Chapter 7. Interventions to Reduce Maternal and Child Morbidity and Mortality A. Metin Gülmezoglu1, Theresa Lawrie1, Natasha Hezelgrave2, Olufemi Oladapo1, João Paulo Souza3, Marijke Gielen4, Joy Lawn5, Rajiv Bahl1, Fernando Althabe6, Agustina Mazzoni6, and G. Justus Hofmeyr7 1UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, Avenue Appia 20, 1201 Geneva, Switzerland. 2 Division of Women's Health, King's College London School of Medicine, London, UK. 3 Department of Social Medicine, Ribeirão Preto School of Medicine, University of São Paulo, Brazil. 4 5 Maternal, Adolescent Reproductive and Child Health (MARCH) Centre, London School of Hygiene & Tropical Medicine, London, UK; Saving Newborn Lives, Save the Children, Washington, DC, USA; Research and Evidence Division, UK AID, London, UK. 6 Institute for Clinical Effectiveness and Health Policy (IECS), Dr. Emilio Ravignani 2024, C1414CPV, Buenos Aires, Argentina. 7 Effective Care Research Unit, East London Hospital Complex, East London, South Africa Boxes: 1 Figures: 1 Tables: 4 1 | P a g e Outline I. Introduction II. Interventions to Reduce Maternal Mortality and Morbidity A. Postpartum Hemorrhage 1. Preventing PPH 2. Treating PPH B. Preeclampsia and Eclampsia 1. Preventing Preeclampsia and Eclampsia 2. Treating Preelampsia and Eclampsia C. Obstructed Labor 1. Preventing Obstructed Labour 2. Managing Obstructed Labour D. Maternal Sepsis 1. Preventing Maternal Sepsis 2. Treating Maternal Sepsis III. Interventions to Reduce Stillbirths and Newborn Mortality and Morbidity A. Antenatal Interventions 1. Nutritional Interventions 2. Treatment of Maternal Infections 3. Treatment of Hypertensive Disorders 4. Treatment of Diabetes Mellitus and Gestational Diabetes 5. Intrauterine Growth Restriction 6. Postterm Pregnancy B. Intrapartum Interventions 1. General Interventions 2. Preterm Labor and Preterm Pre-Labor Rupture of Membranes 3. Newborn Resuscitation 4. Essential Newborn Care C. Neonatal Interventions 1. Birth Asphyxia 2. Respiratory Distress Syndrome 3. Neonatal Sepsis 4. Pipeline Interventions IV. Cost-effectiveness V. Conclusions 2 | P a g e Introduction In 2010, an estimated 287,000 women died as a result of pregnancy and childbirth-related complications. Most of these deaths occurred in low-income countries (LICs). Sub-Saharan Africa has the highest maternal mortality ratio (MMR), estimated at 500 maternal deaths per 100,000 live births in 2010; by contrast, the MMR for developed regions was estimated at 16 maternal deaths per 100,000 live births (Souza and others 2013). Although significant progress has been made since 1990 toward achieving the MDGs, with a reduction in the global MMR from 400 to 210 maternal deaths per 100,000 live births, much work remains to be done, as this reduction (almost 50 percent) falls short of the 2015 MDG 5 target of 75 percent. Similarly, mortality for children under five years (MDG 4) has declined by 47 percent, from nearly 12.4 million in 1990 to 6.6 million in 2012, short of the 2015 target of 67 percent (Souza and others 2013; UNICEF and WHO 2013). Again, the distribution of the global burden of child mortality is disparate. Within countries when the population is disaggregated by income, education, or place of residence, wide disparities can be shown, even in those areas where the overall mortality seems low. Communicable, maternal, neonatal, and nutritional causes account for 25 percent of deaths and remain dominant causes of premature mortality in Sub-Saharan Africa (Hewitt 1988; Ngoc and others 2006). Newborns account for almost half (44 percent) of all under-five deaths, with this percentage reaching 50 percent or higher in several countries (United Nations 2013). Preterm birth and birth asphyxia account for 21% of under-five child mortality in 2008 (Black and others 2010). 3 | P a g e The tracking of progress in meeting the MDGs does not include declines in the numbers of stillbirths. In 2009, an estimated 2.64 million stillbirths occurred in the last trimester of pregnancy, with more than 45 percent in the intrapartum period (Cousens and others 2011; Lawn and others 2011). The majority of these stillbirths (98 percent) occur in low- and middle-income countries (LMICs) (Black and others 2010). Box 1 Millennium Development Goals 4 and 5 MDG 4: Reduce child mortality Target: 1. Reduce by two thirds, between 1990 and 2015, the under-five mortality rate. MDG 5: Improve maternal Health Targets: 1. Reduce by three quarters, between 1990 and 2015, the maternal mortality ratio 2. Achieve, by 2015, universal Access to reproductive health Significant proportions of these maternal, fetal, and newborn deaths are preventable and underscore the importance of initiatives to meet the Millennium Development Goals (MDG) 4 and 5.This chapter discusses and recommends the implementation of interventions in the context of people’s right to access good quality, respectful, and timely care—wherever they may live. Interventions to Reduce Maternal Mortality and Morbidity Major obstetric causes of maternal mortality include hemorrhage, hypertensive diseases of pregnancy (mainly preeclampsia/eclampsia), sepsis, and obstructed labor. In a cross-sectional study conducted across 29 countries in Asia, Latin America and the Caribbean, the Middle East and North Africa, and Sub- Saharan Africa, postpartum hemorrhage and preeclampsia/eclampsia accounted for 27 percent and 26 percent, respectively, of severe maternal outcomes (Souza and others 2013). Table 7.1 provides an overview of evidence-based effective interventions to reduce poor maternal outcomes. The contribution of indirect causes of maternal deaths, such as medical disorders, malaria, tuberculosis, and HIV seem to be increasing, which raises the importance of integrating service delivery during pregnancy and childbirth. 4 | P a g e Table 7.1 Some Evidence-Based Effective Interventions that Reduce Maternal Morbidity and Mortality Type of Main effects Quality of Source of intervention evidencea evidence Postpartum hemorrhage Oxytocin Halves PPH risk when used High Westhoff, Cotter, routinely and Tolosa 2013 Is well tolerated Is recommended for prevention and treatment Misoprostol Reduces PPH risk and the need for Moderate Tunçalp, blood transfusion Hofmeyr, and Side effects of shivering and fever Gülmezoglu 2012 Recommended for PPH prevention if oxytocin unavailable Preeclampsia and eclampsia Calcium Halves preeclampsia risk in all High Hofmeyr and supplementation women others 2014 Risk reduction is greatest in high risk women and those with low dietary calcium intake Aspirin Reduces the risk of preeclampsia in High Duley and others supplementation high-risk women 2007 Magnesium Reduces the risk of seizures in High Altman and sulphate women with preeclampsia, with a others 2002 trend to reduced maternal mortality Timing of delivery Induction of labour after 36 weeks’ High Koopmans and gestation reduces poor maternal others 2009 outcomes in mild preeclampsia Sepsis Prophylactic Reduces risk of febrile morbidity, High Smaill and Gyte antibiotics at wound infection, endometritis and 2010 cesarean section serious maternal infectious morbidity General interventions Posture in labour Upright and ambulant postures High Lawrence and reduces labor duration and the need others 2013 for cesarean sections Note: a = Based on GRADE Working Group grades of evidence. (Atkins and others 2004) 5 | P a g e Postpartum Hemorrhage Preventing Postpartum Hemorrhage The most effective intervention for preventing postpartum hemorrhage is the use of uterotonics—drugs that contract the uterus—during the third stage of labor when the placenta is delivered. An injectable uterotonic is the drug of choice; however, oral or sublingual misoprostol may be used when injectable uterotonics are not available. Other interventions include uterine massage, cord clamping, and controlled cord traction (table 7.1). Table 7.2 Interventions to Prevent Postpartum Hemorrhage Evidence-Based Effective Interventions for PPH Prevention Uterotonics used during the third stage of labor: Oxytocin (10 IU IM or IV) is the drug of choice. (Westhoff, Cotter, and Tolosa 2013) In settings where oxytocin is unavailable, other injectable uterotonics (ergot alkaloids if appropriate, or the fixed drug combination of oxytocin/ergometrine), or oral misoprostol (600 μg) are recommended. (WHO 2012) Interventions with No Evidence, or Inconclusive Evidence, for PPH Prevention Uterine massage (Hofmeyr, Abdel-Aleem, and Abdel-Aleem 2013) Early vs late cord clamping (McDonald and others 2013) Controlled cord traction (Gülmezoglu and others 2012b; Deneux- Tharaux and others 2013) Uterotonic Agents. Two uterotonic agents used prophylactically are oxytocin and misoprostol. [bullet]Oxytocin and ergot alkaloids. A Cochrane review assessed the effect of prophylactic oxytocin given during the third stage of labor on PPH (blood loss greater than 500 mL) (Westhoff, Cotter, and Tolosa 2013). The review included 20 randomized clinical trials (RCTs) involving 10,806 women. Prophylactic oxytocin, compared with placebo, halved the risk of PPH and, when compared with ergot alkaloids, reduced the risk of PPH by 25 percent.. There was no significant difference in the risk of PPH with the combination of oxytocin/ergometrine versus ergot alkaloids alone. Oxytocin was better tolerated than ergot alkaloids. [bullet]Misoprostol.