exercise. As the combinations and sequencing of health system policies, world moves towards the post-2015 development agenda, actions, and advocacy. Community-based nutrition pro­ it is important to draw attention to the unfinished rammes need meticulous planning, a rights-based agenda of maternal and child undernutrition and to the framework for engagement of communities and other emerging issues of obesity. Our review reconfirms the sectors, and piloting. Other health system pillars are existence of feasible and low cost evidence-based crucial to success, including training and support for interventions and the fact that coverage rates for many community health workers, strengthening of the supply of these inter­ventions remain poor203 and for some, non- chain, simplified in­formation systems, monitoring, and existent. In view of the importance of fetal nutrition and regular feedback. poverty alleviation strategies to reach those in greatest The model used in this review estimates feasible need, priority must be given to scaling up nutrition reductions in mortality and stunting with enhanced specific and sensitive interventions in some of the investments. The same investments that can achieve highest burden countries. At the same time, in view of these results will also lead to other improvements in the increasing importance of non-communicable cognitive and socioemotional development. Although diseases, concerted efforts must be made to develop and these outcomes are not included in the model, partly implement interventions to reduce the risk of obesity. because the costing database differs (ie, LiST mainly Contributors addresses mortality), substantial evidence from a range of ZAB conceptualised the review in consultation with the coordinators models and longitudinal studies confirms that the (PW, AL, SH, and REB) and wrote the first draft of the paper with substantial inputs from JKD. NW, YT, and AR developed the modification benefits in terms of overall development on human of LiST for assessment of effect and equity. Costing for selected capacity are appreciable. interventions was done by MFG and SH. VW contributed to the scientific In terms of cost, an annual outlay of an additional literature search, screening, collection, and analysis of data for the $9·6 billion to bring to scale a range of nutrition deworming review. LL led the review of severe and moderate acute malnutrition. KW led the obesity prevention review and contributed to interventions that would save nearly 1 million lives is the severe and moderate acute malnutrition reviews. CM and SZ oversaw reasonable since many interventions would be scaled up the obesity reviews. BAH assessed the effect of maternal multiple from negligible coverage rates. The cost per (discounted) micronutrient supplements, neonatal vitamin A supplementation, and life-year saved is about $370 for a set of interventions that deworming in pregnant women. ZL contributed to reviews of complementary feeding strategies and community platforms. RAS could effectively deliver optimum nutrition to pregnant contributed to reviews of micronutrient powders and breastfeeding. AI women, infants, and children, and manage SAM. These contributed to the reviews of calcium, balanced protein supplementation figures suggest that the nutrition interventions are well in pregnancy, and vitamin A supplementation. All authors and members within the cost-effectiveness benchmark (less than of the review groups (below) saw successive drafts of the paper and provided input. ZAB finalized the paper and is the overall guarantor. three-times per person income) for all countries. More than half the $9·6 billion is accounted for by two large The Lancet Nutrition Interventions Review Group Zulfiqar A Bhutta, Arjumand Rizvi, Jai K Das, Rehana A Salam, countries that could rely heavily on domestic resources Aisha Yousafzai (Aga Khan University, Pakistan), Zohra S Lassi (India and Indonesia). Consumables (whether drugs, or (University of Adelaide, Australia), Lindsey Lenters, Ceilidh McPhail, other items such as for transport or administration) Kerri Wazny, Michelle F Gaffey, Stanley Zlotkin (Hospital for Sick account for slightly less than half the $9·6 billion, and all Children, Canada), Aamer Imdad (SUNY Upstate Medical University, USA), Batool Azra Haider (Harvard School of Public Health, USA), but the poorest countries can be expected to cover most of Vivian Welch (University of Ottawa, Canada), Reynaldo Martorell (Emory the expenditures on personnel; $3–4 billion from external University, USA), Robert E Black, Neff Walker, Yvonne Tam (Johns donors could make a substantial difference to child Hopkins University, USA), Tahmeed Ahmad (International Center for nutrition. What proportion of development assistance for Diarrheal Diseases Research, Bangladesh). health is earmarked for nutrition is unclear. Global Maternal and Child Nutrition Study Group tracking data from the Institute for Health Metrics and Robert E Black (Johns Hopkins Bloomberg School of Public Health, USA), Cesar Victora (Universidad de Federal de Pelotas, Brazil), Evaluation were unable to disaggregate nutrition-related Susan Walker (The University of the West Indies, Jamaica), funding from the annual funding of $5·17 billion for Harold Alderman (International Food Policy Research Institute, USA), maternal, newborn, and child health programmes.200 The Zulfiqar A Bhutta (Aga Khan University, Pakistan), Stuart Gillespie Countdown col­laboration estimates nutrition-specific (International Food Policy Research Institute, USA), Lawrence Haddad (Institute of Development Studies, UK), Susan Horton (University of funding for the same year (2012) at $324·5 million.201

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Waterloo, Canada), Anna Lartey (University of Ghana, Ghana), 9 Haldre K, Rahu K, Karro H, Rahu M. Is a poor pregnancy outcome Venkatesh Mannar (The Micronutrient Initiative, Canada), Marie Ruel related to young maternal age? A study of teenagers in Estonia (International Food Policy Research Institute, USA), Patrick Webb during the period of major socio-economic changes (from 1992 to (Tufts University, USA) 2002). Eur J Obstet Gynecol Reprod Biol 2007; 131: 45–51. 10 Paranjothy S, Broughton H, Adappa R, Fone D. Teenage pregnancy: Series Advisory Committee who suffers? Arch Dis Child 2009; 94: 239. Marc Van Ameringen (Gain Health Organization, Switzerland), 11 WHO. Adolescent pregnancy: unmet needs and undone deeds. Mandana Arabi (New York Academy of Sciences, USA), Shawn Baker Geneva: World Health Organization, 2007. (Helen Keller International, USA), Martin Bloem (United Nations World 12 UNFPA. Marrying too young: end child marriage. New York, NY: Food Programme, Italy), Francesco Branca (WHO, Switzerland), UN Population Fund, 2012. Leslie Elder (The World Bank, USA), Erin McLean (Canadian 13 Conde-Agudelo A, Rosas-Bermudez A, Kafury-Goeta AC. Birth International Development Agency, Canada), Carlos Monteiro (University spacing and risk of adverse perinatal outcomes: a meta-analysis. of São Paulo, Brazil), Robert Mwadime (Makerere School of Public JAMA 2006; 295: 1809. Health, Uganda), Ellen Piwoz (Bill & Melinda Gates Foundation, USA), 14 Conde-Agudelo A, Rosas-Bermudez A, Castaño F, Norton MH. Werner Schultink (UNICEF, USA), Lucy Sullivan (1000 Days, USA), Effects of birth spacing on maternal, perinatal, infant, and child Anna Taylor (Department for International Development, UK), health: a systematic review of causal mechanisms. Stud Fam Plann Derek Yach (The Vitality Group, USA). The Advisory Committee provided 2012; 43: 93–114. advice in a meeting with Series Coordinators for each paper at the 15 WHO. Meeting report. Meeting to develop a global consensus on beginning of the process to prepare the Series and in a meeting to review preconception care to reduce maternal and childhood mortality and and critique the draft reports. morbidity; Geneva; Feb 6–7, 2012. 16 Rosenthal AN, Paterson Brown S. Is there an incremental rise in the Conflicts of interest risk of obstetric intervention with increasing maternal age? BJOG REB serves on the Boards of the Micronutrient Initiative, Vitamin 1998; 105: 1064–69. Angels, the Child Health and Nutrition Research Initiative, and the 17 Carolan M. The graying of the obstetric population: implications for Nestlé Creating Shared Value Advisory Committee. VM serves on the the older mother. J Obstet Gynecol Neonatal Nurs 2003; 32: 19–27. Nestlé Creating Shared Value Advisory Committee. The other authors 18 Alkema L, Kantorova V, Menozzi C, Biddlecom A. National, regional, declare that they have no conflicts of interest. As corresponding author and global rates and trends in contraceptive prevalence and unmet Zulfiqar A Bhutta states that he had full access to all data and final need for family planning between 1990 and 2015: a systematic and responsibility to submit for publication. comprehensive analysis. Lancet 2013; published online March 13. http://dx.doi.org/10/1016/S0140-6736(12)62204-1. Acknowledgments 19 De-Regil LM, Fernandez-Gaxiola AC, Dowswell T, Pena-Rosas JP. Funding for the preparation of the Series was provided to the Johns Effects and safety of periconceptional folate supplementation for Hopkins Bloomberg School of Public Health through a grant from the preventing birth defects. Cochrane Database Syst Rev 2010; Bill & Melinda Gates Foundation. The sponsor had no role in the 10: CD007950. analysis and interpretation of the evidence or in writing the paper and 20 Lassi ZS, Salam RA, Haider BA, Bhutta ZA. Folic acid the decision to submit for publication. We thank the Aga Khan supplementation during pregnancy for maternal health and University, Karachi, Pakistan and the Program for Program for Global pregnancy outcomes. Cochrane Database Syst Rev 2013; 3: CD006896. Pediatric Research, Global Child Health, Hospital for Sick Children 21 Fernandez-Gaxiola AC, De-Regil LM. Intermittent iron (Toronto, ON, Canada) for support to ZAB during the course of this supplementation for reducing anaemia and its associated work. impairments in menstruating women. Cochrane Database Syst Rev 2011; 12: CD009218. References 1 Black RE, Victora CG, Walker SP, and the Maternal and Child 22 Pena-Rosas JP, De-Regil LM, Dowswell T, Viteri FE. Daily oral iron Nutrition Study Group. Maternal and child undernutrition and supplementation during pregnancy. Cochrane Database Syst Rev overweight in low-income and middle-income countries. Lancet 2012; 12: CD004736. 2013; published online June 6. http://dx.doi.org/10.1016/S0140- 23 Haider BA, Bhutta ZA. 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Cochrane at birth, low income countries, both sexes combined, 2011. http:// Database Syst Rev 2008; 4: CD005124. apps.who.int/gho/data/view.main.700?lang=en (accessed April 8, 168 Diego MA, Field T, Hernandez-Reif M, Deeds O, Ascencio A, 2013). Begert G. Preterm infant massage elicits consistent increases in 190 Amouzou A, Richard SA, Friberg IK, et al. How well does LiST vagal activity and gastric motility that are associated with greater capture mortality by wealth quintile? A comparison of measured weight gain. Acta Paediatr 2007; 96: 1588–91. versus modelled mortality rates among children under-five in 169 Vickers A, Ohlsson A, Lacy JB, Horsley A. Massage for promoting Bangladesh. Int J Epidemiol 2010; 39 (suppl 1): i186–92. growth and development of preterm and/or low birth-weight infants. 191 National Institute of Population Studies. Pakistan Demographic Cochrane Database Syst Rev 2009; 2: CD000390. and Health Survey 2006–07. Islamabad, Pakistan. http://www. 170 Field T, Diego M, Hernandez-Reif M. Preterm infant massage measuredhs.com/pubs/pdf/FR200/FR200.pdf (accessed on March 2, therapy research: a review. Infant Behav Dev 2011; 33: 115–24. 2013). 171 Lerch C, Meissner T. Interventions for the prevention of nutritional 192 Bhutta ZA, Hafeez A, Rizvi, et al. Reproductive, maternal, newborn, rickets in term born children. Cochrane Database Syst Rev 2007; and child in Pakistan: challenges and opportunities. Lancet 2013; 4: CD006164. published online May 17. http://dx.doi.org/10.1016/S0140- 172 Haider BA, Lassi ZS, Ahmed A, Bhutta ZA. Zinc supplementation 6736(12)61999-0. as an adjunct to antibiotics in the treatment of pneumonia in 193 Futures Institute. UN integrated costing tool. http://www.who.int/ children 2 to 59 months of age. Cochrane Database Syst Rev 2011; workforcealliance/knowledge/toolkit/10/en/ (accessed Dec 7, 2012). 10: CD007368. 194 Horton MS, McDonald C, Mahal A. Scaling-up nutrition: what will it 173 Basnet S, Shrestha PS, Sharma A, et al. A randomized controlled cost? Washington DC: World Bank Directions in Development, 2009. trial of zinc as adjuvant therapy for severe pneumonia in young 195 WHO. Health systems and information. http://www.who.int/ children. Pediatrics 2012; 129: 701–08. healthinfo/global_burden_disease/definition_regions/en/ (accessed 174 Das RR, Singh M, Shafiq N. Short-term therapeutic role of zinc in April 20, 2013). children <5 years of age hospitalised for severe acute lower 196 Winkvist A, Rasmussen KM, Habicht JP. A new definition of respiratory tract infection. Paediatr Respir Rev 2012; 13: 184–91. maternal depletion syndrome. Am J Public Health 1992; 82: 691–94. 175 Shah GS, Dutta AK, Shah D, Mishra OP. Role of zinc in severe 197 Stevens GA, Finucane MM, Paciorek CJ, et al. Trends in mild, pneumonia: a randomized double bind placebo controlled study. moderate, and severe stunting and underweight, and progress Ital J Pediatr 2012; 38: 36. towards MDG 1 in 141 developing countries: a systematic analysis of 176 Srinivasan MG, Ndeezi G, Mboijana CK, et al. Zinc adjunct population representative data. Lancet 2012; 380: 824–34. therapy reduces case fatality in severe childhood pneumonia: 198 UNICEF. Improving child nutrition: the increasing imperative for a randomized double blind placebo-controlled trial. BMC Med global progress. New York, NY: United Nations International 2012; 10: 14. Children’s Fund, 2013. 177 Bhatnagar S, Wadhwa N, Aneja S, et al. Zinc as adjunct treatment in 199 Victora CG, Barros AJ, Axelson H, et al. How changes in coverage infants aged between 7 and 120 days with probable serious bacterial affect equity in maternal and child health interventions in infection: a randomised, double-blind, placebo-controlled trial. 35 Countdown to 2015 countries: an analysis of national surveys. Lancet 2012; 379: 2072–78. Lancet 2012; 380: 1149–56. 178 Mehta K, Bhatta NK, Majhi S, Shrivastava MK, Singh RR. Role of 200 IHME. Financing global health 2012: the end of the golden age? zinc in neonatal sepsis: a double blinded, randomized, placebo Seattle, WA: Institute for Health Metrics and Evaluation, 2012. controlled trial. Indian Pediatr 2013; 50: 390–93. 201 Hsu J, Pitt C, Greco G, Berman P, Mills A. Countdown to 2015: 179 Phuka J, Malete K, Thakwalakwa C. Complementary feeding with changes in official development assistance to maternal, newborn, fortified spread and incidence of severe stunting in 6–8 month-old and child health in 2009-10, and assessment of progress since 2003. rural Malawians. Arch Pediatr Adolesc Med 2008; 162: 619–26. Lancet 2012; 380: 1157–68. 180 Phuka JC, Maleta K, Thakwalakwa C, et al. Postintervention growth 202 Adair L, Fall CHD, Osmond C, et al, for the COHORTS group. of Malawian children who received 12-mo dietary complementation Associations of linear growth and relative weight gain during early with a lipid-based nutrient supplement or maize-soy flour. life with adult health and human capital in countries of low and Am J Clin Nutr 2009; 89: 382–90. middle income: findings from five birth cohort studies. Lancet 2013; 181 Adu-Afarwuah S, Lartey A, Brown KH, Zlotkin S, Briend A, published online March 28. http://dx.doi.org/10.1016/S1040- Dewey KG. Randomized comparison of 3 types of micronutrient 6736(13)60103-8. supplements for home fortification of complementary foods in 203 Bhutta ZA, Chopra M. The Countdown for 2015: what lies ahead? Ghana: effects on growth and motor development. Am J Clin Nutr Lancet 2012; 380: 1125–27. 2007; 86: 412–20.

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Maternal and Child Nutrition 3 Nutrition-sensitive interventions and programmes: how can they help to accelerate progress in improving maternal and child nutrition?

Marie T Ruel, Harold Alderman, and the Maternal and Child Nutrition Study Group*

Published Online Acceleration of progress in nutrition will require effective, large-scale nutrition-sensitive programmes that address June 6, 2013 key underlying determinants of nutrition and enhance the coverage and effectiveness of nutrition-specific http://dx.doi.org/10.1016/ interventions. We reviewed evidence of nutritional effects of programmes in four sectors—agriculture, social safety S0140-6736(13)60843-0 nets, early child development, and schooling. The need for investments to boost agricultural production, keep prices This is the third in a Series of four papers about maternal and low, and increase incomes is undisputable; targeted agricultural programmes can complement these investments by child nutrition supporting livelihoods, enhancing access to diverse diets in poor populations, and fostering women’s empowerment. *Members listed at end of paper However, evidence of the nutritional effect of agricultural programmes is inconclusive—except for vitamin A from Poverty, Health and Nutrition biofortification of orange sweet potatoes—largely because of poor quality evaluations. Social safety nets currently Division, International Food provide cash or food transfers to a billion poor people and victims of shocks (eg, natural disasters). Individual studies Policy Research Institute, show some effects on younger children exposed for longer durations, but weaknesses in nutrition goals and actions, Washington, DC, USA (M T Ruel PhD, H Alderman PhD) and poor service quality probably explain the scarcity of overall nutritional benefits. Combined early child development Correspondence to: and nutrition interventions show promising additive or synergistic effects on child development—and in some cases Dr Marie T Ruel, Poverty, Health nutrition—and could lead to substantial gains in cost, efficiency, and effectiveness, but these programmes have yet to and Nutrition Division, be tested at scale. Parental schooling is strongly associated with child nutrition, and the effectiveness of emerging International Food Policy school nutrition education programmes needs to be tested. Many of the programmes reviewed were not originally Research Institute, Washington, DC 20006, USA designed to improve nutrition yet have great potential to do so. Ways to enhance programme nutrition-sensitivity [email protected] include: improve targeting; use conditions to stimulate participation; strengthen nutrition goals and actions; and optimise women’s nutrition, time, physical and mental health, and empowerment. Nutrition-sensitive programmes can help scale up nutrition-specific interventions and create a stimulating environment in which young children can grow and develop to their full potential.

Introduction increasing incomes, and urbanisation—shifts that raise The food system is threatened by food and oil price concerns about diet quality and food safety, while volatility, diversion of resources from production of food threatening water, land, and other finite natural to biofuels, climate change and related water shortages, resources.5–8 In view of these challenges, protection­ of persistent conflicts and emergencies, and natural nutrition, let alone acceleration of progress, will entail disasters affecting agriculture production and yields.1–4 more than bringing nutrition-specific interventions­ to These challenges are compounded by changes in demand scale. It will require a new and more aggressive focus on for food that are brought about by growing populations, coupling effective nutrition-specific interventions (ie, those that address the immediate determinants of Key messages nutrition) with nutrition-sensitive programmes­ that address the underlying causes of under­nutrition • Nutrition-sensitive interventions and programmes in agriculture, social safety nets, (panel 19,10). early child development, and education have enormous potential to enhance the scale Nutrition-sensitive programmes draw on comple­ and effectiveness of nutrition-specific interventions; improving nutrition can also help mentary sectors such as agriculture, health, social pro­ nutrition-sensitive programmes achieve their own goals. tection, early child development, education, and water • Targeted agricultural programmes and social safety nets can have a large role in and sanitation to affect the underlying determinants of mitigation of potentially negative effects of global changes and man-made and nutrition, including poverty; food insecurity; scarcity of environmental shocks, in supporting livelihoods, food security, diet quality, and access to adequate care resources; and to health, water, women’s empowerment, and in achieving scale and high coverage of nutritionally and sanitation services.11 Key features that make pro­ at-risk households and individuals. grammes in these sectors potentially nutrition-sensitive • Evidence of the effectiveness of targeted agricultural programmes on maternal and are: they address crucial underlying determinants of child nutrition, with the exception of vitamin A, is limited; strengthening of nutrition nutrition; they are often implemented at large scale and goals and actions and rigorous effectiveness assessments are needed. can be effective at reaching poor populations12 who (Continues on next page) have high malnutrition rates; and they can be leveraged to serve as delivery platforms for nutrition-specific

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interventions. Nutrition-sensitive programmes might there­fore help to accelerate progress in improving (Continued from previous page) nutrition by enhancing the household and community • The feasibility and effectiveness of biofortified vitamin A-rich orange sweet potato environ­ment in which children develop and grow, and for increasing maternal and child vitamin A intake and status has been shown; by increasing the effectiveness, coverage, and scale of evidence of the effectiveness of biofortification continues to grow for other nutrition-specific interventions. micronutrient and crop combinations. Nutrition-sensitive programmes can help protect poor • Social safety nets are a powerful poverty reduction instrument, but their potential populations from the negative consequences of global to benefit maternal and child nutrition anddevelopment is yet to be unleashed; to food security threats and mitigate the effects of finan­cial, do so, programme nutrition goals and interventions, and quality of services need to weather-related, and man-made shocks (eg, conflicts). be strengthened. Such shocks make poor populations increasingly vul­ • Combinations of nutrition and early child development interventions can have nerable to undernutrition, as shown by food and fuel additive or synergistic effects on child development, and in some cases, nutrition price crises in the past 6 years,4 and documented effects outcomes. Integration of stimulation and nutrition interventions makes sense of conflicts on morbidity and mortality among affected programmatically and could save cost and enhance benefits for both nutrition and popu­lations.13,14 Climate change and the expected development outcomes. increased frequency of droughts and flooding are likely • Parental schooling is consistently associated with improved nutrition outcomes and to reduce food availability and dietary diversity, and schools provide an opportunity, so far untapped, to include nutrition in school increase rates of infectious diseases such as diarrhoea or curricula for prevention and treatment of undernutrition or obesity. malaria.15 Under these circumstances, nutrition-sensitive • Maternal depression is an important determinant of suboptimum caregiving and programmes can help to protect the assets and welfare of health-seeking behaviours and is associated with poor nutrition and child development poor people and their investments in the health, nutri­ outcomes; interventions to address this problem should be integrated in tion, and development of their children. nutrition-sensitive programmes. Nutrition-sensitive programmes are likely to affect • Nutrition-sensitive programmes offer a unique opportunity to reach girls during nutrition through changes in food and non-food prices preconception and possibly to achieve scale, either through school-linked conditions and income, and through women’s empowerment. and interventions or home-based programmes. Panel 216,17 and figures 118,19 and 218,19 show results of • The nutrition-sensitivity of programmes can be enhanced by improving targeting; using analyses of the links between income growth and conditions; integrating strong nutrition goals and actions; and focusing on improving maternal and child anthropometry and anaemia women’s physical and mental health, nutrition, time allocation, and empowerment. (appendix p 1). Appendix p 2 summarises evidence regarding the association between women’s empower­ See Online for appendix ment and child nutrition. We review evidence of the nutritional effect of pro­ grammes from different sectors, and discuss how such Panel 1: Definition of nutrition-specific and nutrition-sensitive interventions investments could be made more nutrition-sensitive. and programmes We selected sectors on the basis of: relevance for Nutrition-specific interventions and programmes nutrition (eg, address crucial underlying determinants • Interventions or programmes that address the immediate determinants of fetal and of nutrition); availability of assessments of their child nutrition and development—adequate food and nutrient intake, feeding, nutritional effect; high coverage of poor populations; caregiving and parenting practices, and low burden of infectious diseases and targeting (programmes are, or could be, targeted to • Examples: adolescent, preconception, and maternal health and nutrition; maternal reach nutritionally vulnerable groups). The two sectors dietary or micronutrient supplementation; promotion of optimum breastfeeding; that most closely meet these criteria are agriculture and complementary feeding and responsive feeding practices and stimulation; dietary social safety nets. Early child development programmes supplementation; diversification and micronutrient supplementation or fortification for do not meet the high coverage criteria but they are children; treatment of severe acute malnutrition; disease prevention and management; included because child development and nutrition nutrition in emergencies outcomes share many of the same risk factors, and there is a growing interest in examination of potential Nutrition-sensitive interventions and programmes integration and synergies in programming and • Interventions or programmes that address the underlying determinants of fetal and outcomes.20,21 Schooling is also included, despite failing child nutrition and development—​food security; adequate caregiving resources at to meet all criteria, because of the importance of the maternal, household and community levels; and access to health services and a parental education for child nutrition and development. safe and hygienic environment—and incorporate specific nutrition goals and actions Health, water and sanitation, and family planning are • Nutrition-sensitive programmes can serve as delivery platforms for nutrition-specific covered in the accompanying report by Zulfiqar Bhutta interventions, potentially increasing their scale, coverage, and effectiveness and colleagues.22 Investments and policies in several • Examples: agriculture and food security; social safety nets; early child development; other sectors (eg, transportation; communication and maternal mental health; women’s empowerment; child protection; schooling; water, infor­mation technology; and global food, agriculture, sanitation, and hygiene; health and family planning services and trade) have the potential to affect nutrition, as do Adapted from Scaling Up Nutrition9 and Shekar and colleagues, 2013.10 more targeted policies (eg, maternity leave); however, www.thelancet.com 67 Series

cost effectiveness studies cannot be easily applied to Panel 2: How responsive is nutrition to income growth? assess or rank these programmes. Similarly, although As economies grow, stunting rates typically decrease, but the predicted decrease is far cost–benefit analysis can be used in principle, this slower than the corresponding poverty reduction associated with economic growth analysis needs a common metric for all outputs, generally (figure 1). Country fixed-effects regressions show that a 10∙0% increase in gross domestic in monetary terms. However, a conversion of a death production (GDP) per person predicts a 5∙9% (95% CI 4∙1–7∙6) reduction in stunting and an averted into monetary values requires an arbitrary 11∙0% (8∙6–13∙4) decrease in the World Bank’s poverty measure of individuals living on assessment of the value of premature deaths averted. $1∙25 per person, per day. The effect of growth in gross national product on nutrition Similarly, although equity is usually deemed socially comes from a combination of increased household resources, and improved infrastructure desirable, its value cannot be easily quantified.25 and nutrition-relevant services. Much unexplained variability exists in the effect of national Therefore, the nutrition outcomes in the programmes income on stunting. As shown in figure 1, countries such as Guatemala, South Africa, and we discuss cannot be directly compared with those in the India have higher stunting rates than expected for their income levels. By contrast, the accompanying report by Zulfiqar Bhutta and colleagues.22 Dominican Republic, Senegal, Ghana, China, and Sri Lanka are among the best performers. However, as we explain, the programmes­ we review are an integral component of an overall strategy to improve The association between prevalence of child underweight and GDP growth is stronger than global nutrition. for stunting, with the rate of decrease with 10∙0% GDP growth being 7∙0% (95% CI 5∙3–8∙8; 16 appendix p 1). This estimate is larger than reported with earlier datasets. Anaemia—​ Agriculture defined as haemoglobin concentrations below 109 g/L—decreases at a slower rate; a Agriculture systems have a crucial role in provision of 10∙0% improvement in income would decrease child anaemia by only 2∙4% (1∙3–3∙6) and food, livelihoods, and income.1 Agriculture is the main maternal anaemia by 1∙8% (0∙4–3∙1). However, severe anaemia—defined as haemoglobin occupation of 80% of poor populations in rural areas, below 70 g/L—decreases at a much higher rate with income growth for both mothers (6∙5%; including women. In Africa, women account for 70% of 95% CI 4∙2–8∙8) and children (9∙0%; 5∙1–12∙9).17 Although data for low birthweights are not agricultural labour and 80% of food processing labour.26,27 as reliable as those for other nutritional indicators, estimates using World Bank data suggest Growing concerns about how to meet the food needs of that a 10∙0% increase in GDP per person typically reduces low birthweight prevalence by only an estimated global population of 9 billion by 2050 have 2∙3% (95% CI 0∙8–4∙1). Bangladesh, India, Sudan, and Haiti have particularly high rates of low spurred renewed efforts to boost agriculture production birthweight prevalence relative to their national levels of income. For women underweight and productivity in the face of increasing threats that (body-mass index <18∙5 kg/m2), a 10∙0% growth in national income results in a 4∙0% affect the global food system. Agriculture growth has (95% CI 1∙7–5∙8) decrease in underweight prevalence, a rate substantially lower than the been shown to reduce undernutrition;28 an additional reduction in child underweight. investment of US$8 billion per year globally would reduce The association between national income growth and women overweight and obesity is the number of underweight children by 10 million and of much stronger than for women underweight: a 10∙0% increase in GDP per person is hungry people by 201 million by 2050, and raise the estimated to increase prevalence of overweight and obesity in women by 7∙0% (95% CI income of many of the world’s poorest people.28 Moreover, 4∙0–10∙0; figure 2). These findings show that when GDP per person increases, prevalence the economic returns to investments in agriculture are of women’s overweight or obesity increases faster than prevalence of women high compared with many other economic investments.29 underweight decreases. Again, some countries are clear outliers, with Egypt and several Although investments to enhance agriculture produc­ Latin American countries having very high levels and several Asian countries (eg, tivity and boost global food supply are crucial for long- Vietnam, India, China, Thailand) having lower than expected levels of overweight and term reductions in poverty, hunger, and malnutrition, obesity in view of their GDP per person. they might not solve the problem of scarcity of access to nutritious and diverse diets (as opposed to scarcity of calories) that poor people face. A new emphasis on we excluded these sectors because of the absence of making agricultural systems and food and agriculture assess­ments of nutritional effects. policies more nutrition-sensitive is called for and several Consistent with the Maternal and Child Nutrition reports discuss approaches and instruments to do so.1,30–33 Series, we focus on adolescent girls and women, An approach that can complement efforts to raise agri­ infants, and young children during the first 1000 days cultural productivity and food supply globally is targeted of life (period from conception to a child’s second agricultural programmes aimed at enhancing poor birthday). Interventions to improve nutrition and child households’ income and access to high-quality diets. development during this period have high rates of Our review focuses on these types of programmes, most return because of their importance in enhancing specifically homestead food production systems, and the economic productivity later in life23 fostered by a biofortification of staple crops, because they both meet combination of improved health, nutrition, and our selection criteria, with the exception of scale. cognition, which lead to more schooling, higher-paying Targeted agricultural programmes can affect nutrition jobs, and overall enhancement of physical, cognitive, through several pathways (panel 334,35). Despite variations and reproductive performance.24 in the way researchers use these pathways, all concur The programmes we reviewed generally have several that women—​their social status, empowerment, con­ objectives, including improving income, food security, trol over resources, time allocation, and health and women’s empowerment, and nutrition. For this reason nutritional status—are key mediators in the pathways

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between agriculture inputs, intra-household resource allocation, and child nutrition.26,30,34–38 Burundi The recognised importance of development of new Afghanistan approaches to stimulate agriculture’s contribution to nutri­ 60 Niger Guatemala Yemen tion has led to an increased interest in examination of the ETH MDG Nepal Angola so far untapped potential of leveraging value chains to BGD SDN DRC improve nutrition. Since this approach is still at a nascent PAK India stage, experience and evidence of effectiveness are scarce. 40 MMR NGA 39–46 VTN Panel 4 provides a brief overview of the approach. CIV KEN PHN Peru South Africa Syria Botswana Haiti IDN Home gardens and homestead food production systems Ghana IRQ Egypt Ecuador Predicted stunting line Several scientific literature reviews of homestead food Senegal China production systems have been done in the past 20 Algeria Kazakhstan Kyrgyzstan Uzbekistan 34,38,47–52 Sri Lanka Thailand decade. These reviews focused on different types of Turkey Moldova Colombia programmes and nutritional outcomes and used different years Stunting prevalence in children aged 0–5 DOM Brazil search strategies and inclusion and exclusion criteria. Predicted poverty line Despite these differences, key conclusions were largely 0 Belarus consistent across all reviews (appendix pp 3–4). First, these 0 2000 4000 6000 8000 10 000 GDP per person (2005 international $) reviews note that there is little evidence of effectiveness of homestead food production programmes on maternal or Figure 1: Prevalence of stunting in children aged 0–5 years and GDP per person child nutritional status (anthropometry or micronutrient Most observations for prevalence of stunting are from 2000–08. The fitted curves are locally weighted regressions status), with the possible exception of vitamin A status. For of prevalence of stunting in children aged 0–5 years and poverty (<$1·25 per person, per day), against GDP per person. The adjustment to international dollar units converts income expressed in nominal dollars to one that is child anthropometry, a few studies reported an effect on at expressed in terms of international dollars, which have the same estimated purchasing power as a dollar in the least one indicator,53–57 but effects were generally small. USA, accounting for local prices. The size of the circles represents the estimated population of stunted children Although meta-analysis might not be the method of choice aged 0–5 years, in about 2005, on the basis of multiplication of stunting prevalence by UN estimates of the 18 for synthesis of evidence from such diverse programmes, population of children aged 0–5 years. Data are sourced principally from the Demographic and Health Surveys, with observations for some countries sourced from WHO.19 GDP=gross domestic product. BGD=Bangladesh. 52 the results of a four-study meta-analysis showed no CIV=Côte d’Ivoire. DOM=Dominican Republic. DRC=Democratic Republic of the Congo. ETH=Ethiopia. overall effect of targeted agricultural pro­grammes on IDN=Indonesia. IRQ=Iraq. MDG=Madagascar. MMR=Myanmar (Burma). KEN=Kenya. NGA=Nigeria. PAK=Pakistan. underweight, wasting, or stunting. Another four-study PHN=Philippines. SDN=Sudan. VTN=Vietnam. meta-analysis51 for vitamin A status, however, reports a small overall difference in serum retinol between intervention and control areas (0·08 μmol/L); a cluster- 80 randomised effectiveness assessment of a biofortified Egypt orange sweet potato intervention in Uganda also showed a

9·5 percen­tage point reduction in the prevalence of low Jordan Bosnia-Herzegovina serum retinol (<1·05 μmol/L) in intervention compared 60 with control children aged 3–5 years at baseline.58 The Swaziland Peru Serbia Bolivia second consistent­ message is that nutritional effect is Nicaragua Turkey South Africa Guatemala more likely when agriculture interventions target women Lesotho Honduras and include women’s empowerment activities, such as 40 Brazil Kyrgyzstan Morocco Dominican improvement in their knowledge and skills through Moldova Republic Ghana Armenia behaviour-change com­munications or promotion of their Cameroon Sierra Thailand increased control over income from the sale of targeted Leone Kenya Nigeria Philippines commodities. No studies, however, have specifically com­ 20 China Pakistan Indonesia pared targeting of men versus women, or mainstreaming­ overweight prevalence, BMI>25 (%) Women gender versus not doing so in the programmes reviewed. Congo India Bangladesh The third key message is that, with the exception of two (DRC) Ethiopia Vietnam studies of biofortified orange sweet potato,58,59 impact 0 0 2000 4000 6000 8000 10 000 evaluation studies have generally been too poor and GDP per person (2005 PPP$) sample sizes often too small to draw definite conclusions­ about effects on nutritional status. Figure 2: Prevalence of women overweight (BMI>25) and GDP per person, for low-income and middle-income countries 38 One review, which specifically looked at effects of Most observations for prevalence of women overweight are from 2000–10. The fitted curve is a locally weighted home­stead food production systems on intermediary regression of prevalence of women overweight against GDP per person. The correlation between prevalence of outcomes along the impact pathway, concluded that, women underweight and the log of GDP per person is 0·71 and is significant at the 1% level. The size of the circles when measured, positive effects are shown for several represents the estimated population of overweight women aged 15–49 years, in about 2005, on the basis of multiplication of prevalence of women overweight by the UN population estimates of the female population aged underlying determinants of nutrition, including house­ 15–49 years. Data are sourced principally from the Demographic and Health Surveys18 and WHO.19 DRC=Democratic hold production and consumption, maternal and child Republic of the Congo. GDP=gross domestic product. PPP=purchasing power parity. www.thelancet.com 69 Series

intake of target foods and micronutrients, and overall Panel 3: Pathways by which agriculture can affect nutrition outcomes dietary diversity. This finding is consistent with results • As a source of food: increases household availability and access to food from own from an impact-pathway focused assessment of a home­ production stead food production system in Cambodia, which • As a source of income: increases income from wages earned by agricultural workers or showed no effect on child anthropometry or anaemia through the marketing of agriculture commodities produced despite effects on household production, consumption, • Food prices: agricultural policies (national and global) affect a range of supply and and dietary diversity.60 demand factors that establish the price of marketed food and non-food crops; this Despite explicit targeting of women in many agri­ price in turn, affects the income of net seller households, the purchasing power of net cultural programmes, few studies have measured buyers, and the budget choices of both specific aspects of women’s empowerment as a pathway • Women’s social status and empowerment: women’s participation in agriculture can to improved nutrition, and results are mixed. Assess­ affect their access to, or control over, resources and assets, and increase their decision- ments of home­stead food production systems in making power regarding intra-household allocation of food, health, and care Bangladesh and Nepal report positive effects on women’s • Women’s time: women’s participation in agriculture can affect their time allocation income, control over resources, or influence in decision and the balance between time spent in income generating activities and time making on a range of issues.53,61–63 In Kenya, a project allocated to household management and maintenance, caregiving, and leisure promoting orange sweet potato production among • Women’s own health and nutritional status: women’s participation in agriculture can women farmers showed that women gained control over affecttheir health (eg, through exposure to agriculture-associated diseases) and selling the product, whereas men maintained control nutritional requirements (eg, through increased energy expenditure); their health and over income.64 Livestock and dairy projects in Kenya and nutritional status can, in turn, affect their agricultural productivity and hence their Bangladesh report increases in women’s income or income from agriculture influence in decision making,65,66 whereas in India, men’s but not women’s income improved as a result of a Adapted from the World Bank34 and Gillespie and colleagues, 201235 dairy project.67 Very few studies have measured the effect of agriculture interventions on women’s time, know­ ledge, practices, health, or nutritional status and none have modelled the potential mediating role of these Panel 4: Value chains for nutrition maternal resources on child nutrition.38 Food supply chains are defined as the series of processes and actors that take a food from its production—including inputs into production—to consumption and disposal Biofortification as waste.41 Broadly defined steps along the supply chain include production, processing, Biofortification is a uniquely nutrition-sensitive agriculture­ distribution, retailing, promotion, labelling, and consumption. The concept of value intervention because it focuses on breeding of staple crops 68 chain refers to the addition of value (usually economic) for chain actors at different that are rich in essential micronutrients. The many 68,69 steps along the chain. advantages of the approach are well documented.­ Bio­ fortification, however, cannot achieve the high con­ In the past 5 years, value chains have been singled out as one potential strategy to leverage centrations of micronutrients needed to treat severe agriculture to improve nutrition.39–41 The approach could be particularly relevant for deficien­cies or to fulfil the high requirements (eg, for iron traditional value chains for micronutrient-rich foods such as dairy, meat, fish, poultry, and and zinc) of pregnant and lactating women and infants; it fruits and vegetables, which are generally lacking in the diets of low-income households is more suited for provision of a daily dose of micronutrients because of scarce availability, perishability, and high prices often compounded by a scarcity (about 50% or more of daily needs) to help prevent of information and knowledge about their health and nutritional benefits. Food value deficiencies in individuals through­out the lifecycle, outside chains are therefore a possible entry point to stimulate both supply and demand of the 1000 days window. As is true for all approaches, (especially among poor populations) for micronutrient-rich foods. biofortification should be considered as one component of Value chain concepts and analysis have unique features that make them a promising a larger strategy to eliminate micro­nutrient deficiencies, approach for tackling both undernutrition and overnutrition: 1) they focus on and the optimum mix of supple­mentation, dietary diversi­ coordination between actors, because all value chain processes and actors are tightly fication, fortifi­cation, bio­forti­fication, and health services linked by each action affecting the others along the chain; 2) they are analytical, versatile, should be defined depending on local context. and solution-oriented and can therefore be used to assess the constraints that affect Three broad milestones need to be achieved for bio­ availability, affordability, acceptability, or quality of nutritious foods in a given context, fortification to succeed: 1) breeding objectives (mini­mum and identify and test solutions that can be implemented at specific leverage points along target concentration for each micronutrient)­ must be met; the chain; 3) they focus on addition of economic value, and could therefore be used to 2) retention and bioavailability of micro­nutrients must be identify points before, during, and after production at which nutritional (and economic) satisfactory so that intake leads to expected improvements value could be added, or losses in nutrients prevented. In view of the importance of in status; and 3) farmer adoption rates and intakes by coordination across sectors and of development of joint solutions to stimulate agriculture target populations must be adequate. HarvestPlus, a and nutrition linkages, value chain concepts and analysis might provide a useful programme that has led a global effort to breed and framework and platform to achieve these goals. disseminate biofortified staple food crops since 2003, has (Continues on next page) made substantial progress in research to test these three steps for vitamin A, zinc, and iron in seven crops: cassava,

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maize, sweet potato, bean, pearl millet, rice, and wheat (table). In addition to achieving major progress in (Continued from previous page) breeding and releasing crops, the programme will Value chains also have important limitations. First, they focus on one food at a time, as complete all planned retention and bioavailability studies opposed to the whole diet and the many nutrients required for healthy living. Efforts to in 2013, and 11 efficacy trials in 2014. Two effectiveness integrate nutrition into value chains should therefore focus on complementary value trials,58,59 which assessed the rollout of orange sweet potato chains to fill the specific dietary and nutrient gaps identified in target populations. Second, in Uganda and Mozambique (milestone three), have been the focus on addition of economic value plus incorporation of nutrition goals might create completed. They showed high farmer adoption and sig­ insurmountable trade-offs for value chains actors. Third, although they might be nifi­cant increases in vitamin A intakes in both countries well-suited to enhance access to micronutrient-rich foods for girls and women during the and in child vitamin A status in Uganda.58,59 Effectiveness reproductive period, their role for addressing the special needs of young children might be trials for the other target crops are expected to be limited to fortified complementary foods or products, and a few target foods such as dairy completed by 2018. products and biofortified crops (eg, biofortified orange sweet potatoes). Thus, present evidence regarding biofortification is Case studies41–43 and a review of on-going programmes44 suggest that several research concentrated on the first two milestones—proof of initiatives and value chain actors are currently exploring the potential of value chains to concept that breeding for micronutrient-rich crops is improve nutrition. One such initiative is homegrown school feeding programmes, which feasible and that micronutrients are retained and bio­ use value chains to link agriculture and nutrition, with potential livelihood and income available—and a growing evidence of efficacy. Results on benefits for farmers and nutrition benefits for young children and their families.45,46 bioconversion of β carotene to retinol in humans and Existing efforts to incorporate nutrition in value chains should also consider addressing bioavailability of zinc and iron from biofortified com­ food safety issues, especially since most of the micronutrient-rich foods of interest are pared with common varieties are very encouraging, also highly perishable and susceptible to food safety problems. Tackling of food-borne suggesting that extra minerals will lead to net increases diseases would improve nutrition. in quantities absorbed. Efficacy studies also confirm that intakes of iron-biofortified rice70 and beans71,72 improve iron status, and that all biofortified crops released so far cash or food, although with improved technology for For more on the HarvestPlus have favourable agronomic qualities, including equal or tracking income transfers, cash transfers are increasingly programme see http://www. higher yields than common varieties, and greater disease the preferred means to support chronically poor house­ harvestplus.org resistance and drought tolerance. Evidence regarding the holds. Between 0·75 and 1·0 billion people in low- effective­ness of biofortification, however, is still confined income and middle-income countries currently receive to vitamin A in orange sweet potato, and the scalability of cash support.73 Although many transfer programmes delivery is yet to be shown. reach only a small share of the vulnerable population, some have extensive coverage, such as Ethiopia’s Social safety nets Productive Safety Net Programme, which reaches 10% of Social safety nets are programmes that distribute the country’s population,74 and transfer programmes in transfers to low-income households. These programmes Brazil and Mexico that reach 25%, and in Ecuador 40%, raise income among vulnerable groups and enhance of their populations.75 The generosity of transfers varies resilience by preventing destitution brought about by widely, ranging from transfers that increase total income loss of assets or reduced investment in human capital marginally to those that boost income by up to a third for during times of crises. Transfers can be in the form of the poorest recipients.75

Country (year of first release)* Status of nutrition studies† Dietary intake Bio-availability Efficacy Effectiveness and retention Vitamin A crops (released) Cassava Nigeria, Democratic Republic of Congo (2012) P P 2013–14 2013–15 Maize Nigeria, Zambia (2012) P P Continuing 2013–15 Orange sweet potato Uganda (2007), Mozambique (2002) P P P P Iron crops (released) Bean Rwanda (2012) P P Continuing ·· Pearl Millet India (2012) P P P 2013–15 Zinc crops (under development—to be released in 2013) Rice Bangladesh and India (2013) P 2013 2013–14 2014–16 Wheat India and Pakistan (2013) P P 2013–14 2014–16

References are provided in appendix pp 5–6. *Approved for release by National Governments after intensive multi-location testing for agronomic traits and micronutrient performance. †Completed though not necessarily reported.

Table: Release schedule for biofortified crops and status of related nutrition studies

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The main goal of social transfers is to augment income, exposed to the programme for long durations.76,77,84 but programmes sometimes include additional inter­ Evidence of effects on micronutrient nutrition is equally ventions or conditions that can enhance their nutrition scant and comes from only a few studies that have looked sensitivity such as: linking of transfers to health and at these outcomes.76 The Mexico conditional cash transfer nutrition services (eg, through conditionality); targeting programme, which distributed a micronutrient-fortified of households with nutritionally vulnerable members, on food to beneficiary mothers and children, showed a the basis of age or physiological status; inclusion of positive effect on child intake of iron, zinc, and vitamin A nutrition-specific interventions for selected individuals among those who consumed the product, but only a within the household (eg, nutrition behaviour-change small effect on mean haemoglobin or anaemia reduc­ communi­cations or distribution of fortified foods or tion.76 Two other programmes, in Honduras and supplements); administration of transfers in a sex- Nicaragua, that assessed effect on haemoglobin showed sensitive manner (eg, by directing transfers to women or no effect.76 The Mexico programme showed reductions in designing them to accommodate time constraints of low birthweight attributed to changes in women’s caregivers); and targeting of populations facing climatic empower­­ment, which in turn were attributed to women’s or economic stress related to seasonality or other shocks, increased demand for better quality prenatal care as a or focusing on emergencies. result of participation in the programme.85 Evidence is also emerging of small effects of conditional cash trans­ Conditional cash transfers fers on child development­ outcomes.86 Conditional cash transfers aim to stimulate households to invest in the health, nutrition, and education of their School feeding programmes children (enhancing human capital) by promotion of the School feeding programmes are a type of conditional use of these services as conditions (conditionalities) for transfer, albeit in kind. Similar to other transfers, they receipt of transfer. Most conditional cash transfers target are mainly a form of social assistance for consumption. transfers to women, on the premise that increasing The links to nutrition are less direct than transfers women’s control over resources will lead to greater targeted to mothers and children during the first investments in children (appendix p 2). Although 1000 days, but school feeding can reduce hunger and conditional cash transfers are implemented worldwide, stimulate learning.87 These programmes, however, are experimental evidence of effectiveness comes mostly implemented in nearly every country in the world.88 from Latin America. In addition to their positive effects Results from a meta-analysis show that school feeding on poverty reduction, household food consumption, and programmes have small effects on school-age children’s dietary diversity,76,77 almost all programmes assessed anthropometry, particularly in low-income settings.89 increased the use of preventive and curative health and Major effects on height are not expected in school-age nutrition services.78,79 The Mexico, Brazil, and Nicaragua children and weight gains can be either positive (in pro­grammes80–83 also showed improvements in women’s under­weight populations) or negative (when risks of control over additional resources, enhanced self-esteem, obesity are high). In middle-income countries, school heightened knowledge and awareness of health and meals might also serve as an opportunity to combat nutrition, and increased opportunities for women to obesity; Brazil and Chile have redesigned their pro­ strengthen their social networks. grammes with this risk in mind.90 Despite the many benefits of conditional cash transfers School meals might also benefit other members of the for households and women, evidence of effects on household when the food provided is shared or when the nutritional outcomes is mixed.76,78 A review77 using pooled school-aged child’s intake at home is reduced.91,92 estimates shows that, overall, conditional cash transfers Randomised controlled trials in Burkina Faso and have had a small, but not statistically significant, effect Uganda showed effects on weight among preschool- on child anthropometry. A forest plot analysis of aged boys (ie, <5 years) whose siblings received school 15 programmes,77 combining conditional cash transfers meals or take-home rations compared with a control and unconditional cash transfers, shows an average group93 (Gilligan D, International Food Policy Research effect of 0∙04 in height-for-age Z score, an effect size Institute, personal communication). Another oppor­ that is neither statistically significant nor biologically tunity offered by school feeding programmes is to affect meaning­ful; similarly, no significant effect was identified iron nutrition, especially for adolescent girls. A review92 for conditional cash transfers only. In view of the of randomised evaluations of iron-rich school meals heterogeneity of populations and pro­gramme designs (fortified or providing animal-source foods) documents and methods, meta-analyses might not be the most that three of four studies improved iron status, irre­ appropriate approach for assessment of effect, but spective of initial status. The addition of a micro­nutrient analyses of individual studies are consistent with the mix to school meals in India improved total body iron, findings. Only a few conditional cash transfer studies but not anaemia, possibly because of worm loads.94 show effects on anthropometry, and these effects are Deworming can, however, be included as part of a larger shown in the youngest or poorest children, or those school health programme, although the timing of

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delivery differs from the daily meal programme. Since school-aged children are the main reservoir of worm Panel 5: Unintended, negative effects of in-kind and cash transfers in Mexico loads in a population, such an intervention could benefit Social safety nets can reduce poverty and increase use of health and education services.79 younger children as well. Depending on their target populations, however, these interventions can have unintended negative consequences. The effects of Mexico’s Programa de Apoyo Alimentario (PAL; Food Unconditional transfers Support Programme) on excess weight gain in women is one such example. PAL is a dual Unconditional transfers, either as cash or in kind, have conditional cash and in-kind transfer programme targeted to poor and remote also been popular, particularly outside of Latin America. communities in rural Mexico. An assessment of PAL99 showed improved household dietary Households commonly spend more on food and health quality, but also increases in total energy consumption in a population that was not with cash transfers—even when they are only indirectly energy-deficient and had a high prevalence of overweight and obesity among women at linked to nutrition and health—than they spend out of baseline (65%). PAL also increased the already steep annual weight gain in adult women in other increases in income.95,96 Moreover, some uncon­ the control group (425 g, SD 80) by 291 g (111) per year in the food basket group ditional cash transfers use so-called soft conditions in the (a 68% increase) and by 222 g (122) per year in the cash group (a 52% increase). The most form of broadly targeted behaviour-change com­muni­ substantial effect was recorded in adult women who were already obese before the cations or social marketing to encourage health-seeking programme started (518g [153] per year in the food basket group and 354 [169] per year behaviour. In Africa, soft conditions or uncon­ditional cash in the food basket group; figure 3).100 The PAL programme’s food basket included several transfers are more common than conditional cash energy-dense staple and basic food products including oil, cookies, and whole milk, and transfers.97 One randomised trial showed that a con­ provided an additional 450 kcal per day per adult. To avoid negative effects on populations ditional cash transfer with health con­ditionality increased experiencing the double burden of child stunting and adult obesity, transfer programmes clinic visits in Burkina Faso, where­as an unconditional should be designed to respond to the identified needs of target populations, and for food cash transfer did not,98 showing the importance of the transfers, their specific nutrient gaps. condition for achieving health-seeking behaviour changes in this setting. Evidence, however, shows an absence of overall effect of both unconditional cash transfers and 700·0 Food basket Cash † conditional cash transfers on child nutritional status.77 Costs will differ between the two approaches as will the 600·0 distribution of benefits for different outcomes; as such, no † 500·0 method dominates in all situations. * * 400·0 † In-kind household food distributions † In-kind household food distributions are currently less 300·0 prominent than they were in previous decades, mostly 200·0 because of cost considerations. They are now largely used as part of an emergency response or in places where the 100·0 logistics of cash transfers are constrained. Evidence from weight gain (g) on annual Estimated effect 0 Mexico suggests that in-kind food transfer programmes All women <25 25 to 30 >30 might have unintended effects on overweight and obesity when the energy contribution of the food basket exceeds BMI group 99,100 the energy gap in the targeted population (panel 5, Figure 3: Estimated effect of Mexico’s Programa de Apoyo Alimentario figure 3). In addition to general family rations, food programme on annual weight gain in women, by initial BMI distribution programmes often provide micronutrient- BMI=body-mass index. *p<0·05. †p<0·01. fortified foods (eg, corn-soy or wheat-soy blend) to mothers and young children. In Haiti, distribution of family rations or cash. Disasters, particularly sudden such food rations to all mothers and children within the onset emergencies such as earthquakes and hurricanes, first 1000 days of life had a greater effect on child growth often disrupt normal market channels, which might than did targeting of underweight children younger than dampen the logistical advantages of cash compared with 5 years.101 In view of the severity of food insecurity in this food transfers. Although food aid deliveries overall popu­lation, no unintended effects on overweight or declined from 15 million metric tonnes (t) in 1999 to obesity were identified. Complementation of this pro­ 4·1 million t in 2011, emergency deliveries have remained gramme with the distribution of iron-fortified micro­ almost constant; they now account for more than 67% of nutrient powders reduced anaemia prevalence by half in total food aid.103 Even when targeted towards overall as little as 2 months.102 household subsistence, aid during disasters can prevent major deteriorations in child undernutrition.104,105 Age- Transfer programmes in emergencies based targeting of fortified foods can help prevent under­ Transfer programmes in emergencies also usually nutrition and complement efforts to tacklecases of severe combine nutritionally enhanced complementary foods for acute malnutrition with specially formulated products. pregnant and lactating women and their young child with The nutritional effects of emergency deliveries can be www.thelancet.com 73 Series

enhanced by inclusion of lipid-based nutrient supplements transfers on child cognitive development, which were in the package of assistance to families.106–108 mediated by increased preschool partici­pation, improved diets, and reduced anaemia (Gilligan D, Roy S, Inter­ Early child development national Food Policy Research Institute, personal Stunting and impaired cognitive development share communication). several of the same risk factors, including deficiencies in Other trials—in India, Pakistan, and Bangladesh116–118— protein, energy, and some micronutrients, intrauterine although successful at improving child development or growth retardation, and social and economic conditions, nutrition outcomes, or both, failed to show additive or such as maternal depression and poverty.109 Some of the synergistic effects between nutrition and stimulation key phases of brain growth and development also interventions. In India,116 beneficiaries of the Integrated encompass the first 1000 days of life, the period of peak Child Development Services (ICDS) programme were susceptibility to nutritional insults. Therefore, some key allocated to groups receiving breastfeeding and comple­ interventions can protect children from both nutritional mentary feeding counselling, or this package plus and developmental risks; these include core maternal responsive feeding and psychosocial stimulation skills. and child nutrition interventions, psychosocial stimu­ Compared with ICDS only, both intervention packages lation and responsive parenting, and interventions to improved child dietary intake and haemoglobin and alleviate poverty, food insecurity, maternal depression, reduced morbidity, but only the nutrition intervention and gender inequity.21 increased length gain, and only the full package includ­ing Evidence of the effect of early child development inter­ stimulation benefited development outcomes.116 A factorial ventions, with or without a nutrition component, on child design trial in Pakistan117 showed no evidence of additive development outcomes has been extensively reviewed in or synergistic effects of a nutrition (counselling and two previous series in The Lancet.20,21 We focus on evidence micronutrient powders) and stimulation intervention of how child stimulation and nutrition interventions can (monthly group meetings and home visits for children have complementary effects on nutrition outcomes aged 0–24 months) on child development or nutrition (appendix pp 7–9). The most compre­hensive, long-term outcomes. Preliminary results show effects of all three study110 of interventions that provided both child stimu­ intervention packages on developmental scores com­pared lation and food supplemen­tation to stunted children aged with control, with larger effect sizes among the two 9–24 months in Jamaica showed an additive effect of the stimulation groups. In Bangladesh,118 psycho­social two interventions on cognitive development, but not on stimulation with or without food supplements among growth. At adoles­cence, the additive effects on cognition severely underweight children aged 6–24 months on were not sus­tained, but the group having received discharge from hospital had an effect on mental stimulation had long-term benefits, which ranged from development and a small effect on WAZ, but no additive improved develop­ment outcomes to educational attain­ or synergistic effects were noted between the two ment and social behaviour.111,112 In Bangladesh, addition of interventions. One intervention that closely ties feeding stimulation­ and home visits to standard nutrition and practices with child stimulation is responsive feeding. health care for severely malnourished children improved Few studies of this approach, however, have been designed development outcomes and weight-for-age Z score to distinguish messaging on complementary feeding (WAZ).113 Another trial in Bangladesh, which added from those on psychosocial care114 and few so far have responsive parenting (including­ feeding) to an informal shown a clear association with nutritional outcomes.119 nutrition and child development education programme, Reduction of maternal depression is another way to showed benefits on several feeding and parenting address risk factors common to both nutrition and child behaviours, child self-feeding, and development­ out­ development.120,121 Efforts are being made to link basic comes; addition of iron-fortified micronutrient powders to health services with a wide range of social support for the intervention improved weight gain and WAZ but had women. Efficacy trials.122,123 show that the benefits might no additional effect on development outcomes.114 A zinc accrue to both mothers and their newborn babies, supplemen­ ­tation and responsive stimulation inter­vention justifying ongoing efforts to bring these initiatives to scale. in under­weight children in Jamaica showed synergistic effects on child development between the two interven­ ­ Schooling tions: greater benefits on development outcomes were Although children are beyond the crucial 1000 days identified in the zinc and stimulation group, compared window when they enter school, their schooling with little or no effect in the groups receiving either.115 This experience might be a strong determinant of the nutrition synergistic effect, however, was not noted for morbidity of the next generation. Parental schooling has been (reduced only in zinc group) or growth (no effect in either consistently associated with child nutritional status, with group). A randomised controlled trial of cash transfers to maternal education often, but not always, having a larger households linked to preschool enrolment in Uganda explanatory power than paternal education, controlling provides an example of joint benefits on cognition­ and for income and schooling choices.124,125 The positive global nutrition; findings showed significant effects of cash trends in schooling are, therefore, encouraging for

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nutrition. Data from developing countries show an health and nutrition curriculum in developing countries average increase in years of schooling from 2∙60 to 7∙62 on undernutrition or health knowledge, let alone on for boys and from 1∙50 to 6∙64 for girls between 1950 parenting skills decades later, are absent. and 2010.126 The girl to boy ratio shows a substantial Schools are also suitable venues to introduce pro­ improvement over this period, from 57∙7% to 85∙9%. grammes to combat obesity. Such programmes can focus Enrolment data show parity in girls’ primary schooling in on healthy diets and promotion of physical activity. A most countries;127 moreover, in many countries more systematic review133 of 22 studies in low-income and girls than boys are now in secondary school. Still, only middle-income countries noted that 82% of such about a fifth of adolescent girls in sub-Saharan Africa programmes had a favourable effect on physical activity, and two fifths of girls in south Asia are enrolled in diet, or both. secondary education.128 We assessed the level of parental education necessary Discussion for a meaningful reduction in child undernutrition by In 2008, The Lancet Maternal and Child Undernutrition analysing 19 datasets from the Demographic and Health Series included conditional cash transfer programmes Survey (collected since 1999) and derived estimates of the and dietary diversification approaches as “general risk of child stunting associated with maternal and nutrition support strategies”, and noted small positive paternal primary and secondary education, controlling for effects of conditional cash transfers on child anthrop­ household wealth, rural versus urban residence, and child ometry in three Latin American countries, and an age and sex. The analysis showed that the risk of stunting absence of a statistically significant of effect of dietary is significantly lower among mothers with at least some diversification strategies on child nutrition outcomes.134 primary schooling (odds ratio [OR] 0·89, 95% CI In the present series, we discuss evidence regarding the 0·85–0·93), and even lower (p<0·001) among mothers nutritional contribution of programmes in four sectors with some secondary schooling (0·75, 0·71–0·79). Paternal and the potential for enhancing their nutrition-sensitivity. education at both the primary and secondary levels also Although the concept of nutrition sensitivity is not new, reduced the risk of stunting although the respective ORs investments in development and implementation of (0·96, 0·93–1·01; and 0·85, 0·81–0·89) are smaller than nutrition-sensitive programmes have intensified in the for maternal schooling. Despite this overall association, past few years, prompted by the 2008 series, and there is appreciable heterogeneity in effect sizes for both spearheaded by the Scaling Up Nutrition movement.9 It For more on the Scaling Up maternal and paternal education in individual countries, is important to recognise, when interpreting the results Nutrition movement see http:// probably indicative of differences in both quality of of our review, that most of the programmes included scalingupnutrition.org education and quality of data. were retrofitted and tagged as nutrition sensitive without Schooling directly increases individual earnings and having been originally designed as such. national income and, through these pathways, can affect Targeted agricultural programmes have an important nutrition in the long term. Thus, programmes to role in supporting livelihoods, improving household increase schooling via the supply of inputs or through food security and healthy diets, and in fostering women’s fee waivers or cash transfers can be expected to reduce empowerment. Yet, our review shows inconclusive evi­ the risk of undernutrition for the next generation. There dence of effects on child nutritional status, with the is a lack of clarity, however, about which aspects of possible exception of benefits on vitamin A intake and, to schooling, beyond the income effect, benefit nutrition. a lesser extent, vitamin A status. These findings are At least five overlapping pathways have been suggested, probably the result of a combination of factors, including: but not formally tested. Schooling might: 1) transmit weaknesses in programme design and implementation information about health and nutrition directly; 2) teach (especially the nutrition, behaviour-change communi­ numeracy and literacy, thereby assisting caregivers in cation, and health components);60 inclusion of house­ acquiring information and possibly nutrition know­ holds with children outside of the 1000 days window with ledge;129,130 3) expose individuals to new environments, little potential to benefit in linear growth; and the fact making them receptive to modern medicine; 4) impart that other pressing constraints to nutrition—such as self-confidence, which enhances women’s roles in infec­tious diseases, helminths, and environmental­ enter­ decision making, and their interactions with health-care opathy associated with scarcity of access to appropriate professionals; and 5) provide women with the water, sanitation, and hygiene—might not be addressed opportunity to form social networks, which can be of by the programmes. Additionally, the assessments of particular importance in isolated rural areas. The most of the programmes we reviewed had crucial question remains as to whether schooling could do even weaknesses such as an absence absence of valid more to directly affect nutrition, both in the short term comparison and control groups, a possibly too-short for school children and in the long term as they duration of intervention, small sample sizes, the transition into their parental role. Although nutrition inclusion of the wrong age group in effectiveness modules are available in some school health education assessments, and the failure to control for potential programmes,131,132 assessments of the effect of a school confounding factors in the analysis. All these assessment www.thelancet.com 75 Series

outcomes. Future work should include testing of pro­ Panel 6: Research priorities grammes with stronger designs, nutrition goals, and • Rigorous, theory-based effectiveness and cost-effectiveness assessments of complex interventions; use of rigorous programme-theory based and large scale nutrition-sensitive programmes. These assessments should include: impact and impact pathway assessments; and assessment • Use of experimental randomised controlled trials, where feasible, to test different of cost and cost-effectiveness (panel 6). methods of delivery and joint packages of interventions. Biofortification has made substantial progress by • Careful assessment of programme impact pathways and quality of service delivery, establishing proof of concept for orange sweet potato and use of process evaluation instruments and mixed methods, including assessment showing effects, through rigorous assessments, on of the capacity and efficiency of front-line health workers. maternal and child intake of vitamin A and child vitamin • Measurement of gender-disaggregated impact indicators; these indicators should A status. The challenges for biofortification now rest in be carefully selected on the basis of nutrition goals and interventions included in showing effectiveness of new crops, refining delivery and programmes and could include: anthropometry, micronutrient status biomarkers, marketing strategies, scaling up successfully, and child development outcomes, child morbidity. integrating new varieties into national agricultural • Measurement of intermediary outcomes along the impact pathway (eg, household research systems. consumption; food security and dietary diversity; dimensions of women’s Social safety nets are a powerful way to reduce poverty, empowerment, maternal physical, and mental health; detailed dietary intake or and currently provide income support to a billion simpler measures such as dietary diversity for target individuals). chronically poor individuals and to shock victims. They • Detailed costing for assessment of cost-effectiveness. have been shown to improve household food availability • Development of methods to allow comparison of the social benefits of complex and dietary quality and to foster certain aspects of women’s programmes with many objectives and joint outcomes, with the benefits of empowerment, and for conditional cash transfers in single-outcome programmes. particular, to stimulate demand for health and education • Formative research and focused ethnographic studies to guide selection, design, and services. Despite these many benefits, pooled evidence implementation of nutrition interventions to be integrated in nutrition-sensitive shows little effect on nutritional outcomes. By contrast programmes, and for overall design of nutrition-sensitive programmes. with agriculture programmes, several effectiveness assess­ • Qualitative research to understand barriers to participation, adoption and use of ments of social safety nets have used rigorous random­ised programme inputs and services (eg, agricultural inputs, compliance with conditions in controlled trial designs, although most of these studies conditional transfers, recommended feeding or caregiving practices). were done in middle-income countries and might under­ • Research to rigorously test the feasibility and desirability of integration of estimate the magnitude of effect that could be achieved in interventions from several sectors versus co-location. Such research would establish poorer settings. Additionally, some aspects of programme whether programme implementers should develop new instruments and methods for design or implementation might have diluted their nutri­ joint planning, implementation, monitoring, and assessment, or whether tional effect, including poor timing and short duration of investments should focus on effective programme co-location and implementation. maternal and child exposure, absence of clear nutrition • Research to test and document the scalability of newly released biofortified crops. goals, and poor selection or implementation of nutrition • Assessment of effectiveness large-scale programmes combining early child interventions in some programmes. Also, the gap between development and nutrition interventions in different contexts and assessment of increased use of health and nutrition services and synergies both in programming and outcomes. nutrition benefits has been attributed, at least partly, to the • Research to test different delivery platforms for programmes to reduce maternal poor quality of services provided.78 Conditional cash depression. transfers are designed to increase health awareness and • Research to test different delivery systems for reaching adolescent girls (eg, school service demand, but ultimately their nutritional effect programmes, social safety nets with conditions to keep girls in school, agricultural rests on the quality of public health services. programmes targeting adolescent girls at home). Our review of early child development interventions • Assessments of school nutrition programmes and their short term effect on provides little evidence that stimulation alone has a direct knowledge of school children and long-term effect on parenting skills. effect on nutrition outcomes, but it suggests that combined early child development and nutrition inter­ ventions can have additive or synergistic effects on design flaws reduce the ability to detect an effect even if development outcomes, and in some cases on nutrition. one exists. The examples of successful joint delivery of these services In view of the complexity and diversity of agricultural point to an area in which programmatic synergies, cost programmes, their many goals, and their long impact savings, and potential benefits for both child development pathways, some argue that impact assessments should and nutrition might be identified. focus on outcomes such as food security and diet quality, Girls’ schooling is increasing in many countries, largely rather than child nutritional status during the 1000 days as a result of government interventions to change incen­ window. Although complexity is a valid concern, the tives and reduce barriers to girls’ school enrolment and many pathways by which agriculture can improve participation. Increases in parental schooling have con­ nutrition—and evidence that effects on several indicators tributed to reductions in stunting, but larger effects could along these pathways are achieved—support giving these probably be achieved if effective nutrition education programmes a fair chance to deliver on child nutrition programmes were incorporated into school curricula.

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Our review shows the potential of programmes in the actions from several sectors, or co-locate programmes four sectors reviewed to improve the lives of poor managed by different sectors so that they reach and households and individuals, both in the short-term and the saturate the same communities, households, and indi­ long-term. It also shows, however, that more needs to be viduals. In view of the complexity of integration,33,137,138 done to increase the nutrition sensitivity of programmes especially across many sectors, it is important to carefully so that their potential to deliver on maternal and child assess whether investments should focus on joint nutrition outcomes is unleashed. The nutrition sensitivity planning, implementation, monitoring, and assessment, of promising programmes can be enhanced in several or on effective programme co-location (panel 6). ways. First, targeting on the basis of nutritional vulnerability (eg, age, physiological status) in addition to Conclusions geographic targeting on the basis of poverty, food Nutrition-sensitive programmes hold great promise for insecurity, or location can help reach households and supporting nutrition improvements and boosting the individuals most likely to benefit from the programme. scale, coverage, and benefits of nutrition-specific actions. Alternatively, targeting of nutri­tionally vulnerable indi­ New incentives are needed to support innovations in viduals could be used as a second level of targeting for nutrition-sensitive programmes and unleash their subgroups of programme beneficiaries who meet pre- potential to tackle nutrition while also achieving their own established criteria. For example, targeting agricultural­ goals. New nutrition-sensitive agriculture44 and social programmes to households with pregnant or lactating safety net programme designs, methods, and packages of women or children younger than 2 years might be neither interventions are being tested and are strengthening links logistically feasible nor optimum for community develop­ with health services. Rigorous impact evaluations, many ment; however, geographic community-level targeting of which are based on strong programme-theory and could be used as a first targeting criteria, with a second impact pathway analysis, are addressing key weaknesses level focusing on reaching mothers and young children encountered in previous evaluations and are assessing with a specific package of preventive nutrition and health impacts on a range of nutrition and child development interventions. Another key target group for nutrition- outcomes and several household and gender outcomes sensitive programmes is adolescent girls; conditions or along the impact pathway. Evidence generated by these other incentives can be used to keep girls in school, help enhanced programmes and assessments in the next delay first pregnancy, address HIV risk factors,135 and 5–10 years will be of crucial importance to inform future improve adolescent girls' nutrition knowledge and micro­ investments in agriculture and social safety net pro­ nutrient status to prepare them for motherhood. grammes to improve nutrition. Second, evidence shows that nutrition improvements The potential benefits of integration of early child are not automatic even with programmes that are success­ development and nutrition programming include cost ful at reducing poverty, food insecurity, and sex inequalities. savings and gains in both child development and nutrition To reach their full potential, programmes such as those outcomes. Leveraging health, agriculture, or social safety reviewed need careful identification of nutrition goals and net platforms for joint early child development and appropriate design and effective implementation of nutrition programming during the first 1000 days of life interventions to achieve them. A third way to enhance the would help focus on the crucial period of peak vulnerability nutrition sensitivity of programmes is to engage women for both nutrition and development. Current work is and include interventions to protect and promote their exploring such approaches. Benefits from psychosocial nutritional wellbeing, physical and mental health, social interventions on cognition, however, extend well beyond status, decision making, and their overall empowerment the first 2 years, and therefore, continued child develop­ and ability to manage their time, resources, and assets. A ment support is required thoughout the entire preschool fourth promising, yet underused approach to enhance the period. Early child development programmes, possibly nutrition sensitivity of programmes is to use them as linked to conditions in transfer programmes or delivered delivery platforms for various nutrition-specific inter­ through preschool or com­munity settings, could offer ventions. Nutrition behaviour-change com­muni­cations, psychosocial stimulation and parenting inter­ventions, which are incor­porated in several agriculture, social safety while also providing relevant­ nutrition interventions for nets, early child development, and school health pro­ children 2 years and older, focusing on micronutrients, grammes are one example of such use. Other opportunities healthy diets, and obesity prevention. With improved include addition of the distribution of micronutrient- guidance and curricula for nutrition education in schools, fortified products to nutritionally vulnerable adolescent a new emphasis on using schools to improve nutrition girls, mothers, and young children,101,136 or of preventive knowledge and practices and preparing school children health inputs to agriculture, social safety net, early child for their future parenting roles should also emerge. development, or school programmes. The immense potential of programmes addressing Finally, a crucial question that remains to be addressed the underlying determinants of undernutrition to when designing nutrition-sensitive programmes is the complement and enhance the effectiveness of nutrition- degree to which programmes should indeed integrate specific interventions is real, but is yet to be unleashed. www.thelancet.com 77 Series

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Maternal and Child Nutrition 4 The politics of reducing malnutrition: building commitment and accelerating progress

Stuart Gillespie,* Lawrence Haddad,* Venkatesh Mannar, Purnima Menon, Nicholas Nisbett, and the Maternal and Child Nutrition Study Group

Published Online In the past 5 years, political discourse about the challenge of undernutrition has increased substantially at national June 6, 2012 and international levels and has led to stated commitments from many national governments, international http://dx.doi.org/10.1016/ organisations, and donors. The Scaling Up Nutrition movement has both driven, and been driven by, this developing S0140-6736(13)60842-9 momentum. Harmonisation has increased among stakeholders, with regard to their understanding of the main This is the fourth in a Series of four papers about maternal and causes of malnutrition and to the various options for addressing it. The main challenges are to enhance and expand child nutrition the quality and coverage of nutrition-specific interventions, and to maximise the nutrition sensitivity of more distal *Joint lead authors interventions, such as agriculture, social protection, and water and sanitation. But a crucial third level of action exists, International Food Policy which relates to the environments and processes that underpin and shape political and policy processes. We focus on Research Institute, this neglected level. We address several fundamental questions: how can enabling environments and processes be Washington, DC, USA cultivated, sustained, and ultimately translated into results on the ground? How has high-level political momentum (S Gillespie PhD); Institute of Development Studies, been generated? What needs to happen to turn this momentum into results? How can we ensure that high-quality, Brighton, UK well-resourced interventions for nutrition are available to those who need them, and that agriculture, social protection, (Prof L Haddad PhD; and water and sanitation systems and programmes are proactively reoriented to support nutrition goals? We use a N Nisbett PhD); Micronutrient six-cell framework to discuss the ways in which three domains (knowledge and evidence, politics and governance, Initiative, Ottawa, ON, Canada (V Mannar MS); and and capacity and resources) are pivotal to create and sustain political momentum, and to translate momentum into International Food Policy results in high-burden countries.

Introduction Key messages The nutrition landscape has shifted fundamentally since • Emerging country experiences show that rates of undernutrition reduction can be the first Lancet Series on Maternal and Child Under­ accelerated with deliberate action. nutrition was published in January, 2008. Since then, • Politicians and policy makers who want to promote broad-based growth and almost every major development agency has published a prevent human suffering should prioritise investment in scale-up of policy document about undernutrition. In a very difficult nutrition-specific interventions, and should maximise the nutrition sensitivity of fiscal climate, official development assistance to the basic national development processes. nutrition category has increased from US$259 million in • Findings from studies of nutrition governance and policy processes broadly concur on 2008, to $418 million in 2011—a rise of more than 60% 1 three factors that shape enabling environments: knowledge and evidence, politics and (although it was $541 million in 2009). Furthermore, the governance, and capacity and resources. G8 countries reported increases of almost 50% in • Framing of undernutrition reduction as an apolitical issue is short sighted and bilateral spending on nutrition-specific and nutrition- 2 self-defeating. Political calculations are at the basis of effective coordination between sensitive interventions between 2009 and 2011. Accord­ sectors, national and subnational levels, private sector engagement, resource ing to Google Trends, “malnutrition”, now matches mobilisation, and state accountability to its citizens. “HIV/AIDS” in terms of internet interest, whereas • Political commitment can be developed in a short time, but commitment must not be 5 years ago, HIV/AIDS received twice as much interest as squandered—conversion to results needs a different set of strategies and skills malnutrition. This shift is attributable to several factors: • Leadership for nutrition, at all levels, and from various perspectives, is fundamentally the food price spikes of 2007–08 sparked renewed media important for creating and sustaining momentum and for conversion of that and policy interest in undernutrition, The Lancet 2008 momentum into results on the ground. Series provided policy makers with a set of tangible • Acceleration and sustaining of progress in nutrition will not be possible without interventions that were effective in various locations, national and global support to a long-term process of strengthening systemic and and the 2008 Copenhagen Consensus concluded that organisational capacities. nutrition interventions were among the most cost 3 • The private sector has substantial potential to contribute to improvements in effective in development. nutrition, but efforts to realise this have to date been hindered by a scarcity of credible The Scaling Up Nutrition (SUN) movement, which evidence and trust. Both these issues need substantial attention if the positive started in September 2010, is the most important symbol 4 potential is to be realised. of the increased interest in nutrition. By the middle • Operational research of delivery, implementation, and scale-up of interventions, and of May, 2013, the movement had grown to include contextual analyses about how to shape and sustain enabling environments, is 35 countries that are committed to the scale-up of essential as the focus shifts toward action. direct nutrition interventions and the advancement of nutrition-sensitive development, including 21 of the

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34 highest burden countries where 41% of the global we reiterate that through the approaches for shaping Research Institute, New Delhi, burden of child stunting is located (or 56% if India is enabling environments for nutrition, described here, we India (P Menon PhD) omitted). As SUN nears its 1000th day, several countries might be better able to advocate for attention to nutrition Correspondence to: have made advances in terms of building multistake­ within these broad development debates. Dr Stuart Gillespie, International Food Policy Research Institute, holder platforms, aligning nutrition-relevant programmes Washington, DC, 20006-1002, within a common results framework, and mobilising Characterisation of enabling environments USA national resources, but it is too soon to evaluate the effect What does an enabling environment for undernutrition [email protected] of SUN on rates of undernutrition reduction. reduction look like? In recognition of the general con­ As interest in nutrition has changed, so too has our sensus that income growth is necessary but not sufficient thinking. The large economic returns to nutrition- for undernutrition reduction,7,13,14 we undertook a system­ specific interventions (paper two in this eriesS 5), are atic review of the nutrition-relevant policy process and clear6 and we recognise the potential of nutrition- governance literature (panel 1). After a surge of activity in sensitive interventions (paper three7) and the impor­ the late 1970s to early 1980s, a two decade gap ensued in tance of an enabling environment for reduction of research of nutrition policy processes, punctuated by one undernutrition—the­ focus of this report.8 Most of the book in 1993, until interest re-emerged in 2003. In the concepts and ideas that we develop about enabling past decade, several multicountry and single-country environments apply to both undernutrition and the studies of such processes have been undertaken, in growing problems of overweight and obesity as which conceptual and analytical frameworks have been documented in the first paper in this Series. We focus applied.15–23 These studies sought to uncover key structures, mainly on undernutrition because as the 2010 Global pathways, and dynamics of policy processes for nutrition, Burden of Disease estimates show, undernutrition with an emphasis on challenges and constraints. In doing remains the number one risk factor in sub-Saharan so, research from other specialties (eg, political science24,25 Africa, and the fourth in south Asia.9 We use evidence and health systems26) was drawn on to adopt and adapt generated within academic and scientific institutions analytical frameworks and research methods to study and that generated in more real-world, action oriented, nutrition policy. transdisciplinary ways that embed nutrition within We define an enabling environment as political and wider social and political contexts.10 We used this policy processes that build and sustain momentum for mixture of evidence types partly because of the paucity the effective implementation of actions that reduce of the first type of evidence and partly in recognition undernutrition. Rather than wait for political will to that the second type is often more appropriate because emerge by chance, our review clearly shows that a it is more practical, politically feasible, and therefore political momentum can be developed and sustained See Online for appendix actionable. However, the second type of evidence is not as easy to independently verify or systematise with standard systematic review protocols. Panel 1: search strategy and selection criteria Beyond the nutrition-sensitive programmes and inter­ For analysis of enabling environments, we searched Medline, Web of Science, and Econlit, ventions discussed in paper three, other macro-level between Nov 12 and 16, 2012, with predefined search terms (“nutrition”, “governance” drivers exist that lie at the end of long causal pathways. and “poli*”, words to appear in the title of paper), with no date or language restrictions. Seemingly quite remote from the nutritional wellbeing Results were exported to a bibliographic reference manager (EndNote). We did further of children, many such drivers are nonetheless crucially searches in ELDIS and Google Scholar to identify references in the grey literature. We important to shape both national and global political screened results for duplicate references and for relevance to this paper. landscapes for nutrition, and basic-level determinants of For assessment of the Scaling Up Nutrition (SUN) movement we used two sources of new nutrition status. These aspects are particularly important data. First, monitoring data from 30 countries (submitted in September, 2012) was because each of the various determinants of nutritional provided by the SUN secretariat, including detailed information about core indices being outcomes can be vulnerable to sudden changes within, tracked by SUN, local expectations and proposed commitments of SUN focal points in or caused by, these drivers. Examples include climate these countries (appendix). The four indicators routinely tracked by SUN relate to the change, trade, the rate and pattern of economic growth, presence of a multistakeholder platform, a legal and political framework, a common food and energy prices and volatility, and land-use results framework, and alignment and mobilisation of resources. Second, we undertook a policies. Previous empirical work at the country level has closed online discussion with the Eldis Communities web platform, a service provided by shown that household income growth is a necessary, but the Institute of Development Studies, with 75 invited participants from six countries 11 not sufficient driver, of nutrition status. In a cross- (Bangladesh, Ethiopia, Indonesia, Kenya, Nepal, and Nigeria) from Nov 27, 2012, to Dec 4, country study of the drivers of nutritional change over 2012, to explore perceived benefits and expectations of joining SUN, the main challenges 12 time, four factors emerged as the most robust predictors and constraints faced by countries, and what needs to happen next. Participants of reductions in undernutrition worldwide: secondary consisted of experts from central and subnational government, multilateral and bilateral education for girls, reductions in fertility, accumulation development agencies, national and international non-governmental organizations, civil of household assets, and increased access to health society organisations, and research institutions—all of whom are working directly or services. In view of the scarce evidence for these drivers indirectly in nutrition (appendix). we do not discuss the related scientific literature. Rather, www.thelancet.com 83 Series

communicated clearly to generate pressure on politicians Panel 2: Framework for creation of an enabling environment for accelerated to act. Second, politics and governance. Various stake­ undernutrition reduction holders and agencies, each with different and frequently Framing, generation, and communication of knowledge and evidence competing agendas (especially in decentralised systems Issues and challenges to creation and sustaining of momentum of governance), need to work together to reduce under­ • Framing and narratives nutrition. All but the most extreme manifestations of • Evidence of outcomes and benefits undernutrition have no visible symptoms and are thus • What works and how well do nutrition interventions work relative to others? open to neglect, so even well-meaning governments • Advocacy to increase priority (civil society) might underinvest in nutrition. Data for nutrition trends • Evidence of coverage, scale, and quality and programme effectiveness are often out of date or scarce, allowing unsubstantiated political narratives to be Issues and challenges to conversion of momentum into results sustained in an evidence vacuum. Third, capacity and • Implementation research (what works, why, and how?) resources. Human and organisational capacity need to • Programme evaluation (impact pathways) encompass not only nutrition know-how, but also a set of • Generation of demand for evidence of effectiveness soft-power skills to operate effectively across boundaries Political economy of stakeholders, ideas, and interests and disciplines, such as leadership for alliance build­ Issues and challenges to creation and sustaining of momentum ing and networking, communication of the case for • Incentivising and delivering of horizontal coherence (multisectoral coordination) collaboration, leveraging of resources, and being able to • Development of accountability to citizens convey evidence clearly to those in power. Strategic and • Enabling and incentivising of positive contributions from the private sector operational capacities of different stakeholders at several Issues and challenges to conversion of momentum into results levels are key. Additional financial resources and much • Delivery of vertical coherence better budget data are needed if undernutrition efforts are • The role of civil society and the private sector in delivery to be scaled up, with innovation from governments and donors to maximise investment. Capacity (individual, organisational, systemic) and financial resources Panel 2 shows the issues and challenges for creation Issues and challenges to creation and sustaining of momentum and conversion of momentum within these three • Leadership and championing parameters. We apply this framework to three case • Systemic and strategic capacity studies (Malawi, Peru, and Maharashtra [a state in India]) • Making the case for additional resource mobilisation where trends from the past few years have been positive Issues and challenges to conversion of momentum into results and rigorous efforts have been made to prioritise • Delivery and operational capacity nutrition, reshape policy, and scale-up or improve • New forms of resource mobilisation nutrition-related programming­ (appendix). • Prioritisation and sequencing of nutrition action • Implementation and scale-up Creation and sustaining of momentum Narratives, knowledge, and evidence The 2008 Lancet Nutrition Series showed how effective through deliberate action.10,23,27 Moreover, translation of marshalling of evidence can create momentum by any such momentum into effect on nutrition status is far identifying a set of interventions that were effective at from automatic and needs the deliberate alignment of reducing undernutrition in various contexts, identifying several factors and processes.10,18–22 Our review also a window of opportunity—1000 days—as a focal point, emphasises three linked factors as being crucial for and imparting a sense of priority and feasibility by building and sustaining of momentum and for con­ showing how undernutrition is concentrated in a small version of that momentum into results. set of high-burden countries. The 2008 Series also First, knowledge and evidence. Undernutrition is a empha­sised the fragmented nature of the international multisectoral challenge that is open to various inter­ nutrition community with regard to messaging, pretations (eg, as a health, economic growth, inter­ priorities, and funding,28 and contributed to birth of the generational rights, or humanitarian issue). Each context SUN movement (panel 3). Undernutrition has unique needs its own enabling narrative or framing. This features that guide the kinds of knowledge and evidence multisectoral nature also raises challenges for imple­ needed for progress (panel 2). mentation of nutrition programmes and increases the importance of quality implementation research and The importance of framing impact evaluation. Undernutrition in early life is irre­ Reduction of undernutrition is a multisectoral activity, versible; therefore timely and reliable information about thus choices exist for how it is framed. In Guatemala nutrition status and its determinants in programmatic­ and Bolivia, framing has been focused on hunger contexts is crucial. Additionally, rigorous research is elimination, strongly determined by Brazil’s own Zero needed to capture the long-term inter­generational Hunger campaign.18–20 In Peru, civil society developed benefits of undernutrition prevention, with evidence under­nutrition reduction as an electoral issue21

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Panel 3: Main points from an online electronic consultation among stakeholders from six Scaling Up Nutrition (SUN) countries SUN represents an unprecedented opportunity for coordination, sectors. Ambassadors and champions for nutrition at various collaboration, cross learning, and advocacy to catalyse sustainable levels, from the prime minister to the community, have pushed nutrition gains at national and global levels. Membership implies nutrition onto the agenda. Policy makers are increasingly aware a national commitment to address undernutrition. SUN’s own of nutrition as a development issue, and some countries have monitoring system is centred on four key indicators (appendix). increased nutrition-relevant budgets. However, to track and compare progress between so many The main perceived challenges and constraints to SUN within countries, monitoring systems will tend to default to quantitative countries include little coordination and collaboration between data of what does or does not exist. Quality and process is not so (and within) different ministries, related scarcity of clarity and easily measured. For this reason, and to help us to uncover local consensus vision on what scaling up means, undefined roles and perceptions about key issues, challenges, and constraints related responsibilities, and few or ineffective policies and political to translation of SUN ambitions on the ground, online commitment. Decentralisation of SUN is a major challenge in discussions—organised by the Institute of Development Studies some countries. Translation of SUN from national to community and the International Food Policy Research Institute—were levels is restricted. The issue of weak capacity (all types and at all undertaken (appendix). 75 key stakeholders from different levels) was raised several times with particular challenges, sectors in Bangladesh, Nepal, Indonesia, Ethiopia, Nigeria, and including inadequately qualified personnel (eg, doctors and Kenya were actively involved over the 8 days of consultation, nurses) and community and extension workers (eg, front-line from Nov 27, 2012, to Dec 4, 2012. workers and health volunteers) in remote areas, and high In brief, perceived expectations of joining SUN are that it employee turnover. Financial resources are often unsustainable provides a framework and platform for improved coordination and unpredictable with funding for nutrition interventions and cooperation in nutrition. SUN encourages advocacy, which largely donor driven. Funding for scale-up is insufficient and has increased the number of stakeholders across sectors who are issues exist about budgetary allocation (emphasis on treatment working to address undernutrition. In turn, this increase is over prevention) and coordination. Poor quality of monitoring hoped to increase leveraging of resources, knowledge sharing, and evaluation data affects assessment of the effect of and institutional capacity. The SUN movement is also interventions, weakens advocacy strategies, and jeopardises considered to hold stakeholders (especially the government) funding. Finally, views about engagement with the private accountable, and secure further commitment to improve sector were mixed and suspicion around motivations was resource mobilisation and allocation. Areas of perceived reported. Private sector involvement needs close regulation and progress include increased awareness and advocacy across a framework within which to engage.

(appendix). In India, nutrition has risen on the agenda to be large. The inclusion of nutrition objectives and through a combination of advocacy around the finding targets within nutrition-sensitive programmes is thought that economic growth has not generated nutritional to be important to leverage resources for nutrition within benefits,29 a strong rights-based movement led by the those programmes; however, this hypothesis needs to Right to Food initiative,30 and a growing stakeholder be tested. consensus of the need for multisectoral action.31 In Ghana, which has achieved the fastest decline in child The timeliness, credibility, and persuasiveness of data stunting in sub-Saharan Africa in the past 5 years The irreversibility of undernutrition early in life makes (from 35% in 2003, to 28% in 2008,32 a rate of quick and effective action crucial. The availability of 1·5 percentage points per year), the agenda was one of timely and credible data presented in accessible ways can investment in agriculture as a driver of economic help governments and other stakeholders to be responsive growth and poverty reduction,33 together with feeding to changing circumstances, and help civil society organ­ initiatives for infants and young children, all in the isations to hold them accountable for the effectiveness­ of context of a stable political environment.34 their interventions. Data from the Demographic and The multisectoral nature of undernutrition reduction Health Survey and the Multiple Indicator Cluster Survey adds some complexity to the implementation of effec­ are essential for evaluation of national trends, but are tive programmes. Even breastfeeding promotion, for only collected every 3–5 years and are less useful for example, needs action on various fronts: behavioural immediate programmatic decision making. Surveillance change from breastfeeding mothers, workplace oppor­ mechanisms, for tracking of nutrition trends and to tunities to breastfeed, responsible advertising about inform timely decision making, only exist in a few breast-milk substitutes, and effective legislation to define countries.35–38 Advances in health management infor­ and monitor unacceptable behaviour or to challenge mation systems and the growing availability of new countervailing narratives. The returns to high-quality technologies could facilitate the real-time monitoring of impact evaluation in the face of such complexity are likely nutrition outcomes and programme coverage and quality. www.thelancet.com 85 Series

When, where, how, and why these new technologies are Political economy and governance practical and will lead to responsive and effective action The politics of undernutrition reduction have long been for nutrition are important research issues.39,40 neglected. The multitude of involved stakeholders at many levels, the invisibility of undernutrition, and the Communication of the benefits to improved nutrition imbalance of power between governments and multi­ The benefits of undernutrition reduction are lifelong, national organisations, generate little accountability for and yet their temporal distribution reduces their political commitment and delivery, and fuel the political economy appeal. The studies in Guatemala of the long-term bene­ of undernutrition reduction. fits of undernutrition prevention41,42 have been extremely influential worldwide, and the Consortium on Health Global governance Orientated Research in Transitional Societies (COHORTS) National governments, civil society (global and national), group is starting to yield multicountry evidence about the international and regional organisations (including UN long-term implications of early childhood nutrition.43,44 The agencies, development banks, and the African Union), challenge is to generate contemporary political payoffs to bilateral donors, charitable foundations, international these nutritionally driven long-term labour-market bene­ research organisations (eg, the Consultative Group on fits. The demo­graphic transition that many developing International Agricultural Research), academia, and countries are experiencing and debating at the highest private-sector companies all have a role in the global policy circles presents an example of one such opportunity institutional architecture for nutrition. 5 years ago, the to communicate the importance of nutrition in ways that stewardship or governance of this system was fragmented resonate. The so-called demographic dividend45 due to the and dysfunctional.28 Since then, a process to reform UN declining ratio of adults of non-working age to those of institutional architecture has started and the SUN working age will be greatly enhanced if those of working movement has emerged (panel 3), engaging more than age can secure market employment. Investments in 100 bodies within these organisations. SUN is governed mater­nal and early childhood nutrition that build human by a lead group of heads of state and other key stake­ capital can be framed as one way to secure this dividend. holders, but is focused mainly on galvanising national and country-led action (panel 3). Despite SUN’s substantial convening power, some Panel 4: Nutrition post-2015 external and country-level confusion exists about the role Despite the negligible presence of nutrition in the Millennium Development Goals (one of the SUN movement, the UN Standing Committee on indicator of one goal), inclusion of the underweight indicator has probably helped donors Nutrition, and the UN REACH programme (the latter two and development agencies justify increased attention to nutrition. This increased attention focus on UN level technical support and governance needs to be shown more fully in the next set of development goals to maintain the high coordination, respectively). Most individuals recognise levels of commitment and to guide action. We recommend the following approach: the continued value of the UN Standing Committee, 1 Find a location for nutrition as an equal partner within a likely goal, such as hunger but it remains in a fragile position and in need of reduction or poverty or health. This location in a vertical goal will raise the profile further internal reform (unpublished). Other important of nutrition global initiatives include the multinational 1000 days 2 Make sure that nutrition indicators—nutrition-specific and nutrition-sensitive—​ partnership, the partnership of G8 countries, and the are located within an additional number of vertical goals, such as gender equity, New Alliance for Food Security and Nutrition (consisting education, and employment. All these indicators should be linked across the different of several African countries and private companies). goals with the framework developed in paper one of this Series to generate a Meanwhile, the UN Secretary-General’s High Level Task horizontal nutrition goal Force on the Global Food Security Crisis and a revitalised 3 Endorse the six global targets for nutrition-specific indicators (including replacing of Committee on Food Security have emerged as important underweight with stunting) proposed by the World Health Assembly in 2012 bodies, coordinating UN and global responses to food Why not advocate for a separate nutrition goal? A stand-alone nutrition goal has many insecurity and comple­menting the role of existing UN desirable features: it makes ignoring of malnutrition harder and is likely to galvanise food and agriculture bodies. The World Health Assembly’s stakeholders in the nutrition (and possibly development) community and in the general agreement on six new global undernutrition targets to be public. However, extensive reading of the post-2015 scientific literature47 suggests that achieved by 2025 has also become an important part of support for a separate goal is insufficient. Building of support might still be possible, but the global nutrition focus; however, questions remain 46 nutrition lags behind other more high-profile disease burdens; stiff competition might come about the achievability of these targets and their from other constituencies who think they should have a separate goal (eg, water, sanitation, incorporation within the framework of the Millennium population); and the case has to be made as to why nutrition would not fit better into closely Development Goals (panel 4). related goals, such as food or health. There are risks to having a separate nutrition goal: The true potential of the SUN movement will be constituencies of the other goals might find it easier to ignore nutrition, and we know that realised through its application in each SUN country. reductions in malnutrition require their engagement. We judge our recommendation as Success of the movement will need maintenance of more feasible politically and if done strategically it could well leverage more resources for support and consensus amongst all SUN stakeholders, nutrition, especially from nutrition-sensitive programmes and interventions. and development of a strong sense of country-level ownership, the absence of which was a major reason for

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the failure of the multisectoral nutrition planning commitment to fighting hunger and malnutrition is experiments of the 1970s.48 As SUN’s global scope needed.54 For governments and donors, the Institute increases, so will demands for effective information and of Development Studies has developed a Nutrition knowledge management. Presentation of results that Commitment Index for cross-country and country- correlate SUN activities with measurable reductions in specific comparisons overtime (panel 5). For food and nutrition indicators will become a key focus. beverage manufacturers, a new index has been launched by the Global Alliance for Improved Nutrition to evaluate The need for horizontal coordination their policies, practices, and performance in contribution Different agencies, each with different and frequently to the reduction of undernutrition and overweight and competing agendas, need to work together if under­ obesity.55 The potential of mechanisms, such as social nutrition is to be reduced. Associations are horizontal (at audits and community monitoring, to promote account­ the same level of government) and vertical (at central, ability and improve the provision of direct public services state, and district levels) and the potential for conflicting is clear50,56 and has been positively appraised,57 but has not agendas in all directions is substantial. A political yet been empirically tested for the provision of frontline analysis21,49 of the horizontal and vertical associations in nutrition services. Empirical evidence about the effect of Brazil, Peru, Ethiopia, Zambia, India, and Bangladesh such accountability mechanisms on the quality of care reached several conclusions regarding the roles of the and health facilities is weak, but encouraging.58,59 A trial executive branch of government and well-resourced of community-based monitoring of health service coordination bodies, the importance of narratives that link provision in Uganda showed a 33% reduction in nutrition with development, and civil society pressure mortality in children younger than 5 years and a signifi­ mechanisms. Another study of multisectoral (horizontal) cant 0·14 increase in weight-for-age Z score.60 coordination in Senegal and Colombia16 emphasised the importance of inclusiveness of institutions­ and stake­ Civil society engagement holders, incentives, and lateral (as opposed to top-down) Most of the roughly 100 organisations who have signed up leadership. SUN has sought to promote horizontal to the SUN movement are civil society organisations. coherence through establishment of multisectoral plat­ Their role in combating undernutrition is as multi-faceted forms to catalyse and enable comple­mentary, coordinated, and multi-functional as the sector itself, but the effect of and integrated action. However the data from six SUN citizen engagement is difficult to evaluate.61 Of the many countries show that convergence and coordination roles of these organisations, four stand out: (1) global and continue to be a challenge (panel 3, appendix). national advocacy to call attention to nutritional depriv­ ation and galvanise commitment to act, (2) ensuring of The need to strengthen accountability accountability for nutrition-relevant service coverage and Providers, governments, donors, and the private sector quality, (3) generation of context-specific knowledge about need strong mechanisms to incentivise and hold them accountable for the quality and effectiveness of any nutrition investment. Although the evidence base for Commitment nutrition lags behind the positive evidence base for a To reduce stunting faster 50 range of other sectors, investments to increase commit­ Data make commitments ment and accountability for nutrition services and transparent measure their effects could be one of the most rewarding Commitment Index applications of research to macro (commitment) and Nutrition Diagnostics micro (accountability) levels. Increases in nutrition com­ Outcomes Accountability mit­ment and accountability could be achieved through Accelerated reductions To incentivise improvements in stunting Methods for building of trialing and identification of various innovative new Data promote feedback commitment to reduce Data guide need for about performance methods and mechanisms (figure), including information undernutrition intensification of commitments and communication technology monitoring systems, Community score cards commit­ment indices, and social accountability mechan­ Real Time Monitoring isms. One such method is the PolicyMaker software for Responsiveness 51 analysis of the political economy of nutrition. Capacity to improve Indices of a country’s progress towards particular performance goals, such as the UN Human Development Index and Data guide change in strategy the International Food Policy Research Institute’s Global Hunger Index, are increasingly common in development Real Time Monitoring and, if methodologically sound, can be a useful focal point for civil society advocacy.52,53 The pros and cons of Figure: Examples of methods to improve the commitment, accountability, and responsiveness to such indices have been evaluated with the conclusion undernutrition reduction that a separate index that measures political will and Reproduced from reference 8, by permission of Palgrave Macmillan. www.thelancet.com 87 Series

Panel 5: The Nutrition Commitment Index Nutrition outcomes are the result of many factors that NCI ranks are set against a country’s nutrition outcome governments do and do not have control of. Climate change and indicators, we can see how the index might be used to guide associated droughts and floods, and cross-border issues such as resources. In countries where commitment is low and arms and drugs trading, mass migration, and capital flight can undernutrition rates are high, some resources need to be have enormous effects on nutrition outcomes. Conversely, the allocated towards strengthening of commitment. Where both commitment to nutrition can be generated and shaped by commitment and undernutrition rates are high, most resources governments, and should, if informed by evidence, be a positive can be allocated to the scale-up of and capacity to deliver force for future undernutrition reduction. If commitment can be nutrition programmes. measured, can it be used to strengthen accountability? Although the countries that do well on the NCI do have high The Nutrition Commitment Index (NCI) is the first attempt to levels of stunting, they have some of the fastest declines in measure government commitment to reducing rates of stunting rates over the past 20 years. The top 12 countries show undernutrition. The index combines secondary data for a decline in stunting rates between the 1990s and 2000s that is 12 indicators across three domains (spending, policies, and twice as high as the remaining countries. Additionally, the ranks legislation) at three levels (direct [nutrition-specific] show that the commitment to hunger reduction and the interventions, indirect [nutrition-sensitive] interventions, and commitment to malnutrition reduction are only weakly the fundamental drivers) to construct an overall index. The correlated: a commitment to hunger reduction does not 2012 NCI results rank, in order, Guatemala (most commitment automatically equate to a commitment to malnutrition to undernutrition reduction), the Gambia, Nepal, Mozambique, reduction. Future econometric work will rigorously explore the Bangladesh, Malawi, Brazil, Indonesia, Madagascar, Tanzania, associations between nutrition outcomes and nutrition Peru, and the Philippines as the top 12 of 45 countries for which commitment, with attention on other independent variables, recent data are available. India, the country which has a third of which could explain stunting and the time lags between the undernutrition burden, is in the bottom half of the changes in commitment and changes in stunting. Future For more on commitment to 45 countries on commitment to reduce undernutrition. The qualitative work will focus on whether and how the NCI helps reduce undernutrition and on appendix shows case studies for Peru and Malawi. When the mobilise commitment for undernutrition reduction. stunting trends see http://www. hancindex.org

key drivers of undernutrition and relevant remedial develop­ments increase the opportunity for the private options, and (4) implementation of nutrition programmes sector to contribute to acceleration of malnutrition and provision of delivery platforms to maximise scale-up reduction.­ For example, new private philanthropic and ensure equity by reaching the unreached. Organ­ support for develop­ment has expanded,67 logistics and isations should also be held accountable for their information and computer technology businesses have commitment and performance in reducing malnutrition. emerged, and m-health (health services using mobile The table outlines key roles and principles of civil society technologies) initiatives have flourished, with benefits to and private sector engagement in nutrition. service delivery and care management.68 New forms of public–private partnerships have emerged in the health Private sector engagement: maximising potential and sector from which lessons can be learned about how to managing risks identify a balance of interests and incentives among The scale, know-how, reach, financial resources, and partners.69 As a result of these many public and private- existing involvement of the private sector in actions that sector intersections, the interest of the public sector determine nutrition status is well known. The share of towards business involvement in undernutrition efforts food and health care purchased through the market is has increased substantially. The SUN Business Network increasing steadily, at all levels of income. This increase is one indication of this change in interest.70 has partly taken place because malnutrition exists at all The fourth paper in the 2008 Lancet Series acknow­ income quintiles and because companies are looking to ledged the “inextricable” role of the private sector and its the base of the pyramid—ie, to the poorest socioeconomic importance, but also called for additional evaluation of groups62,63—to expand market share64 if the initial market effectiveness and documentation of best practices.71 size is large enough.62,65 Private sector involvement in However, although the private sector is now even more food and health-care choices goes well beyond the important in the national nutrition system, too few large multinational food and pharmaceutical companies. independent and rigorous evaluations have been done of Agri-food businesses, medium-scale and small-scale the effectiveness of involvement of the commercial processors­ of staple foods, and private health networks sector in nutrition. In the absence of such evaluations, now have an active involvement in the production, distrust of the private sector, especially the food industry, marketing, and consumer choice in the purchase of food remains high and is somewhat linked to the decades- and other nutrition-relevant goods and services.66 Other long tension related to the marketing of breast-milk

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Civil society Private sector Framing, generation, and Surveillance to generate data showing severity and distribution of Generation of evidence about the positive and negative effects of communication of knowledge and undernutrition private sector and market-led approaches to nutrition evidence Global and national advocacy; framing and packaging of information to Building of recognition of how the private sector already strongly galvanise commitment and push nutrition up the development agenda determines nutrition status (food, pharmaceutical sectors, health care) Assurance of (cost-shared) monitoring and evaluation and absolute transparency of any public–private endeavour (including open data and open-access research) Political economy of stakeholders, Assurance of accountability of different stakeholders (including civil The public sector (elected governments) should set a regulatory ideas, and interests society organisations themselves) for coverage, quality, and equity of framework and policy direction; national nutrition plans are needed actions to reduce undernutrition Need to positively shape the substantial and existing effect of the Contribute to multistakeholder platforms for decision making (eg, private sector, to harness innovation (eg, mobile health and other in-country support of the Scaling Up Nutrition movement) information and communication technologies in nutrition), and to Strengthening of the voice of communities, women, and children explore any comparative advantage in goods and service delivery Capacity (individual, organisational, Extra layer of capacity to deliver services and reach marginalised Harness extensive private sector resources (including consumer systemic) and financial resources communities spending) by creation of demand-side and supply-side incentives for Ability to raise financial resources through effective public campaigning nutritious foods and provision of health care and sanitation services (eg, public–private partnerships for new nutritious products, the potential for cobranding, and price guarantees) Improved public sector and private sector capacity to understand the potential contributions, opportunities, weaknesses, and threats

Table: Key roles and principles of civil society and private sector engagement in nutrition substitutes in developing countries and sugar-sweetened health,77–79 which suggest that such solutions can be beverages and fast foods worldwide.72 Much of the identified on the basis of sufficient trust and verification. private-sector dialogue centres around the International Such experiences suggest that some urgency exists towards Code of Marketing of Breast-milk Substitutes (ie, how to building of trust, especially around infant feeding. Recom­ enforce it and the extent of its domain73,74) and around men­dations for building of trust in companies manu­ whether the Codex Alimentarius food and nutrient facturing infant formula feeds include establishment of a standards give businesses too much freedom to public register of meetings between companies and downgrade nutrition concerns.75 Some commentators governments about the International Code of Marketing of have argued that particular inter­pretations of the code Breast-milk Substitutes, strengthening of whistleblowing have almost completely driven the private sector out of procedures within companies, and implementation of efforts to improve the nutrition of children aged prevention of code violations into the job descriptions of 6–24 months.73 But caution is essential in view of the companies’ senior representatives in each country.74 continued code violations by several large-scale private- Governments need to play their part by enshrining the sector enterprises.74 code and subsequent resolutions into national law, and A troubled history combined with continued violations putting independent, transparent, and effective monitor­ makes it increasingly difficult for the private sector to be ing mechanisms in place. a major contributor to the collective creation and sustenance of momentum for malnutrition reduction. Capacity and resources This sector has yet to earn the trust of some groups of the Leadership in nutrition nutrition community. In view of the needs and the All the nutrition success stories—eg, in Brazil, Peru, considerable resources, effect, and convening power of Vietnam, and Thailand—have strong and effective the private sector, this opportunity might be missed. networks of national nutrition leaders at their core.21,80 Additionally, opportunities exist for collaboration around For undernutrition reduction to be sustained, nutrition advocacy, monitoring, value chains, technical and leaders at all levels should be able to forge strong scientific collaboration, and fortification of staple foods alliances (across and between government, civil society, that are uncontentious and deserve further exploration. and the private sector), take timely and decisive action, When the interests of different participants are not and create and be subject to strong accountability. perfectly aligned and when substantial information and Enhancement of effective leadership needs investment power asymmetries exist, such as between large and yet only a handful of courses in nutrition leadership corporations and under-resourced governments, the are offered worldwide. Every year, the African Nutrition search for win–win solutions for undernutrition and Leadership Programme, an African-led initiative, overweight and obesity is a matter of governance arrange­ enrolls 30 participants for 10 days81—less than one ments: how rules are set, monitored, and enforced. professional per African country per year. No nutrition Lessons need to be learned from the long experience of the leadership programme exists in south Asia; however, regulation and legislation of fortified foods76 and from the UNICEF India’s engagement with young political experiences of public–private partnerships in international leaders through the Citizens’ Alliance Against www.thelancet.com 89 Series

Malnutrition seeks to strengthen political leader­ship. Creditor Reporting System, which is maintained by the Panel 6 summarises research done to identify what Development Assistance Committee of the Organisation makes a champion in nutrition. for Economic Cooperation and Development,­ show that Leaders and champions in nutrition need systemic and a substantial proportion of spending designated as nutri­ organisational capacity to create and sustain nutrition tional, is actually being spent on non-nutrition projects. policy and institutional change. Again, civil society can Similarly, much nutrition spending is in categories that play a strong part in this aspect as shown, for example, in are not nutritional.93,94 Data for donor spending on Peru where civil society champions were linked with nutrition often do not match those of governments political and financial decision makers (appendix). (unpublished). However, cost–benefit estimates are quite favourable. Understanding of the financial resources available to build With assumptions about the 11% uplift in income commitment for nutrition attributable to prevention of a third of stunting by age A focus on three areas is needed to make the case for 3 years, and about the 5% discount rate of future benefit additional resources to build and sustain momentum for streams, average cost–benefit estimates have been undernutrition reduction: the cost, an understanding of generated for 20 countries,6 with a median ratio of 18 present resource flows to nutrition, and more and better (Bangladesh). These ratios compare extremely favour­ estimates than presently exist of benefit to cost ratios for ably with other investments for which public funds nutrition investments at the country level. Answers to compete.95 Findings from the COHORTS study96 these questions could help convince financial analysts in reinforce the consensus that the first 1000 days is the the public and private sectors to invest. Estimations for key window of opportunity for investments. With data the SUN movement clearly show the costs of addressing from five countries, the COHORTS investigators undernutrition via nutrition-specific interventions.92 reported that the growth effects on human capital are More work is needed to contextualise and specify these largest at age 2 years. The most powerful way of costs for different countries and this work is ongoing. building commitment to increased resource allocation Unfortunately, investments in nutrition are hard to track to nutrition could be shown in the example set by because of the weak designation of donor and govern­ countries that have achieved scale-up. The three case ment spending. For example, analyses of data from the studies identified in the appendix provide examples of

Panel 6: What makes a nutrition champion? In seeking to achieve large-scale, systemic changes to address context of fragmentation and competing interests between undernutrition, several initiatives have recognised the and within various groups of stakeholders.23,82,86,87 important role of key individuals—leaders, champions, Preliminary findings show that these individuals have, in catalysts, and policy entrepreneurs—in the development of addition to extensive knowledge and experience in nutrition, 21,25,82,83 beneficial policy changes. Because level of change does relatively strongly developed stakeholder awareness and not necessarily correspond to levels of formal power, visibility, perspective awareness. They show an understanding of the ambition, or technical knowledge, research is being done to stakeholders relevant to nutrition policy processes and the identify and better understand the capacities and attributes of associations among them, and tend to view the properties of the individuals who have substantially contributed to policy their own and others’ perspectives as perspectives with advances for nutrition. This research is based on principles and complex contributory causes. Patterns of sense making concepts from complexity science and adult development. generally shape one’s goals and activities,88–90 and the catalytic Through network and power mapping and consultations with individuals identified in this study tended to identify ways in key informants, relevant stakeholders were identified in Kenya which shifts in stakeholder views and associations can lead to and Bangladesh (about 75 stakeholders per country) and positive outcomes; genuinely adapt behaviour, language, and semi-structured interviews were done with a purposive framing of issues to different stakeholders; and focus on sample of these stakeholders (30 in Kenya and 24 in establishment of associations of mutual trust, rather than Bangladesh). These interviews provided information to assess unidirectional forms of influence. This research, led by the For more on the Transform the attributes of the interviewee and other influential Transform Nutrition consortium), is ongoing and will continue Nutrition consortium see http:// stakeholders (ie, self-reporting and peer-reporting) and in Ethiopia and India. Future research will focus on the ways to www.transformnutrition.org provided further insights into network and power dynamics move beyond identification and assessment of champions to and case studies. In Kenya and Bangladesh, this research evaluating ways of supporting them, including through training shows that a handful of catalytic individuals, well-connected and capacity building, curricula development, public 84,85 and trusted in their formal and informal social networks, recognition and support for identified champions (eg,through have played a crucial part in transfer of information, changing awards and scholarships); and the development of competency of perceptions, and resolving of conflicts; achievements that frameworks and institutional and workplace incentives.91 have proven essential to advance the nutrition agenda in the

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what can be done to improve nutrition. A few SUN Monitoring of programme coverage countries should show that increased commitment can Inherent in the SUN process is the acknowledgment that be turned into real results—such examples will act as a programme coverage of nutritionally vulnerable popu­ spur for many others. lations has to increase from very low levels; how­ ever, routine mechanisms to monitor nutrition-related Conversion of momentum into results inter­vention coverage worldwide are poorly designed. Knowledge and evidence Research of child survival100 has shown the large gap in Building of momentum for undernutrition reduction is scale-up of evidence-based interventions for maternal, not an easy task, nor is it sufficient; such momentum newborn, and child survival, many of which have sub­ needs to be translated into ground-level results. Again stantial benefits for nutrition, but several nutrition the three dimensions of an enabling environment come indicators are not yet embedded in these monitoring into play: knowledge and evidence about how to scale up processes. WHO’s Nutrition Landscape Information interventions in an effective way, the political economy System123 needs to be strengthened by generation of a behind the interplay between national and subnational consensus on, and expansion of the range of, inter­ levels of government, and the capacity and resources ventions to be tracked. needed to scale and expand coverage of programmes while retaining cost-effectiveness. Programme evaluations to learn and improve Programme evaluations play a crucial part in inform­ Implementation research: what works, why, and how? ing the scale-up, reconfiguration, or cessation of pro­ Despite calls to action,97,98 and by stark contrast with the grammes. Solid guidance now exists to bring rigour to Countdown to 2015 report on maternal, newborn, and evaluations of nutrition programmes.52,100,124–126 This gui­ child survival,99 no systematic process is in place for dance is needed to create solid ground for evaluation of collation of the implementation-related evidence base the progress, and pathways to progress, of nutrition about how to scale up the vast array of nutrition-specific interventions,110,127,128 with theory-driven and qualitative and nutrition-sensitive interventions with quality and evaluations exploring the whys and hows of progress and equity. Development of this scientific literature needs the extent.100,129 Analyses of effectiveness and operational careful attention to several factors, but perhaps most evaluations of innovations that are introduced into importantly, needs a relentless focus on unpacking of scaled-up programmes, or of the process of scale up of programme impact pathways to effects71,100,101 and docu­ innovative programmes from small-scale pilots to a large menting of contextual factors that affect implemen­ scale, are essential, but challenging. tation. Comprehensive frameworks already exist to provide insights into the types of process-related and Learning during crisis contextual factors that need to be further studied Increases in the frequency of natural disasters130 and the through implemen­tation research. A process convened persistence and repeated cycles of conflict131 raise by the New York Academy of Sciences and WHO for humanitarian needs and stifle progress in reduction of setting of research agendas in nutrition emphasises undernutrition in fragile contexts. The need for effec­ crucial gaps and a framework to undertake implemen­ tive surveillance; early warning; mitigation; and timely, tation research in nutrition.102 Examples of such research appropriate, and effective responses to nutrition-related have been emerging in the form of feasibility studies crises is greater than ever. Yet little new evidence has been and formative research,103–106 operations research and generated of the effectiveness of emergency interven­ process evaluations,107–111 and costing studies.112–114 How­ tions since the first Lancet Series was published—partly ever, the scientific literature about implementation because of persisting ethical concerns and conceptual through delivery platforms, such as community-based and practical difficulties posed by research in such or health-facility-based programmes, is more developed situations.132 The time has come for increasing recognition than is that of the use of mass media or market-based of government accountability to lead in the provision of approaches to scale up interventions.115,116 services that are needed to meet short-term emergency- Much implementation research is from small-scale related spikes in demand.133 This situation creates a interventions, as opposed to large-scale programmes or growing tension between stakeholders who are driven by interventions, for which the challenges to ensurance of the humanitarian imperative to deliver timely and quality, intensity, equity, and coverage are different and effective assistance, and those who seek to strengthen need various factors to operate in concert.117–122 Analyses government systemic capacity to lead general efforts to of scaled-up programmes or of scale-up of small area or scale up nutrition-related interventions and services. A pilot interventions raise several challenges—eg, estab­ pertinent example is the community-level treatment of lishing of counterfactuals, assurance that real-time wasting, which in the past decade has moved from being process documentation captures nuances of organi­ a programme led by non-governmental organisations, to sational changes that facilitated or hampered scale-up, a service integrated within national health systems, which and that research generated is of a publishable quality. is intended to be accessible to children in need throughout www.thelancet.com 91 Series

the year.134 How to enable such systems to protect and nutrition initiatives in the past (eg, LINKAGES) and of reinforce the resilience of populations in fragile contexts, some health-sector initiatives (eg, Integrated Manage­ and to create a surge in response to increases in acute ment of Childhood Illness), published works of what is needs, is still a major challenge. needed, and how to achieve integration, are scarce. Integration of nutrition into other sectors, which are less Political economy and governance oriented to nutrition, is hampered by issues related to Subnational governance motivations, capacities, and clear guidance.20 Therefore, Just as building and sustaining of commitment is a building of experiential learning and systematic evidence political process, so too is conversion of momentum into about processes related to intersectoral and multisectoral results. Political scientists often conclude that most integration of actions is urgently needed to reduce policy is formulated at the front line, and the situation undernutrition. should be no different for efforts to reduce undernutrition. Findings from the six country nutrition governance Private sector engagement study21,49 suggest that in addition to the key ingredients Several promising areas for private sector engagement in for building of momentum, a further five are crucial to nutrition value chains have been summarised in the generate change: (1) local government capacity to deliver past few years.66,140 Similarly, many promising non-peer effective nutrition services, (2) local politicians who care reviewed case studies exist about how food fortification about nutrition and are empowered via decentralised not only generates sales and reputational gains for budgets and knowledge that nutrition can be a vote businesses, but also nutritional benefits via increased winner, (3) timely data for undernutrition, (4) nutrition consumption of fortified foods.141,142 The potential of other funding channelled through one funding mechan­ types of private sector companies to contribute to nutrition ism rather than fragmented funding streams, and scale-up is also considered important (eg, via mobile (5) earmarked and protected nutrition funding commit­ technology providers). A major constraint in realisation of ments and exploration of new revenue streams. this potential is the dearth of independent peer-reviewed The findings for local government incentives and studies of such activities and the com­plete absence of any capacity are highly relevant because many countries in review of the available evidence, although a review is Asia and sub-Saharan Africa are rapidly moving to underway by the Trans­form Nutrition consortium. decentralised political, administrative, and financial Of peer-reviewed studies relating to the first 1000 days systems. Decentralisation necessitates building of of life, one noted that marketing and selling of multi­ commitment­ and capacity at various political and nutrient powders in China to the caregivers of children bureaucratic levels at which decisions are made and aged 6–24 months reduced the risk of anaemia by 87%.143 resources allocated. Although scientific literature is Another reported decreases in iron and vitamin A emerging for decentralisation of health systems,77,135 the deficiency in children aged 6–35 months in western research base is limited to a handful of studies.20,27,135–137 In Kenya from the sale of multinutrient powders via Vietnam for instance, the role of provincial planning for community vendors.144 The private sector has a part to nutrition has been identified as an important bottleneck play in the provision of fortified foods that could assist in to translation of national policy intent and frameworks addressing undernutrition. Attention should be paid to, into plans and actions at the provincial level.27 and guidance be given to, the appropriate marketing of complementary foods for young children older than Intersectoral action 6 months, that both protects breastfeeding and allows for The wide recognition that action from several sectors is caregivers to make informed choices from available needed to address nutrition has gained momentum, and fortified complementary foods. several country governments are implementing multi­ Beyond direct private-sector support through core sectoral and intersectoral plans. However, few examples business operations and investments, many individuals exist of the factors and processes that should align to have argued that the sector has a much broader enable intersectoral action to generate scaled up responsibility to ensure the health, nutrition, and welfare nutrition-specific interventions and a nutrition-sensitive of their workforces and the larger communities that are household and community environment in which dependent upon them. The creation of shared value provisions for water, sanitation, social protection, health approach is intended to be achieved through creation of care, and food security are ensured. Research so far has economic value via company’s policies and operating been of intersectoral planning and action at a policy practices, with simultaneous advancement of the level,16,138 whereas several questions remain about how economic and social conditions in the communities in best to achieve such outcomes at subnational and local which it operates.145 Results of this approach should be levels. Even integration of nutrition actions within the carefully monitored, and best practices underscored, health sector (which is arguably the most ready to absorb through initiatives such as the Ethical Trading Initiative, nutrition actions) often raises many challenges.139Although which none of the leading food and beverage companies such integration has been the focus of several large-scale on the Access to Nutrition Index have signed up to.146

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On the basis of the suggested guidelines in the table, and of insights from other sectors,147 several factors are Panel 7: Key issues and core elements of nutrition-relevant capacity key to maximising the private sector’s potential con­ Individual capacity: methods and skills tribution to nutrition status with minimisation of the • Performance capacity: are the methods, money, and equipment, for example, risks to vulnerable populations: (1) understand the bottle­ available to do the job? necks that the private sector could help overcome; • Personal capacity: are staff sufficiently knowledgable, skilled, and confident to (2) incentivise positive roles and the development of perform properly? Do they need training, experience, or motivation? Are they business models that support them; (3) regulate ongoing deficient in technical, managerial, interpersonal, or specific role-related skills? activities for potential risks to nutrition, with strong monitoring processes; (4) be transparent about the role Organisational capacity: staff and infrastructure of the private sector in the policy process and any • Workload capacity: do enough staff have broad enough skills to cope with the potential conflicts of interest; and (5) independently workload? Are job descriptions practicable? Is skill mix appropriate? evaluate public–private partnership activities and make • Supervisory capacity: are reporting and monitoring systems in place? Are lines of the data and analyses publicly available. accountability clear? Can supervisors physically monitor all staff? Are effective incentives and sanctions available? Capacity and resources • Facility capacity: are training centres, offices, and workshops big enough, with the Sequencing and prioritisation of nutrition actions right staff in sufficient numbers, to support the workload? Ideally, all the links in the nutrition chain would be • Support service capacity: are there training institutions, supply organisations, addressed at the same time; if this is not possible for building services, administrative staff, research facilities, quality control services? resource, capacity, or political reasons, priorities need to Systemic capacity: structure, systems, and roles be set. A frequently heard complaint from ministries of • Structural capacity: are there decision-making forums or multistakeholder platforms finance in high-burden countries is what to do first when at which intersectoral discussion of nutrition could take place, consensus is it comes to stimulation of economic growth? In response generated, collective decisions are made and recorded, and individuals called to to this question, a group of researchers at Harvard account for non-performance? University and elsewhere have developed an economic • Systems capacity: do flows of information, money, and managerial decisions happen 148 growth diagnostics process. The process combines in a timely and effective manner? Are proper filing and information systems in use? evidence about the technical (what works here?), capacity Can private sector services be contracted as needed? Is there good communication (can we scale-up?) and, importantly, the political (are with the community? Are links with non-governmental organisations sufficient? there any windows of opportunity for change?) aspects. • Role capacity: have individuals, teams, and committees been empowered to make The rationale is that sequencing matters and some issues decisions to ensure effective performance—eg, regarding schedules, money, and can be highly rate-limiting. With nutrition, specific staff appointments? factors need to be in place for specific processes to take place. Similar nutrition diagnostic methods need to be developed to help prioritise nutrition plans of action. implementers who in turn will be mentors for the generation after that. Capacity for scale up Several types of capacity are needed for effective scale up Financial resources to support scale up of priority nutrition interventions (panel 7149). Insights The second paper in this Series estimates that at least can also be gained from the wider scientific literature of Int$9·6 billion per year will be needed to scale up human resources in health systems research,119 including the 11 proven nutrition-specific interventions for the the need to agree on exactly what should be scaled up, 34 countries that account for 90% of the burden of consider lessons on scale-up from related areas, honestly stunting.5 If this scale-up could be achieved, at least a document experiences, and understand that scaling up quarter of present stunting cases could be addressed.7 of interventions requires a scaling down of certainties, Paper two suggests that roughly $3 billion to $4 billion of and inclusiveness and building of relations to sustain this total could come from external donors and, as SUN momentum. Finally, we suggest that the existence of requires, would work together with established guidelines poor quality training programmes and academic for aid effectiveness, including the importance of country curricula in nutrition in regions of poor quality service ownership and the avoidance of aid dependency. Scaling delivery is not a coincidence.150–153 Many of these studies up of nutrition programmes continues to be the place to are from high-burden regions and they find the training start to reduce malnutrition; however, we need estimates and curricula to be outdated, impractical, and misaligned of what it would take to make agriculture, social protection, with local nutrition priorities. We reiterate the conclusion education, and women’s empowerment policies and pro­ of the 2008 Series that much more needs to be done to grammes, for example, sufficiently nutrition-sensitive to strengthen strategic and operational capacity.71,154 Govern­ have a further substantial effect on malnutrition rates. ments and donors should allocate more resources to Paper three provides some suggestions about how to establish a more sustainable foundation for nutrition reallocate nutrition-sensitive programme resources to implementation by training the next generation of achieve win–win solutions. The extra resources needed to www.thelancet.com 93 Series

Panel 8: Research priorities to build commitment and accelerate progress Framing, generation, and communication of knowledge • When has private sector involvement enhanced nutrition and evidence status and how? Creation and sustaining of momentum for undernutrition reduction • Do effective accountability mechanisms contribute to • What types of issue framing approaches and narratives yield improved nutrition outcomes? attention to nutrition in different contexts? • What are effective incentives to help mainstream nutrition • What advocacy and policy engagement strategies are most into potentially nutrition-sensitive sectors? effective at galvanising political attention to nutrition? Capacity (individual, organisational, systemic) and • What types of evidence are most powerful for creation versus financial resources sustaining of national and subnational attention to nutrition? Creation and sustaining of momentum for undernutrition reduction • Can real-time monitoring of nutrition outcomes and • What are the characteristics of nutrition policy champions? coverage lead to more responsive nutrition actions and What effect do university curricula and leadership training improved nutrition outcomes? investments have in creation of nutrition leaders? Conversion of momentum to effect on nutrition status • What types of institutional investments and capacity • How can nutrition interventions be mainstreamed and building activities yield the best systemic and strategic integrated into other sectors capacity for nutrition within national and subnational • What types of programme evaluations and operations organisations? research are crucial to enabling programmatic actions at • How should the resources allocated to nutrition-sensitive different stages in the life of nutrition investments? programmes be assigned to nutrition improvement? • What types of learning mechanisms best enable inclusive • To what extent can research on the costing of interventions stakeholder engagement with evidence? and the tracing of financial flows mobilise additional • What types of stakeholder engagement approaches can resources for nutrition and improve the effectiveness of enhance the demand for evidence of effect? resource allocation? Political economy and governance of stakeholders, ideas, • What methods are effective in helping to prioritise and and interests sequence nutrition actions? Creation and sustaining of momentum for undernutrition reduction Conversion of momentum to effect on nutrition status • What strategies are most effective at enabling multisectoral • What institutional and front line capacities are most coordination and strategic coherence for nutrition? important to enable scale-up of different types of direct • Which accountability strategies are most effective at nutrition interventions through community-based mobilising commitment at different levels of government progammes and the health sector? and society (eg, indices, scorecards, social audits, • How can nutrition-sensitive sectors operationalise their community monitoring)? interventions to achieve nutrition results for women and • In what ways can the private sector be regulated to protect children? and support exclusive breastfeeding? • Which new forms of resource mobilisation show the Conversion of momentum to effect on nutrition status greatest promise for improvement of nutrition status? • What aspects of decentralisation are most crucial for • Does prioritising and sequencing of simple nutrition actions enabling vertical translation of national guidance to (eg, vitamin A supplementation, micronutrients, treatment programmatic action? of severe acute malnutrition) create enabling conditions for • What types of roles can (and should) the private sector and closing gaps on more complex interventions (behaviour civil society have in supporting service delivery and scaling up? change interventions for infant and young-child feeding?).

incentivise such reallocations might well be modest, but and more analysis is needed about the variety and more experience and evidence are needed to identify the effectiveness of these mechanisms. surplus requirement. The allocation of scarce public We previously discussed private sector possibilities resources between nutrition and other activities (and for additional resources. For public sources, high- indeed among nutrition activities) will be guided by burden countries together with donors and multilateral political and technical considerations. Nutrition tends to organisations have a responsibility to increase allo­ have no institutional champion, hence the emphasis cations to nutrition-specific and nutrition-sensitive within SUN on institu­tional mechanisms to address this programmes. To do this within an official development issue, both formally (via multisector platforms) and assis­tance budget that has peaked, albeit with informally via the framing around movements. Other increasing tax revenues from high-burden countries,155 mechanisms for promotion and protection of nutrition will be politically challenging, hence the need to build spending exist, such as the example in Peru of embedding leadership, commit­ment, and accountability at national of nutrition within electoral commitments (appendix), and international levels.

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However, the gap is unlikely to be closed from these that interest in nutrition is locked into the post-2015 sources. Innovation is needed across all sectors to development settlement (panel 4). If nutrition is to be leverage private-sector and public-sector resources and embedded into broader development processes, the to generate additional public funding. The nutrition nutrition community needs to actively forge alliances sector can draw on several innovative ideas from with those for whom malnutrition reduction is not a top other sectors,156 including advance market contracts to priority and to do this in a politically aware manner. We promote invest­ment, market levies, and taxes, on either have drawn on a range of evidence in this report, both unhealthy externalities or external sectors, as in the academic and from the field. The academic evidence we airline ticket levy by UNITAID157 or the mining levy used is valuable, but much of it is from areas outside of funding health in Zambia. Nutritional impact bonds are nutrition. We call for more research of what defines another option, entailing the creation of a social impact enabling environments for nutrition. We also call for partnership fund by private investors, which receives more systematic ways to capture and share the learning public funds if key service delivery targets are met. In from policy and programme operations. Panel 8 shows this way, public funds catalyse and leverage private priority areas for research. investment for which the service providers bear the risk, Finally, the core problem itself is changing as the but also stand to generate additional revenue. Key to burden of disease caused by poor nutrition continues to the success of these schemes is the collection of cred­ shift from undernutrition to a double burden of ible metrics. More research and experimentation is undernutrition and overweight and obesity.7 Future desperately needed in this area. Lancet series on nutrition will have to pay much greater attention to this double burden than we have. But the Looking ahead disease burden attributable to child underweight remains In the past 5 years, the nutrition community has made substantial in many countries, in other words, there is an major progress, but it should be judged against the effect enormous unfinished agenda. emerging in the next 5 years and beyond. Momentum Contributors needs to be sustained and converted into lasting effects. All authors contributed to the conceptualisation and structuring of the SUN will reach its 1000th day when this Lancet Series is paper, and reviewed all drafts. SG led overall development and finalisation of the paper and appendix, and coordinated inputs of launched in June, 2013. Since SUN’s own launch in coauthors and contributors. He led on the enabling environments September 2010, the movement has substantially section, Scaling Up Nutrition (SUN) electronic consultation, and case elevated and energised the discourse on nutrition and studies; prepared the first draft of the conceptual framework; wrote the has changed institutional arrangements. In some coun­ sections about capacity, civil society, the abstract, and introductory and closing sections; contributed to other sections of the paper; and tries, the movement is beginning to catalyse resource prepared and submitted the final draft. LH first proposed to focus the mobilisation and programme alignment. Emphasis paper on the politics of nutrition and led on drafting the sections about should now escalate to action, translating commitment the wider context, financial resources, horizontal and vertical into results on the ground. SUN needs to build on its coordination, the private sector, the nutrition commitment index, and the post-2015 discussions; and had responsibility for construction of the commitment to be country led and results driven. To first complete draft of the paper. VM prepared background sections on enable this development, SUN should harness and private sector, SUN, civil society, and financing, which were used in the catalyse national leadership, capacity and resources, development of those sections, and made contributions to each draft. politics, and knowledge generation. Documented SUN PM wrote sections about implementation research and translation of commitment to action, and provided written inputs to the private sector proof-of-concept success stories are also needed to and enabling environment sections. NN prepared the accountability and galvanise further action. global governments sections and the Peru case study, contributed to the One clear overarching priority is the need to strengthen enabling environments section and coedited one of the first full drafts. strategic and operational capacity to scale up nutrition Four of the authors are researchers and one (VM) is a practitioner. The researchers combine expertise in nutrition, economics, politics, interventions and embed nutrition considerations in other sociology, and anthropology. All authors are embedded in the global sectoral actions. This point was emphasised in the 2008 policy community and all are very familiar with one or more country Lancet series and remains the case today.156 National and policy communities. All authors operate at the interface between policy, global resources need to be invested in the long term to practice, and research and three have done so since the 1980s. This is the basis for their collective knowledge. support capacity development, at individual, organ­ isational, and systemic levels. Leadership is needed to Maternal and Child Nutrition Study Group Robert E Black (Johns Hopkins Bloomberg School of Public Health, galvanise and spearhead action, and this again will need to USA), Harold Alderman (International Food Policy Research Institute, be seeded, funded, and nurtured. For too long the issue of USA), Zulfiqar A Bhutta (Aga Khan University, Pakistan), capacity has been recognised but over­looked—a convenient Stuart Gillespie (International Food Policy Research Institute, USA), excuse for failed plans. It is easy to neglect such issues Lawrence Haddad (Institute of Development Studies, UK), Susan Horton (University of Waterloo, Canada), Anna Lartey when constructing business plans to support nutrition (University of Ghana, Ghana), Venkatesh Mannar (The Micronutrient strategies and yet without sufficient capacity of the right Initiative, Canada), Marie Ruel (International Food Policy Research type at the right level, plans become hollow wish lists. Institute, USA), Cesar Victora (Universidade Federal de Pelotas, Fairly silent to date, the nutrition community needs to Brazil), Susan Walker (The University of the West Indies, Jamaica), Patrick Webb (Tufts University, USA). be a lot more engaged in the post-2015 process to ensure www.thelancet.com 95 Series

Series Advisory Committee 6 Hoddinott J, Alderman H, Behrman JR, Haddad L, Horton S. The Marc Van Ameringen (Global Alliance for Improved Nutrition, economic rationale for investing in stunting reduction. Washington, Switzerland), Mandana Arabi (New York Academy of Sciences, USA), DC: IFPRI, 2013. Shawn Baker (Helen Keller International, USA), Martin Bloem (United 7 Ruel M, Alderman H, and the Maternal and Child Nutrition Study Nations World Food Programme, Italy), Francesco Branca (WHO, Group. Nutrition-sensitive interventions and programmes. Lancet Switzerland), Leslie Elder (The World Bank, USA), Erin McLean 2013; published online June 6. http://dx.doi.org/10.1016/S0140- (Canadian International Development Agency, Canada), Carlos Monteiro 6736(13)60843-0. (University of São Paulo, Brazil), Robert Mwadime (Makerere School of 8 Haddad L. How can we build an enabling political environment to Public Health, Uganda), Ellen Piwoz (Bill & Melinda Gates Foundation, fight undernutrition? Eur J Dev Res 2012; 25: 13–20. USA), Werner Schultink (UNICEF, USA), Lucy Sullivan (1000 Days, 9 Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment USA), Anna Taylor (Department for International Development, UK), of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis Derek Yach (The Vitality Group, USA). The Advisory Committee provided for the Global Burden of Disease Study 2010. Lancet 2012; advice in a meeting with Series Coordinators for each paper at the 471: 2224–60. beginning of the process to prepare the Series and in a meeting to review 10 Pelletier DL, Porter CM, Aarons GA, Wuehler SE, Neufeld LM. and critique the draft reports. Expanding the frontiers of nutrition research: new questions, new Conflicts of interest methods, and new approaches. Adv Nutr 2012; 4: 92–114. REB serves on the Boards of the Micronutrient Initiative, Vitamin 11 Haddad L, Alderman H, Appleton S, Song L, Yohannes Y. Reducing Angels, the Child Health and Nutrition Research Initiative, and the child malnutrition: how far does income growth take us? Nestlé Creating Shared Value Advisory Committee. VM serves on the World Bank Econ Rev 2003; 17: 107–31. Nestlé Creating Shared Value Advisory Committee. The other authors 12 Headey D. Developmental drivers of nutritional change: declare that they have no conflicts of interest. As corresponding author, a cross-country analysis. World Dev 2013; 42: 76–88. Stuart Gillespie states that he had full access to all data and final 13 Masset E, Haddad L. Income growth and nutrition status: a critical responsibility for the decision to submit for publication. review of the estimated relationship. Brighton, UK: Institute of Development Studies, 2013. Acknowledgments 14 Headey D. Pro-nutrition economic growth: what is it, and how do I Funding for the preparation of the Series was provided to the Johns achieve it? Washington, DC: IFPRI, 2011. Hopkins Bloomberg School of Public Health through a grant from the 15 Benson T. Improving nutrition as a development priority: Bill & Melinda Gates Foundation. The sponsor had no role in the addressing undernutrition in national policy processes in analysis and interpretation of the evidence or in writing the paper and sub-saharan africa. Washington, DC: IFPRI, 2008. the decision to submit for publication. We thank the contributors for 16 Garrett, JL. Natalicchio M. Working multisectorally in nutrition: their specified contributions, and the Bill & Melinda Gates Foundation principles, practices, and case studies. Washington, DC: IFPRI, 2010. for financial support for the preparation of this paper. SG received some 17 Gillespie S, McLachlan M, Shrimpton R, eds. Combating funding from the Transform Nutrition Research Programme undernutrion: time to act. Washington, DC: World Bank, 2003. Consortium with UK aid from the UK Government. The development of 18 Hill R, Gonzalez W, Pelletier DL. The formulation of consensus on the Nutrition Commitment Index was made possible by support from nutrition policy: policy actors’ perspectives on good process. UK Aid and Irish Aid. The views expressed in this paper do not Food Nutr Bull 2011; 32: 92S–104S. necessarily reflect the UK Government’s official policies. Representatives 19 Hoey L, Pelletier DL. The management of conflict in nutrition of the Bill & Melinda Gates Foundation and the UK Department for policy formulation: choosing growth-monitoring indicators in the International Development took part in series preparation meetings. context of dual burden. Food Nutr Bull 2011; 32: S82–91. Neither donor had a role in conceptualisation, data collection, analysis, 20 Hoey L, Pelletier DL. Bolivia’s multisectoral Zero Malnutrition or drafting of the paper. program: insights on commitment, collaboration, and capacities. Many individuals have contributed to this paper beyond the coauthors. Food Nutr Bull 2011; 32: 70S–81S. We thank Jody Harris for the literature review of nutrition policy 21 Mejia Acosta A, Fanzo J. Fighting maternal and child processes and Jody Harris and Andrew Kennedy (both International malnutrition: analysing the political and institutional determinants of delivering a national multisectoral response in Food Policy Research Institute [IFPRI]) for support in the production of six countries. A synthesis paper. Brighton, UK: Institute of the report; Tom Barker, Jessica Meeker, Karine Gatellier, and Development Studies, 2012 Adrian Bannister (Institute of Development Studies [IDS]) for 22 Natalicchio M, Garrett J, Mulder-Sibanda M, Ndegwa S, organising the online SUN discussions in six countries; Voorbraak D. Carrots and sticks: the political economy of nutrition Mara van den Bold and Andrew Kennedy (IFPRI) for preparation of daily policy reforms. HNP Discussion Paper. Washington, DC: IFPRI and summaries of these discussions, and for other background work on The World Bank, 2009. SUN (appendix); Elise Wach and Dolf te Lintelo (IDS) for panels on 23 Pelletier DL, Frongillo EA, Gervais S, et al. Nutrition agenda setting, nutrition champions and Nutrition Commitment Index; Victor Aguayo policy formulation and implementation: lessons from the (UNICEF India) and Kavita Singh (IFPRI New Delhi) for the Mainstreaming Nutrition Initiative. Health Policy Plan 2012; Maharashtra case study, Andrew Kennedy for the Malawi case study, and 27: 19–31. Andres Mejia Acosta (IDS) for the Peru case study; and Victoria Sibson 24 Clark TW. The policy process: a practical guide for natural resources (Save the Children UK) for contributions on nutrition crises. professionals. 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Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis

Joanne Katz, Anne CC Lee, Naoko Kozuki, Joy E Lawn, Simon Cousens, Hannah Blencowe, Majid Ezzati, Zulfiqar A Bhutta, Tanya Marchant, Barbara A Willey, Linda Adair, Fernando Barros, Abdullah H Baqui, Parul Christian, Wafaie Fawzi, Rogelio Gonzalez, Jean Humphrey, Lieven Huybregts, Patrick Kolsteren, Aroonsri Mongkolchati, Luke C Mullany, Richard Ndyomugyenyi, Jyh Kae Nien, David Osrin, Dominique Roberfroid, Ayesha Sania, Christentze Schmiegelow, Mariangela F Silveira, James Tielsch, Anjana Vaidya, Sithembiso C Velaphi, Cesar G Victora, Deborah Watson-Jones, Robert E Black, and the CHERG Small-for-Gestational-Age-Preterm Birth Working Group

Summary Published Online Background Babies with low birthweight (<2500 g) are at increased risk of early mortality. However, low birthweight June 6, 2013 includes babies born preterm and with fetal growth restriction, and not all these infants have a birthweight less than http://dx.doi.org/10.1016/ 2500 g. We estimated the neonatal and infant mortality associated with these two characteristics in low-income and S0140-6736(13)60993-9 middle-income countries. Department of International Health, Johns Hopkins Bloomberg School of Public Methods For this pooled analysis, we searched all available studies and identified 20 cohorts (providing data for Health, Baltimore, MD USA 2 015 019 livebirths) from Asia, Africa, and Latin America that recorded data for birthweight, gestational age, and vital (Prof J Katz ScD, A C Lee MD, statistics through 28 days of life. Study dates ranged from 1982 through to 2010. We calculated relative risks (RR) and N Kozuki MSPH, Prof A H Baqui DrPH, risk differences (RD) for mortality associated with preterm birth (<32 weeks, 32 weeks to <34 weeks, 34 weeks to Prof P Christian DrPH, <37 weeks), small-for-gestational-age (SGA; babies with birthweight in the lowest third percentile and between the Prof J Humphrey ScD, third and tenth percentile of a US reference population), and preterm and SGA combinations. L C Mullany PhD, Prof J Tielsch PhD, Prof R E Black MD); Brigham and Findings Pooled overall RRs for preterm were 6·82 (95% CI 3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) Women’s Hospital, Boston, MA, for post-neonatal mortality. Pooled RRs for babies who were SGA (with birthweight in the lowest tenth percentile of USA (A C Lee); Saving Newborn the reference population) were 1·83 (95% CI 1·34–2·50) for neonatal mortality and 1·90 (1·32–2·73) for post-neonatal Lives and Save the Children mortality. The neonatal mortality risk of babies who were both preterm and SGA was higher than that of babies with USA, Washington, DC, USA (Prof J E Lawn PhD); Maternal either characteristic alone (15·42; 9·11–26·12). Reproductive and Child Health Centre, London School of Interpretation Many babies in low-income and middle-income countries are SGA. Preterm birth affects a smaller Hygiene and Tropical Medicine, London, UK (Prof J E Lawn, number of neonates than does SGA, but is associated with a higher mortality risk. The mortality risks associated with T Marchant PhD, B A Willey PhD); both characteristics extend beyond the neonatal period. Differentiation of the burden and risk of babies born preterm Faculty of Epidemiology and and SGA rather than with low birthweight could guide prevention and management strategies to speed progress Population Health, London towards Millennium Development Goal 4—the reduction of child mortality. School of Hygiene and Tropical Medicine, London, UK (Prof S Cousens DipMathStat, Funding Bill & Melinda Gates Foundation. H Blencowe MRCPCH, B A Willey); MRC-HPA Centre for Introduction Few studies in LMICs have investigated differences in Environment and Health, Department of Epidemiology An estimated 20 million infants every year are born with mortality by extent of prematurity, IUGR, or the two in 1 3,4 and Biostatistics, School of low birthweight (LBW; <2500 g), and these infants have combination, or mortality risk in infants who are SGA Public Health, Imperial College an increased risk mortality in the first year of life. The pri­ stratified by gestational age.5–10 Examination of the London, London, UK mary causes of LBW are preterm birth, intrauterine mortality risk by degree of prematurity and SGA as a (Prof M Ezzati PhD); Division of Women and Child Health, growth restriction (IUGR), or a combination of the proxy for IUGR might be crucial in understanding the Aga Khan University, Karachi, two. Of 135 million children born in low-income and attributable disease burden, especially because regions Pakistan (Prof Z A Bhutta PhD); middle-income countries (LMICs) in 2010, an estimated such as south Asia have a reported SGA prevalence of Faculty of Infectious Disease 29·7 million were born both term and small-for-gestational- about 40%.11,12 Such mortality risk estimates and and Tropical Diseases, London School of Hygiene and Tropical age (SGA), 10·9 million were born preterm and appropriate- attributable burden could enable the specific targeting of Medicine, London, UK for-gestational-age, and 2·8 million were born preterm and these disorders with appropriate interventions to more (Tanya Marchant); Malaria SGA.2 Risk factors and interventions to reduce the number effectively save lives. Centre, London School of of babies born SGA might differ from those to reduce the The Child Health Epidemiology Reference Group Hygiene and Tropical Medicine, London, UK (T Marchant, number of babies born preterm. The survival and growth (CHERG) previously examined the risk of infant B A Willey, D Watson-Jones PhD); patterns of preterm or growth-restricted newborn babies mortality associated with term-LBW as a proxy for University of North Carolina are not well described in LMICs and the contribution to IUGR.13 However, term-LBW excludes growth-restricted School of Public Health, NC, USA mortality of non-LBW babies (≥2500 g) who are preterm or infants weighing more than 2500 g and high risk (Prof L Adair PhD); those with IUGR in such settings is unknown. infants born both preterm and SGA, and such

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associations between mortality and SGA-non-LBW or (moderate preterm), and 34 weeks to less than 37 weeks Programa de Pós-graduacao em SGA-preterm have not been well described in LMICs. (late preterm).14 Epidemiologia, Universidade With more population-based studies in LMICs now Weight was analysed if measured within 72 h. SGA was Federal de Pelotas, Pelotas, RS, Brazil (Prof F Barros PhD, collecting data for gestational age in addition to birth­ defined as birthweight below the tenth percentile of a M F Silveira PhD, weight, the CHERG identified an opportunity to standard optimal reference population for a given Prof C G Victora PhD); Programa assess the mortality risk of SGA and preterm on early gestational age and sex. Appropriate-for-gestational-age de Pós-graduação em Saúde e Comportamento, neonatal, late neonatal, neonatal, post-neonatal, and (AGA) was defined as above the tenth percentile. WHO Univertsidade Católica de infant mortality. previously recommended data in a study by Williams and Pelotas, Centro, Pelotas, colleagues (collected in California from 1972 to 1976) as the RS, Brazil (Prof F Barros); Methods reference.15 We chose the more recent and commonly cited Department of Nutrition, 16 Harvard School of Public Health, Dataset identification Alexander reference, which includes 3 134 879 nationally Boston, MA, USA We searched Medline, WHO regional databases (African representative, multi-ethnic births in the USA in 1991. (Prof W Fawzi DrPH); Department Index Medicus, LILAS, EMRO), bibliographies of Because that dataset provided data at only the tenth of Epidemiology, Harvard School sentinel articles and reviews, and grey literature to percentile, we identified another dataset (Oken and of Public Health, Boston, MA, 17 USA (Prof W Fawzi, A Sania PhD); identify potential datasets from low-income and middle- colleagues ) based on US data from 1999–2000 Department of Global Health income countries that recorded data for gestational age (6 690 717 births) that provided Z scores. We created two and Population, Harvard School and birthweight, and systematically recorded vital status categories of SGA using a combination of these two of Public Health, Boston, MA, from delivery through at least 28 days of life. The most reference popu­lations:16,17 the tenth percentile of Alexander16 USA (Prof W Fawzi); Pontificia 17 Universidad Católica de Chile, recent search was done on Feb 22, 2010. We applied no to the third percentile of Oken and colleagues, and the School of Medicine, Santiago, no date or language restrictions. Search terms included lowest third percentile of Oken and colleagues. AGA Chile (Prof R Gonzalez MD); “preterm or SGA”, “neonatal or infant mortality”, and included large-for-gestational-age (LGA) infants (≥90% Clínica Santa María, Santiago, “developing country” (see appen­dix for detailed search birth­weight for gestational age). However, in these Chile (Prof R Gonzalez MD); Zvitambo, Borrowdale, Harare, terms). CHERG investigators­ also identified additional datasets, the prevalence of LGA was very small and their Zimbabwe (Prof J Humphrey); datasets that were not retrieved in our search. We inclusion in the reference population likely had very little Department of Food Safety and excluded datasets for the following reasons: greater than effect on mortality risk. Food Quality, Ghent University, 25% missing data for birthweight or gestational age, or We created four mutually exclusive exposures to capture Ghent, Belgium (L Huybregts PhD, loss to follow-up; measured weight only after the first interaction between preterm (<37 weeks) and SGA (<10%): Prof P Kolsteren PhD); Woman week of life; did not have systematic follow-up of vital term and appropriate-for-gestational-age (as reference), and Child Health Research status in the first month of life; determined gestational term-SGA, preterm and appropriate-for-gestational-age, Center, Department of Public age in months or by fundal height; or when we deemed and preterm and SGA. We defined mortality as early Health, Institute of Tropical Medicine, Antwerpen, Belgium gestational age deter­mination inaccurate or poorly neonatal (birth to 7 days), late neonatal (8–28 days), (L Huybregts, Prof P Kolsteren, linked to birthweight (appendix). We aimed to include neonatal (birth to 28 days), post-neonatal (29–365 days), D Roberfroid PhD); ASEAN only datasets that were population-based, representing and infant (birth to 365 days) mortality. For late neonatal Institute for Health all deliveries arising from specific geographical or and post-neonatal infant mortality, the denominators were Development, Mahidol University, Nakhon Pathom, catchment areas, whether home-based or facility-based. infants alive at the start of the interval of interest with vital Thailand (A Mongkolchati PhD); We excluded stillbirths from the analyses of these status available through the end of the interval. Vector Control Division, Ministry cohorts. We approached principal investigators to do a of Health, Kampala Uganda set of standard analyses themselves, or to share their Analysis of individual datasets (R Ndyomugyenyi PhD); Fetal Maternal Medicine Unit, Clinica data with the CHERG working group to do the analyses. The same analysis was done on each dataset. We used an Davila, Santiago, Chile Datasets that were shared with the working group did algorithm developed by Alexander and colleagues16 to (J K Nien MD); Faculty of not contain personal identifiers and were therefore exclude infants with incompatible birthweight-gesta­ Medicine, Universidad de Los Andes, Santiago, Chile (J K Nien); deemed exempt by the Johns Hopkins Bloomberg tional age combinations. Gestational ages of less than Institute for Global Health, UCL School of Public Health institutional review board. 24 weeks and more than 48 weeks were also excluded. We Institute of Child Health, Datasets analysed by the original study investigators calculated the prevalence of LBW, preterm, SGA, and the London, UK (D Osrin PhD, were covered under existing institutional review board overlap of these disorders for each dataset. We calculated A Vaidya PhD); Department of Global Health, George approvals. relative risks (RRs) and risk differences (RDs) for early, Washington School of Public late, neonatal, post-neonatal, and infant mortality asso­ Health and Health Services, Exposure definitions ciated with preterm and SGA categories. George Washington University, If more than one gestational age measurement was RRs were adjusted for all confounders available in Washington, DC, USA (Prof J Tielsch); Centre for Medical available we used estimates in the following order of each dataset (including occupation of head of house­ Parasitology, Institute of preference: ultrasound, best obstetric estimate (com­bin­ hold, land ownership, years of maternal and paternal International Health, ation of ultrasound, date of last menstrual period, and education or literacy, and maternal age and parity). We Immunology, and Microbiology, neonatal clinical exam), last menstrual period, or clinical did adjusted analyses on 13 of the 20 datasets. University of Copenhagen and Department of Infectious examin­ation of the infant within 72 h of birth. Prematurity Regression coefficients for the primary associations of Diseases, Copenhagen University was defined as a gestational age of less than 37 completed interest were attenuated at less than 10% in all datasets Hospital, Copenhagen, Denmark weeks. We categorised prematurity into less than except for one,32 for which the parameters were not (C Schmiegelow PhD); 32 weeks (early preterm), 32 weeks to less than 34 weeks statistically significant. Department of Paediatrics, www.thelancet.com 101 Articles

Division of Neonatology, Chris Missing exposure data all statistical analyses. Random effects models used the Hani Baragwaneth Hospital, All studies had few missing gestational age data (<10%). DerSimonian-Laird pooled RRs and 95% CIs, given University of Witwatersrand, Analyses of mortality risk by preterm categories used all between-study heterogeneity.19 Soweto, South Africa (S C Velaphi Mmed); Mwanza available gestational age data, irrespective of missing Intervention Trial Unit, National birthweight (full gestational age cohort). There were two Role of the funding source Institutes of Medical Research, main reasons for missing birthweight data (most of The sponsor of the study had no role in study design, Mwanza, Tanzania (D Watson-Jones) which were from home deliveries): some infants who data collection, data analysis, data interpretation, or died soon after delivery were not weighed, and infants writing of the report. The corresponding author had Correspondence to: Prof Joanne Katz, Department of who were weighed were measured at different times full access to most of the datasets, had access to all International Health, Johns after delivery. For risk estimates associated with SGA, we summary estimates from each dataset for meta- Hopkins School of Public Health, included infants with weights taken within 72 h of birth analysis, and had final responsibility for the decision to 615 N Wolfe Street, W5009, (weighed cohort). For four Asian and two African studies submit for publication. Baltimore, MD 21205, USA [email protected] with missing data for birthweight or that measured some weights after 72 h, we used multiple imputation18 to Results See Online for appendix impute birthweights (appendix). The imputed datasets We included 20 datasets with 2 015 019 livebirths from were used to estimate the RRs and RDs. sub-Saharan Africa, Latin America, and south and southeast Asia, with gestational age available for Pooled analysis 2 008 675 babies and both gestational age and birth­ Because multivariate adjustment did not substantially weight available for 1 996 763 babies (table and modify estimates of associations, we used the crude RRs appendix).4,20–40 Study dates ranged from 1982 through to and 95% CIs, and pooled data for the major UN 2010. The Chilean national birth registry35 provided Millennium Development Goal regions (Asia, Africa, much of these data. The prevalence of preterm and Latin America). We estimated overall and regional birth (<37 weeks) in the study datasets ranged from RRs of mortality for each exposure variable (preterm, 2·7% to 28%, with varying methods of gestational SGA, and combinations). We used Stata (version 11) for age determination (see appendix for specific study

Setting Primary study design Study population N N (analysed cohort NMR IMR Systematic % % % % (original for preterm/for (deaths (deaths follow-up LBW preterm SGA facility cohort) SGA) per 1000 per 1000 period delivery livebirths) livebirths) Asia Bangladesh Rural Sylhet Cluster RCT of Population-based 10 585 10 585/10 550* 31 ·· 1 month 30% 19% 50% 6% (2005)21 community sepsis recruitment of all treatment pregnant women in study area India Rural Tamil RCT of newborn Population-based 13 294 12 693/12 693* 38 ·· 6 months 33% 14% 62% 63% (2000)26 Nadu vitamin A recruitment of all supplementation pregnant women in study area Nepal Rural Sarlahi Cluster RCT of multiple Recruitment of all 4130 4122/4094* 42 67 1 year 39% 22% 56% 6% (1999)22 micronutrient pregnant women in supplementation study area Nepal Peri-urban/rural RCT of antenatal Antenatal clinic- 1106 1106/1052 25 ·· 1 month 22% 7% 53% 53% (2003)25 Dhanusha micronutrient based recruitment of supplementation pregnant women in study area Nepal Rural Sarlahi Cluster RCT of newborn Population-based 23 662 23 650/22 723* 32 ·· 6 months 30% 18% 52% 10% (2004)29 skin-umbilical cord recruitment of all cleansing with pregnant women in chlorhexidine study area Pakistan Rural Sindh Cluster RCT of Population-based 1548 1464/1434 18 ·· 1 month 19% 28% 28% 100% (2003)39 maternal recruitment of all micronutrient pregnant women in supplementation study villages Philippines Urban Cebu Longitudinal health- Population-based, 3080 3050/2785 14 36 2 years 11% 18% 25% 34% (1983)20 nutritional survey of random cluster infant feeding patterns sample of census Thailand Urban Bangkok Prospective follow-up Longitudinal birth 4245 4032/3860 5 6 1 year 8% 9% 22% 99% (2001)24 of birth cohort cohort of all births in four districts (Continues on next page)

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Setting Primary study design Study population N N (analysed cohort NMR IMR Systematic % % % % (original for preterm/for (deaths (deaths follow-up LBW preterm SGA facility cohort) SGA) per 1000 per 1000 period delivery livebirths) livebirths) (Continued from previous page) Sub-Saharan Africa Burkina Faso Rural Hounde RCT of multiple Prospective, 1373 1311/1212* 21 67 1 year 17% 16% 35% 77% (2004)27 micronutrient community-based supplementation cohort Burkina Faso Rural Hounde RCT of maternal Prospective, 1316 1261/1067 20 ·· 1 month 16% 18% 29% 84% (2006)36 fortified food community-based supplementation cohort South Africa Urban Soweto RCT of birth canal and Facility-based 8113 8113/8098 7 ·· 1 month 8% 4% 16% 100% (2004)34 newborn skin cleansing delivery, tertiary-care with chlorhexidine hospital Tanzania Rural Mwanza Maternal syphilis Facility-based 1496 1425/1172 16 ·· 3 months 10% 3% 25% 98% (1998)32 treatment, recruitment; urban, observational cohort antenatal clinics Tanzania Urban Dar es RCT of mutivitamin Facility-based, 7752 7740/7557 28 ·· 6 weeks 8% 17% 20% 97% (2001)23 Salaam supplementation antenatal clinics Tanzania Rural Korogwe Observational malaria Facility-based 915 820/731 33 ·· 28 days 11% 5% 22% 88% (2008)38 study recruitment, antenatal clinics, community follow-up. Uganda Rural Kabale RCT intermittent Facility-based 1561 1553/1477 17 ·· 1 month 7% 6% 10% 100% (2005)37 district preventive malaria recruitment ANC therapy and clinics; only include insecticide-treated facility births nets Zimbabwe Urban Harare RCT of maternal- Facility-based 14 110 13 960/13 914 12† 93 1 year 14% 8% 33% 100% (1997)33,40 neonatal vitamin A recruitment, 14 supplementation maternity clinics and hospitals Latin America Brazil Urban Pelotas Longitudinal birth Population-based, all 5914 4675/4670 11 28 1 year 7% 6% 17% 100% (1982)30 city, Rio Grande cohort survey births in Pelotas do Sul, hospitals (100% southern Brazil facility delivery) Brazil Urban Pelotas Longitudinal birth Population-based, all 5279 4707/4632 7 14 1 year 9% 11% 19% 100% (1993)31 city, Rio Grande cohort survey births in Pelotas do Sul, hospitals (100% southern Brazil facility delivery) Brazil Urban Pelotas Longitudinal birth Population-based, all 4287 3903/3837 10 17 1 year 11% 16% 15% 100% (2004)28 city, Rio Grande cohort survey births in Pelotas do Sul, hospitals (100% southern Brazil facility delivery) Chile Chilean national Birth registry Population-based 1 901 611 1 898 250/ 5 ·· 1 month 6% 7% 7% 98% (2000)35 birth registry registry 1 898 250

RCT=randomised controlled trial. SGA=small for gestational age. NMR=neonatal mortality rate. IMR=infant mortality rate. LBW=low birthweight. *Weights imputed for datasets that met criteria described in appendix. †Enrolment of newborn babies occurred up to 96 h after birth, and the study might have missed neonatal deaths that happened before enrolment.

Table: Study characteristics of 20 included datasets methods). The proportions of preterm births before LBW infants were SGA and 33% were preterm (67% of 32 weeks of gestation ranged from 0% to 4% (appendix). LBW were term and SGA). In the African cohorts, 79% Comparison of preterm prevalence by method of of LBW infants were SGA and 38% were preterm (62% assessment was not possible because few studies used of LBW were term and SGA). In the Latin American more than one method. The prevalence of SGA was cohorts, 53% of LBW infants were SGA and 71% were generally higher than that of preterm births, ranging preterm (29% of LBW were term and SGA). South Asia from 7% in the Chile national registry to 62% in a had the highest prevalence of preterm births and community-based trial in south India (appendix). The number of LBW and SGA infants. A substantial proportion of LBW infants who were SGA or preterm proportion of SGA infants did not have LBW in Asia varied by region (figure 1). In the Asian cohorts, 83% of (54%), Africa (65%), and Latin America (59%). The www.thelancet.com 103 Articles

proportion of children who were both SGA and preterm infants were more often SGA than were preterm infants, was small in these datasets (4% in Asia, 1% in Africa, but the opposite was true in Latin America (figure 1). and 2% in Latin America). In Africa and Asia, term Neonatal mortality rates and relative risks increased with decreasing gestational age across studies and regions (figure 2). Although the highest relative risks A (RRs) were seen in Latin America (mainly due to the very low mortality in the reference group), the risk differences were similar across regions. The overall

≥2500 g N=5711 (7%) N=38 297 (49%) pooled RRs across all regions were 6.82 (3·56–13·07) for neonatal mortality and 2·50 (1·48–4·22) for post- neonatal mortality. The overall pooled RRs across Appropriate for gestational age all regions for late preterm (34 weeks to <37 weeks), Small for gestational age when most preterm births occur, were 3·05 (2·02–4·60; figure 2 and appendix). The RDs per 1000

Birthweight N=16 656 (21%) livebirths for late preterm ranged from nine (95% CI 2500 g N=3020 0–18) in Africa to 18 (9–28) in Asia, with an overall RD (4%) per 1000 livebirths of 13 (9–18; appendix). The overall Low pooled RRs for early preterm (<32 weeks) were 28·82 N=2748 (15·51–53·56; figure 2 and appendix), although the RDs (4%) N=11 616 (15%) per 1000 livebirths ranged from 196 (95–297) in Asia to 350 (189–511) in Latin America, with an overall RD of B 245 per 1000 livebirths (192–297; appendix). Early and late neonatal and post-neonatal infant mortality followed similar patterns, but the RRs were more

≥2500 g N=1949 (5%) N=26 567 (68%) attenuated the longer the follow-up period extended (appendix), except for early preterm in Latin America, when mortality risk decreased substantially across the early-post-neonatal to late-post-neonatal periods. How­

Appropriate for gestational age ever, a statistically significantly increased mortality risk

Birthweight Small for gestational age persisted into the post-neonatal infant period in all regions for preterm compared to term. Imputation of missing birthweights did not alter the N=6230 (16%) 2500 g prevalence of SGA, which was already high, although it N=885 did increase the risk of mortality associated with SGA Low (2%) N=707 (figure 3 and appendix). Neonatal mortality rates in­creased (2%) N=2610 (7%) with severity of SGA (figure 3). The overall pooled RRs for SGA across all regions were 1·83 (1·34–2·50) for neonatal C mortality and 1·90 (1·32–2·73) for post-neonatal mortality. The highest RR for SGA in neonates below the third percentile was in Latin America, compared with N=52 671 ≥2500 g N=1 663 506 (87%) 1·91 (1·40–2·60) in Asia, although the CIs overlapped. (3%) The overall RR was 2·41 (1·66–3·50). Regional pooled RDs per 1000 livebirths for SGA below the third percentile ranged from 12 (10–15) in Asia to 23 (17–29) in Latin America, with an overall RD per 1000 livebirths of 14 Birthweight (9–19; appendix). The RRs associated with SGA were of similar magnitude in the early-neonatal, late-neonatal, Appropriate for gestational age and post-neonatal periods across regions (appendix). The Small for gestational age N=83 297 (4%) RRs associated with SGA were overall of smaller 2500 g N=52 819 magnitude than preterm, and the association with (3%) Low N=26 397 increased mortality did not attenuate beyond the neonatal (2%) N=32 044 (2%) period and persisted through the first year of life. PretermF37 weeks ull-term Relative to term and AGA, the increased risk of neo­ Gestational age natal mortality was lowest in those born term-SGA (overall RR 2·44, 1·67–3·57) and highest in preterm-SGA Figure 1: The relation between birthweight and gestational age in Asia (A), Africa (B), and Latin America (C) For Asian cohorts (A), percentages are for 78 048 infants. For African cohorts (B), percentages are for infants (15·42, 9·11–26·12). RRs were similar for Asia 38 948 infants. For Latin American cohorts (C), percentages are for 1 910 734 infants. and Africa, but higher in Latin America (figure 4). These

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higher RRs in Latin America were probably driven by the 1000 low mortality rate (2·4 per 1000) in the reference group. Pooled RDs were similar across regions (appendix). The RRs for term-SGA babies did not vary by timing of mortality (figure 5). For preterm-AGA and preterm-SGA 100 100·10 babies, RRs were highest in the early neonatal period and 18·98 25·79 lowest in the post-neonatal period, although the CIs 16·60 largely overlapped (ie, no statistically significant between- 10 11·02

group differences; figure 5 and appendix). This pattern of Relative risk 5·35 5·44 attenuated risk by length of follow-up was probably 2·64 2·74 driven by prematurity and not SGA. 1 Asia Asia Asia Asia

Discussion Africa Africa Africa Africa We identified a large percentage of infants who were

SGA but not LBW or preterm (21% in Asia, 16% in America Latin America Latin America Latin America Latin Africa, and 4% in Latin America), although their ≥37 weeks (reference) 34 to <37 weeks 32–33 weeks <32 weeks Gestational age mortality rates were lower than preterm infants or SGA- Median neonatal 18·7 9·2 3·5 40·6 22·3 14·2 77·5 63·9 63·2 274·8 306·5 237·5 LBW infants. Although most LBW was in term and SGA mortality rate babies in Asia and Africa, the majority of babies with (per 1000 livebirths)

LBW in Latin America were preterm. Preterm mortality Figure 2: Relative risk of neonatal mortality associated with gestational age risk associations were generally higher at all gestational Error bars are 95% CI. age categories (late, moderate, and early preterm) than SGA (3% to <10% or <3%). However, the attributable 10 mortality risk for SGA infants is substantial, because many infants in LMICs are born SGA, especially in south Asia. The predominant increased mortality risk asso­ ciated with preterm birth occurred in the first week of 4·01 life, with statistically significant but attenuated risk remaining in the late-neonatal and post-neonatal periods. Although CIs overlapped, mortality risks associated­ with Relative risk 2·23 1·93 1·91 SGA were slightly higher in the late than early neonatal period, with persistent risk in the post-neonatal period. 1·20 1·27 The highest neonatal and infant mortality rates were 1 detected in the Asian and African studies. The highest Asia Asia Asia Africa Africa RRs for all exposures were seen in Latin America, Africa although absolute risk differences were more comparable across regions. This higher RR in Latin America is due to America Latin America Latin America Latin Appropriate for Small for Small for very low mortality in the reference group in Latin America gestational age gestational age gestational age compared with Africa and Asia. In particular, the Latin (reference) (3–10%) (<3%) America analysis was dominated by national registry Size for gestational age data from Chile in which term neonatal mortality was Median neonatal 12·0 21·6 8·84 15·1 18·0 12·6 26·9 20·9 27·6 mortality rate 1·7 per 1000 livebirths. By comparison with these data, (per 1000 livebirths) the average term neonatal mortality was 11 per 1000 live­ births in the African datasets and 19 per 1000 livebirths in Figure 3: Relative risk of neonatal mortality associated with small for gestational age the Asian ones. Alternately, preterm infants might be more severely preterm and survive delivery in Latin Evidence-based, low-cost interventions are feasible for America but have delayed mortality. LMICs and could reduce mortality related to preterm birth Preterm birth was associated with an increased mortality complications, such as antenatal cortico­steroids for risk compared with term birth. The proportion of infants preterm labour, Kangaroo mother care, and treatment of born within 32 weeks of gestation was low but these neonatal infections.41–43 Our findings suggest that simple infants had substantially higher mortality risks than did interventions to target the improved care of late and term infants in the first week of life. Late preterm birth moderate preterm infants could have a large effect on the comprised 50–96% of preterm births, and was associated reduction of mortality burden in preterm infants. In areas with a smaller but statistically significant neonatal mor­ with a large proportion of facility deliveries and much tality risk ranging from 2·52 in Asia to 5·58 in Latin post-delivery care, clinical inter­ventions such as surfactant America (risk differences per thousand livebirths were administration and continuous positive airway pressure nine in Africa, 11 in Latin America, and 18 in Asia). might also improve survival. www.thelancet.com 105 Articles

100 2500 g or more, although their mortality risk was similar to that of term-AGA babies. The very high rates of SGA in South Asia might be explained by higher rates of 39·48 25·77 adolescent pregnancy­ , chronic maternal malnutrition, 16·73 low pre-pregnancy body-mass index, low weight gain in pregnancy, and low maternal height.44–46 10 10·05 6·96 The mortality risk associated with being preterm-SGA

Relative risk 6·21 5·34 was substantially higher than for either alone. An 3·43 estimated 2·8 million infants are born both preterm and 2·01 SGA in LMICs annually2 and these infants are at a 10–40 times increased risk of dying in the first month of 1 life compared with term and appropriate-for-gestational- Asia Asia Asia Asia Africa Africa Africa Africa age infants. These children are key targets for public health interventions.

Latin America Latin America Latin America Latin America Latin A strength of this analysis was the large number of Term and Term and Preterm and Preterm and representative livebirths analysed from a wide range of appropriate for small for appropriate for small for gestational age gestational age gestational age gestational age studies and geographical regions, producing internal Characteristics at birth validity and reduced variance of estimates. We adjusted Median neonatal 7·9 8·4 2·4 17·6 11·9 10·1 23·5 64·2 53·0 106·5 70·2 75·5 for several covariates but noted that they did not alter the mortality rate (per 1000 livebirths) risk estimates. Although the cohort sizes varied sub­ stantially, with the Chilean national registry data domin­ Figure 4: Relative risk of neonatal mortality associated with preterm and size for gestational age ating in absolute numbers, the use of random effects models to do meta-analyses downweights the effect of 100 such large datasets. Although it constitutes 92% of the data, its contribution to the Latin American mor­tality risk estimate is about 50% and its contribution to the global estimate is 9·7%. While Chile is proably a good 18·65 15·97 representation of a middle-income country in Latin

10 9·06 America, it does not represent other low-income coun­ tries in the region. The earliest Brazilian cohort30 might

Relative risk 5·74 5·77 be more representative of such countries because it was 3·12 3·09 2·85 done in a low-income setting. 2·2 We re-analysed individual data to estimate SGA preva­ 1 lence and risk, applying a common SGA reference popu­ l l l lation. This reduced the variation associated with the use of different SGA reference populations commonly seen across studies. Although the use of a common reference Late-neonatal Late-neonatal Late-neonatal Post-neonata Post-neonata Post-neonata Early-neonatal Early-neonatal Early-neonatal population is a controversial issue, with argu­ments made Term and Preterm and Preterm and small for appropriate for small for about whether it is appropriate to apply one standard to all gestational age gestational age gestational age populations, we selected one reference population to be Characteristics at birth able to better compare our analyses across populations. Figure 5: Relative risk of early-neonatal, late-neonatal, and post-neonatal infant mortality associated with Our use of a birthweight rather than fetal growth standard preterm and size for gestational age might have system­atically under-­represen­ted SGA in pre­ term infants because preterm infants might have more Using a common US birthweight reference population, pathological IUGR than fetuses that remain in the womb For The Intergrowth Study see the prevalence of SGA and term-SGA babies was very for longer. The Intergrowth Study is collecting data for a http://www.intergrowth21.org.uk high (higher than 50%) in many of the community-based common fetal growth reference using healthy populations South Asian cohorts.11,12 In statistical modelling to esti­ from many countries. The use of this standard will help mate national and regional prevalences of SGA, we resolve this limitation in the future. estimated that 42% of babies were term-SGA and that 3% The large sample size allowed us to stratify preterm of babies were preterm-SGA.2 These findings contrast and SGA into severity categories and to pool mortality with a much lower prevalence of SGA in Africa, despite risk associated with each category by re-analysing the high prevalence of risk factors such as malaria and primary data. Available covariates varied by study and HIV infection in pregnancy. SGA neonates had roughly residual con­founding could have occurred. However, double the mortality risk of appropriate-for-gestational- these findings might not be generalisable to countries age infants, with slightly higher risk in those with more or regions as a whole because they are derived from severe SGA. A large proportion of SGA infants weighed cohorts or randomised trials in which the geographical

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areas might have been selected for specific risk improves in LMICs, targeting inter­ventions and tracking characteristics as evidenced by the range of preterm outcomes that reduce the incidence and improve the prevalence across studies (table). However, the use of survival of babies born preterm and SGA rather than meta-analyses with random effects of 20 cohorts with a LBW might more clearly guide progress towards probably reduced the bias and increased the precision of the reduction of child mortality. regional and global risk estimates. Although the Contributors prevalence of preterm and SGA births seemed quite JK, ACL, and NK did the literature review, collected the data, analysed variable across these datasets, the mortality differences the data, and drafted the paper. JEL, SC, HB, ME, ZAB, and REB helped draft the analysis plan and reviewed the paper. JKN, AS, MFS, and AV associated with these characteristics were stable within did analyses of their individual studies, contributed data, and reviewed regions. Hence these estimates are likely to be valid for the paper. TM, BAW, LA, FB, AHB, PC, WF, RG, JH, LH, PK, AM, use in attributable risk calculations if representative LCM, RN, DO, DR, CS, JT, SCV, CGV, and DW-J contributed data and estimates of preterm and SGA prevalence are used and reviewed the paper. residual confounding was minimal. Conflicts of interest A limitation of our community-based datasets was the We declare that we have no conflict of interest. exclusion of early deaths in infants who were not Acknowledgments weighed. We used multiple imputation to address the Funding was provided by the Bill & Melinda Gates Foundation (810- 2054) by a grant to the US Fund for UNICEF to support the activities of potential effect on mortality associations. Nevertheless, the Child Health Epidemiology Reference Group. Financial support for we might have underestimated the mortality risks analysis was offered to investigators through a subcontract mechanism associated with SGA given that we were missing some administered by the US Fund for UNICEF. For funding information for covariate data with which to impute birthweight. Another the individuals studies please see appendix. We thank the additional members of the CHERG SGA-Preterm Birth working group: limitation is the variability and accuracy of gestational Siân Clarke, Simon Kariuki, John Lusingu, James Ndirangu, age measurement between datasets. Nine studies Marie-Louise Newell, Robert Ntozini, Heather Rosen, and included ultrasound dating, whereas the remainder Feiko O Ter Kuile. The individual studies would like to acknowledge the relied on maternal recall of their last menstrual period or role played by following people in those studies: Ramesh Adhikari, Christian Coles, Anthony Costello, Gary Darmstadt, Sheela Devi, clinical exam. We used the best gestational age deter­ Subarna Khatry, Hermann Lanou, Steven LeClerq, Dharma Manandhar, mination, excluding datapoints with improbable gesta­ Daniel Minja, Gernard I Msamanga, R D Thulasiraj, Willy Urassa, tional age and birthweight combinations­ and datasets Helen Weiss, and Keith West. We would like to thank with poor gestational age measures. Gestational age Joanna Schellenberg for her support of this work. categories might have been subject to some mis­ References 1 UNICEF. WHO. Low birthweight: country, regional and global classification although these were probably mini­mised estimates. New York 2004. by the active, frequent pregnancy surveillance in many 2 Lee ACC, Katz J, Blencowe H, et al. Born too small: national and studies. Stillbirths were excluded from these analyses, regional estimates of term and preterm small-for-gestational-age in 138 low-income and middle-income countries in 2010. but it is possible that there was misclassification of Lancet Glob Health (in press). stillbirths and livebirths, especially in home deliveries 3 Kramer MS, Demissie K, Yang H, Platt RW, Sauvé R, Liston R, and that relied on maternal report, but the direction of this the Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. The contribution of mild and moderate misclassification is unclear. Although assessment of preterm birth to infant mortality. JAMA 2000; 284: 843–49. cause of death by adverse pregnancy outcome is of 4 Marchant T, Willey B, Katz J, et al. Neonatal mortality risk interest, very few studies had cause of death, and most associated with preterm birth in East Africa, adjusted by weight for population-based studies that did, had cause assigned by gestational age: individual participant level meta-analysis. PLoS Med 2012; 9: e1001292. physician via verbal autopsy. Assessing causes of death 5 Narchi H, Skinner A, Williams B. Small for gestational age associated with SGA or preterm in these contexts would neonates—are we missing some by only using standard population be a valuable future contribution to the design of appro­ growth standards and does it matter? J Matern Fetal Neonatal Med 2010; 23: 48–54. priate mortality reduction interventions. 6 Clausson B, Cnattingius S, Axelsson O. Preterm and term births of Many babies are born SGA in LMICs, especially in small for gestational age infants: a population-based study of risk south Asia and sub-Saharan Africa, and such babies have factors among nulliparous women. Br J Obstet Gynaecol 1998; 47 105: 1011–17. increased risk of mortality and poor growth. Preterm 7 Kristensen S, Salihu HM, Keith LG, Kirby RS, Fowler KB, Pass MA. birth affects a smaller number of neonates but is SGA subtypes and mortality risk among singleton births. associated with a higher mortality risk and seems to be a Early Hum Dev 2007; 83: 99–105. 8 Pulver LS, Guest-Warnick G, Stoddard GJ, Byington CL, Young PC. greater contributor to attributable risk in Latin America Weight for gestational age affects the mortality of late preterm than in Asia. In both these regions, these risks extend infants. Pediatrics 2009; 123: e1072–77. beyond the neonatal period. Although few effective 9 Regev RH, Reichman B. Prematurity and intrauterine growth interventions to prevent preterm exist,48 several inter­ retardation—double jeopardy? Clin Perinatol 2004; 31: 453–73. 10 Grisaru-Granovsky S, Reichman B, Lerner-Geva L, et al. Mortality ventions exist to improve preterm survival. Interventions­ and morbidity in preterm small-for-gestational-age infants: shown to reduce SGA have focused mainly on increasing a population-based study. Am J Obstet Gynecol 2012; 206: 150 e1–7. calories and protein during pregnancy, and more 11 Wu LA, Katz J, Mullany LC, et al. The association of preterm birth and small birthweight for gestational age on childhood disability recently (during the past decade) maternal micro­nutrient screening using the Ten Questions Plus tool in rural Sarlahi district, supplementation.48 As measurement of gesta­tional age southern Nepal. Child Care Health Dev 2012; 38: 332–40. www.thelancet.com 107 Articles

12 Osendarp SJ, van Raaij JM, Arifeen SE, Wahed M, Baqui AH, 32 Watson-Jones D, Changalucha J, Gumodoka B, et al. Syphilis in Fuchs GJ. A randomized, placebo-controlled trial of the effect of pregnancy in Tanzania. I. Impact of maternal syphilis on outcome zinc supplementation during pregnancy on pregnancy outcome in of pregnancy. J Infect Dis 2002; 186: 940–47. Bangladeshi urban poor. Am J Clin Nutr 2000; 71: 114–19. 33 Malaba LC, Iliff PJ, Nathoo KJ, et al, and the ZVITAMBO Study 13 Black RE, Allen LH, Bhutta ZA, et al, and the Maternal and Child Group. Effect of postpartum maternal or neonatal vitamin A Undernutrition Study Group. Maternal and child undernutrition: supplementation on infant mortality among infants born to global and regional exposures and health consequences. Lancet HIV-negative mothers in Zimbabwe. Am J Clin Nutr 2005; 81: 454–60. 2008; 371: 243–60. 34 Cutland CL, Madhi SA, Zell ER, et al, and the PoPS Trial Team. 14 Barfield WD, Lee KG. Late preterm infants. 2012; http://www. Chlorhexidine maternal-vaginal and neonate body wipes in sepsis uptodate.com/contents/late-preterm-infants (accessed July 5, 2012). and vertical transmission of pathogenic bacteria in South Africa: 15 Williams RL, Creasy RK, Cunningham GC, Hawes WE, Norris FD, a randomised, controlled trial. Lancet 2009; 374: 1909–16. Tashiro M. Fetal growth and perinatal viability in California. 35 Gonzalez R, Merialdi M, Lincetto O, et al. Reduction in neonatal Obstet Gynecol 1982; 59: 624–32. mortality in Chile between 1990 and 2000. Pediatrics 2006; 16 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United 117: e949–54. States national reference for fetal growth. Obstet Gynecol 1996; 36 Huybregts L, Roberfroid D, Lanou H, et al. Prenatal food 87: 163–68. supplementation fortified with multiple micronutrients increases 17 Oken E, Kleinman KP, Rich-Edwards J, Gillman MW. A nearly birth length: a randomized controlled trial in rural Burkina Faso. continuous measure of birth weight for gestational age using a Am J Clin Nutr 2009; 90: 1593–600. United States national reference. BMC Pediatr 2003; 3: 6. 37 Ndyomugyenyi R, Clarke SE, Hutchison CL, Hansen KS, Magnussen 18 Rubin DB. Multiple imputation after 18+ years. J Am Stat Assoc P. Efficacy of malaria prevention during pregnancy in an area of low 1996; 91: 473–89. and unstable transmission: an individually-randomised 19 DerSimonian R, Laird N. Meta-analysis in clinical trials. placebo-controlled trial using intermittent preventive treatment and Control Clin Trials 1986; 7: 177–88. insecticide-treated nets in the Kabale Highlands, southwestern Uganda. Trans R Soc Trop Med Hyg 2011; 105: 607–16. 20 Adair LS. Low birth weight and intrauterine growth retardation in Filipino infants. Pediatrics 1989; 84: 613–22. 38 Schmiegelow C, Minja D, Oesterholt M, et al. Factors associated with and causes of perinatal mortality in northeastern Tanzania. 21 Baqui AH, El-Arifeen S, Darmstadt GL, et al, and the Projahnmo Acta Obstet Gynecol Scand 2012; 91: 1061–68. Study Group. Effect of community-based newborn-care intervention package implemented through two service-delivery strategies in 39 Bhutta ZA, Rizvi A, Raza F, et al. A comparative evaluation of Sylhet district, Bangladesh: a cluster-randomised controlled trial. multiple micronutrient and iron-folic acid supplementation during Lancet 2008; 371: 1936–44. pregnancy in Pakistan: impact on pregnancy outcomes. Food Nutr Bull 2009; 30 (suppl): S496–505. 22 Christian P, West KP, Khatry SK, et al. Effects of maternal micronutrient supplementation on fetal loss and infant mortality: 40 Humphrey JH, Hargrove JW, Malaba LC, et al, and the ZVITAMBO a cluster-randomized trial in Nepal. Am J Clin Nutr 2003; Study Group. HIV incidence among post-partum women in 78: 1194–202. Zimbabwe: risk factors and the effect of vitamin A supplementation. AIDS 2006; 20: 1437–46. 23 Fawzi WW, Msamanga GI, Urassa W, et al. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. N Engl J Med 41 Lawn JE, Mwansa-Kambafwile J, Barros FC, Horta BL, Cousens S. 2007; 356: 1423–31. ‘Kangaroo mother care’ to prevent neonatal deaths due to pre-term birth complications. Int J Epidemiol 2010; 39 (suppl 1): 144–54. 24 Isaranurug S, Mo-suwan L, Choprapawon C. A population-based cohort study of effect of maternal risk factors on low birthweight in 42 Mwansa-Kambafwile J, Cousens S, Hansen T, Lawn JE. Antenatal Thailand. J Med Assoc Thai 2007; 90: 2559–64. steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth. Int J Epidemiol 2010; 25 Osrin D, Vaidya A, Shrestha Y, et al. Effects of antenatal multiple 39 (suppl 1): i122–33. micronutrient supplementation on birthweight and gestational duration in Nepal: double-blind, randomised controlled trial. Lancet 43 March of Dimes, The Partnership of Maternal, Newborn, and Child 2005; 365: 955–62. Health, Save the Children, World Health Organization. Born too soon: the global action report on preterm birth. Geneva, 26 Rahmathullah L, Tielsch JM, Thulasiraj RD, et al. Impact of 2012. supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in southern India. 44 Mehra S, Agrawal D. Adolescent health determinants for pregnancy BMJ 2003; 327: 254. and child health outcomes among the urban poor. Indian Pediatr 2004; 41: 137–45. 27 Roberfroid D, Huybregts L, Lanou H, et al, and the MISAME Study Group. Effects of maternal multiple micronutrient supplementation 45 Bott SJS, Shah I, Puri C, eds. Towards adulthood: exploring the on fetal growth: a double-blind randomized controlled trial in rural sexual and reproductive health of adolescents in South Asia. Burkina Faso. Am J Clin Nutr 2008; 88: 1330–40. Geneva: World Health Organization, 2000. 28 Santos IS, Barros AJ, Matijasevich A, Domingues MR, Barros FC, 46 Monden CW, Smits J. Maternal height and child mortality in Victora CG. Cohort profile: the 2004 Pelotas (Brazil) birth cohort 42 developing countries. Am J Hum Biol 2009; 21: 305–11. study. Int J Epidemiol 2011; 40: 1461–68. 47 Black RE, Victora CG, Walker SP, and the Maternal and Child 29 Tielsch JM, Darmstadt GL, Mullany LC, et al. Impact of newborn Nutrition Study Group. Maternal and child undernutrition and skin-cleansing with chlorhexidine on neonatal mortality in southern overweight in low-income and middle-income countries. Lancet Nepal: a community-based, cluster-randomized trial. Pediatrics 2007; 2013; published online June 6. http://dx.doi.org/10.1016/S0140- 119: e330–40. 6736(13)60937-X. 30 Victora CG, Barros FC. Cohort profile: the 1982 Pelotas (Brazil) 48 Bhutta ZA, Das JK, Rizvi A, et al, The Lancet Interventions Review birth cohort study. Int J Epidemiol 2006; 35: 237–42. Group, and the Maternal and Child Nutrition Study Group. Evidence based interventions for improvement of maternal and child nutrition: 31 Victora CG, Hallal PC, Araújo CL, Menezes AM, Wells JC, what can be done and at what cost? Lancet 2013; published online Barros FC. Cohort profile: the 1993 Pelotas (Brazil) birth cohort June 6. http://dx.doi.org/10.1016/S0140-6736(13)60996-4. study. Int J Epidemiol 2008; 37: 704–09.

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Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies

Linda S Adair, Caroline H D Fall, Clive Osmond, Aryeh D Stein, Reynaldo Martorell, Manuel Ramirez-Zea, Harshpal Singh Sachdev, Darren L Dahly, Isabelita Bas, Shane A Norris, Lisa Micklesfield, Pedro Hallal, Cesar G Victora, for the COHORTS group

Summary Background Fast weight gain and linear growth in children in low-income and middle-income countries are associated Published Online with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult March 28, 2013 cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood http://dx.doi.org/10.1016/ S0140-6736(13)60103-8 are related to health and human capital outcomes in young adults. See Online/Comments http://dx.doi.org/10.1016/ Methods We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and S0140-6736(13)60716-3 South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, Department of Nutrition, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With University of North Carolina at linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically Chapel Hill, Chapel Hill, NC, USA (Prof L S Adair PhD); MRC independent measures representing linear growth and weight gain independent of linear growth (relative weight Lifecourse Epidemiology Unit, gain) in three age periods: 0–2 years, 2 years to mid-childhood, and mid-childhood to adulthood. University of Southampton, Southampton General Hospital, Findings We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was Southampton, UK (Prof C H D Fall DM, consistently associated with an adult body-mass index of greater than 25 kg/m² (odds ratio 1·28, 95% CI 1·21–1·35) and Prof C Osmond PhD); Hubert a reduced likelihood of short adult stature (0·49, 0·44–0·54) and of not completing secondary school (0·82, 0·78–0·87). Department of Global Health, Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20–0·52; mid- Rollins School of Public Health, childhood: 0·39, 0·36–0·43) and of not completing secondary school (age 2 years: 0·74, 0·67–0·78; mid-childhood: Emory University, Atlanta, GA, USA (Prof A D Stein PhD, 0·87, 0·83–0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17–1·31; mid-childhood: 1·12, 1·06–1·18) Prof R Martorell PhD); Unit of and elevated blood pressure (age 2 years: 1·12, 1·06–1·19; mid-childhood: 1·07, 1·01–1·13). Faster relative weight gain Nutrition and Chronic Diseases, was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43–1·60; mid-childhood: 1·76, 1·69–1·91) Institute of Nutrition of Central and elevated blood pressure (age 2 years: 1·07, 1·01–1·13; mid-childhood: 1·22, 1·15–1·30). Linear growth and relative America and Panama, Guatemala City, Guatemala weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the (M Ramirez-Zea MD); Sitaram disorder (0·89, 0·81–0·98). Bhartia Institute of Science and Research, New Delhi, India Interpretation Interventions in countries of low and middle income to increase birthweight and linear growth during (Prof H S Sachdev MD); Centre for Epidemiology and the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from Biostatistics, University of adult chronic disease risk factors, with few adverse trade-offs. Leeds, Leeds, UK (D L Dahly PhD); Office of Population Studies Funding Foundation, University of San Wellcome Trust and Bill & Melinda Gates Foundation. Carlos, Cebu, Philippines (I Bas MA); Medical Research Introduction Separation of their effects is important because, although Council/Wits Developmental Promotion of faster weight gain in children with growth early linear growth strongly predicts adult height,8 lean Pathways for Health Research 9,10 11 12 Unit, Department of Pediatrics, failure is an important goal of paediatric care in countries body mass, attained schooling, employment, and Faculty of Health Sciences, 13,14 of low and middle income, in view of the well known earnings, excess adiposity is a well recognised risk University of the associations between poor growth and impaired cognitive factor for cardiometabolic diseases. The key questions for Witwatersrand, Johannesburg, development and increased morbidity and mortality. paediatricians and policy makers are: what is the South Africa (S A Norris PhD, L Micklesfield PhD); and However, some studies suggest that rapid weight gain in optimum age for promotion of growth for enhanced Universidade Federal de Pelotas, the first 2 years of life is related to an increased risk of survival and human capital, and will this promotion Pelotas, Brazil (P Hallal PhD, obesity1,2 and insulin resistance3,4 later in life. Reports necessarily lead to an increase in cardiometabolic disease? Prof C G Victora MD) about this so-called catch-up dilemma5–7 draw attention to We explored how birthweight, linear growth, and Correspondence to: the potential risks and benefits of faster early growth. weight gain relative to linear growth in childhood and Prof Linda S Adair, Carolina Population Center, University of Much of the concern is based on studies of weight gain in adulthood are related to body size and composition, North Carolina at Chapel Hill, children in high-income countries, without a concomitant cardiometabolic risk factors (blood pressure and plasma Chapel Hill, NC 27516–2524, USA consideration of how linear growth and weight gain glucose concentrations), and human capital outcomes [email protected] relative to linear growth affect outcomes later in life. (height and attained schooling) in young adults. We www.thelancet.com 109 Articles

compared results across these diverse outcomes to slower relative weight gain or linear growth. For example, explore possible trade-offs. We focused on birth and the a child with a positive value for mid-childhood conditional period from 0 to 2 years to provide additional insights height is taller than expected in view of previous size and For more on the first 1000 days into the long-term importance of the first 1000 days— thus had a faster rate of linear growth than would be see http://www.thousanddays.org widely recognised as a particularly sensitive period for expected from age 2 years to mid-childhood. Our expo­ child health and development. sure variables represent birthweight and conditional height and conditional relative weight when aged 2 years, Methods during mid-childhood, and during adulthood. Equiva­ Study design and participants lents of the conditional variables (g or kg, and cm) are For details of each cohort study We used data from five prospective birth cohort studies shown in the appendix (p 20). see http://www.cohortsgroup.org included in the Consortium for Health Orientated We calculated conditional variables separately for each Research in Transitional Societies (COHORTS):15 the 1982 site and sex from the largest sample with complete non- Pelotas Birth Cohort (Brazil);16 the Institute of Nutrition of pregnant anthropometric data at all selected ages to avoid Central America and Panama Nutrition Trial Cohort bias as a result of including only individuals with adult (Guatemala);17 the New Delhi Birth Cohort (India);10 outcomes. Because birthlength was not available for Brazil the Cebu Longitudinal Health and Nutrition Survey and South Africa, we included only birthweight in the (Philippines);18 and the Birth to Twenty Cohort (South regression models for all sites. In separate analyses of the Africa).19 All studies of these cohorts were reviewed and three sites for which data for birthlength were available, we approved by appropriate ethics review boards. compared results with and without the inclusion of birthlength. Associations of the resulting conditional Procedures relative weight and conditional height variables with later We identified common ages of childhood measurements outcomes were similar with each method. across the five sites, and focused on birthweight, birth­ Height, weight, and waist circumference were measured length (available for Guatemala, India, and the Philippines), with standard techniques. Binary variables represent over­ weight and length at age 2 years, and weight and height weight and obesity (body-mass index [BMI] ≥25 kg/m² or mid-childhood (aged 4 years for Brazil, Guatemala, India, the International Obesity Task Force equivalent for and South Africa; 8 years for the Philippines). Birthweight individuals aged <18 years22) and short stature (height-for- was measured in hospitals at delivery in South Africa and age Z score23 <–2 when aged <19 years; or <150·1 cm for Brazil, in the community by research staff within 72 h of women and <161·9 cm for men if aged ≥19 years). Fat birth in India, in hospitals or at home by birth attendants mass, fat-free mass, and percentage body fat were provided with project scales in the Philippines, and by a calculated with site-specific methods (bioelectrical impe­ project nurse at home or in a health-care centre in dance in Brazil; validated equations including weight, Guatemala. Gestational age estimates were based on the height, and abdominal circumference in Guatemala, or mother’s report of the date of her last menstrual period. skinfold thickness in India and the Philippines; and dual Birthlength was measured by trained research staff within x-ray absorptiometry [Delphi, Hologic] in South Africa).9 72 h of birth in India, within 6 days in the Philippines, and Within each site and sex, we used a Fisher-Yates trans­ 15 days after birth in Guatemala. formation to express fat mass and fat-free mass in SD Statistical methods are needed to separate the effects of units to enable comparisons within and between sites. linear growth and weight gain because they are strongly Blood pressure was measured by aneroid sphyg­ correlated, as are repeat measurements taken in the momanometer in Brazil, mercury sphygmo­manometer in same individual. We derived standardised residuals by the Philippines, and digital devices elsewhere (UA-767 regressing current size (represented as Fisher-Yates [A and D Medical] in Guatemala; Omron M6 [Omron] in transformed weight-for-age and length-for-age Z scores) South Africa; and Omron 711 [Omron] in India). on all previous size measures to produce conditional size Participants were measured seated after 5–10 min of rest, measures.20,21 Conditional height is present length or with appropriate cuff sizes. We used the mean of three height accounting for previous length or height, and measurements (Philippines), two measurements (Brazil weight (but not present weight). Conditional relative and India), or the second and third of three measurements weight is present weight accounting for present height (Guatemala and South Africa). In accordance with inter­ and all previous weight and height measures. For national recommendations, elevated blood pressure was example, adult conditional relative weight is derived defined as a systolic blood pressure of 130 mm Hg or from a regression of adult weight on adult height, weight more or a diastolic blood pressure of 85 mm Hg or more24 and height at mid-childhood, weight and length when in view of the young ages and low prevalence of hyper­ aged 2 years, and birthweight. tension in several cohorts. Conditional variables represent children’s deviation Fasting blood glucose concentration was measured in from the expected size on the basis of their own previous all cohorts except in Brazil, where a random finger-prick measures and the growth of the other children in each capillary whole-blood sample was obtained and adjusted cohort, and can be interpreted as representing faster or for time since previous meal.25 Adjustments were made

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for differences in plasma, whole venous blood, and (gestational age <37 weeks) affected the coefficients of capillary values.26,27 Participants with glucose concen­ the conditional variables. trations of 6·1 mmol/L or more, or those taking drugs for diabetes were considered to have dysglycaemia (ie, Statistical analysis impaired fasting glucose or diabetes).28 We used linear regression for continuous outcomes and The number of completed years of schooling was logistic regression for categorical outcomes to esti­mate recorded in all sites.11 As an adverse outcome, a binary associations with conditional height and conditional­ variable indicates failure to complete secondary school. relative weight at different ages. Models for each outcome Socioeconomic status at birth was represented by included the largest sample with com­plete data. We mother’s education and a site-specific indicator of excluded women who were pregnant at the time of household wealth, which was a summary measure of measure­ment from all analyses. We compared our main housing type and ownership and type of dwelling analysis sample with samples with adult data but incom­ (India), or an asset index based on household plete anthropometry, and with those with birth measures possessions (all other sites). Additionally, we tested but without adult outcome data by use of Bonferroni- whether inclusion of gestational age or premature birth adjusted ANOVA to account for multiple comparisons. To

Brazil Guatemala India Philippines South Africa Men Women Men Women Men Women Men Women Men Women (n=1889) (n=1702) (n=171) (n=155) (n=775) (n=553) (n=1006) (n=889) (n=584) (n=638) Birthweight (kg) 3·29 (0·52) 3·17 (0·51) 3·09 (0·52) 3·02 (0·43) 2·85 (0·44) 2·76 (0·39) 3·03 (0·42) 2·98 (0·41) 3·14 (0·53) 3·02 (0·48) Birthlength (cm) NA NA 49·8 (2·4) 48·8 (2·1) 48·6 (2·1) 48·1 (2·0) 49·4 (2·0) 48·9 (2·0) NA NA Gestational age (weeks) 39·3 (1·9) 39·1 (3·0) 39·5 (3·0) 38·7 (2·6) 39·1 (2·5) 38·6 (2·2) 38·9 (2·1) 38·2 (1·9) 38·1 (1·9) 39·3 (1·9) Adult age (years) 22·7 (0·4) 22·7 (0·4) 31·4 (1·4) 31·1 (1·3) 29·1 (1·3) 29·2 (1·4) 21·3 (0·8) 21·1 (1·0) 18·1 (0·6) 18·1 (0·6) Adult height (cm) 173·8 (6·9) 160·9 (6·2) 163·0 (6·1) 151·1 (5·2) 169·6 (6·2) 154·9 (5·6) 163·0 (5·9) 151·1 (5·4) 170·8 (7·8) 159·65 (6·21) Adult weight (kg) 72·1 (14·0) 60·6 (12·6) 64·3 (10·1) 61·3 (11·5) 71·8 (13·8) 59·2 (13·1) 56·0 (9·3) 46·3 (7·9) 60·1 (11·7) 57·8 (10·5) Adult body-mass index 23·8 (4·1) 23·4 (4·7) 24·1 (3·3) 26·8 (4·6) 24·9 (4·3) 24·6 (5·0) 21·0 (3·1) 20·3 (3·1) 20·6 (3·7) 22·7 (3·9) (kg/m2) Adult waist circumference 80·9 (10·2) 74·8 (10·5) 85·3 (8·3) 92·3 (11·2) 90·3 (11·9) 79·6 (12·2) 72·1 (7·5) 67·7 (7·3) NA NA (cm) Adult body fat (%) 16·3 (3·8) NA* 19·4 (5·9) 34·9 (6·9) 24·2 (5·8) 34·2 (6·9) 16·7 (5·1) 32·7 (4·8) 14·3 (5·7) 32·4 (6·4) Adult fat mass (kg) 12·2 (5·0) NA* 13·0 (5·9) 22·1 (8·5) 18·0 (6·9) 20·9 (7·9) 9·7 (4·5) 15·4 (4·6) 8·9 (5·3) 19·4 (7·4) Adult fat-free mass (kg) 60·4 (9·6) NA* 51·3 (5·2) 39·1 (3·3) 53·8 (7·8) 38·1 (5·7) 46·3 (5·8) 31·0 (4·2) 50·9 (6·5) 38·9 (5·5) Adult systolic blood pressure 123·5 (14·4) 111·2 (13·0) 117·0 (10·4) 107·7 (11·2) 118·4 (11·4) 106·8 (11·1) 111·8 (10·9) 99·4 (10·0) 120·6 (10·7) 114·7 (9·8) (mm Hg) Adult diastolic blood pressure 75·6 (11·7) 71·6 (10·7) 72·6 (9·2) 69·3 (9·0) 78·0 (10·3) 73·6 (9·2) 75·8 (9·6) 67·8 (8·6) 70·9 (8·8) 71·9 (8·5) (mm Hg) Adult plasma glucose 5·1 (0·7) 4·9 (0·7) 5·2 (0·6) 5·1 (1·1) 5·5 (1·1) 5·3 (0·8) 4·7 (0·6) 4·5 (0·5) 4·7 (0·5) 4·5 (0·4) concentration (mmol/L) Number of completed years of 8·9 (3·2) 9·9 (3·1) 5·0 (3·5) 4·8 (3·5) 13·2 (3·4) 13·9 (3·1) 10·3 (3·4) 11·5 (2·8) 10·8 (1·5) 11·4 (1·3) schooling Mother’s height (cm) 156·7 (6·1) 156·3 (5·8) 148·5 (4·8) 148·5 (5·3) 152·0 (5·6) 151·9 (5·0) 150·6 (4·9) 150·5 (4·9) 158·5 (6·6) 158·1 (6·5) Number of years mother 6·5 (4·1) 6·6 (4·3) 1·3 (1·6) 1·2 (1·5) 5·7 (4·5) 5·8 (4·5) 7·0 (3·3) 6·9 (3·2) 9·7 (2·5) 9·6 (2·5) spent in school Body-mass index >25 kg/m2 584/1882 437/1701 54/157 86/141 370/775 253/551 102/1004 68/883 54/573 162/630 (31·0%) (25·7%) (34·4%) (61·0%) (47·7%) (45·9%) (10·2%) (7·7%) (9·4%) (25·7%) Elevated blood pressure† 666/1884 224/1702 29/161 10/152 209/769 67/546 174/1004 20/885 118/555 60/617 (35·4%) (13·2%) (18·0%) (6·6%) (27·2%) (12·3%) (17·3%) (2·3%) (21·3%) (9·7%) Dysglycaemia‡ 148/1590 98/1503 4/114 5/133 161/762 75/540 8/870 7/709 4/358 1/367 (9·3%) (6·5%) (3·5%) (3·7%) (21·1%) (13·9%) (0·9%) (1·0%) (1·1%) (0·3%) Short stature§ 74/1883 57/1701 69/157 59/141 78/775 105/551 432/1004 374/888 41/573 36/631 (3·9%) (3·4%) (43·9%) (41·8%) (10·1%) (19·1%) (43·0%) (42·1%) (7·1%) (5·7%) Did not complete secondary 952/1770 651/1619 154/168 144/154 114/775 42/553 370/1006 185/889 271/568 171/621 school (53·8%) (40·2%) (91·7%) (93·5%) (14·7%) (7·6%) (36·8%) (20·8%) (47·7%) (27·5%)

Data are mean (SD) or n/N (%). Participants had at least one adult outcome of interest and complete anthropometric data. NA=not available. *Female body composition not measured in Brazil because examination occurred at an army recruitment centre. †Systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg.24 ‡Plasma glucose concentration >6·1 mmol/L or taking drugs for diabetes.24 §Height-for-age Z score <–2 when aged <19 years; or <150·1 cm for women or <161·9 cm for men if aged ≥19 years.

Table 1: Characteristics of participants in the five cohorts

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A assess potential bias related to attrition and missing data, Men Women 29 Pooled data for all men with 95% CI Pooled data for all women with 95% CI we compared results estimated by Heckman selection Brazil Guatemala India Philippines South Africa models with standard regression models. 2·0 We assessed site and sex heterogeneity with F tests, allowing other predictors (eg, age and socioeconomic

1·5 status) to vary across sites. To measure the variation of effect sizes between combinations of sex and site, we

) per SD change used restricted maximum likelihood to estimate the SD 2 1·0 of the effect size for each site and sex around their pooled value. This SD value is close to the SD of estimates specific to each site and sex for each growth variable with 0·5 each outcome. When it is zero, the effect sizes for each sex and site are compatible with a fixed-effects model. in conditional growth variable 0 Glucose and blood-pressure models included birth­ weight, and conditional height and conditional relative

Change in body-mass index (kg/m weight when aged 2 years, at mid-childhood, and during –0·5 adulthood. Because attained schooling cannot be affected Birthweight* Age 2 years* Mid-childhood* Age 2 years* Mid-childhood by subsequent growth in people who dropped out as Conditional relative weight Conditional height children or adolescents, schooling models exclude adult B conditional relative weight and conditional height. Adult 0·6 size outcomes (height, BMI, and body composition measures) also exclude adult conditional height and con­ 0·5 ditional relative weight. Because conditional height and

0·4 conditional relative weight variables are not correlated, they can be included together in models without concerns 0·3 about colinearity. Because we noted heterogeneity by site and sex for at 0·2 least one conditional relative weight or conditional height variable in most models, we present results stratified by 0·1 sex and site; stratified by sex and adjusted for site; and in conditional growth variable pooled, adjusted for site and sex. Because of the large Change in fat mass (SD) per SD change 0 number of outcomes, we created detailed tables (appendix) that include all estimated coefficients, but summarised –0·1 results graphically to present site and sex-specific Birthweight* Age 2 years* Mid-childhood* Age 2 years* Mid-childhood* coefficients, with sex-stratified pooled results. We adjusted Conditional relative weight Conditional height all models for adult age. Adjustment for gestational age or C socioeconomic status at birth did not meaningfully alter 0·6 coefficients or p values in the models for body composition or cardiometabolic outcomes, so for these models we 0·5 present results unadjusted for these factors. We adjusted height and schooling models for socioeconomic status at 0·4 birth, and additionally adjusted height for maternal height to account for differences in genetic growth potential. 0·3 Information about paternal height was not available. We used Stata (version 12) for analyses. 0·2 Role of the funding source 0·1

in conditional growth variable The sponsors of the study provided financial support for data management and data analysis, but had no other

Change in fat-free mass (SD) per SD change Change in fat-free 0 role in study design, data collection, data analysis, data

–0·1 interpretation, or writing of the report. The corresponding Birthweight Age 2 years Mid-childhood* Age 2 years Mid-childhood* author had full access to all the data in the study and all

Conditional relative weight Conditional height authors made the decision to submit for publication. Figure 1: Association of birthweight, conditional relative weight and conditional height with Results (A) body-mass index, (B) fat mass, and (C) fat-free mass Site-specific datapoints represent β coefficients from linear regression models done separately for each site and We obtained data for 8362 participants who had provided sex. *Significant heterogeneity between sexes and sites. information about at least one adult outcome of interest

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Body-mass index >25 kg/m2 Elevated blood pressure* Dysglycaemia† Short stature‡ Did not complete secondary school Overall number affected 2170/8297 (26·2%) 1571/8233 (19·1%) 511/6947 (7·4%) 1325/8302 (16·0%) 3054/8121 (37·6%) Birthweight 1·28 (1·21–1·35) 0·93 (0·88–0·99) 0·89 (0·81–0·98) 0·49 (0·44–0·54) 0·82 (0·78–0·87) Conditional relative weight at age 2 years 1·51 (1·43–1·60) 1·07 (1·01–1·13) 0·95 (0·86–1·04) 0·94 (0·86–1·03) 0·95 (0·90–0·99) Conditional relative weight mid-childhood 1·76 (1·66–1·86) 1·22 (1·15–1·30) 1·08 (0·98–1·18) 1·13 (1·04–1·23) 1·04 (0·99–1·10) Conditional height at age 2 years 1·24 (1·17–1·31) 1·12 (1·06–1·19) 0·98 (0·89–1·18) 0·23 (0·20–0·25) 0·74 (0·67–0·78) Conditional height mid-childhood 1·12 (1·06–1·18) 1·07 (1·01–1·13) 0·94 (0·86–1·03) 0·39 (0·36–0·43) 0·87 (0·83–0·92)

Data are n/N (%) or odds ratio (95% CI). Odds ratios calculated with logistic regression models of the pooled sample and indicate how a difference of 1 SD in each measure affects the likelihood of the adverse outcome. All models were adjusted for adult age. The models for short stature and completion of secondary school were further adjusted for mother’s education and household wealth at birth; the model for short stature was also adjusted for mother’s height. *Systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg. †Plasma glucose concentration ≥6·1 mmol/L or taking drugs for diabetes. ‡Height-for-age Z score <–2 when aged <19 years; <150·1 cm for women or <161·9 cm for men when aged ≥19 years.

Table 2: Association of birthweight, conditional relative weight gain, and conditional height with adverse outcomes

(table 1). Participants who were lost to follow-up or were similar to those for fat mass and BMI. Heterogeneity excluded because of missing data rarely differed signifi­ between sexes and sites was greater for fat mass than for cantly from those who were included (appendix p 2). fat-free mass. See Online for appendix Mean adult age at which measurements were taken Birthweight was unrelated to systolic blood pressure ranged from about 18 years in South Africa to more than (figure 2, appendix p 11). Higher conditional relative 31 years in Guatemala (table 1). The prevalence of adverse weight at all ages was associated with higher systolic outcomes generally reflects the age and relative economic blood pressure, and the associations strengthened with development of the five samples. Adult height and fat- increasing age at measurement (figure 2). Conditional free mass were highest in Brazilian men (table 1). height at age 2 years and mid-childhood was also Dysglycaemia was too rare to analyse in sex-stratified positively related to systolic blood pressure (figure 2). models in the South African cohort (table 1). The association between birthweight and systolic blood Higher birthweight and conditional relative weight at pressure was not the same in Guatemala as in other sites age 2 years and mid-childhood were consistently asso­ (figure 2, appendix p 11). The β coefficients for asso­ ciated with higher adult BMI in men and women (figure 1, ciations between conditional relative weight at mid- appendix p 5). The association between conditional childhood and adulthood and conditional height at relative weight and BMI strengthened with age at 2 years were larger in men than in women (appendix measure­ment: overall, BMI increased by 0·5 kg/m² per p 11). The findings were similar for diastolic blood SD increase in birthweight, by 1·0 kg/m² at 2 years, and pressure and elevated blood pressure (table 2, appendix 1·3 kg/m² in mid-childhood. Higher conditional height at pp 12–13, 23), except that higher birthweight was 2 years and mid-childhood was also associated with higher associated with a reduced likelihood of elevated blood adult BMI, but coefficients were smaller than were those pressure in adulthood (table 2). for conditional relative weight and diminished with age Conditional relative weight in adulthood and, in women (figure 1). The findings were similar for the binary only, in mid-childhood were associated with higher outcome of obesity (table 2, appendix p 6). Heterogeneity plasma glucose concentration in adulthood (figure 2, between sexes and sites was primarily a result of size appendix p 14). Conditional relative weight at age 2 years rather than direction of coefficients. was unrelated to glucose, and birthweight was inversely All conditional relative weight and conditional height associated with plasma glucose concentration in women variables were associated with higher adult fat mass and (figure 2, appendix p 14). Conditional height at any age fat-free mass (figure 1, appendix pp 7–8). Coefficients was unrelated to adult plasma glucose concentration for birthweight and relative weight increased with the (figure 2, appendix p 14). The findings were similar for age at which size was measured, while conditional dysglycaemia (table 2, appendix p 15). Heterogeneity height coefficients decreased (figure 1). Birthweight and between sexes and sites was significant only for conditional relative weight at age 2 years were more conditional height at age 2 years (appendix). strongly associated with fat-free mass than with fat Each SD of birthweight predicted 1·5 cm higher adult mass, contrasting with stronger associations of con­ height in the pooled sample (figure 3). Conditional ditional relative weight in mid-childhood with fat mass relative weight at age 2 years was unrelated to adult than with fat-free mass (appendix pp 7–8). Conditional height, but conditional relative weight at mid-childhood height at age 2 years and mid-childhood were more was inversely related (figure 3, appendix p 16). By contrast, strongly associated with fat-free mass than with fat increased conditional height at age 2 years and mid- mass, and both associations were stronger at 2 years childhood strongly predicted an increase in adult height than at mid-childhood. The findings for percentage body in all sites (3·2 cm per SD increase in conditional height fat and waist circumference (appendix pp 9–10, 21–22) at age 2 years and 1·9 cm per SD mid-childhood; figure 3, www.thelancet.com 113 Articles

inversely related to attained schooling in both sexes A Men Women (appendix p 19); by contrast, higher conditional height at Pooled data for all men with 95% CI Pooled data for all women with 95% CI 2 years was strongly related to higher attained schooling Brazil Guatemala India Philippines South Africa (except in South Africa), with one SD in conditional height 6·0 at 2 years relating to a half year increase in the pooled

5·0 sample (figure 3). Lower birthweight and conditional height at age 2 years were associated with increased odds 4·0 of failing to complete high school (table 2, appendix p 19). Overall, heterogeneity reflected differences between sites 3·0 rather than between sexes.

2·0 Estimations produced by Heckman selection models did not produce coefficients that were substantially 1·0 different from those estimated with standard linear and logistic regression models. 0

Change in systolic blood pressure (mm Hg) Discussion

per SD change in conditional growth variable –1·0 We have shown that higher birthweight is related to –2·0 increased liklihood of adult overweight in five populations Birthweight Age 2 years Mid- Adult* Age 2 years* Mid- Adult childhood childhood in countries of low and middle income, but to lower likelihood of other adverse outcomes. Although higher Conditional relative weight Conditional height conditional relative weight at age 2 years was associated B with higher risk of adult overweight and a slightly increased 0·3 risk of elevated blood pressure, it was unrelated to dysglycaemia, adult stature, or educational attainment. By

0·2 contrast, conditional relative weight in mid-childhood was associated with higher likelihood of adult overweight and elevated blood pressure, but was unrelated to schooling. 0·1 Although associated with slightly increased likelihood of adult overweight (mostly related to lean mass) and elevated 0 blood pressure, higher conditional heights at age 2 years and at mid-childhood were related to lower risk of short –0·1 stature and poor educational attainment. Few studies from low-income and middle-income –0·2 settings have followed up cohorts to adulthood. Individuals per SD change in conditional growth variable

Change in log plasma glucose concentration (SD) in the cohorts that we studied were born when poor early life nutrition was more common than it is now, which is –0·3 Birthweight Age 2 years Mid- Adult Age 2 years* Mid- Adult shown by the high prevalence of stunting during infancy.30 childhood childhood However, the individuals grew up in rapidly changing Conditional relative weight Conditional height environments that fostered development of obesity and chronic disease risk. Countries that are challenged by the Figure 2: Association of birthweight, conditional relative weight, and conditional height with (A) systolic blood pressure and (B) log plasma glucose concentrations dual burden of persistent undernutrition and emerging Site-specific datapoints represent β coefficients from linear regression models done separately for each site and obesity need information about the many effects of early sex. *Significant heterogeneity between sexes and sites. child growth, particularly during the important first 1000 days. Although the studies included in our analysis appendix p 16). Heterogeneity was a result of site and sex cannot be fully representative of the countries in which differences in the size rather than direction of coefficients they were done, the many similarities of results across (coefficients in men more than coefficients in women). settings suggest that results may be generalised to other Birthweight and conditional height at age 2 years and low-income and middle-income settings. mid-childhood were strongly inversely related to the Another strength of our study is that we were able to chance of short adult stature (table 2, appendix p 17). separate linear growth from relative weight gain. Weight One SD higher birthweight predicted about 0·2 years gain is a result of linear growth and soft tissue gain (fat more schooling (figure 3, appendix p 18). One SD higher mass and fat-free mass); our conditional relative weight conditional relative weight at 2 years was associated with variables represent weight change that is separated 0·14 years more schooling in men, but there was no from change in height. Conditional relative weight and association in women. Conditional relative weight at mid- conditional height variables are uncorrelated, and we childhood was unrelated to attained schooling (figure 3). expressed them in SD units to allow direct comparison of In Guatemala, conditional relative weight at 2 years was coefficients within regression models. Our variables

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therefore have advantages when compared with other A representations of growth, and give more nuanced Men Women results than do those that are based on weight gain alone. Pooled data for all men with 95% CI Pooled data for all women with 95% CI In our study, one SD in conditional relative weight at Brazil Guatemala India Philippines South Africa 2 years corresponds to change in weight-for-age Z score 4·0 from birth to 2 years that is slightly less than the 0·67 units typically used to define rapid weight gain.5 In a 3·0 previous COHORTS report,11 one SD of conditional weight at age 2 years related to 0·4 years more schooling. Here, we showed that attained schooling was pre­ 2·0 dominantly associated with conditional height in the first 2 years, and an increase in conditional relative weight in this period contributed to a rise of only 0·09 years of 1·0 schooling. These findings are important, because an extra half year of schooling is associated with a 5% in conditional growth variable 0 annual return to income.11 Change in adult height (cm) per SD change Each estimate for conditional relative weight or con­ ditional height represents an independent age-specific –1·0 association. We noted that associations of conditional Birthweight* Age 2 yearsMid-childhood Age 2 years* Mid-childhood* relative weight with adult adiposity and cardiometabolic Conditional relative weight Conditional height risk factors strengthened substantially with age. Thus, the most important period for adverse associations of higher B relative weight gain with adult cardiometabolic risk was 1·0 after the age of 2 years. This finding is consistent with the ALSPAC study31 in the UK, which also showed that associations of conditional weight for length after infancy 0·5 with systolic blood pressure and BMI were strongest at age 10 years, and with previous studies32–34 that showed increased risks related to fast weight gain after infancy. By 0 contrast, for cardiometabolic risk factors, conditional height coefficients were smaller than conditional relative weight coefficients and decreased with age, which is consistent with a Brazilian study.35 –0·5 In view of the nature of conditional growth variables, we changein conditional growth variable could assess independent associations of birthweight with of schooling per SD years Change in completed subsequent outcomes, without concern about statistical –0·1 Birthweight Age 2 years* Mid-childhood Age 2 years* Mid-childhood* issues such as the reversal paradox.36 Furthermore, in our analysis, gestational age was not a confounder of the Conditional relative weight Conditional height relation between conditional variables and adult outcomes. Figure 3: Association of birthweight, conditional relative weight, and conditional height with (A) adult A separate analysis of COHORTS data (unpublished) height and (B) years spent at school established that a premature birth or being small for Site-specific datapoints represent β coefficients from linear regression models done separately for each site and gestational age were related to persistent deficits in adult sex. *Significant heterogeneity between sexes and sites. height and schooling, but did not affect blood pressure or plasma glucose concentrations. gain was more strongly associated with fat mass than fat- We addressed potential trade-offs of different early free mass, and increased risk of elevated blood pressure growth patterns by comparing human capital outcomes and dysglycaemia. The positive associations of all growth known to be associated with impaired child growth and variables at all ages with adult BMI and risk of overweight development with cardiometabolic disease risk factors. and obesity are probably a result of their joint effect on fat Birthweight and faster conditional relative weight in the mass and fat-free mass, and the fact that overweight adults first 2 years of life had little relation with adult cardio­ have highly variable amounts of body fat. metabolic risk factors, but were important for fat-free Despite being restricted to participants with complete mass. Indeed, early weight gain was more strongly data, the sample that we analysed differed little from associated with adult fat-free mass than with adult fat individuals who were excluded, and estimates produced mass. This finding could explain the negative associations with Heckman selection models were not different of birthweight and the small or non-significant associations from models estimated with conventional methods. of early relative weight gain with elevated blood pressure There­fore, our estimated coefficients do not seem to and dysglycaemia. Faster mid-childhood relative weight have been biased by attrition or missing data. Some www.thelancet.com 115 Articles

cohort rather than what we might have chosen for the Panel: Research in context greatest biological signal, such as within the first Systematic review 2 years. A 2008 systematic review30 examined how birthweight and Heterogeneity, as represented by significant site or sex weight-for-age and length-for-age Z scores at age 2 years interactions, or both, with key exposures, could be a result related to adult human capital and chronic disease risk. of the differences between cohorts or true effect modifi­ Therefore, we searched PubMed for reports published in any cation. Although data for 48 months were not available in language since Jan 1, 2009, which related birthweight and the Philippines, mid-childhood estimates did not differ childhood growth rates to these same adult outcomes. We systematically from other sites. Although our cohorts focused on studies that attempted to assess both weight gain differed in childhood size and adult cardio­metabolic risk and linear growth at different ages, and that involved profile, significant site and sex hetero­geneity mostly appropriate statistical methods to differentiate their effects reflected differences in size of associations,­ not direction. on subsequent outcomes. Our search terms were “weight Therefore, use of pooled analyses to draw conclusions gain”, “linear growth”, “rapid weight gain”, “birth cohorts”, seems to be justified. Outliers were usually from and “prospective studies”. Few identified studies were done Guatemala (which provided the smallest sample) or South in low-income and middle-income countries, and few used Africa (the youngest). For example, the unique absence of the statistical methods needed to model correlated life an association between early height gain and schooling in course data. Although many reports associate rapid weight South Africa is probably because participants aged 18 years gain with obesity and related outcomes, we identified only had no opportunity for education after secondary school. two31,35 that directly compared how linear growth and relative Additionally, the absence of significant predictors of glu­ weight gain related to adult blood pressure, glucose cose concentration in South Africa is probably a result of metabolism, body composition, height, or schooling. No the cohort’s young age and little variation in glucose reports directly compared several outcomes representing concentration (few concentrations were >6 mmol/L). health and human capital to enable assessment of risks and Our findings suggest that interventions to increase benefits of early growth patterns. birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and Interpretation schooling (key aspects of human capital), and give some We have studied life course determinants of young adult protection from development of adult chronic disease risk human capital and disease risk factors in five countries of low factors, with no or negligible adverse trade-offs. Consistent and middle income, by using appropriate statistical methods with a growing body of research, our results indicate that to directly compare how faster relative weight gain and faster faster relative weight gain after the age of 2 years has little linear growth relate to these outcomes. We have shown that benefit for human capital, and weight gain after mid- effects on the different outcomes are age specific. Fast linear childhood could lead to large adverse effects on later growth in the first 2 years of life is associated with increased cardiovascular risk factors. Notably, this finding is adult height and amount of schooling. Adverse associations particularly true for weight gain that is not accompanied by with fast relative weight gain are largely confined to height gain. Our data support the present focus on mid-childhood and adulthood. Our data support the current promotion of improved nutrition and linear growth in the focus on promotion of nutrition and linear growth in the first first 1000 days of life, and also reinforce the importance of 1000 days of life (from conception to age 2 years), and also prevention of rapid relative weight gain after age 2 years. reinforce the importance of prevention of rapid relative Although the associations we describe do not prove weight gain after age 2 years. These findings have implications causation, our results challenge several programmes in for present practices in low-income and middle-income countries of low and middle income (panel). Rapid weight countries, particularly emphasising the need to monitor linear gain should not be promoted after the age of 2–3 years in growth as well as weight, and to avoid promotion of excess children who are underweight but not wasted. Growth weight gain in children older than 2 years. Optimum growth monitoring programmes should incorporate length and patterns in early life are likely to lead to less undernutrition, height measures, not just weight measures. New increased human capital, and reduced risks of obesity and interventions that specifically promote linear growth non-communicable diseases, thus addressing both instead of weight gain should be developed, tested, and components of the double burden of nutrition. promoted; exclusive breastfeeding, high-quality protein (eg, animal), and micronutrients could be further investigated.37 Traditional school feeding programmes differ­ences between our cohorts were unavoidable, that increase BMI with little effect on height38 might be such as methods for measurement of birthweight, doing more harm than good in terms of future health. plasma glucose concentration, blood pressure, and Mortality and undernutrition are falling substantially in adult body composition, and also age at mid-childhood most parts of the world, except for Sub-Saharan Africa, and adult­hood. Our choice of age intervals was and new targets are being formulated to replace the determined by the availability of measurements in each present set of 2015 Millennium Development Goals.39 Our

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analyses provide strong justification for the proposal of a 8 Stein AD, Wang M, Martorell R, et al. Growth patterns in early new goal for optimum linear growth that is expressed as a childhood and final attained stature: data from five birth cohorts from low- and middle-income countries. Am J Hum Biol 2010; reduction in stunting. This goal should replace the present 22: 353–59. target of a reduction in underweight alone, which is one of 9 Kuzawa CW, Hallal PC, Adair L, et al. Birth weight, postnatal weight the indicators for the first Millennium Development Goals gain, and adult body composition in five low and middle income countries. Am J Hum Biol 2012; 24: 5–13. towards the eradication of extreme poverty. Whereas 10 Sachdev HS, Fall CH, Osmond C, et al. Anthropometric indicators promotion of linear growth in early life could build human of body composition in young adults: relation to size at birth and capital in adults without increasing the burden of non- serial measurements of body mass index in childhood in the New Delhi birth cohort. Am J Clin Nutr 2005; 82: 456–66. communicable diseases, the present focus on underweight 11 Martorell R, Horta BL, Adair LS, et al. Weight gain in the first might have detrimental repercussions, particularly if two years of life is an important predictor of schooling outcomes interventions take place after 1000 days. in pooled analyses from five birth cohorts from low- and middle-income countries. J Nutr 2010; 140: 348–54. Contributors 12 Carba DB, Tan VL, Adair LS. Early childhood length-for-age is LSA, CHDF, and CO led the writing team. LSA and CO did data associated with the work status of Filipino young adults. analysis. LSA and CHDF wrote the report and had final responsibility Econ Hum Biol 2009; 7: 7–17. for the content. All authors contributed to data collection, and reviewed 13 Thomas D, Frankenberg E. Health, nutrition and prosperity: and commented on the report and approved its final content. a microeconomic perspective. Bull World Health Organ 2002; 80: 106–13. COHORTS group members 14 Hoddinott J, Maluccio JA, Behrman JR, Flores R, Martorell R. Effect Universidade Federal de Pelotas, Brazil: Cesar G Victora, Fernando C Barros, of a nutrition intervention during early childhood on economic Denise Gigante, Pedro C Hallal, Bernardo L Horta; Hubert Department of productivity in Guatemalan adults. Lancet 2008; 371: 411–16. Global Health, Emory University, USA: Reynaldo Martorell, Aryeh Stein, 15 Richter LM, Victora CG, Hallal PC, et al. Cohort profile: the Yaw Addo, Wei Hao; Instituto de Nutrición de Centra América y Panamá, Consortium of Health-Orientated Research in Transitioning Guatemala: Manual Ramirez-Zea; Sunderlal Jain Hospital, India: Societies. Int J Epidemiol 2012; 41: 621–26. Santosh K Bhargava; Sitaram Bhartia Institute of Science and Research, 16 Victora CG, Barros FC. Cohort profile: the 1982 Pelotas (Brazil) India: Harshpal Singh Sachdev; MRC Lifecourse Epidemiology Unit, UK: birth cohort study. Int J Epidemiol 2006; 35: 237–42. Caroline Fall, Clive Osmond; University of North Carolina at Chapel Hill, 17 Stein AD, Melgar P, Hoddinott J, Martorell R. Cohort profile: the USA: Linda Adair; Office of Population Studies, University of San Carlos, Institute of Nutrition of Central America and Panama (INCAP) Philippines: Isabelita Bas, Nanette Lee, Judith Borja; University of Leeds, Nutrition Trial Cohort Study. Int J Epidemiol 2008; 37: 716–20. UK: Darren Dahly; Northwestern University, USA: Christopher Kuzawa; 18 Adair LS, Popkin BM, Akin JS, et al. Cohort profile: the Cebu Developmental Pathways for Health Research Unit, University of the longitudinal health and nutrition survey. Int J Epidemiol 2011; Witwatersrand, South Africa: Linda Richter, Shane Norris, Julia De Kadt. 40: 619–25. Conflicts of interest 19 Richter L, Norris S, Pettifor J, Yach D, Cameron N. Cohort profile: We declare that we have no conflicts of interest. Mandela’s children: the 1990 Birth to Twenty study in South Africa. Int J Epidemiol 2007; 36: 504–11. Acknowledgments 20 Keijzer-Veen MG, Euser AM, van Montfoort N, Dekker FW, The COHORTS collaboration is funded by the Wellcome Trust Vandenbroucke JP, Van Houwelingen HC. A regression model with (089257/Z/09/Z). Additional funding for data analysis for this study was unexplained residuals was preferred in the analysis of the fetal origins provided by the Bill & Melinda Gates Foundation (OPP1020058). The of adult diseases hypothesis. J Clin Epidemiol 2005; 58: 1320–24. cohort studies in Guatemala and the Philippines were funded by the US 21 Li H, Stein AD, Barnhart HX, Ramakrishnan U, Martorell R. National Institutes of Health; that in Brazil by the Wellcome Trust; that Associations between prenatal and postnatal growth and adult body in India by the Indian Council of Medical Research, US National Center size and composition. Am J Clin Nutr 2003; 77: 1498–505. for Health Statistics, UK Medical Research Council, and British Heart 22 Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard Foundation; and that in South Africa by the Wellcome Trust, Human definition for child overweight and obesity worldwide: international Sciences Research Council, South African Medical Research Council, survey. BMJ 2000; 320: 1240–43. South-African Netherlands Programme on Alternative Development, 23 WHO. Child Growth Standards based on length/height, weight and Anglo American Chairman’s Fund, and University of the Witwatersrand age. Acta Paediatr Suppl 2006; 450: 76–85. in South Africa. We thank Jane Pearce for producing graphs and 24 International Diabetes Federation. The IDF consensus worldwide formatting tables. definition of the metabolic syndrome. Brussels: International Diabetes Federation, 2006. References 25 Norris SA, Osmond C, Gigante D, et al. Size at birth, weight gain in 1 Stettler N, Iotova V. Early growth patterns and long-term obesity infancy and childhood, and adult diabetes risk in five low- or risk. Curr Opin Clin Nutr Metab Care 2010; 13: 294–99. middle-income country birth cohorts. Diabetes Care 2012; 35: 72–79. 2 Demerath EW, Reed D, Choh AC, et al. Rapid postnatal weight gain 26 Kumar G, Sng BL, Kumar S. Correlation of capillary and venous and visceral adiposity in adulthood: the Fels Longitudinal Study. blood glucometry with laboratory determination. 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