WHO Recommendations on Antenatal Care for a Positive Pregnancy Experience WHO Library Cataloguing-In-Publication Data

WHO recommendations on antenatal care for a positive pregnancy experience WHO Library Cataloguing-in-Publication Data

WHO recommendations on antenatal care for a positive pregnancy experience. I.World Health Organization.

ISBN 978 92 4 154991 2

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Printed in Luxembourg Contents

Acknowledgements v Acronyms and abbreviations vii Executive summary ix 1. Introduction 1 2. Methods 4 3. Evidence and recommendations 13 A. Nutritional interventions 14 B. Maternal and fetal assessment 40 C. Preventive measures 63 D. Interventions for common physiological symptoms 74 E. Health systems interventions to improve the utilization and quality of ANC 85 4. Implementation of the ANC guideline and recommendations: introducing the 2016 WHO ANC model 105 5. Research implications 118 6. Dissemination, applicability and updating of the guideline and recommendations 120 References 123 Annex 1: External experts and WHO staff involved in the preparation of this guideline 137 Annex 2: Other WHO guidelines with recommendations relevant to routine ANC 141 Annex 3: Summary of declarations of interest from the Guideline Development Group (GDG) members and how they were managed 143 Annex 4: Implementation considerations for ANC guideline recommendations 145

Web annexes: WHO recommendations on antenatal care for a positive pregnancy experience* Web annex 1: Priority questions and outcomes for the antenatal care (ANC) interventions identified for this guideline Web annex 2: Changes from the approved scope of this guideline Web annex 3: Guideline Development Group (GDG) judgements related to the recommendations

Web supplement: WHO recommendations on antenatal care for a positive pregnancy experience: evidence base* The standardized criteria used in grading the evidence and the GRADE tables have been published in this separate Web supplement. These evidence tables are referred to within this document by number, prefixed with "EB" (for evidence base), for ease of reference.

* available at: www.who.int/reproductivehealth/publications/maternal_perinatal_health/anc-positive-pregnancy-experience/en/ « To achieve the Every Woman Every Child vision and the Global Strategy for Women's, Children's and Adolescents' Health, we need innovative, evidence-based approaches to antenatal care. I welcome these guidelines, which aim to put women at the centre of care, enhancing their experience of pregnancy and ensuring that babies have the best possible start in life. » Ban Ki-moon, United Nations Secretary-General Acknowledgements

The Departments of Reproductive Health and Research (RHR), Nutrition for Health and Development (NHD), and Maternal, Newborn, Child and Adolescent Health (MCA) of the World Health Organization (WHO) gratefully acknowledge the contributions that many individuals and organizations have made to the development of this guideline.

A. Metin Gülmezoglu, Matthews Mathai, Olufemi Oladapo, Juan Pablo Peña-Rosas and Özge Tunçalp were the members of the WHO Steering Group that managed the guideline development process. The members of the Guideline Development Group (GDG) included Mohammed Ariful Aram, Françoise Cluzeau, Luz Maria De-Regil, Aft Ghérissi, Gill Gyte, Rintaro Mori, James Neilson, Lynnette Neufeld, Lisa Noguchi, Nafissa Osman, Erika Ota, Tomas Pantoja, Bob Pattinson, Kathleen Rasmussen, Niveen Abu Rmeileh, Harshpal Singh Sachdev, Rusidah Selamat, Charlotte Warren and Charles Wisonge. James Neilson served as chair of the GDG.

We would also like to thank the following WHO regional advisors for their contributions: Karima Gholbzouri, Gunta Lazdane, Bremen de Mucio, Mari Nagai, Leopold Ouedraogo, Neena Raina and Susan Serruya. We would also like to thank the following individuals for their contributions to the guideline process, including the scoping: Manzi Anatole, Rifat Atun, Himanshu Bhushan, Jacquelyn Caglia, Chompilas Chongsomchai, Morseda Chowdhury, Mengistu Hailemariam, Stephen Hodgins, Annie Kearns, Ana Langer, Pisake Lumbiganon, Taiwo Oyelade, Jeffrey Smith, Petra ten Hoope-Bender, James Tielsch and Rownak Khan.

Special thanks to the authors of the Cochrane systematic reviews used in this guideline for their assistance and collaboration in preparing or updating them. Sonja Henderson, Frances Kellie and Nancy Medley coordinated the updating of the relevant Cochrane systematic reviews. Soo Downe and Kenny Finlayson performed the scoping and qualitative reviews on the views of women and providers with regard to antenatal care (ANC). For the evidence on interventions, Edguardo Abalos, Monica Chamillard and Virginia Dias reviewed and graded the scientific evidence. For the evidence on test accuracy, Khalid Khan and Ewelina Rogozinska reviewed and graded the scientific evidence. Theresa Lawrie reviewed the evidence grading, and drafted the evidence summaries. Simon Lewin and Claire Glenton contributed to the preparation of the evidence summaries on ANC delivery options and provided technical support on the DECIDE framework (Developing & Evaluating Communication strategies to support Informed Decisions & Practice based on Evidence). Emma Allanson coordinated the population of the DECIDE frameworks. Jenny Moberg reviewed and summarized the indirect evidence on ANC delivery. Ipek Gurol-Urganci, Charles O’Donovan and Inger Scheel reviewed data on the implementation of focused ANC (FANC) from country case studies to support the guideline recommendations. The members of the WHO Steering Group and Theresa Lawrie drafted the final guideline document.

We thank the observers who represented various organizations during the guideline development process, including: France Donnay of the Bill & Melinda Gates Foundation; Rita Borg-Xuereb of the International Confederation of Midwives (ICM); Diogo Ayres-de-Campos and CN Purandare of the International Federation of Gynecology and Obstetrics (FIGO); Luc de Bernis of the United Nations Population Fund (UNFPA); and Roland Kupka of the United Nations Children’s Fund (UNICEF); and Deborah Armbruster and Karen Fogg of the United States Agency for International Development (USAID).

We appreciate the feedback provided by a large number of international stakeholders during the scoping exercise that took place as part of the guideline development process. We also would like to thank the following individuals who contributed to this process and reviewed the guideline document: Andrea Bosman, Maurice Bucagu, Jahnavi Daru, Claudia Garcia-Moreno, Haileyesus Getahun, Rodolfo Gomez, Tracey Goodman, Tamar Kabakian, Avinash Kanchar, Philipp Lambach, Sarah de Masi, Frances McConville, Antonio Montresor, Justin Ortiz, Anayda Portela, Jeremy Pratt, Lisa Rogers, Nathalie Roos, Silvia Schwarte, Maria Pura Solon, João Paulo Souza, Petr Velebil, Teodora Wi, Ahmadu Yakubu, Yacouba Yaro and Gerardo Zamora.

Acknowledgements v vi WHO recommendations on antenatal care for a positive pregnancy experience this guideline. in HumanReproduction (HRP) core budget. The views of thefundingbodieshave notinfluenced the content of UNDP/UNFPA/UNICEF/WHO/World BankSpecialProgramme ofResearch, Development andResearch Training Funding was provided for thisguidelineby USAID andtheBill&MelindaGates Foundation, supplemented by the Acronyms and abbreviations

ANC antenatal care ASB asymptomatic bacteriuria BMI body mass index CERQual Confidence in the Evidence from Reviews of Qualitative Research CI confidence interval CTG cardiotocography DECIDE Developing and Evaluating Communication strategies to support Informed Decisions and Practice based on Evidence DOI declaration of interest EB evidence base EGWG excessive gestational weight gain ERG External Review Group FANC focused antenatal care FIGO International Federation of Gynecology and Obstetrics GBS group B streptococcus GDG Guideline Development Group GRADE Grading of Recommendations Assessment, Development and Evaluation GRC Guidelines Review Committee GREAT Guideline-driven, Research priorities, Evidence synthesis, Application of evidence, and Transfer of knowledge Hb haemoglobin HIC high-income country HIV human immunodeficiency virus HRP UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction ICM International Confederation of Midwives IPTp intermittent preventive treatment in pregnancy IPTp-SP intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine IQR interquartile range IUGR intrauterine growth restriction IVR Initiative for Vaccine Research LMIC low- and middle-income country MCA Department of Maternal, Newborn, Child and Adolescent Health (at WHO) MD mean difference MLCC midwife-led continuity of care MMN multiple micronutrient MUAC mid-upper arm circumference NHD Department of Nutrition for Health and Development (at WHO) NRS non-randomized study

Acronyms and abbreviations vii viii WHO recommendations on antenatal care for a positive pregnancy experience WHO UTI USAID US$ UNIMMAP UNICEF UNFPA UNDP UN TWG TT-CV TT TDF Tdap TBA TB SP SGA SFH RUTI RR RHR Rh RCT PWG PROM PrEP PMR PMNCH PLA PICO PCG PAHO OR

United Nationsint tetanus t tetanus/ sulfado World HealthOr urinary tract inf United Stat United Stat United NationsC United NationsP United NationsDe Unit Technical W t tenof traditional bir tuber small for g s recurr r ofR Department rhesus randomiz participat prelabour ruptur pr perinatal mortalit The P participat population (P), int Pr Pan AmericanHealthOr odds etanus toxoid etanus risk elative ymphysis-fundal height ymphysis-fundal egnancy andChildbirth Group (Cochrane Collaboration) e-exposure prophylaxis e-exposure ed Nations ed ovir disoproxil fumarate culosis ratio artnership for Maternal, Newborn &Child Health ent urinarytract infections xine-pyrimethamine diphtheria/acellular pertussis oxoid-containing vaccine ed controlled trial ory women’s group ory learningandaction estational age es Agency for International Development es (US) dollar orking Group th attendant ection e ofmembranes eproductive HealthandResearch (atWHO) ganization opulation Fund hildren’s Fund y rate ernational multiplemicronutrient preparation ervention (I),comparator (C), outcome (O) velopment Programme ganization (WHORegional Office fortheAmericas) Executive summary

Introduction

In 2016, at the start of the Sustainable Development Goals (SDGs) era, pregnancy-related preventable morbidity and mortality remains unacceptably high. While substantial progress has been made, countries need to consolidate and increase these advances, and to expand their agendas to go beyond survival, with a view to maximizing the health and potential of their populations.

The World Health Organization (WHO) envisions a world where every pregnant woman and newborn receives quality care throughout the pregnancy, childbirth and the postnatal period. Within the continuum of reproductive health care, antenatal care (ANC) provides a platform for important health-care functions, including health promotion, screening and diagnosis, and disease prevention. It has been established that by implementing timely and appropriate evidence-based practices, ANC can save lives. Crucially, ANC also provides the opportunity to communicate with and support women, families and communities at a critical time in the course of a woman’s life. The process of developing these recommendations on ANC has highlighted the importance of providing effective communication about physiological, biomedical, behavioural and sociocultural issues, and effective support, including social, cultural, emotional and psychological support, to pregnant women in a respectful way. These communication and support functions of ANC are key, not only to saving lives, but to improving lives, health-care utilization and quality of care. Women’s positive experiences during ANC and childbirth can create the foundations for healthy motherhood.

This is a comprehensive WHO guideline on routine ANC for pregnant women and adolescent girls. The aim is for these recommendations to complement existing WHO guidelines on the management of specific pregnancy- related complications. The guidance is intended to reflect and respond to the complex nature of the issues surrounding the practice and delivery of ANC, and to prioritize person-centred health and well-being – not only the prevention of death and morbidity – in accordance with a human rights-based approach.

The scope of this guideline was informed by a systematic review of women’s views, which shows that women want a positive pregnancy experience from ANC. A positive pregnancy experience is defined as maintaining physical and sociocultural normality, maintaining a healthy pregnancy for mother and baby (including preventing or treating risks, illness and death), having an effective transition to positive labour and birth, and achieving positive motherhood (including maternal self-esteem, competence and autonomy).

Recognizing that a woman’s experience of care is key to transforming ANC and creating thriving families and communities, this guideline addresses the following questions: nnWhat are the evidence-based practices during ANC that improve outcomes and lead to a positive pregnancy experience? nnHow should these practices be delivered?

Guideline development methods

These ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. The guideline was developed using standard operating procedures in accordance with the process described in the WHO handbook for guideline development. Briefly, these procedures include: (i) identification of priority questions and outcomes; (ii) evidence retrieval and synthesis; (iii) assessment of the evidence; (iv) formulation of the recommendations; and (v) planning for implementation, dissemination, impact evaluation and updating of the guideline. The quality of the scientific evidence underpinning the recommendations was graded using the Grading of Recommendations Assessment, Development and

Executive summary ix x WHO recommendations on antenatal care for a positive pregnancy experience interventions thatare notrecommended. interventions thatare recommended, onlyrecommended undercertain conditions (includingresearch), and clinical practices. Table 1summarizes thelistofallinterventions evaluated by theGDGandtherefore includes manual for health-care practitioners, whichwillincorporate ANCrecommendations andestablishedgood other quality-improvement activities.Derivative products ofthisguidelinewillincludeapractical implementation (see Recommendation E.7 inTable 1).The recommendations inthisguidelineshouldbeimplemented alongside facilitate assessment ofwell-being andprovision ofinterventions to improve outcomes ifproblems are identified the recommended numberofcontacts between themotherandhealth-care providers attimepointsthatmay lesser satisfaction ofwomen withthefour-visit model(alsoknown asfocused orbasicANC),decidedto increase guideline asawholewere discussed. The GDG,emphasizingtheevidence indicatingincreased fetal deathsand At theTechnical Consultations, theimplementation considerations ofindividualrecommendations andofthe WHO welcomes suggestions regarding additionalquestionsfor inclusioninfuture updates oftheguideline. updated following the identificationofnew evidence, withmajor reviews andupdates atleast every five years. In accordance withWHOguidelinedevelopment standards, theserecommendations willbereviewed and experience are summarized inTable 1. providing acomprehensive documentfor end-users. All49 recommendations onANCfor apositive pregnancy systematically identifiedand10such recommendations were consolidated into thisguideline for thepurposeof addition, ANC-relevant recommendations from current guidance produced by were otherWHOdepartments should refer to theseremarks, whichare presented alongwiththeevidence summarieswithintheguideline.In recommendation, andthecontributing experts provided additionalremarks where needed.Users oftheguideline and appliedinpractice, thecontext ofallcontext-specific recommendations isclearlystated withineach and context, ifany, oftherecommendation. To ensure thateachrecommendation iscorrectly understood conditions basedontheGDG’s judgements according to theDECIDE criteria, whichinformed boththedirection and quality ofANC.Interventions were eitherrecommended, notrecommended, orrecommended undercertain D. Interventions for common physiological symptoms, andE.Healthsystem interventions to improve utilization of interventions: A.Nutritional interventions, B.Maternal andfetal assessment, C.Preventive measures, The WHOTechnical Consultations ledto thedevelopment of39recommendations related to five types Recommendations Consultations between October 2015 andMarch 2016. international group ofexperts assembled for thepurposeofdeveloping thisguideline–atthree Technical to guidetheformulation andapproval ofrecommendations by theGuidelineDevelopment Group (GDG) –an tool thatincludesintervention effects, values, resources, equity, acceptability and feasibility criteria, was used Strategies Informed to support DecisionsandPractice basedonEvidence) framework, anevidence-to-decision to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication approaches, for quantitative andqualitative evidence, respectively. Up-to-date systematic reviews were used Evaluation (GRADE) andConfidence inthe Evidence from Reviews ofQualitative research (GRADE-CERQual) Table 1: Summary list of WHO recommendations on antenatal care (ANC) for a positive pregnancy experience

These recommendations apply to pregnant women and adolescent girls within the context of routine ANC

A. Nutritional interventions

Recommendation Type of recommendation

Dietary A.1.1: Counselling about healthy eating and keeping physically active Recommended interventions during pregnancy is recommended for pregnant women to stay healthy and to prevent excessive weight gain during pregnancy.a

A.1.2: In undernourished populations, nutrition education on increasing Context-specific daily energy and protein intake is recommended for pregnant women to recommendation reduce the risk of low-birth-weight neonates.

A.1.3: In undernourished populations, balanced energy and protein Context-specific dietary supplementation is recommended for pregnant women to reduce recommendation the risk of stillbirths and small-for-gestational-age neonates.

A.1.4: In undernourished populations, high-protein supplementation Not recommended is not recommended for pregnant women to improve maternal and perinatal outcomes.

Iron and folic acid A.2.1: Daily oral iron and folic acid supplementation with 30 mg to 60 mg Recommended supplements of elemental ironb and 400 g (0.4 mg) of folic acidc is recommended for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight, and preterm birth.d

A.2.2: Intermittent oral iron and folic acid supplementation with 120 Context-specific mg of elemental irone and 2800 g (2.8 mg) of folic acid once weekly is recommendation recommended for pregnant women to improve maternal and neonatal outcomes if daily iron is not acceptable due to side-effects, and in populations with an anaemia prevalence among pregnant women of less than 20%.f

Calcium A.3: In populations with low dietary calcium intake, daily calcium Context-specific supplements supplementation (1.5–2.0 g oral elemental calcium) is recommended for recommendation pregnant women to reduce the risk of pre-eclampsia.g

Vitamin A A.4: Vitamin A supplementation is only recommended for pregnant Context-specific supplements women in areas where vitamin A deficiency is a severe public health recommendation problem,h to prevent night blindness.i

Executive summary xi xii WHO recommendations on antenatal care for a positive pregnancy experience n. m. l. k. j.

intake Restricting caffeine B.1: Maternal assessment violence (IPV) Intimate partner bacteriuria (ASB) Asymptomatic Anaemia B. Maternal andfetal assessment supplements Vitamin D supplements Vitamin EandC supplements (pyridoxine) Vitamin B6 supplements micronutrient Multiple Zinc supplements

guidelines (2013). This recommendation isconsistent withResponding violence to intimate andsexual partner violence againstwomen: WHOclinical andpolicy disclosure. minimum response orbeyond; private setting;confidentiality ensured; system for referral inplace; andtime to allow for appropriate Minimum requirements are: aprotocol/standard operating procedure; training onhow to askaboutIPV, andonhow to provide the sounds, was notassessed by theGDGasthese activitiesare considered ofgood to bepart clinicalpractice. Evidence onessential ANCactivities,suchasmeasuringmaternal bloodpressure, proteinuria andweight, andcheckingfor fetal heart chocolate, caffeine tablets). This includesany product, beverage orfood containing caffeine (i.e. brewed coffee, tea, cola-type drinks, soft caffeinated energy drinks, pregnant women (2012). This recommendation supersedes theprevious recommendation found intheWHOpublicationGuideline:vitamin Dsupplementation in neonates. recommended to reduce theriskofpregnancy loss andlow-birth-weight Recommendation 300 mg perday), A.10: For pregnant women withhighdailycaffeine intake (more than appropriate) andwhere theWHOminimumrequirements are met. capacity to provide asupportive response (includingreferral where to improve clinicaldiagnosisandsubsequentcare, where there isthe assessing conditions thatmay becausedorcomplicated by IPVinorder (IPV) shouldbestrongly considered atantenatal care visitswhen B.1.3: Clinical enquiryaboutthepossibility violence ofintimate partner diagnosing ASBinpregnancy. staining isrecommended over theuseofdipsticktests asthemethodfor where urineculture isnotavailable, on-site midstream urineGram- diagnosing asymptomatic bacteriuria (ASB) inpregnancy. Insettings B.1.2: Midstream urineculture istherecommended methodfor method for diagnosinganaemiainpregnancy. recommended over theuseofhaemoglobincolour scaleasthe available, on-site haemoglobintesting withahaemoglobinometer is anaemia inpregnancy. Insettingswhere fullbloodcount testing isnot B.1.1: Full bloodcount testing istherecommended methodfor diagnosing women to improve maternal andperinataloutcomes. A.9: Vitamin Dsupplementationisnotrecommended for pregnant women to improve maternal andperinataloutcomes. A.8: Vitamin EandCsupplementationisnotrecommended for pregnant pregnant women to improve maternal andperinataloutcomes. A.7: Vitamin B6(pyridoxine) supplementationisnotrecommended for pregnant women to improve maternal andperinataloutcomes. A.6: Multiplemicronutrient supplementationisnotrecommended for the context ofrigorous research. A.5: Zincsupplementationfor pregnant women isonlyrecommended in k lowering dailycaffeine intake duringpregnancy is l j m n recommendation Type of recommendation Context-specific Not recommended recommendation Context-specific recommendation Context-specific recommendation Context-specific Not recommended Not recommended Not recommended (research) recommendation Context-specific Recommendations integrated from other WHO guidelines that are relevant to ANC maternal assessment

Gestational B.1.4: Hyperglycaemia first detected at any time during pregnancy Recommended diabetes mellitus should be classified as either gestational diabetes mellitus (GDM) or (GDM) diabetes mellitus in pregnancy, according to WHO criteria.o

Tobacco use B.1.5: Health-care providers should ask all pregnant women about their Recommended tobacco use (past and present) and exposure to second-hand smoke as early as possible in the pregnancy and at every antenatal care visit.p

Substance use B.1.6: Health-care providers should ask all pregnant women about their Recommended use of alcohol and other substances (past and present) as early as possible in the pregnancy and at every antenatal care visit.q

Human immuno- B.1.7: In high-prevalence settings,r provider-initiated testing and Recommended deficiency virus counselling (PITC) for HIV should be considered a routine component (HIV) and syphilis of the package of care for pregnant women in all antenatal care settings. In low-prevalence settings, PITC can be considered for pregnant women in antenatal care settings as a key component of the effort to eliminate mother-to-child transmission of HIV, and to integrate HIV testing with syphilis, viral or other key tests, as relevant to the setting, and to strengthen the underlying maternal and child health systems.s

Tuberculosis (TB) B.1.8: In settings where the tuberculosis (TB) prevalence in the general Context-specific population is 100/100 000 population or higher, systematic screening recommendation for active TB should be considered for pregnant women as part of antenatal care.t B.2: Fetal assessment

Daily fetal B.2.1: Daily fetal movement counting, such as with “count-to-ten” kick Context-specific movement charts, is only recommended in the context of rigorous research. recommendation counting (research)

Symphysis-fundal B.2.2: Replacing abdominal palpation with symphysis-fundal height Context-specific height (SFH) (SFH) measurement for the assessment of fetal growth is not recommendation measurement recommended to improve perinatal outcomes. A change from what is usually practiced (abdominal palpation or SFH measurement) in a particular setting is not recommended.

Antenatal cardio- B.2.3: Routine antenatal cardiotocographyu is not recommended for Not recommended tocography pregnant women to improve maternal and perinatal outcomes.

o. This is not a recommendation on routine screening for hyperglycaemia in pregnancy. It has been adapted and integrated from the WHO publication Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy (2013), which states that GDM should be diagnosed at any time in pregnancy if one or more of the following criteria are met: • fasting plasma glucose 5.1–6.9 mmol/L (92–125 mg/dL) • 1-hour plasma glucose > 10.0 mmol/L (180 mg/dL) following a 75 g oral glucose load • 2-hour plasma glucose 8.5–11.0 mmol/L (153–199 mg/dL) following a 75 g oral glucose load. Diabetes mellitus in pregnancy should be diagnosed if one or more of the following criteria are met: • fasting plasma glucose > 7.0 mmol/L (126 mg/dL) • 2-hour plasma glucose > 11.1 mmol/L (200 mg/dL) following a 75 g oral glucose load • random plasma glucose > 11.1 mmol/L (200 mg/dL) in the presence of diabetes symptoms. p. Integrated from WHO recommendations for the prevention and management of tobacco use and second-hand smoke exposure in pregnancy (2013). q. Integrated from the WHO publication Guidelines for the identification and management of substance use and substance use disorders in pregnancy (2014). r. High-prevalence settings are defined in the 2015 WHO publication Consolidated guidelines on HIV testing services as settings with greater than 5% HIV prevalence in the population being tested. Low-prevalence settings are those with less than 5% HIV prevalence in the population being tested. In settings with a generalized or concentrated HIV epidemic, retesting of HIV-negative women should be performed in the third trimester because of the high risk of acquiring HIV infection during pregnancy; please refer to Recommendation B.1.7 for details. s. Adapted and integrated from the WHO publication Consolidated guidelines on HIV testing services (2015). t. Adapted and integrated from the WHO publication Systematic screening for active tuberculosis: principles and recommendations (2013). u. Cardiotocography is a continuous recording of the fetal heart rate and uterine contractions obtained via an ultrasound transducer placed on the mother’s abdomen.

Executive summary xiii xiv WHO recommendations on antenatal care for a positive pregnancy experience aa. z. y. x. w. v.

vaccination Tetanus toxoid for HIVprevention prophylaxis (PrEP) Pre-exposure pregnancy (IPTp) treatment in preventive intermittent Malaria prevention: Recommendations integrated from otherWHOguidelinesthatare relevant to ANC treatment anthelminthic Preventive administration immunoglobulin Antenatal anti-D infections urinary tract prevent recurrent prophylaxis to Antibiotic bacteriuria (ASB) asymptomatic Antibiotics for C. Preventive measures vessels of fetal blood Doppler ultrasound Ultrasound scan

maximizes thebenefits relative to therisks and costs. incidence) to make offering PrEP potentially cost-saving (or cost-effective). Offering PrEP topeople atsubstantialriskofHIV infection Substantial riskofHIVinfection isdefined by anincidence ofHIVinfection intheabsence of PrEP thatissufficientlyhigh(> 3% Integrated from theWHOpublicationGuidelineonwhento antiretroviral start therapy andonpre-exposure prophylaxis for HIV (2015). health system contact withwomen at13weeks ofgestation. To ensure thatpregnant women inendemicareas IPTp-SP start asearlypossible inthesecond trimester, policy-makers shouldensure interventions for preventing malariaduringpregnancy, whichincludespromotion anduseofinsecticide-treated nets,aswell asIPTp-SP”. early aspossible inthesecond trimester, provided thatthedosesofSPare given WHOrecommends atleast1monthapart. apackage of of moderate-to-high malariatransmission ofAfrica, IPTp-SP begiven to allpregnant women as ateachscheduledANCvisit, starting Integrated from theWHOpublicationGuidelinesfor thetreatment ofmalaria (2015), whichalsostates: “WHOrecommends that,inareas depends ontheprevious tetanus vaccination exposure. This recommendation isconsistent withtheWHO guidelineonMaternal immunization againsttetanus (2006).The dosingschedule (2016, inpress). Consistent withtheWHOpublicationGuideline:preventive chemotherapy to control soil-transmitted helminthinfections inhigh-riskgroups Areas withgreater than20% prevalence ofinfection withany soil-transmitted helminths. trimester ofpregnancy. Doppler ultrasound technology evaluates (andotherfetal umbilicalartery arteries) waveforms to assess fetal well-being inthethird mortality from tetanus. depending onprevious tetanus vaccination exposure, to prevent neonatal C.5: Tetanus toxoid vaccination isrecommended for allpregnant women, Recommendation combination prevention approaches. for pregnant women atsubstantialriskofHIVinfection of aspart fumarate (TDF)shouldbeoffered asanadditionalprevention choice C.7: Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil ensuring thatatleastthree dosesare received. doses shouldbegiven withtheobjective atleast onemonthapart, of for allpregnant women. inthesecond Dosingshouldstart trimester, and treatment withsulfadoxine-pyrimethamine (IPTp-SP) isrecommended C.6: Inmalaria-endemicareas inAfrica, intermittent preventive C.4: Inendemicareas, research. RhD alloimmunization isonlyrecommended inthecontext ofrigorous Rh-negative pregnant women at28and34weeks ofgestation to prevent Antenatal prophylaxisC.3: withanti-Dimmunoglobulininnon-sensitized research. urinary tract infections inpregnant women inthecontext ofrigorous AntibioticprophylaxisC.2: isonlyrecommended to prevent recurrent bacteriuria, preterm andlow weight. birth birth women withasymptomatic bacteriuria (ASB) to prevent persistent C.1: Aseven-day antibioticregimen isrecommended for allpregnant pregnant women to improve maternal andperinataloutcomes. RoutineB.2.5: Dopplerultrasound examination isnotrecommended for improve awoman’s pregnancy experience. pregnancies, reduce inductionoflabourfor post-term pregnancy, and gestational age, improve detection offetal anomaliesandmultiple ultrasound) isrecommended for pregnant women to estimate OneultrasoundB.2.4: scanbefore 24 weeks ofgestation (early worm infection reduction programmes. recommended for pregnant women thefirst of after trimester aspart

w y preventive anthelminthic treatment is aa x

z v

recommendation Type of recommendation Context-specific recommendation Context-specific recommendation Context-specific Recommended Not recommended (research) recommendation Context-specific (research) recommendation Context-specific Recommended Recommended D. Interventions for common physiological symptoms

Recommendation Type of recommendation

Nausea and D.1: Ginger, chamomile, vitamin B6 and/or acupuncture are Recommended vomiting recommended for the relief of nausea in early pregnancy, based on a woman’s preferences and available options.

Heartburn D.2: Advice on diet and lifestyle is recommended to prevent and Recommended relieve heartburn in pregnancy. Antacid preparations can be offered to women with troublesome symptoms that are not relieved by lifestyle modification.

Leg cramps D.3: Magnesium, calcium or non-pharmacological treatment options can Recommended be used for the relief of leg cramps in pregnancy, based on a woman’s preferences and available options.

Low back and D.4: Regular exercise throughout pregnancy is recommended to prevent Recommended pelvic pain low back and pelvic pain. There are a number of different treatment options that can be used, such as physiotherapy, support belts and acupuncture, based on a woman’s preferences and available options.

Constipation D.5: Wheat bran or other fibre supplements can be used to relieve Recommended constipation in pregnancy if the condition fails to respond to dietary modification, based on a woman’s preferences and available options.

Varicose veins and D.6: Non-pharmacological options, such as compression stockings, Recommended oedema leg elevation and water immersion, can be used for the management of varicose veins and oedema in pregnancy, based on a woman’s preferences and available options.

E. Health systems interventions to improve the utilization and quality of antenatal care

Recommendation Type of recommendation

Woman-held case E.1: It is recommended that each pregnant woman carries her own case Recommended notes notes during pregnancy to improve continuity, quality of care and her pregnancy experience.

Midwife-led E.2: Midwife-led continuity-of-care models, in which a known midwife Context-specific continuity of care or small group of known midwives supports a woman throughout the recommendation antenatal, intrapartum and postnatal continuum, are recommended for pregnant women in settings with well functioning midwifery programmes.

Group antenatal E.3: Group antenatal care provided by qualified health-care professionals Context-specific care may be offered as an alternative to individual antenatal care for pregnant recommendation women in the context of rigorous research, depending on a woman’s (research) preferences and provided that the infrastructure and resources for delivery of group antenatal care are available.

Community-based E.4.1: The implementation of community mobilization through facilitated Context-specific interventions participatory learning and action (PLA) cycles with women’s groups is recommendation to improve recommended to improve maternal and newborn health, particularly in communication rural settings with low access to health services.ab Participatory women’s and support groups represent an opportunity for women to discuss their needs during pregnancy, including barriers to reaching care, and to increase support to pregnant women.

E.4.2: Packages of interventions that include household and community Context-specific mobilization and antenatal home visits are recommended to improve recommendation antenatal care utilization and perinatal health outcomes, particularly in rural settings with low access to health services. ab. Integrated from WHO recommendations on community mobilization through facilitated participatory learning and action cycles with women’s groups for maternal and newborn health (2014).

Executive summary xv xvi WHO recommendations on antenatal care for a positive pregnancy experience ae. ad. ac. areas in rural andremote retention ofstaff Recruitment and contact schedules Antenatal care delivery antenatal care components of Task shifting

improved retention: globalpolicyrecommendations (2010). Recommendation adapted andintegrated from theWHOpublication Increasing access to healthworkers inremote andrural areas through postnatal care andfamily planning;immunization according to nationalguidelines. nutritional supplements;othercontext-specific supplementsandinterventions; HIV testing during pregnancy; exclusive breastfeeding; sleeping underinsecticide-treated bednets;skilledcare for companionship nutritionaladvice; childbirth; inlabourandchildbirth; Including promotion ofthefollowing: care-seeking behaviour andANCutilization; preparedness birth andcomplication readiness; newborn healthinterventions through (OptimizeMNH) task shifting (2012). Recommendations adapted andintegrated from theWHOguidelineonOptimizinghealthworker roles to improve access to key maternal and ae ac nurses, nurses, midwives anddoctors isrecommended. for malariaprevention to abroad range ofcadres, includingauxiliary supplements andintermittent preventive treatment inpregnancy (IPTp) TaskE.5.2: thedistributionofrecommended shifting nutritional recommended. lay healthworkers, auxiliarynurses, nurses, midwives anddoctors is experience ofcare. recommended to reduce perinatalmortality andimprove women’s E.7: Antenatal care modelswithaminimumofeightcontacts are qualified health workers inrural and remote areas. and personal andprofessional interventions support to recruit andretain E.6: Policy-makers shouldconsider educational,regulatory, financial, maternal andnewborn health E.5.1: Task thepromotion shifting ofhealth-related behaviours for ad to abroad range ofcadres, including Recommended Recommended Recommended recommendation Context-specific 1. Introduction

1.1 Background near-misses (9), ANC also provides an important opportunity to prevent and manage concurrent International human rights law includes fundamental diseases through integrated service delivery (10). commitments of states to enable women and adolescent girls to survive pregnancy and childbirth In low- and middle-income countries (LMICs), ANC as part of their enjoyment of sexual and reproductive utilization has increased since the introduction in health and rights and living a life of dignity (1). The 2002 of the WHO ANC model, known as focused World Health Organization (WHO) envisions a world ANC (FANC) or basic ANC, which is a goal- where “every pregnant woman and newborn receives orientated approach to delivering evidence-based quality care throughout the pregnancy, childbirth and interventions carried out at four critical times during the postnatal period” (2). However, approximately pregnancy (11, 12). However, globally, during the 303 000 women and adolescent girls died as a result period 2007–2014, only 64% of pregnant women of pregnancy and childbirth-related complications in attended the WHO-recommended minimum four 2015 (3). Around 99% of maternal deaths occur in contacts for ANC, suggesting that much more work low-resource settings and most can be prevented (4). needs to be done to address ANC utilization and Similarly, approximately 2.6 million babies were quality. stillborn in 2015, also mainly in low-resource settings (5). Nevertheless, there is evidence that Currently, WHO guidance on routine ANC is effective interventions exist at reasonable cost for the fragmented, with related recommendations published prevention or treatment of virtually all life-threatening across several different WHO guidelines and maternal complications (6), and almost two thirds practical manuals. The 2002 FANC implementation of the global maternal and neonatal disease burden manual, for example (12), does not contain relevant could be alleviated through optimal adaptation and context-specific guidance, which needs to be sought uptake of existing research findings (7). But a human elsewhere. In addition, evidence on the possible harm rights-based approach is not just about avoiding of the FANC model has recently become available, death and morbidity – it is about enabling health and necessitating a review. well-being while respecting dignity and rights. This up-to-date, consolidated guideline for routine Antenatal care (ANC) can be defined as the care ANC has been produced by the WHO Department provided by skilled health-care professionals to of Reproductive Health and Research (RHR), in pregnant women and adolescent girls in order to collaboration with the Department of Nutrition for ensure the best health conditions for both mother Health and Development (NHD) and the Department and baby during pregnancy. The components of of Maternal, Newborn, Child and Adolescent Health ANC include: risk identification; prevention and (MCA), as part of WHO’s normative work on management of pregnancy-related or concurrent supporting evidence-informed policies and practices. diseases; and health education and health promotion. By reviewing, updating and bringing together ANC- related WHO recommendations regarding “what” ANC reduces maternal and perinatal morbidity should be offered and “how” it should be delivered and mortality both directly, through detection and in the form of this guideline, it is hoped that policy- treatment of pregnancy-related complications, and makers will more easily be able to adapt, adopt indirectly, through the identification of women and and implement these new ANC recommendations, girls at increased risk of developing complications presented in Chapter 3, which have also been during labour and delivery, thus ensuring referral configured to form the 2016 WHO ANC model, to an appropriate level of care (8). In addition, as presented in Chapter 4. indirect causes of maternal morbidity and mortality, such as HIV and malaria infections, contribute A scoping review was conducted to inform this to approximately 25% of maternal deaths and guideline, and it revealed that what women want and

Chapter 1. Introduction 1 2 WHO recommendations on antenatal care for a positive pregnancy experience professionals. and academicstaffinvolved intraining health midwives, nurses andgeneral medical practitioners) health professionals (includingobstetricians, management ofmaternal andchildhealthservices, professional societiesinvolved intheplanningand concerned nongovernmental and otherorganizations, and localmaternal andchildhealthprogrammes, makers, implementers andmanagers ofnational includes nationalandlocalpublichealthpolicy- Therefore, thetarget audience ofthisguideline local-level healthpoliciesandclinicalprotocols. to inform thedevelopment ofrelevant national-and The recommendations inthisguidelineare intended Target1.2 audience experience”. expect from ANCisto have a“positive pregnancy antenatal, intrapartum andpostnatalcontinuum. care for mothers andtheirbabiesthroughout the evidence-based guidelinesto improve quality of oftheongoingis part work ofWHOindeveloping human rights-basedapproach. This ANCguideline care thatthey want andneed,inaccordance witha adolescent girls to access thetype ofperson-centred practices thatempowers allpregnant women and provide aclear, evidence-based framework for ANC other women. Therefore, theaimofthisguidelineisto minorities, amongothers) canbegreater thanfor displaced and war-affected women, ethnicand racial concerns, women livingwithHIV, sex workers, women withdisabilities,women withmentalhealth adolescent girlsandvulnerable groups (including The emotional,psychological andsocialneedsof n n n n A positive pregnancy experience isdefinedas: n n n n autonomy) (13). maternal self-esteem, competence and achieving positive motherhood(including and and birth, having aneffective transition to positive labour risks, illness anddeath) and baby (includingpreventing andtreating maintaining ahealthy pregnancy for mother normality maintaining physical andsociocultural guideline are describedinWeb annex 2. to theapproved scope ofpriority questionsfor the priority questionsandoutcomes. Changes made For information, further seesection2.6: Identifying Priority questions related complications. existing WHOguidance onspecificpregnancy- on routine ANC.Itistherefore complementary to guideline, whichisaimedatproviding guidance pregnancies isbeyond thescope ofthisANC of women andadolescent girlswithhigh-risk from adifferent provider. Thus, themanagement referral for additionalmanagement orspecialist care or diseases,where theconsequence ofdetection is the subsequenttreatment ofsuchcomplications diseases atroutine ANCvisits,itdoesnotaddress complications andtheprevention ofconcurrent addresses thedetection ofpregnancy-related unborn fetuses andnewborns. Whiletheguideline facility orcommunity-based setting,andto their adolescent girlsreceiving ANCinany health-care This guidelineisrelevant to allpregnant women and Population ofinterest Scope oftheguideline 1.3 E. D. C. B. A. Chapter 3ofthisdocument: addressed by therecommendations, aspresented in headings, whichreflect thefive typesofinterventions in Web annex 1 according to thefollowing five recommendations inthisANCguideline are listed the evidence review andsynthesis for the The priority questionsandoutcomes guiding

utilization andquality ofANC. Health systems interventions to improve the symptoms Interventions for common physiological Preventive measures Maternal andfetal assessment Nutritional interventions Outcomes of interest

The outcomes of interests included maternal and fetal/neonatal outcomes, as well as test accuracy and health system outcomes (Box 1).

Box 1: Guideline outcomes of interest

Maternal outcomes Fetal/neonatal outcomes Infections Neonatal infections

Anaemia Small for gestational age

Pre-eclampsia/eclampsia Low birth weight

Gestational diabetes mellitus Preterm birth

Mode of delivery Congenital anomalies

Excessive weight gain Macrosomia/large for gestational age

Intimate partner violence Fetal/neonatal mortality

Side-effects

Symptomatic relief

Maternal mortality

Maternal satisfaction and/or women’s rating of usefulness of treatment

Test accuracy outcomes Health system outcomes Sensitivity and specificity ANC coverage

Facility-based delivery

Chapter 1. Introduction 3 4 WHO recommendations on antenatal care for a positive pregnancy experience and updatingoftheguideline. implementation, dissemination, impactevaluation of recommendations, andplanningfor the and synthesis oftheevidence, formulation outcomes, retrieval ofevidence, assessment included: identificationofpriority questionsand guideline development the methodsdescribedinWHOhandbookfor The guidelinewas developed inaccordance with 2. Methods on the RHR departmental websiteon theRHRdepartmental priorto theGDG curriculum vitaeofthemembers were published including apatient/consumer representative. The to interventions for ANCandservice delivery, also methods, andclinicalpolicy and programmes relating with expertise inresearch, guidelinedevelopment interest. The GDGwas adiverse group ofindividuals gender balance, conflicts andnoimportant of to form theGDG,ensuringgeographic representation, experts andstakeholders from thesixWHOregions The Steering Group identifiedandinvited 20 external GuidelineDevelopment2.2 Group (GDG) will oversee dissemination oftheguideline. guideline document.Additionally, theSteering Group recommendations, andfinalized andpublishedthe Technical Consultations (or GDGmeetings), drafted evidence retrieval andsynthesis, organized the the External Review Group (ERG), supervisedthe the GuidelineDevelopment Group (GDG) and and asmembers ofthesystematic review teams, invited asguidelinemethodologists to participate comparator, outcome), identifiedindividuals to be questions inPICO format (population,intervention, of theguidelineanddrafted thekey recommendation process. The Steering Group drafted theinitialscope intheguidelinedevelopmentalso participated of members). Regional advisors from WHOregions and Development (NHD) (see Annex 1 for thelist (MCA), ofNutrition for andtheDepartment Health Maternal, Newborn, Child andAdolescent Health Health andResearch of (RHR),theDepartment staff members from of theDepartment Reproductive guideline development process comprised WHO The WHOSteering Group thatguidedtheentire 2.1 WHOSteering Group (14). Insummary, theprocess 2.3 External Review2.3 Group (ERG) systematic reviews following thestandard processes guideline andsupervisedthe updatingofallrelevant Group (PCG) provided inputonthescoping ofthe interventions, theCochrane Pregnancy andChildbirth quantitative evidence ontheeffectiveness ofdifferent and guidelinemethodologists.Inrelation to The TWG comprised systematic review teams 2.4 Technical Working Group (TWG) the GDG. change recommendations previously formulated by policy-makers. Itwas notwithintheERG’s remit to pregnant women, health-care professionals and affected by the recommendations, including contextual values andpreferences ofpersons processes hadconsidered andincorporated the group ensured thattheguidelinedecision-making issues, andimplicationsfor implementation.The comment onthe clarity ofthelanguage, contextual guideline documentto identifyany factual errors and based ANC.This group peerreviewed thefinal sufficient interests inthe provision of evidence- technical experts andotherstakeholders with There were sixmembers oftheERG, including from serving(see Annex 1 for thelistof members). conflicts ofinterest thatprohibited any member and gender-balanced, andthere were noimportant The membership oftheERG was geographically found inAnnex approval. Alistofthemembers oftheGDGcanbe the WHOGuidelinesReview Committee (GRC) for final guidelinedocumentbefore itssubmission to to-face meetings,andreviewed andapproved the formulated thefinal recommendations at face- advised ontheinterpretation ofthisevidence, appraised theevidence usedto inform theguideline, guided theevidence reviews. The GDGasawhole questions andtheprioritization ofoutcomes, which the drafting ofthescope oftheguideline,PICO Selected members oftheGDGprovided inputinto the meetingsbasedontheirexpertise. and March 2016). Subgroups were invited to eachof meetings (which occurred between October 2015 1 . of the Cochrane Collaboration. The WHO Steering 2.6 Identifying priority questions and Group worked closely with methodologists from the outcomes Centro Rosarino de Estudios Perinatales (CREP), in Argentina, to appraise the evidence from systematic The WHO Department of RHR, in collaboration with reviews using GRADE (Grading of Recommendations methodologists from CREP, conducted a scoping Assessment, Development and Evaluation) exercise in 2014 to identify and map clinical practice methodology (15). guidelines related to ANC. Eighty-five documents with ANC recommendations were identified For qualitative data related to women’s and health- – 15 related to routine ANC and 70 to specific care professionals’ views on ANC, two qualitative situations relevant to ANC (18). Of the 15 related to meta-synthesis experts from the University of routine ANC, three were issued by WHO (19–21), Central Lancashire, in the United Kingdom of Great while the rest were issued by governmental and Britain and Northern Ireland (United Kingdom), nongovernmental organizations (NGOs) in Australia, systematically reviewed qualitative studies and Canada, Hong Kong, India, Japan, Poland, the United synthesized the evidence to inform the GDG’s Kingdom and the United States of America (USA). decision-making, in collaboration with the Steering Similarly, of the 70 guidelines related to specific Group and methodologists from the Norwegian Public situations relevant to ANC, 91% were from Canada, Health Institute. the United Kingdom and the USA, i.e. high-income countries (HICs), while low- and middle-income In addition, methodologists from Queen Mary countries (LMICs) were poorly represented. An University of London, in the United Kingdom, existing, recent, up-to-date guideline relevant to conducted test accuracy reviews of diagnostic tests routine ANC that was adaptable to different resource relevant to the provision of ANC to support this settings was not identified. This scoping exercise guideline. The Steering Group also worked closely also informed the choice of outcomes for the ANC with experts from the Norwegian Public Health guideline, which was supplemented by outcomes Institute, who assisted with methodological issues identified by a preliminary search of the Cochrane relating to the GRADE, GRADE-CERQual (Confidence Database of Systematic Reviews for existing key in the Evidence from Reviews of Qualitative Research) systematic reviews relevant to the antenatal period. (16), and DECIDE (Developing and Evaluating Communication Strategies to Support Informed Based on these initial steps, the WHO Steering Group Decisions and Practice Based on Evidence) (17) tools developed a framework for discussion at a scoping (see sections 2.8, 2.10 and 2.11). In addition, the meeting, held in Geneva in April 2014, to identify Steering Group consulted two researchers from the priority questions about the provision of ANC as London School of Hygiene and Tropical Medicine and well as to inform the scoping for the guideline in the Norwegian Public Health Institute, who reviewed terms of approach, focus, questions and outcomes. country case studies to investigate implementation At this meeting, it was decided that the scope of issues relating to the WHO focused ANC (FANC) this guideline should prioritize the applicability of model. Members of the TWG are listed in Annex 1. interventions in LMIC settings. Specific genetic tests for detection of inherited conditions were considered 2.5 External partners and observers beyond the scope of this guideline. In addition, the scoping process highlighted the need to identify Representatives of the International Federation of women-centred interventions and outcomes for Gynecology and Obstetrics (FIGO), the International ANC. To this end, a qualitative systematic review was Confederation of Midwives (ICM), the United conducted to understand what women want, need Nations Population Fund (UNFPA), the United States and value in pregnancy and ANC (22). The findings Agency for International Development (USAID) of this systematic review suggested that the primary and the United Nations Children’s Fund (UNICEF) outcome for pregnant women is a “positive pregnancy were invited to the final GDG meeting to serve as experience” (as defined in section 1.1), which observers. All these organizations are potential requires the provision of effective clinical practices implementers of the proposed guideline with a (interventions and tests), relevant and timely history of collaboration with the WHO Departments information, and psychosocial and emotional support of RHR and MCA in guideline dissemination and by practitioners with good clinical and interpersonal implementation. skills, within a well functioning health system. Initially

Chapter 2. Methods 5 6 WHO recommendations on antenatal care for a positive pregnancy experience to bebeyond thescope ofthe guideline;for these, complications andconcurrent diseaseswere deemed on management andtreatment ofriskfactors, scope oftheguideline,whereas recommendations HIV) duringANCwere considered to bewithinthe and theidentificationofrisk factors (e.g. smoking, WHO guidelinesthatrelated to healthpromotion ANC guideline.Recommendations found inother them throughout theprocess ofdeveloping thisnew relevant guidance to engage andcollaborate with andtechnical units thathadissued the departments and theSteering Group reached outto theWHO to thepriority questionsfor thisnew guideline Annex 2).These recommendations were mapped containing recommendations relevant to ANC(see approved guidelinesandidentified 21guidelines publications, we searched allrelevant WHOGRC- recommendations across and WHOdepartments To avoid duplicationandensure harmonization of WHO guidelines 2.7 ANC-related recommendations inother and outcomes are listed inWeb annex 1. healthy mother andahealthy baby. These questions a positive pregnancy experience thatincludesa and healthsystems interventions aimedatachieving related to theeffectiveness ofclinical, test accuracy, identification ofpriority questionsandoutcomes This scoping andconsultation process ledto the from stakeholders. April 2014 andMarch feedback 2015 to elicitfurther meetings andinternational conferences between and approach were alsopresented atanumberof technical expertise into thescoping. The process antenatal period,incorporating theirfeedback and that have issued guidelineswithimplicationsfor the consulted andengaged withotherWHOdepartments Throughout thescoping process, theSteering Group intervention.usefulness ofaparticular intervention,a particular andmaternal rating ofthe included assessment ofmaternal satisfaction with including values andpreferences related to ANC,we Informed by thequalitative review ofwomen’s views, prioritized separately for individualquestions. potential outcomes, theseoutcomes were further between thetypes ofinterventions andtherange of ANC period.However, differences dueto important a listofANCoutcomes was prioritized for thewhole n n data sources, assummarized inBox. 2 work streams, usingbothquantitative and qualitative the ANCguidelinewas organized according to five of DECIDE ( synthesize andexamine evidence across thedomains resources, equity, acceptability andfeasibility (17).To of relevant criteria, includingbenefits,harms, values, developed to helpdecision-makers consider arange The DECIDE framework isatool thathasbeen and follow-up isbeyond thescope ofthisguideline. that require additionaltreatment orspecialistcare complications orconcurrent diseasesorriskfactors ANC visits.The management ofidentified package thatallwomen shouldreceive atroutine The guidelinefocuses onthecore ANCclinical following: questions addressed by thisguidelinefocused onthe meet women’s needs). Therefore, theoverarching the care isprovided, andhow thecare isprovided to content ofthemodel,whoprovides thecare, where the context ofdifferent countries (i.e. in terms ofthe flexibility to employ a variety ofoptionsbasedon women andadolescent girlsshouldreceive, withthe essential core package ofANCthatallpregnant continuum ofcare, thefocus ofthisguidelineisthe within thecontext ofhealthsystems andthe issues thatare duringtheANCperiod, important To capture andexamine thecomplex nature ofthe 2.8 Focus andapproach “remarks” following eachrecommendation. WHO guidance viaaweblink provided alongwiththe the guidelineuserisreferred to therelevant separate n n following? ANC periodfor improving outcomes related to the What are theevidence-based practices duringthe – delivered to improve outcomes? How – – – – – – – – – utilization and quality ofANC(see section3.E). health systems interventions to improve the symptoms (see section3.D) interventions for common physiological preventive measures (see section3.C) maternal andfetal assessment (see section3.B) nutritional interventions (see section3.A) shouldtheseevidence-based practices be see section 2.11), thepreparatory work for Box 2: Five work streams for preparation of the ANC guideline

ANC guideline work streams Methodology Assessment of evidence

Individual interventions for clinical Effectiveness reviews, systematic GRADE practices and delivery of ANC reviews

Antenatal testing Test accuracy reviews GRADE

Barriers and facilitators to access to Qualitative evidence synthesis GRADE-CERQual and provision of ANC

Large-scale programme review/ Mixed-methods review, focusing Not applicable country case studies of ANC on contextual and health system factors affecting implementation

Health-system level interventions to Effectiveness reviews GRADE improve access to and provision of ANC services

2.9 Evidence identification and retrieval assessed and rated by reviewers to be at low, high or unclear risk of bias for sequence generation, Evidence to support this guideline was derived from allocation concealment, blinding of study personnel a number of sources by the Technical Working Group and participants, attrition, selective reporting and (TWG) of methodologists and systematic review other sources of bias, such as publication bias. The teams that worked closely with the Steering Group. assessment of these six criteria provides an overall Evidence on effectiveness was mostly derived from risk of bias that indicates the likely magnitude and Cochrane reviews of randomized controlled trials direction of the bias and how it is likely to impact the (RCTs). The Steering Group, in collaboration with review findings. the Cochrane PCG and methodologists from CREP, initially identified all Cochrane systematic reviews The WHO Steering Group and the methodologists in and protocols relevant to ANC. The Cochrane the TWG determined the suitability of each Cochrane PCG Trials Register1 was searched for new trials systematic review to provide the evidence base for and the relevant systematic reviews were updated the key PICO questions. For suitable reviews, CREP accordingly. The updating or completion of Cochrane methodologists retrieved the evidence relevant to reviews was a collaborative process between authors ANC guideline outcomes, which was evaluated of the individual reviews, staff of the PCG, and according to standard operating procedures approved methodologists from CREP. by the Steering Group.

Assessment of the quality of individual studies If a low-quality review or no systematic review was included in Cochrane reviews of intervention identified on a priority question, a new systematic studies follows specific and explicit methods for review was commissioned from external experts. This assessing the risk of bias using six standard criteria was the case with all DTA reviews, the qualitative outlined in the Cochrane handbook for systematic reviews on women’s and health-care providers’ reviews of interventions (23). Each included study is views on ANC, and the review on “factors affecting ANC intervention implementation at country level”. In these instances, the external researchers 1 The Cochrane PCG Trials Register is maintained by the PCG’s Trial Search Coordinator and contains trials identified were asked to prepare standard protocols before from: monthly searches of the Cochrane Central Register of embarking on the systematic reviews, including clear Controlled Trials (CENTRAL); weekly searches of MEDLINE; PICO questions, criteria for identification of studies weekly searches of Embase; hand-searches of 30 journals and the proceedings of major conferences; weekly “current (including search strategies for different bibliographic awareness” alerts for a further 44 journals; and monthly databases), methods for assessing risk of bias and the BioMed Central email alerts (24). For further information, see: http://pregnancy.cochrane.org/pregnancy-and-childbirth- plan for data analysis. The protocols were reviewed groups-trials-register and endorsed by the Steering Group and selected

Chapter 2. Methods 7 8 WHO recommendations on antenatal care for a positive pregnancy experience The review focused onmethodsofuptake and studies reporting theexperiences ofcountries. Public areview HealthInstitute undertook ofcase Hygiene andTropical Medicineandthe Norwegian Finally, two researchers from theLondon Schoolof ANC visits(12). ANC model,whichincludesfour goal-orientated 2002 introduction oftheWHOFANC or“basic” also intended to capture thetimeperiod since the generation ofANCproviders. This date range was of women whomay encounter ANC,andthecurrent ensure thatthedatareflected thecurrent generation Studies publishedbefore 2000were excluded, to 2. 1. United Kingdom: experts from theUniversity ofCentral Lancashire, Two qualitative reviews were commissioned from literature was soughtby searching GreyOpen. searched from inception to January2015, and grey MEDLINE (OVID), SCOPUS andWeb ofScience were Kingdom. For thesereviews, Embase,LILACS, Queen MaryUniversity ofLondon, intheUnited were commissioned from methodologistsfrom The DTA reviews onhaemoglobinandurinetests evidence. 2011 to January2016), butfound noadditional covering thepreceding five years (i.e. from January for indirect evidence oneffects oftheseinterventions Health Institute whoconducted asystematic search commissioned from experts attheNorwegian Public due to apaucity ofdirect evidence. This work was pregnant women), indirect evidence was sought, interventions to communicate withandsupport those onwomen-held casenotes, group ANC,and three questionsrelated to healthsystems (i.e. In additionto theCochrane review evidence, for strategies. information retrieval specialistsreviewed thesearch content experts amongtheGDGmembers. WHO

good quality routine ANCservices. form barriers to, orfacilitators of, theirprovision of income countries inrelation to factors thatmight health-care providers inhigh-,medium-andlow- To explore theviews, attitudesandexperiences of use ofroutine ANCservices. that mightform barriers to, orfacilitators of, their and low-income countries inrelation to factors pregnant andpostnatalwomen inhigh-,medium- To explore theviews, attitudesandexperiences of be found inWeb supplement. strategies for evidence identificationand retrieval can challenges andagree onsolutions.The search communication withtheSteering Group to discuss was iterative, withthemethodologistsinconstant The entire systematic review development process Republic ofTanzania. included Argentina, Kenya, Thailand andtheUnited stakeholders for eachcountry casestudy, which strategy), andsemi-structured interviews withkey dependability and/or confirmability ofthestudy(25). are very likely to affect thecredibility, transferability, D indicatingthepresence ofsignificantflaws that criteria, andthenallocated ascore from Ato D, with a validated instrumentthatrated studies against 11 subjected to asimplequality appraisal system using Studies identified for thequalitative reviews were operating procedures approved by theSteering Group. of London, respectively, inaccordance withstandard and themethodologistsfrom QueenMaryUniversity evidence andDTA evidence was performed by CREP need for downgrading. Grading ofCochrane review rating ifthere were nolimitationsthatindicated a magnitude ofeffect, could lead to upgrading ofthe observational studies,otherconsiderations, suchas imprecision, indirectness andpublicationbias.For on consideration ofriskbias,inconsistency, baseline quality rating was thendowngraded based studies provided “low-quality” evidence. This while non-randomized trialsandobservational a baseline,RCTs provided “high-quality” evidence, “low”, or“very low” basedonasetofcriteria. As for eachoutcome was rated as“high”,“moderate”, within eachPICO. Accordingly, thequality ofevidence profile was prepared for eachquantitative outcome outcomes identifiedinthePICOs, andaGRADE of quantitative evidence was usedfor allthecritical The GRADEapproach (15)to appraising thequality evidence 2.10 Quality assessment andgrading ofthe 2 documents (see theWeb supplement from publishedstudies,reports andotherpolicy and thebroader context. Data were collected experienced by service users andotherstakeholders, implementation oftheWHOFANC model,problems

Available at: en/ maternal_perinatal_health/anc-positive-pregnancy-experience/ www.who.int/reproductivehealth/publications/ 2 for thesearch Studies scoring D were excluded on grounds of poor importance is surrounded by any uncertainty. A quality. scoping review of what women want from ANC informed the ANC guideline (13). Evidence showed The findings of the qualitative reviews were appraised that women from high-, middle- and low-resource for quality using the GRADE-CERQual tool (16, 26). settings generally valued having a “positive The GRADE-CERQual tool, which uses a similar pregnancy experience” achieved through three approach conceptually to other GRADE tools, equally important ANC components – effective provides a transparent method for assessing and clinical practices (interventions and tests), relevant assigning the level of confidence that can be placed and timely information, and psychosocial and in evidence from reviews of qualitative research. The emotional support – each provided by practitioners qualitative review team used the GRADE-CERQual with good clinical and interpersonal skills within tool to assess the confidence in qualitative review a well functioning health system. Reviewers findings, which were assigned to evidence domains had high confidence in the evidence. Therefore, on values, acceptability and feasibility according to interventions that facilitated this composite four components: methodological limitations of the outcome were more likely to lead to a judgement in individual studies, adequacy of data, coherence and favour of the intervention. relevance to the review question of the individual studies contributing to a review finding. nnResources: The most relevant resources in the context of the implementation of the ANC 2.11 Formulation of the recommendations interventions in this guideline mainly included costs for providing medicines, supplies, equipment The Steering Group supervised and finalized the and skilled human resources. A judgement in preparation of evidence summaries and evidence favour or against the intervention was likely profiles in collaboration with the guideline where the resource implications were clearly methodologists, using the DECIDE framework (17). advantageous or disadvantageous. Cost evaluation DECIDE is an evidence-to-decision (EtD) tool that relied on reported estimates obtained during includes explicit and systematic consideration of the evidence retrieval process, a 2013 treatment evidence on interventions in terms of six domains: assumption report (27), the WHO compendium effects, values, resources, equity, acceptability and of innovative health technologies for low-resource feasibility. For each priority question, judgements settings (28), as well as experiences and opinions are made on the impact of the intervention on each of the GDG members. It was recognized that of these domains, in order to inform and guide actual costing of interventions is context-specific the decision-making process. Using the DECIDE and not feasible for a global guideline. framework, the Steering Group created summary documents for each priority question covering nnEquity: This section was informed by the 2015 evidence on each of the six domains. WHO report on inequalities in reproductive, maternal, newborn and child health, which nnEffects: The evidence on maternal and perinatal showed that women in LMICs who are poor, least outcomes was described. Where benefits clearly educated, and residing in rural areas have lower outweighed harms, or vice versa, there was a ANC coverage and worse pregnancy outcomes greater likelihood of a clear judgement in favour than the more advantaged women in LMICs (29). of or against the option, respectively. Uncertainty Their neonates also have worse health outcomes. about the net benefits or harms and small net Therefore, judgements were more likely to favour benefits often led to a judgement that neither the interventions if they could reduce health favoured the intervention nor the comparator. The differences among different groups of women and higher the certainty of evidence on benefits across their families. outcomes, the higher the likelihood of a judgement in favour of the intervention. nnAcceptability: Qualitative evidence from the systematic reviews on women's and providers’ nnValues: This relates to the relative importance views informed judgements for this domain. The assigned to the outcomes of the intervention by lower the acceptability, the lower the likelihood of those affected by them, how such importance a judgement in favour of the intervention. varies within and across settings, and whether this

Chapter 2. Methods 9 10 WHO recommendations on antenatal care for a positive pregnancy experience n n n review the evidence and formulate recommendations 2016 (see Annex 1 for afulllistofparticipants) to the first two inOctober 2015 andthethird inMarch at theWHOheadquarters inGeneva, Switzerland, Consultations (alsocalledGDGmeetings) organized subsequently invited to attend three Technical The GDGmembers were andotherparticipants (EPOC) Group (30). Cochrane Effective Practice and Organization ofCare to guidance onreporting review evidence from the was systematically interpreted inthetext according certainty ofthegraded evidence oneffectiveness Technical Consultations ontheANCguideline.The GDG for comments inadvance oftheseriesthree related documents,were provided to members ofthe recommendations, includingGRADEtables andother These evidence summariesanddraft within therecommendation). intervention (where thecontext isexplicitly stated lead to acontext-specific recommendation for the such evidence ofpotential harmwas more likely to the level ofcertainty andlikely impactoftheharm, have evidence benefits,dependingon ofimportant found for interventions thatwere alsofound to the option.Where evidence ofpotential harmwas potential harmledto arecommendation against In theabsence ofevidence ofbenefits, evidence of namely: Three types ofdraft recommendation were made, presented inChapter 3). summary (see text for eachrecommendation considerations” sub-sectionofeachevidence consequences was describedinthe“additional Additional evidence ofpotential harmsorunintended n n n n n Not recommended. – – – Context-specific recommendation: Recommended be madeinfavour oftheintervention. existed, itwas less likely thatajudgement would judgements for thisdomain.Where barriers reviews andcountry casestudiesinformed training. Qualitative evidence from thesystematic such astheresources available, infrastructure and Feasibility: Feasibility isinfluenced by factors – – – only inotherspecific contexts only withtargeted monitoring andevaluation only inthecontext ofrigorous research been putto avote, by ashow ofhands. recommendation, orany otherdecision,would have had beenunableto reach aconsensus, thedisputed across thedomainsevaluated. IfGDGmembers benefits anddisadvantages oftheinterventions discussions around thebalance ofevidence on by thesameprocess ofconsensus, basedon context ofrecommendations atthemeetings GDG members). The GDGalsodetermined the by consensus (i.e. fullagreement amongall adoption ofeachrecommendation was confirmed through aprocess ofgroup discussion. The final each oftheserecommendations was revised drafted by theSteering Group. Where necessary, to discuss eachoftherecommendationsparticipants Each ofthethree meetingswas designedto allow The GDGmeetingswere guidedby aclearprotocol. meetings 2.12 Decision-makingduringtheGDG electronic copy oftheircurriculumvitaealong with In addition,experts were requested to submitan update andreview conflicts ofinterest accordingly. interests duringthecourse oftheprocess, inorder to responsible technical officer of any change in relevant Allexperts wereparticipate. instructed to notifythe DOI forms before finalizing invitationsexperts’ to officer. TheWHO Steering Group reviewed allthe and sentelectronically to theresponsible technical for DOIwas completed andsignedby eachexpert development process. The standard WHOform invitation intheANC guideline to participate academic, financialorother)atthetimeof declare inwritingany competing interests (whether and otherexternal collaborators were asked to development (14),allGDGmembers, ERG members In accordance withtheWHOhandbookfor guideline external contributors 2.13 Declaration ofinterests (DOI)by recommendations. and evaluation, andresearch prioritiesrelated to the (if any), andto discuss implementation,monitoring recommendation, includingitsdirection andcontext reach consensus oneachjudgement andeach feedback. The purposeofthemeetingswas to and any comments received through preliminary the evidence summaries,thedraft recommendations leadership oftheGDGchair, GDGmembers reviewed for theANCguideline.At thesemeetings,underthe the completed DOI form. The responsible technical language to address any lack of clarity. The revised officer collated and reviewed signed DOI forms and final version was returned electronically to the GDG curriculum vitae, in conjunction with the director of for final approval. the WHO Department of RHR and, with input from the Steering Group, determined whether a conflict of 2.15 Presentation of guideline content interest existed. Where any conflict of interest was declared, the Steering Group determined whether it A summary of the recommendations is presented in was serious enough to affect the individual’s ability Table 1 within the executive summary at the beginning to make objective judgements about the evidence of this guideline. As evidence was evaluated for or recommendations. To ensure consistency, the several outcomes and six domains (effects, values, Steering Group applied the criteria for assessing the resources, equity, acceptability, feasibility) for severity of a conflict of interest in the WHO handbook each recommendation, we have not presented the for guideline development (14). decisions on quality of evidence in this summary table. Summary tables of the main considerations All findings from the received DOI statements (including certainty of the evidence on effects) for were managed in accordance with the WHO DOI each recommendation are presented in Web annex 3. guidelines on a case-by-case basis. Where a conflict of interest was not considered significant enough to The “Evidence and recommendations” section of pose any risk to the guideline development process the guideline (Chapter 3) summarizes the evidence or reduce its credibility, the expert was only required and other considerations reviewed by the GDG at to declare such conflict at the GDG meeting and no the Technical Consultations. To improve readability, further action was taken. Conflicts of interest that the “values” domain has been described (and warranted action by WHO staff arose where experts highlighted in a box entitled “Women’s values”) at had performed primary research or a systematic the beginning of each section for the five types of review related to any guideline recommendations; interventions, instead of for each recommendation, in such cases, the experts were restricted from to avoid repetition. The language used to interpret participating in discussions and/or formulating any the Cochrane review evidence on effects is consistent recommendation related to the area of their conflict with the EPOC approach (30). Evidence assessed as of interest. At the final GDG meeting, members being of very low certainty is not presented in the were required again to state any conflicts of interest text, but can be found in the Web supplement. openly to the entire group, and were required to submit a signed and updated version of their earlier The Steering Group consolidated recommendations DOI statements. A summary of the DOI statements into this guideline from other recent, GRC-approved and information on how conflicts of interest were WHO guidelines relevant to the provision of managed are included in Annex 3. comprehensive, integrated routine ANC to women in certain contexts or for certain conditions. In most 2.14 Document preparation and peer instances, these recommendations are identical review to those found in the specific separate guideline. Where we have integrated recommendations, Following these three GDG meetings, members of the the strength of the recommendation and quality Steering Group prepared a draft of the full guideline of the evidence as determined by the respective document with revisions to accurately reflect the GDGs for those guidelines has been recorded in deliberations and decisions of the GDG participants. the remarks section of the recommendation. Such This draft guideline was then sent electronically to recommendations are indicated by a footnote the GDG participants for further comments before in the ANC guideline text specifying that the it was sent to the ERG. The Steering Group carefully recommendation has been “integrated from” the evaluated the input of the peer reviewers for inclusion specific guideline. A few recommendations required in the guideline document and made revisions to the adaptation for the purposes of the ANC guideline, guideline draft as needed. After the GDG meetings and the Steering Group consulted the relevant WHO and peer review process, further modifications to departments that produced the specific guidance the guideline by the Steering Group were limited to to confirm that adaptations were consistent with corrections of factual errors and improvements in original recommendations. Such recommendations

Chapter 2. Methods 11 12 WHO recommendations on antenatal care for a positive pregnancy experience interventions only. Inallinstances, guidelineusers adapted ofroutine to applyto thetaskshifting ANC recommendations onmultipleinterventions were for therecommendation where ontaskshifting, the guideline. Anexample ofwhere thiswas doneis been “adapted andintegrated from” the specific text specifyingthattherecommendation has are indicated by afootnote intheANCguideline in Annex 4. related to eachGDGrecommendation canbefound in Chapter 4,andimplementationconsiderations ANC guidelineandrecommendations isdiscussed for theserecommendations. Implementationofthe details, includingimplementationconsiderations, are referred to thespecificWHOguidance for more 3. Evidence and recommendations

This ANC guideline includes 39 recommendations The corresponding GRADE tables for adopted by the Guideline Development Group recommendations are referred to in this chapter as (GDG), and 10 recommendations relevant to ANC “evidence base” (EB) tables, numbered according that have been consolidated into this guideline to the specific recommendations they refer to. from other existing WHO guidelines that have These tables are presented separately in the been recently approved by the Guidelines Review Web supplement to this document.3 Evidence-to- Committee (GRC). Evidence on the effectiveness of decision tables with GDG judgements related to interventions was derived from 47 systematic reviews the evidence and considerations for all domains (41 Cochrane systematic reviews, 2 test accuracy are presented in Web annex 3 of this guideline. reviews and 4 non-Cochrane reviews of non- In addition, implementation considerations and randomized studies) and was summarized in GRADE research priorities related to these recommendations, tables. A scoping review of what women want from based on the GDG discussions during the Technical ANC and what outcomes matter to women informed Consultations, can be found in the next chapters of the values domain. Two qualitative systematic the guideline (Chapter 4: Implementation of the ANC reviews on women’s and providers’ views and a guideline and recommendations; Chapter 5: Research review of country case studies contributed evidence implications). on the acceptability and feasibility of interventions. Evidence and considerations on equity and resources also informed the GDG recommendations.

This chapter provides the recommendations with the corresponding narrative summaries, grouped according to the type of intervention, namely:

A. Nutritional interventions

B. Maternal and fetal assessment

C. Preventive measures

D. Interventions for common physiological symptoms

E. Health systems interventions to improve the utilization and quality of ANC.

3 Available at: www.who.int/reproductivehealth/publications/ maternal_perinatal_health/anc-positive-pregnancy-experience/ en/

Chapter 3. Evidence and recommendations 13 14 WHO recommendations on antenatal care for a positive pregnancy experience < 70 g/L) (33).Inpregnancy,< 70 g/L) severe anaemiais (defined asabloodhaemoglobin concentration pregnant women globallyhave severe anaemia prevalence ofanaemia. Itisestimated that0.8 million such assickle-cell disease,contribute to the tuberculosis (TB) andHIV, andhaemoglobinopathies are endemic.Inaddition,chronic infections suchas schistosomiasis, inareas where theseinfections parasitic infections suchasmalaria,hookworm and Major contributory factors to anaemiainclude (25.8%) (33). Pacific (24.3%), theAmericas(24.9%) and Europe prevalence intheWHOregions oftheWestern Mediterranean Region (38.9%) andthe lowest Africa (46.3%), mediumprevalence intheEastern in theWHOregions ofSouth-EastAsia(48.7%) and pregnant women globally, withthehighestprevalence of A deficiencies.Itisestimated to affect 38.2% Anaemia isassociated withiron, folate andvitamin advantaged to disadvantaged populations(32). intheburdenshift ofoverweight andobesity from with affluence, there issome evidence tosuggest a obesity hashistorically beenacondition associated gain excessive weight duringpregnancy. While outcomes andmany women inavariety ofsettings overweight isalsoassociated withpoorpregnancy poor perinataloutcomes (31).However, obesity and prevalent andisrecognized asakey determinant of and south-east Asia, maternal undernutrition is highly poor countries insub-Saharan Africa, south-central nutritional deficienciesoften co-exist. In resource- and middle-income countries (LMICs) where multiple in insufficient tomeettheseneeds,particularly low- of vegetables, meat,dairyproducts andfruitisoften However, for many pregnant women, dietaryintake and minerals to meetmaternal andfetal needs. an adequate intake ofenergy, protein, vitamins Pregnancy requires ahealthy dietthatincludes Background A. Nutritionalinterventions pregnancy. on theimpact,ifany, ofcaffeine restriction during world (40), andtheGDGalsoevaluated evidence the mostwidelyusedpsychoactive substance inthe the impactoftheseconditions. Caffeine ispossibly the effects of various dietaryinterventions to reduce their babies,theGDGalsoevaluated evidence on negative consequences for pregnant women and undernourishment andovernourishment may have and perinataloutcomes. Inaddition,asboth that mighttheoretically leadto improved maternal evidence onvarious vitaminandmineral supplements For theANCguideline,GDGevaluated the interactions have healthconsequences (39). for absorption, anditisunclearwhethersuch and othermineral supplementsmay compete iron absorptionfrom thegut;however, zinc,iron impaired immunity (39).Vitamin Cintake enhances pre-eclampsia. Zincdeficiencyisassociated with zinc, have alsobeenpostulated to play arole in vitamins andminerals, suchasvitaminE,C,B6 and risk ofpre-eclampsia (38),anddeficienciesofother Calcium deficiencyisassociated withanincreased blindness (37). mostly inAfrica andSouth-EastAsia,causing night deficiency affects about19 million pregnant women, also linked to fetal neural tubedefects (vitamin B9) deficiency, inaddition to anaemiaitis status andmorbidity from infections (35).F performance, andalsoadversely affects immune muscles and,thus,physical capacity andwork adversely affects theuseofenergy sources by In additionto causinganaemia,iron deficiency malaria-endemic areas. be quite variable andislikely to bemuchlower in to iron supplementation(33);however, thismay the anaemiafound inpregnant women isamenable infant mortality (34).Itisestimated thatabouthalfof associated withanincreased riskofmaternal and (36). Vitamin A olate Women’s values

A scoping review of what women want from ANC and what outcomes they value informed the ANC guideline (13). Evidence showed that women from high-, medium- and low-resource settings valued having a positive pregnancy experience, the components of which included the provision of effective clinical practices (interventions and tests, including nutritional supplements), relevant and timely information (including dietary and nutritional advice) and psychosocial and emotional support, by knowledgeable, supportive and respectful health-care practitioners, to optimize maternal and newborn health (high confidence in the evidence).

A.1: Dietary interventions

A1.1: Counselling on healthy eating and physical activity

RECOMMENDATION A.1.1: Counselling about healthy eating and keeping physically active during pregnancy is recommended for pregnant women to stay healthy and to prevent excessive weight gain during pregnancy. (Recommended)

Remarks • A healthy diet contains adequate energy, protein, vitamins and minerals, obtained through the consumption of a variety of foods, including green and orange vegetables, meat, fish, beans, nuts, whole grains and fruit (41). • Stakeholders may wish to consider culturally appropriate healthy eating and exercise interventions to prevent excessive weight gain in pregnancy, particularly for populations with a high prevalence of overweight and obesity, depending on resources and women’s preferences. Interventions should be woman-centred and delivered in a non-judgemental manner, and developed to ensure appropriate weight gain (see further information in points below). • A healthy lifestyle includes aerobic physical activity and strength-conditioning exercise aimed at maintaining a good level of fitness throughout pregnancy, without trying to reach peak fitness level or train for athletic competition. Women should choose activities with minimal risk of loss of balance and fetal trauma (42). • Most normal gestational weight gain occurs after 20 weeks of gestation and the definition of “normal” is subject to regional variations, but should take into consideration pre-pregnant body mass index (BMI). According to the Institute of Medicine classification (43), women who are underweight at the start of pregnancy (i.e. BMI < 18.5 kg/m2) should aim to gain 12.5–18 kg, women who are normal weight at the start of pregnancy (i.e. BMI 18.5–24.9 kg/m2) should aim to gain 11.5–16 kg, overweight women (i.e. BMI 25–29.9 kg /m 2) should aim to gain 7–11.5 kg, and obese women(i.e. BMI > 30 kg/m2) should aim to gain 5–9 kg. • Most evidence on healthy eating and exercise interventions comes from high-income countries (HICs), and the GDG noted that that there are at least 40 ongoing trials in HICs in this field. The GDG noted that research is needed on the effects, feasibility and acceptability of healthy eating and exercise interventions in LMICs. • Pregnancy may be an optimal time for behaviour change interventions among populations with a high prevalence of overweight and obesity, and the longer-term impact of these interventions on women, children and partners needs investigation. • The GDG noted that a strong training package is needed for practitioners, including standardized guidance on nutrition. This guidance should be evidence-based, sustainable, reproducible, accessible and adaptable to different cultural settings.

Chapter 3. Evidence and recommendations 15 16 WHO recommendations on antenatal care for a positive pregnancy experience these findings. average). Subgroup analyses were consistent with effect of91 fewer women with EGWG per1000on 95% confidence interval [CI]: 0.73–0.87; absolute (24 trials,7096 women; relative risk[RR]:0.80, prevent EGWG are less likely to experience EGWG diet and/or exercise interventions ofANCto aspart High-certainty evidence shows thatwomen receiving Maternal outcomes combined dietandexercise interventions. in theoverall analyses were derived from trialsof the riskofweight-related complications. Mostdata were performed according to type ofintervention and using therandom effects model.Separate analyses and theaverage effects across trials were estimated exercise counselling, dietandsupervisedexercise) of intervention (i.e. dietonly, exercise only, dietand delivery. Data were grouped according to thetype sessions), type ofintervention andmethodof in thenumberofcontacts (i.e. counselling/exercise weeks ofgestation. There was substantialvariation Most trialsrecruited women between 10and20 (EGWG). aimed to prevent excessive gestational weight gain were usuallycompared with“standard ANC”and group exercise class) orboth.These interventions daily walking), supervised(e.g. aweekly supervised either prescribed/unsupervised (e.g. 30minutes of sustain orimprove healthorfitness, andthese were any activity requiring physical effort, carriedout to Exercise interventions were defined by reviewers as were mostcommonly “healthy eating”types ofdiets. intake was to which aparticipant restricted, which defined asaspecialselectionof food orenergy review’s meta-analyses. Dietinterventions were involving 11 444women contributed data to the high riskofgestational diabetes. Intotal, 49 RCTs and seven recruited women definedasbeingat 24 trialsrecruited overweight and/or obesewomen (i.e. women ofawiderange ofBMIsatbaseline), trials recruited women from thegeneral population (RCTs), mostlyconducted inHICs(44). Thirty-four review thatincluded65randomized controlled trials exercise interventions was derived from aCochrane The evidence ontheeffects ofhealthy eatingand interventions (EBTable A.1.1) compared withnodietandexercise Effects ofdietand exercise interventions Summary ofevidence andconsiderations not reported inthereview. neonates isvery uncertain. Perinatal mortality was CI: 0.68–1.22), andtheevidence onlow-birth-weight preterm (16trials,5923 birth women; RR:0.91, 95% exercise interventions may have littleornoeffect on Low-certainty evidence suggests thatdietand/or 0.26–0.85). women (2 studies,2256 women; RR:0.47, 95% CI: controls, amongoverweight particularly andobese diet andexercise counselling interventions than respiratory morbidity may occur less frequently with Low-certainty evidence suggests thatneonatal (4 trials, 3253neonates; RR:1.02, 95% CI:0.57–1.83). RR: 0.95, 95% CI:0.76–1.18) orshoulderdystocia neonatal hypoglycaemia (4 trials,2601 neonates; interventions probably have littleornoeffect on certainty evidence indicates thatdietandexercise RR: 0.85, 95% CI:0.73–1.00). However, moderate- counselling interventions (9trials,3252 neonates; and obesewomen receiving dietandexercise 0.93, 95% CI:0.86–1.02), inoverweight particularly neonatal macrosomia (27 trials, 8598 women; RR: and/or exercise interventions probably prevent Moderate-certainty evidence suggests thatdiet Fetal andneonatal outcomes women; RR:0.82, 95% CI:0.67–1.01). gestational diabetes mellitus(GDM) (19trials,7279 or exercise interventions may reduce theriskof Low-certainty evidence suggests thatdietand/ women; RR:1.06, 95% CI:0.94–1.19). no difference to inductionoflabour(8trials, 3832 and/or exercise interventions probably make littleor Moderate-certainty evidence indicates thatdiet (9 trials, 3406women; RR:0.87, 95% CI: 0.75–1.01). section rates may bepossible withthisintervention of trialssuggests thatreductions incaesarean from thedietandexercise counselling subgroup 95% CI:0.88–1.03); however, low-certainty evidence caesarean section(28trials, 7534 women; RR:0.95, exercise interventions may have littleornoeffect on Low-certainty evidence suggests thatdietand/or 5162 women; RR:0.70, 95% CI:0.51–0.96). probably prevent hypertension inpregnancy (11trials, indicates thatdietand/or exercise interventions CI: 0.77–1.16). However, moderate-certainty evidence eclampsia risk(15trials,5330women; RR:0.95, 95% exercise interventions have littleornoeffect onpre- High-certainty evidence shows thatdietand/or Additional considerations populations. These risks might be further exacerbated nnHigh-certainty evidence from the review also among women in low-resource community settings, shows that low gestational weight gain is more as these settings may not be equipped to deal with likely to occur with these interventions (11 trials, complications. 4422 women; RR: 1.14, CI: 1.02–1.27); the clinical relevance of this finding is not known. Acceptability nnThe effects, acceptability and feasibility of diet Qualitative evidence indicates that women in a and exercise interventions in LMICs has not been variety of settings tend to view ANC as a source established. of knowledge and information and that they generally appreciate any advice (including dietary Values or nutritional) that may lead to a healthy baby and Please see “Women’s values” in section 3.A: a positive pregnancy experience (high confidence in Background (p. 15). the evidence) (22). It also suggests that women may be less likely to engage with health services if advice Resources is delivered in a hurried or didactic manner (high Cost implications of diet and exercise interventions confidence in the evidence) (22). Therefore, these for health services are highly variable. For example, types of interventions are more likely to be acceptable supervised diet and exercise interventions can if the interventions are delivered in an unhurried have high associated costs, mainly due to staff and supportive way, which may also facilitate better costs for time spent supervising, while counselling engagement with ANC services. Qualitative evidence interventions might have relatively low costs. For on health-care providers’ views of ANC suggests pregnant women, the interventions might also have that they may be keen to offer general health-care resource implications in terms of transport costs, advice and specific pregnancy-related information time off work and child-minding costs, particularly if (low confidence in the evidence) but they sometimes the intervention requires additional antenatal visits. feel they do not have the appropriate training and lack the resources and time to deliver the service in Equity the informative, supportive and caring manner that Most of the evidence came from trials conducted women want (high confidence in the evidence) (45). in HICs. Recent studies have reported a shift in the burden of overweight and obesity from Feasibility advantaged to disadvantaged populations (32). Such In a number of LMIC settings, providers feel that a trend increases the risk of associated pregnancy a lack of resources may limit implementation of complications, as well as cardiometabolic problems, recommended interventions (high confidence in the among pregnant women from disadvantaged evidence) (45).

Chapter 3. Evidence and recommendations 17 18 WHO recommendations on antenatal care for a positive pregnancy experience (300 women; RR:0.04, 95% CI:0.01–0.14), butmay education may reduce low-birth-weight neonates Low-certainty evidence shows thatantenatal dietary Fetal andneonataloutcomes maternal outcomes inthe review for thiscomparison. certainty. There was nootherevidence available on Evidence ongestational weight gain was ofvery low Maternal outcomes study alsoinvolved cookery demonstrations. energy, protein, vitaminsandiron. The Bangladesh of thenutritionalvalue ofdifferent foods, including energy andprotein intake, orimprove knowledge education to improve the“quality” ofdiet,increase one-to-one oringroup classes andincluded Nutritional educationinterventions were delivered women, contributed datato this comparison. Greece andtheUSA, involving 1090pregnant conducted between 1975 and2013 inBangladesh, derived from aCochrane review (47). Five trials Evidence ontheeffects ofnutritionaleducation was education intervention (EBTable A.1.2) energy andprotein intake versus nonutritional Effects ofnutritionaleducation to increase Summary ofevidence andconsiderations A.1.2: Nutritioneducationonenergyandprotein intake • • • • • Remarks birth-weight neonates. (Context-specific recommendation) daily energyandprotein intake isrecommended for pregnant women to reduce theriskoflow- RECOMMENDATION A.1.2: Inundernourishedpopulations,nutritioneducationonincreasing

(see Recommendation A.1.3). additional complementary interventions, suchasdistribution of balanced protein andenergy supplements Areas thatare highlyfood insecure orthosewithlittleaccess to avariety offoods may wishto consider reminders) for andtaskshifting delivery ofthisintervention. Stakeholders mightwishto consider alternative delivery platforms (e.g. peercounsellors, media adaptable to different cultural settings. guidance onnutrition.This guidance shouldbeevidence-based, sustainable,reproducible, accessible and The GDGnoted thatastrong training package isneededfor practitioners, includingstandardized relevant. account by regularly reassessing theprevalence ofundernutritionto ensure thattheintervention remains Anthropometric characteristics ofthegeneral populationare changing,andthisneedsto betaken into based oncontext-specific cost–benefit analyses (31). population (31).However, theoptimalcut-off pointsmay need to bedetermined for individual countries identify protein–energy malnutritioninindividualpregnant women andto determine itsprevalence inthis is considered avery highprevalence (46). Mid-upperarmcircumference (MUAC) may alsobeusefulto prevalence ofunderweight women isconsidered ahighprevalence ofunderweight and40% orhigher Undernourishment isusuallydefined by alow BMI(i.e. beingunderweight). For adults,a20–39%

with better ANC adherence amongwomen with supplementation interventions might beassociated supplements inrural Bangladeshsuggest thatfood antenatal food supplementation andmicronutrient rural populations(48). Findings from astudyof widespread poverty andhunger, among particularly Many low-income countries stillstrugglewith least educated andresiding inrural areas (29). coverage are worse amongwomen whoare poor, In many LMICs,pregnancy outcomes andANC Equity staffing and counsellingtime. Resource costs are variable andmainlyrelated to Resources Background (p. 15). Please see“Women’s values” insection3.A: Values low certainty. Evidence onpreterm was birth judged to beofvery 95%(1 trial,448women; CI:0.35–4.72). RR:1.28, RR: 0.37, 95% CI:0.07–1.90) orneonatal deaths 95% CI:0.21–0.98), (1trial,431women; stillbirths (SGA) neonates (2trials,449 women; RR:0.46, have littleornoeffect onsmall-for-gestational-age less education but not among those with more and supportive way, which may also facilitate better education (49). Therefore, providing antenatal food engagement with ANC services. Qualitative evidence supplements could help to address inequalities by on health-care providers’ views of ANC suggests improving maternal nutritional status and increasing that they may be keen to offer general health-care ANC coverage among disadvantaged women. advice and specific pregnancy-related information (low confidence in the evidence) but they sometimes Acceptability feel they do not have the appropriate training and Qualitative evidence indicates that women in a lack the resources and time to deliver the service in variety of settings tend to view ANC as a source the informative, supportive and caring manner that of knowledge and information and that they women want (high confidence in the evidence) (45). generally appreciate any advice (including dietary or nutritional) that may lead to a healthy baby and Feasibility a positive pregnancy experience (high confidence in In a number of LMIC settings, providers feel that the evidence) (22). It also suggests that women may a lack of resources may limit implementation of be less likely to engage with health services if advice recommended interventions (high confidence in the is delivered in a hurried or didactic manner (high evidence) (45). confidence in the evidence) (22). Therefore, these types of interventions are more likely to be acceptable if the interventions are delivered in an unhurried

Chapter 3. Evidence and recommendations 19 20 WHO recommendations on antenatal care for a positive pregnancy experience A.1.3: Energyandprotein dietarysupplements • • • • • • • • • Remarks for-gestational-age neonates. (Context-specific recommendation) supplementation isrecommended for pregnant women to reduce andsmall- theriskofstillbirths RECOMMENDATION A.1.3: Inundernourishedpopulations,balanced energyandprotein dietary

women withahighBMI. The GDGnoted thatitisnotknown whetherthere are risks associated withproviding thisintervention to included. account to ensure thatonlythosewomen whoare likely to benefit(i.e. onlyundernourished women) are Anthropometric characteristics ofthegeneral populationare changing,andthisneedsto betaken into production anddistribution–canleadto better orequivalent results. to energy andprotein supplements–suchascashorvouchers, orimproved localandnationalfood different types in different seasons). Inaddition,abetter understanding isneededofwhetheralternatives should consider thisandadaptto theconditions asneeded(e.g. provision ofmore orless food of sub-national levels. For instance, where seasonality isapredictor offood availability, theprogramme Each country will needto understand thecontext-specific etiologyofundernutrition atthenationaland wastage, retailing, sharing andotherissues related to food distribution. Monitoring andevaluation shouldincludeevaluation ofhousehold-level storage facilities, spoilage, – – – experiences. Examples relevant to thisguidelineinclude: Programmes shouldbedesignedandcontinually improved basedonlocallygenerated dataand understanding andinvestment inprocurement andsupplychainmanagement. A continual, adequate supplyofsupplementsisrequired for programme success. This requires aclear process isestablished. supplements mightbemitigated by localproduction ofsupplements,provided thataquality assurance environment. The cost andlogisticalimplicationsassociated withbalanced energy andprotein protein food supplementsare manufactured, packaged andstored inacontrolled anduncontaminated Establishment ofaquality assurance process to guarantee isimportant thatbalanced energy and benefit analyses (31). optimal cut-off pointsmay need to bedetermined for individual countries basedon context-specific cost– in individualpregnant women andto determine itsprevalence inthispopulation(31).However, the considered avery highprevalence (46). MUAC may alsobeusefulto identifyprotein–energy malnutrition prevalence ofunderweight women isconsidered ahighprevalence ofunderweight and40% orhigheris Undernourishment isusuallydefined by alow BMI(i.e. beingunderweight). For adults,a20–39% undernourished. of undernourishedpregnant women, andnotfor individualpregnant women identifiedasbeing The GDGstressed thatthisrecommendation isfor populationsorsettingswithahighprevalence – – – may vary. Values andpreferences related to thetypes andamountsofbalanced energy andprotein supplements community healthworkers, inspecific settings). taskshifting first visit comes too late, consideration should begiven to alternative platforms for delivery (e.g. additional visitsshouldbeconsidered. Intheabsence ofantenatal visits,too few visits,orwhenthe local scheduleofANCvisits;additionalvisitsmay needto bescheduled.The costs related to these Distribution ofbalanced energy andprotein supplementsmay notbefeasible onlythrough the overcoming supplyandutilization barriers). Improving delivery, acceptability andutilization ofthisintervention by pregnant women (i.e. Summary of evidence and considerations Equity In many LMICs, pregnancy outcomes and ANC Effects of balanced energy and protein coverage are worse among women who are poor, supplements compared with no supplements or least educated and residing in rural areas (29). placebo (EB Table A.1.3) Many low-income countries still struggle with Evidence on the effects of balanced energy and protein widespread poverty and hunger, particularly among supplements compared with no supplementation or rural populations (48). Findings from a study of placebo was derived from a Cochrane review (47). antenatal food supplementation and micronutrient Twelve trials, involving 6705 women, were included supplements in rural Bangladesh suggest that food in this comparison. Most data were derived from supplementation interventions might be associated trials conducted in LMICs, including Burkina Faso, with better ANC adherence among women with Colombia, Gambia, Ghana, India, Indonesia, South less education but not among those with more Africa and Taiwan, China. The balanced energy and education (49). Therefore, providing antenatal food protein supplements used were in various forms, supplements could help to address inequalities by including fortified beverages, biscuits and powders. improving maternal nutritional status and increasing ANC coverage among disadvantaged women. Maternal outcomes The only maternal outcome reported for this Acceptability comparison in the review, of those outcomes Qualitative evidence indicates that women in a prioritized for this guideline, was pre-eclampsia. variety of settings tend to view ANC as a source However, the evidence on this outcome, based on two of knowledge and information and that they small trials, was assessed as very uncertain. generally appreciate any advice (including dietary or nutritional) that may lead to a healthy baby and Fetal and neonatal outcomes a positive pregnancy experience (high confidence in Moderate-certainty evidence shows that balanced the evidence) (22). It also suggests that women may energy and protein supplementation probably be less likely to engage with health services if advice reduces SGA neonates (7 trials, 4408 women; RR: is delivered in a hurried or didactic manner (high 0.79, 95% CI: 0.69–0.90) and stillbirths (5 trials, confidence in the evidence) (22). Therefore, these 3408 women; RR: 0.60, 95% CI: 0.39–0.94), but types of interventions are more likely to be acceptable probably has no effect on preterm birth (5 trials, if the interventions are delivered in an unhurried 3384 women; RR: 0.96, 95% CI: 0.80–1.16). Low- and supportive way, which may also facilitate better certainty evidence suggests that it may have little or engagement with ANC services. Qualitative evidence no effect on neonatal deaths (5 trials, 3381 women; on health-care providers’ views of ANC suggests RR: 0.68, 95% CI: 0.43–1.07). Low birth weight was that they may be keen to offer general health-care not reported for this comparison in the review. advice and specific pregnancy-related information (low confidence in the evidence) but they sometimes Additional considerations feel they do not have the appropriate training and nnIn the review, mean birth weight (in grams) was lack the resources and time to deliver the service in reported and the findings favoured the balanced the informative, supportive and caring manner that energy and protein supplementation group women want (high confidence in the evidence) (45). (11 trials, 5385 neonates; mean difference [MD]: 40.96, 95% CI: 4.66–77.26). This evidence was Feasibility graded as moderate-quality evidence in the review Providing balanced protein and energy supplements (47). may be associated with logistical issues, as supplements are bulky and will require adequate Values transport and storage facilities to ensure continual Please see “Women’s values” in section 3.A: supplies. Qualitative evidence from LMIC settings Background (p. 15). indicates that providers feel that a lack of resources may limit implementation of recommended Resources interventions (high confidence in the evidence) (45). The cost of balanced energy and protein supplements is relatively high. There may also be cost implications with respect to transport, storage and training.

Chapter 3. Evidence and recommendations 21 22 WHO recommendations on antenatal care for a positive pregnancy experience respect to transport, storage andtraining. high. There may alsobecost implicationswith The cost ofhigh-protein supplementsisrelatively Resources Background (p. 15). Please see“Women’s values” insection3.A: Values 529 neonates; RR:2.78, 95% CI:0.75–10.36). due to imprecision) andneonataldeaths(1trial, 95% CI:0.31–2.15; certainty ofevidence downgraded no effect (1trial, 529 babies; RR: on stillbirths 0.81, that high-protein supplementationmay have littleor 95% CI:0.83–1.56). Low-certainty evidence suggests effect onpreterm (1study, birth 505 women; RR:1.14, protein supplementationprobably haslittleorno Moderate-certainty evidence indicates thathigh- 505 neonates; RR:1.58,95% CI:1.03–2.41). supplementation increases SGA neonates (1 trial, High-certainty evidence shows thathigh-protein Fetal andneonatal outcomes were reported for thiscomparison inthereview. None oftheoutcomes prioritized for thisguideline Maternal outcomes involving 1051 low-income, blackwomen intheUSA. micronutrient supplementconducted inthe1970s, high-protein supplementationcompared witha and A.1.3 (47) Cochrane review asfor Recommendations A.1.2 supplementation was derived from thesame Evidence ontheeffects ofhigh-protein compared withcontrols (EBTable A.1.4) Effects ofhigh-protein supplementation Summary ofevidence andconsiderations A.1.4: High-protein supplements • • Remarks recommended) is notrecommended for pregnant women to improve maternal andperinataloutcomes. (Not RECOMMENDATION A.1.4: Inundernourishedpopulations,high-protein supplementation

considered aresearch priority. Further research ontheeffects ofhigh-protein supplementsinundernourishedpopulationsisnot The GDGnoted thatthere isinsufficient evidence onthebenefits,if any, ofhigh-protein supplementation. . The review includedonetrialof ANC coverage amongdisadvantaged women. improving maternal nutritionalstatusandincreasing supplements could helpto address inequalitiesby populations (48). Therefore, providing antenatal food poverty andhunger, amongrural particularly low-income countries stillstrugglewithwidespread least educated andresiding inrural areas (29).Many coverage are worse amongwomen whoare poor, In many LMICs,pregnancy outcomes and ANC Equity the evidence) (45) of recommended interventions (highconfidence in feel thatalackofresources may limitimplementation evidence from LMICsettingsindicates thatproviders facilities to ensure continual supplies.Qualitative bulky andwillrequire adequate transport and storage associated with logisticalissues, assupplementsare Providing high-protein supplementsmay be Feasibility evidence) (45). manner thatwomen want (highconfidence inthe the service intheinformative, supportive andcaring training andlacktheresources andtimeto deliver they sometimesfeel they do nothave theappropriate information (low confidence inthe evidence) but health-care advice andspecificpregnancy-related suggests thatthey may bekeen to offer general evidence onhealth-care providers’ views ofANC (high confidence inthe evidence) (22). Qualitative advice isdelivered inahurriedordidacticmanner may beless likely to engage withhealthservices if in theevidence) (22). Italsosuggests thatwomen a positive pregnancy experience (highconfidence or nutritional)thatmay leadto ahealthy baby and generally appreciate any advice (includingdietary of knowledge andinformation andthatthey variety ofsettingstend to view ANCasasource Qualitative evidence indicates thatwomen ina Acceptability . A.2: Iron and folic acid supplements

A.2.1: Daily iron and folic acid supplements

RECOMMENDATION A.2.1: Daily oral iron and folic acid supplementation with 30 mg to 60 mg of elemental irona and 400 µg (0.4 mg) folic acidb is recommended for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight, and preterm birth.c (Recommended)

Remarks • This recommendation supersedes the 2012 WHO Guideline: daily iron and folic acid supplementation in pregnant women (36) and should be considered alongside Recommendation A.2.2 on intermittent iron. • In settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin [Hb] concentration < 110 g/L), a daily dose of 60 mg of elemental iron is preferred over a lower dose. • In the first and third trimesters, the Hb threshold for diagnosing anaemia is 110 g/L; in the second trimester, the threshold is 105 g/L (50). • If a woman is diagnosed with anaemia during pregnancy, her daily elemental iron should be increased to 120 mg until her Hb concentration rises to normal (Hb 110 g/L or higher) (34, 51). Thereafter, she can resume the standard daily antenatal iron dose to prevent recurrence of anaemia. • Effective communication with pregnant women about diet and healthy eating – including providing information about food sources of vitamins and minerals, and dietary diversity – is an integral part of preventing anaemia and providing quality ANC. • Effective communication strategies are vital for improving the acceptability of, and adherence to, supplementation schemes. • Stakeholders may need to consider ways of reminding pregnant women to take their supplements and of assisting them to manage associated side-effects. • In areas with endemic infections that may cause anaemia through blood loss, increased red cell destruction or decreased red cell production, such as malaria and hookworm, measures to prevent, diagnose and treat these infections should be implemented. • Oral supplements are available as capsules or tablets (including soluble tablets, and dissolvable and modified-release tablets) (52). Establishment of a quality assurance process is important to guarantee that supplements are manufactured, packaged and stored in a controlled and uncontaminated environment (53). • A better understanding of the etiology of anaemia (e.g. malaria endemnicity, haemoglobinopathies) and the prevalence of risk factors is needed at the country level, to inform context-specific adaptations of this recommendation. • Standardized definitions of side-effects are needed to facilitate monitoring and evaluation. • Development and improvement of integrated surveillance systems are needed to link the assessment of anaemia and iron status at the country level to national and global surveillance systems. • To reach the most vulnerable populations and ensure a timely and continuous supply of supplements, stakeholders may wish to consider task shifting the provision of iron supplementation in community settings with poor access to health-care professionals (see Recommendation E.6.1, in section E: Health systems interventions to improve the utilization and quality of ANC).

a The equivalent of 60 mg of elemental iron is 300 mg of ferrous sulfate hepahydrate, 180 mg of ferrous fumarate or 500 mg of ferrous gluconate. b Folic acid should be commenced as early as possible (ideally before conception) to prevent neural tube defects. c This recommendation supersedes the previous WHO recommendation found in the 2012 Guideline: daily iron and folic acid supplementation in pregnant women (36).

Chapter 3. Evidence and recommendations 23 24 WHO recommendations on antenatal care for a positive pregnancy experience 0.5–0.92). Low-certainty evidence shows thatdaily infections (4 trials,4374 women; RR:0.68, 95% CI: probably reduces theriskofmaternal puerperal evidence shows thatdailyiron supplementation Regarding maternal morbidity, moderate-certainty 1.18–8.02). or later) (8trials,2156women; RR:3.07, 95% CI: at34weeks ofgestation near term (Hb> 130 g/L proportion ofwomen withahighmaternal Hbator higher, 95% CI:6.96–10.8 g/L) andmay increase the or more) (19trials,3704 women; MD:8.88 g/L concentrations atornearterm (34weeks ofgestation iron supplementationmay increase maternal Hb Low-certainty evidence alsoshows thatdaily (8 trials, 1339women; RR:0.04, 95% CI:0.01–0.28). severe anaemia(defined postpartum asHb< 80 g/L) 2199 women; RR:0.30, 95% CI:0.19–0.46) and at37 weeks ofgestation orlater) (14trials, < 110 g/L anaemia atterm (defined asbloodHb concentration daily iron supplementationmay reduce theriskof puerperium. Low-certainty evidence shows that at different timepointsduringpregnancy andthe Anaemia was reported inmany different ways and Maternal outcomes folic acidwas 400 µgdaily. iron was 60 mgdaily(range: 30–240 mg) andthatof delivery. The mostcommonly useddoseofelemental gestation andcontinued takingsupplementsuntil began takingsupplementsbefore 20 weeks of with noiron supplementation.Inmosttrials,women derived from studiescomparing iron supplementation without iron orfolic acid).Mostoftheevidence was intervention, othervitamin and mineral supplements various control groups (folic acidonly, placebo, no or othervitaminandmineral supplements,with oral iron supplementation,withorwithoutfolic acid review’s meta-analyses. The trialscompared daily involving 43 274 women contributed datato the reported malariaoutcomes. Overall, 44 trials in countries withsomemalariarisk,ofwhichtwo countries (54).Twenty-three trialswere conducted 61 trials conducted inlow-, middle-andhigh-income folic acidwas derived from aCochrane review of The evidence ontheeffects ofdailyiron and/or folic acidsupplements(EBTable A.2.1) supplements compared withnodailyiron and Effects ofany dailyiron and folic acid Summary ofevidence andconsiderations outcomes. Neonatal infections andSGA were notreviewed as trials, 16 603 neonates; RR:0.91, 95% CI:0.71–1.18). probably haslittleornoeffect on neonataldeaths (4 Moderate-certainty evidence indicates thatdailyiron trials, 14 636neonates; RR:0.88, 95% CI:0.58–1.33). have littleorno effect on congenital anomalies (4 Low-certainty evidence suggests thatdailyiron may (5 trials, 3749 women; RR:0.51, 95% CI:0.29–0.91). preterm (i.e. birth less than34weeks ofgestation) 95% CI:0.84–1.03), butitdoesreduce theriskofvery weeks ofgestation (13trials,19 286women; RR:0.93, it doesnotreduce theriskofpreterm before birth 37 CI: 0.69–1.03). High-certainty evidence shows that (< 2500 g) (11trials,17 613 neonates; RR:0.84, 95% may reduce theriskoflow-birth-weight neonates Low-certainty evidence shows thatdailyiron Fetal andneonatal outcomes 1088 women; RR:0.55, 95% CI:0.32–0.93). less common withdailyiron supplements(3trials, High-certainty evidence shows thatdiarrhoeais (4 trials,1377 95% women; CI:0.72–2.03). RR:1.21, has littleornoeffect onnauseaisoflow certainty 0.88, 95% CI:0.59–1.30). Evidence thatdailyiron 0.86–1.66) andvomiting (4 trials, 1392 women; RR: (3trials,1323women;heartburn RR:1.19, 95% CI: (4 trials,1495 women; RR:0.95, 95% CI:0.62–1.43), and thatitmay have littleornoeffect on constipation (11 trials,2425 women; RR:1.29, 95% CI:0.83–2.02), no effect onthe riskof experiencing any side-effect that dailyiron supplementationprobably haslittleor Side-effects: Moderate-certainty evidence indicates little difference between dailyiron and control groups. evaluated inonesmalltrial(49 women), whichfound 0.33, 95% CI:0.01–8.19). Women’s satisfaction was maternal mortality (2trials,12 560women; RR: supplementation may have littleornoeffect on Low-certainty evidence shows thatdailyiron low certainty. placental abruptionandbloodtransfusions, isofvery Evidence onothermorbidity outcomes, including (4 trials,1488women; RR:0.93, 95% CI:0.59–1.49). has littleornoeffect haemorrhage onpostpartum moderate-certainty evidence shows thatitprobably 1157 women; RR:1.48, 95% CI:0.51–4.31), and CI: 0.87–3.07) haemorrhage andantepartum (2 trials, pre-eclampsia (4 trials,1704 women; RR:1.63, 95% iron supplementationmay have littleornoeffect on Additional considerations might help to address maternal and newborn health nnEvidence from subgroups tended to be consistent inequalities. with the overall findings for the main outcomes. More details can be found in the Web supplement Acceptability (EB Table A.2.1). Qualitative evidence suggests that the availability of iron supplements may actively encourage women to Values engage with ANC providers (low confidence in the Please see “Women’s values” in section 3.A: evidence) (22). However, where there are additional Background (p. 15). costs associated with supplementation or where the supplements may be unavailable (because of Resources resource constraints) women are less likely to engage Daily iron and folic acid supplements are relatively with ANC services (high confidence in the evidence). low cost, at less than 1 United States dollar (US$ 1) Lower doses of iron may be associated with fewer per pregnant woman (27). side-effects and therefore may be more acceptable to women than higher doses. Equity Iron deficiency and parasitic infections are more Feasibility common in LMICs and disadvantaged populations. Qualitative evidence about the views of health-care Poor, rural and least-educated populations also providers suggests that resource constraints, both in experience the highest maternal, infant and child terms of the availability of the supplements and the mortality (29). Increasing coverage of effective lack of suitably trained staff to deliver them, may limit nutritional interventions to prevent anaemia, implementation (high confidence in the evidence) particularly among disadvantaged populations, (45).

A.2.2: Intermittent iron and folic acid supplements

RECOMMENDATION A.2.2: Intermittent oral iron and folic acid supplementation with 120 mg of elemental irona and 2800 µg (2.8 mg) of folic acid once weekly is recommended for pregnant women to improve maternal and neonatal outcomes if daily iron is not acceptable due to side- effects, and in populations with an anaemia prevalence among pregnant women of less than 20%. (Context-specific recommendation)

Remarks • This recommendation supersedes the previous WHO recommendation in the 2012 Guideline: intermittent iron and folic acid supplementation in non-anaemic pregnant women (55) and should be considered alongside Recommendation A.1.1. • In general, anaemia prevalence of less than 20% is classified as a mild public health problem (33). • Before commencing intermittent iron supplementation, accurate measurement of maternal blood Hb concentrations is needed to confirm the absence of anaemia. Therefore, this recommendation may require a strong health system to facilitate accurate Hb measurement and to monitor anaemia status throughout pregnancy. • If a woman is diagnosed with anaemia (Hb < 110 g/L) during ANC, she should be given 120 mg of elemental iron and 400 µg (0.4 mg) of folic acid daily until her Hb concentration rises to normal (Hb 110 g/L or higher) (34, 51). Thereafter, she can continue with the standard daily antenatal iron and folic acid dose (or the intermittent regimen if daily iron is not acceptable due to side-effects) to prevent recurrence of anaemia. • Stakeholders may need to consider ways of reminding pregnant women to take their supplements on an intermittent basis and of assisting them to manage associated side-effects. a The equivalent of 120 mg of elemental iron is 600 mg of ferrous sulfate hepahydrate, 360 mg of ferrous fumarate or 1000 mg of ferrous gluconate.

Chapter 3. Evidence and recommendations 25 26 WHO recommendations on antenatal care for a positive pregnancy experience one smalltrial(110women) was assessed as Limited evidence onmaternal morbidity from severe anaemiaisofvery postpartum low certainty. on meanHbconcentrations atornearterm and reporting thisoutcome (1240 women). The evidence severe anaemiaoccurred ineither group insixtrials women; RR:0.53, 95% CI:0.38–0.74). Noevents of than dailyiron (15trials,2616more than130 g/L likely to beassociated withaHbconcentration of intermittent iron supplementationisprobably less women; RR:1.66, 95%1.09–2.53), CI: and that than dailyiron supplementation(8trials,1385 probably occurs more frequently withintermittent at34weeks ofgestation orlater) Hb of< 110g/L shows thatanaemiaatornearterm (defined asa 95% CI:0.84–1.80). Moderate-certainty evidence anaemia atterm (4 trials,676 women; RR:1.22, and dailyiron supplementationintheeffect on be littleornodifference between intermittent trials. Low-certainty evidence suggests there may Anaemia was reported indifferent ways across Maternal outcomes daily dosefor control groups. 3500 µg weekly) compared withtheusualstandard the intermittent supplementgroups (range: 400– provided inthetrials,itwas administered weekly in 40–120 mg daily). Where folic acidwas also most commonly 60 mgelementaliron daily(range: weekly), whichwas compared withdailyregimens, 120 mg elementaliron perweek (range: 80–200 mg women takingweekly supplements, mostcommonly Most oftheintermittent iron regimens involved malaria-endemic area. trial specifically thatit reported was conducted ina Lanka, Thailand andViet Nam); however, onlyone Malaysia, Mexico, Pakistan, Republic ofKorea, Sri India, Indonesia,theIslamicRepublic ofIran, Malawi, risk (Argentina, Bangladesh,China, Guatemala, conducted inLMICswithsomedegree ofmalaria to thereview’s meta-analyses (56).Alltrialswere 21 trials(involving 5490 women) contributed data included 27 trialsfrom 15countries; however, only folic acidwas derived from aCochrane review that The evidence ontheeffects ofintermittent iron and acid supplements(EB Table A.2.2) supplements compared withdailyiron andfolic Effects ofintermittent iron and folic acid Summary ofevidence andconsiderations more acceptable thandaily iron supplementation, Women may findintermittent iron supplementation with ANCservices (highconfidence inthe evidence). resource constraints) women are less likely to engage the supplementsmay beunavailable (becauseof costs associated withsupplementation orwhere evidence) (22). However, where there are additional engage withANCproviders (low confidence inthe iron supplementsmay actively encourage women to Qualitative evidence suggests that theavailability of Acceptability common indisadvantaged populations. and folic acid supplementation, asanaemiaismore have less impactonhealthinequalitiesthan dailyiron Intermittent iron andfolic acidsupplementationmay Equity of iron. supplementation dueto thelower total weekly dose might cost alittle less thandailyiron andfolic acid Intermittent iron andfolic acidsupplementation Resources Background (p. 15). Please see“Women’s values” insection3.A: Values the review. infections and SGA outcomes were notincludedin neonatal mortality is alsovery uncertain.Neonatal intermittent versus dailyiron supplementationon very uncertain.Evidence ontherelative effects of andverybirth preterm was birth assessed as CI: 0.50–1.22). However, theevidence onpreterm (< 2500 g) (8trials,1898 neonates; RR:0.82, 95% to dailyiron supplementationonlow weight birth iron supplementationmay have asimilareffect Low-certainty evidence suggests thatintermittent Fetal andneonataloutcomes low certainty. orvomiting)heartburn orany side-effect isof very other specificside-effects (constipation, diarrhoea, 95% CI:0.37–0.97). However, thee supplementation (7trials,1034 women; RR: 0.60, less commonly associated withnauseathandailyiron that intermittent iron supplementationisprobably Side-effects: Moderate-certainty evidence shows satisfaction were notevaluated inthereview. very uncertain.Maternal infections andmaternal vidence on particularly if they experience side-effects with daily Feasibility iron supplements. Intermittent iron may be more feasible in some low- resource settings if it costs less than daily iron.

A.3: Calcium supplements

RECOMMENDATION A.3: In populations with low dietary calcium intake, daily calcium supplementation (1.5–2.0 g oral elemental calcium) is recommended for pregnant women to reduce the risk of pre-eclampsia. (Context-specific recommendation)

Remarks • This recommendation is consistent with the 2011 WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia (57) (strong recommendation, moderate-quality evidence) and supersedes the WHO recommendation found in the 2013 Guideline: calcium supplementation in pregnant women (38). • Dietary counselling of pregnant women should promote adequate calcium intake through locally available, calcium-rich foods. • Dividing the dose of calcium may improve acceptability. The suggested scheme for calcium supplementation is 1.5–2 g daily, with the total dose divided into three doses, preferably taken at mealtimes. • Negative interactions between iron and calcium supplements may occur. Therefore, the two nutrients should preferably be administered several hours apart rather than concomitantly (38). • As there is no clear evidence on the timing of initiation of calcium supplementation, stakeholders may wish to commence supplementation at the first ANC visit, given the possibility of compliance issues. • To reach the most vulnerable populations and ensure a timely and continuous supply of supplements, stakeholders may wish to consider task shifting the provision of calcium supplementation in community settings with poor access to health-care professionals (see Recommendation E.6.1, in section E: Health systems interventions to improve the utilization and quality of ANC). • The implementation and impact of this recommendation should be monitored at the health service, regional and country levels, based on clearly defined criteria and indicators associated with locally agreed targets. Successes and failures should be evaluated to inform integration of this recommendation into the ANC package. • Further WHO guidance on prevention and treatment of pre-eclampsia and eclampsia is available in the 2011 WHO recommendations (57), available at: http://apps.who.int/iris/ bitstream/10665/44703/1/9789241548335_eng.pdf

Summary of evidence and considerations recommendations on calcium supplementation to prevent pre-eclampsia in populations with low dietary Effects of calcium supplements compared calcium intake (38, 57). with no calcium supplements (for outcomes other than hypertension/pre-eclampsia) In 14 trials, daily calcium doses ranged from (EB Table A.3) 1000 mg to 2000 mg, and in the remainder it was Evidence on the effects of calcium supplements on less than 1000 mg. Eleven trials started calcium outcomes other than hypertension/pre-eclampsia supplementation at or after 20 weeks of gestation, was derived from a Cochrane systematic review (58). five trials started before 20 weeks, and the rest did The review included data from 23 trials involving not specify when supplementation was initiated. The 18 587 pregnant women. The aim of the review was primary outcome of 16 of the trials was pregnancy- to determine the effect of calcium on maternal and induced hypertension. For outcomes other than perinatal outcomes other than hypertension. There hypertension, few trials contributed to each outcome; is a separate Cochrane review on the latter (59), this is the evidence presented in this section. which has been referenced to support existing WHO

Chapter 3. Evidence and recommendations 27 28 WHO recommendations on antenatal care for a positive pregnancy experience evidence shows thatitprobably haslittleornoeffect 0.87, 95% CI:0.72–1.06), and moderate-certainty to perinatalmortality(8trials,15 785 women; RR: supplementation may make littleornodifference Low-certainty evidence suggests thatcalcium women; RR:0.81, 95% CI:0.66–0.99). tation probably reduces preterm (12 trials,15 479 birth ty evidence shows thathigh-dosecalciumsupplemen- by dose(< 1000 mgvs ≥ 95% CI:0.70–1.05). However, whentrialsare stratified weeks ofgestation (13trials,16 139women; RR:0.86, may have littleornoeffect onpreterm before birth 37 CI: 0.81–1.07). Low-certainty evidence suggests thatit inconsistency (6trials,14 162 women; RR:0.93, 95% ed by evidence thatwas ofmoderate certainty dueto fect on Calcium supplementationprobably haslittleornoef Fetal andneonatal outcomes 518 95% women; CI:0.48–3.85). RR:1.35, have littleornoeffect ontheriskof gallstones (1trial, evidence. Low-certainty evidence suggests thatitmay 95% CI:0.51–1.64), allassessed asmoderate-certainty impaired renal function(1trial,4589 women; RR:0.91, (1 trial,8312women; RR:1.67, 95% CI:0.40–6.99) and 13 419 women; RR:1.11, 95% CI:0.48–2.54), renal colic or nodifference to the risk ofurinarystones (3 trials, RR: 1.02, 95% CI:0.93–1.12), andprobably makes little dyspepsia and abdominalpain(1trial,8312women; backache, swelling, vaginal andurinarycomplaints, composite outcome includingheadache,vomiting, or nodifference to the risk of “any a side-effect”, Side-effects: Calciumsupplementationmakes little included intheCochrane review. satisfaction was notreported inany ofthetrials week, 95% CI:–119.80 to 60.89 g perweek). Maternal to maternal weight gain (3trials;MD:–29.46 g per supplementation may make littleornodifference Low-certainty evidence suggests thatcalcium (3 trials, 1743 women; RR:0.95, 95% CI:0.69–1.30). no difference to theriskofurinarytract infections 95% CI:0.06–1.38) maternal mortality (2trials,8974 women; RR:0.29, supplementation probably has littleornoeffect on Moderate-certainty evidence indicates thatcalcium (9 trials, 7440 women; RR:0.99, 95% CI:0.89–1.10). 1.04, 95% CI:0.90–1.22) orcaesarean sectionrates on maternal anaemia(1trial,1098women; RR: supplementation doesnothave effects important High-certainty evidence shows thatcalcium Maternal outcomes low-birth-weight babies(< 2500 g), asindicat and probably makes littleor

1000 mg), moderate-certain- - - n n (high confidence in the evidence) (22). However, to ahealthy baby andapositive pregnancy experience advice (includingdietaryornutritional)that may lead and information andthatthey generally appreciate any of settingstend to view ANCasasource ofknowledge Qualitative evidence indicates thatwomen inavariety Acceptability couldbirth helpto address healthinequalities. disadvantaged populationsaimedatreducing preterm LMICs. Therefore, effective nutritionalinterventions in mortality, withthemajority ofdeathsoccurring in Preterm isthemostcommon birth causeofneonatal outcomes thandomore advantaged women (29) . and residing inrural areas have worse pregnancy In many LMICs, women whoare poor, leasteducated Equity to storage andtransport. also have cost andlogisticalimplicationswithrespect iron andfolic acid.The weight ofthesupplementmay relatively highcompared withsupplementssuchas 600 mg perday for 6months=US$ 11.50)(27) is The GDGnoted thatthecost ofcalcium(3 × Resources Background ( Please Values Additional considerations RR: 0.91, 95% CI:0.72–1.14) orfetalon stillbirths deaths(6trials,15 269 women; n n consequence ofpre-eclampsia. pre-eclampsia, aspreterm isfrequently birth a probably notdistinctfrom theeffect onpreventing that theeffect ofcalciumonpreterm is birth “non-hypertensive” effects, theGDGagreed In considering theevidence from thereview of dietary calciumintake (57). sia amongwomen orpopulationswithlow baseline riskreductiona 64% (CI: 35–80%)inpre-eclamp- tion isbasedonmoderate-quality evidence showing (strong recommendation)” (57). those athighriskofdeveloping pre-eclampsia of pre-eclampsia inallwomen, butespeciallyin tal calcium/day) isrecommended for theprevention tion duringpregnancy (atdoses of1.5 dietary calciumintake islow, calciumsupplementa- recommendation oncalciumstates: “In areas where treatment ofpre-eclampsia andeclampsia(2011), the In theWHOrecommendations for prevention and see “Women’s values” insection3.A: p. 15). .

This recommenda - – 2.0 g elemen- 1 tablet 1 tablet calcium carbonate tablets might be unpalatable Feasibility to many women, as they can be large and have a In addition to the cost, providing calcium powdery texture (59). In addition, this intervention supplements may be associated with logistical issues usually involves taking three tablets a day, which (e.g. supplements are bulky and require adequate significantly increasing the number of tablets a woman transport and storage to maintain stock in facilities) is required to take on a daily basis (i.e. in addition to and other challenges (e.g. forecasting). Qualitative iron and folic acid). This could have implications for evidence on health-care providers’ views suggests that both acceptability and compliance, which needs to be resource constraints may limit implementation (high assessed in a programmatic context. confidence in the evidence) (45).

A.4: Vitamin A supplements

RECOMMENDATION A.4: Vitamin A supplementation is only recommended for pregnant women in areas where vitamin A deficiency is a severe public health problem, to prevent night blindness. (Context-specific recommendation)

Remarks • This recommendation supersedes the previous WHO recommendation found in the 2011 Guideline: vitamin A supplementation in pregnant women (60). • Vitamin A is not recommended to improve maternal and perinatal outcomes. • Vitamin A deficiency is a severe public health problem if 5% or more of women in a population have a history of night blindness in their most recent pregnancy in the previous 3–5 years that ended in a live birth, or if 20% or more of pregnant women have a serum retinol level below 0.70 µmol/L (61). Determination of vitamin A deficiency as a public health problem involves estimating the prevalence of deficiency in a population by using specific biochemical and clinical indicators of vitamin A status. • Pregnant women should be encouraged to receive adequate nutrition, which is best achieved through consumption of a healthy, balanced diet, and to refer to WHO guidance on healthy eating (41). • In areas where supplementation is indicated for vitamin A deficiency, it can be given daily or weekly. Existing WHO guidance suggests a dose of up to 10 000 IU vitamin A per day, or a weekly dose of up to 25 000 IU (60). • A single dose of a vitamin A supplement greater than 25 000 IU is not recommended as its safety is uncertain. Furthermore, a single dose of a vitamin A supplement greater than 25 000 IU might be teratogenic if consumed between day 15 and day 60 from conception (60). • There is no demonstrated benefit from taking vitamin A supplements in populations where habitual daily vitamin A intakes exceed 8000 IU or 2400 µg, and the potential risk of adverse events increases with higher intakes (above 10 000 IU) if supplements are routinely taken by people in these populations (62).

Summary of evidence and considerations conducted in vitamin A deficient populations, with one study including only women living with HIV. Trials Effects of vitamin A supplements compared with varied considerably in design, including in the dose no vitamin A supplements (EB Table A.4) and timing of the intervention. Ten trials contributed The evidence was derived from a Cochrane data to the comparison of vitamin A alone versus systematic review of 19 trials of vitamin A (with placebo or no treatment. or without other supplements) compared with no vitamin A (or placebo, or other supplements) Maternal outcomes involving over 310 000 women (63). All but one trial Moderate-certainty evidence shows that vitamin A (conducted in the United Kingdom) were conducted supplementation in vitamin A deficient populations in LMICs, including Bangladesh, China, Ghana, during pregnancy probably reduces maternal anaemia India, Indonesia, Malawi, Nepal, South Africa and (3 trials, 15 649 women; RR: 0.64, 95% CI: 0.43– the United Republic of Tanzania. Most trials were 0.94), but that it probably has little or no effect on

Chapter 3. Evidence and recommendations 29 30 WHO recommendations on antenatal care for a positive pregnancy experience n n Additional considerations congenital anomalieswere notreported inthetrials. RR: 0.98, 95% CI:0.94–1.01). Neonatalinfections and or noeffect on preterm (5trials, 40 137 birth women; low-certainty evidence suggests thatitmay have little 14 599 neonates; RR:0. 1.02, 95% CI:0.89–1.16), and or noeffect on low birth weight (< 2500 g) (4 trials, that vitaminAsupplementationprobably haslittle 0.98–1.10). Moderate-certainty evidence indicates (2 trials,122 850 neonates; RR:1.04, 95% CI: neonates; RR:0.97, 95% CI:0.90–1.05) orstillbirths CI: 0.95–1.07), neonatalmortality (3trials,89 556 perinatal mortality (76 176 women; RR:1.01, 95% supplementation makes littleornodifference to High-certainly evidence shows thatvitaminA Fetal andneonataloutcomes guideline outcomes were notreported inthetrials. 0.2–0.99). Side-effects andothermaternal ANC (5 trials, 17 313women; average RR:0.45, 95% CI: supplementation may reduce maternal infection and/or bacterial vaginosis) suggests thatvitamin A puerperal fever greater than 38°C, subclinical mastitis fever for more thanoneweek atoneweek postnatally, composite outcome for maternal infection (including 95% CI:0.65–1.20). Low-certainty evidence ona maternal mortality (4 trials,101 574 women; RR:0.88, n n consultation in 1998concluded thatdailydoses of days ofconception; however, aWHOexpert group associated withhighvitaminAintake within60 Miscarriage andteratogenicity have been 0.64–0.98). approximately 100 000women; RR:0.79, 95% CI: with ahighprevalence ofthiscondition (2trials, blindness inpregnant women livinginareas vitamin Asupplementationreduces night Moderate-certainty evidence shows that evidence) (22) . positive pregnancy experience (highconfidence inthe or nutritional)thatmay leadto ahealthy baby anda generally appreciate any advice (includingdietary of knowledge andinformation andthatthey variety ofsettingstend to view ANCasasource Qualitative evidence suggests thatwomen ina Acceptability maternal health. by improving nutritionalstatusandpromoting good populations could helpto address healthinequalities Effective nutritionalinterventions indisadvantaged Equity supplement. Vitamin Acanbegiven asadailyorweekly (10 000 IU perday or25 000 IUperweek) (27). at approximately US$ 0.30perwoman permonth Vitamin Asupplementsare relatively inexpensive Resources Background (p. 15). Please see“Women’s values” insection3.A: Values ANC (45). evidence), women may beless likely to engage with of resource constraints (low confidence inthe recommended intervention isunavailable because (high confidence inthe evidence) orwhere the additional costs associated withsupplements Qualitative evidence shows thatwhere there are Feasibility is common (62). safe, especiallyinareas where vitaminAdeficiency up to 3000 µgperday day after 60are probably A.5: Zinc supplements

RECOMMENDATION A.5: Zinc supplementation for pregnant women is only recommended in the context of rigorous research. (Context-specific recommendation – research)

Remarks • Many of the included studies were at risk of bias, which influenced the certainty of the review evidence on the effects of zinc supplementation. • The low-certainty evidence that zinc supplementation may reduce preterm birth warrants further investigation, as do the other outcomes for which the evidence is very uncertain (e.g. perinatal mortality, neonatal sepsis), particularly in zinc-deficient populations with no food fortification strategy in place. Further research should aim to clarify to what extent zinc supplementation competes with iron and/or calcium antenatal supplements for absorption. The GDG considered that food fortification may be a more cost–effective strategy and that more evidence is needed on the cost–effectiveness of food fortification strategies.

Summary of evidence and considerations newborns; RR: 1.02; 95% CI: 0.94–1.11) or low-birth- weight neonates (14 trials, 5643 neonates; RR: 0.93, Effects of zinc supplements compared with no 95% CI: 0.78–1.12). However, low-certainty evidence zinc supplements (EB Table A.5) suggests that zinc supplementation may reduce The evidence was derived from a Cochrane review preterm birth (16 trials, 7637 women; RR: 0.86, 95% that included 21 trials involving more than 17 000 CI: 0.76–0.97), particularly in women with presumed women (64). Most studies were conducted in low zinc intake or poor nutrition (14 trials, 7099 LMICs, including Bangladesh, Chile, China, Egypt, women; RR: 0.87, 95% CI: 0.77–0.98). Ghana, Indonesia, the Islamic Republic of Iran, Nepal, Pakistan, Peru and South Africa. Six trials were Low-certainty evidence suggests that zinc supple conducted in Denmark, the United Kingdom and mentation may have little or no effect on congenital the USA. Daily zinc supplementation was compared anomalies (6 trials, 1240 newborns; RR: 0.67, 95% CI: with no intervention or placebo. There was a wide 0.33–1.34) and macrosomia (defined in the review as variation among trials in terms of trial size (range: “high birth weight”; 5 trials, 2837 neonates; RR: 1.00, 56–4926 women), zinc dosage (range: 5–90 mg per 95% CI: 0.84–1.18). Evidence on perinatal mortality day), nutritional and zinc status at trial entry, initiation and neonatal sepsis is of very low certainty. and duration of supplementation (starting before conception in one trial, first or second trimester in the Additional considerations majority, or after 26 weeks of gestation in two trials, nnThe trials were clinically heterogeneous, therefore until delivery), and compliance with treatment. it is unclear what dose and timing of zinc supplementation, if any, might lead to a possible Maternal outcomes reduction in preterm birth. Moderate-certainty evidence indicates that zinc nnThere is little or no evidence on side-effects of supplementation probably makes little or no zinc supplementation. In addition, it is unclear to difference to the risk of any maternal infections what extent zinc might compete with iron and/or (3 trials, 1185 women; RR: 1.06; 95% CI: 0.74–1.53). calcium for absorption. Maternal anaemia was not The evidence on caesarean section, pre-eclampsia evaluated in the review. and side-effects (maternal taste and smell dysfunction) is of very low certainty, and the review Values did not include anaemia, maternal mortality or Please see “Women’s values” in section 3.A: maternal satisfaction as review outcomes. Background (p. 15).

Fetal and neonatal outcomes Resources Moderate-certainty evidence indicates that zinc Zinc costs approximately US$ 1.30 for 100 tablets of supplementation probably makes little or no 20 mg (i.e. less than US$ 3.00 for a 6-month supply difference to the risk of having SGA (8 trials, 4252 based on a daily dose of 20 mg) (27).

Chapter 3. Evidence and recommendations 31 32 WHO recommendations on antenatal care for a positive pregnancy experience the UNinternational MMNpreparation (UNIMMAP) selenium andzinc,withexactly thesame dosages as B12, C,DandE,copper, folic acid, iodine, iron, niacin, 15 micronutrients, includingvitaminA,B1,B2,B6, iron only. Ninetrialsevaluated supplementswith for onetrialinwhichthecontrol arm comprised with iron andfolic acidsupplementsonly, except 13–15 micronutrients (includingiron andfolic acid) (1). The trialscompared supplements containing Nepal (2),Niger (1), Pakistan (1)andZimbabwe (2), Guinea-Bissau (1),Indonesia(2),Mexico (1), in LMICs:Bangladesh(2),BurkinaFaso (1),China this comparison. These 14trialswere allconducted (65); however, only14trialscontributed datato that included17trialsinvolving 137 791 women The evidence was derived from aCochrane review acid supplements(EBTable A.6) different MMNs) compared withiron and folic Effects ofMMNsupplements (with 13–15 Summary ofevidence andconsiderations A.6: Multiplemicronutrient (MMN)supplements variety ofsettingstend to view ANCasasource Qualitative evidence suggests thatwomen ina Acceptability be agood indicator ofzincdeficiencyinLMICs (39). residence inLMICs.The prevalence ofstuntingmay according to economic status,educationandplace of as well asstuntingprevalence, canbedemonstrated inequalities inneonatal,infant andchildmortality, health inequalities.AWHOreport shows that in disadvantaged populationscould helpto address Effective interventions to improve maternal nutrition Equity • • Remarks pregnant women to improve maternal andperinataloutcomes. (Notrecommended) RECOMMENDATION A.6: Multiplemicronutrient supplementationisnotrecommended for

and how thesecanbeoptimallycombined into asinglesupplement. More research isneededto determine whichmicronutrients improve maternal andperinataloutcomes, supplements thatincludeiron andfolic acid. MMN supplementsonmaternal healthto outweigh thedisadvantages, andmay chooseto give MMN makers inpopulationswithahighprevalence ofnutritionaldeficienciesmight consider thebenefitsof overall there was insufficient evidence to warrant a recommendation, the group agreed thatpolicy- also someevidence gaps intheevidence. ofrisk,andsomeimportant AlthoughtheGDGagreed that micronutrients (includingiron andfolic acid)over iron andfolic acidsupplementsalone,butthere is There issomeevidence ofadditional benefitofMMNsupplements containing 13–15 different stunting inchildren. insettingswithahighprevalenceparticularly of rather thanto provide zincasasinglesupplement, It may bemore feasible to fortifyfood withzinc Feasibility relating to maternal satisfaction orside-effects. RR: 0.97, 95% CI: 0.63–1.48). There was noevidence have littleornoeffect onmaternal mortality (3trials; and low-certainty evidence suggests thatthey may section rates (4 trials;RR:1.03, 95% CI:0.75–1.43) probably make littleornodifference to caesarean certainty evidence indicates that MMNsupplements Compared to iron andfolic acidonly, moderate- anaemia (5trials;RR:0.98, 95% CI:0.85–1.13). acid supplementsonly(standard care) onmaternal supplementation hasasimilareffect to iron and folic High-certainty evidence shows thatMMN Maternal outcomes found intheWeb supplement(EBTable A.6). or 30mg) usedinthecontrol arm.Analyses canbe were performed according to thedoseofiron (60mg using therandom effects method.Subgroup analyses supplements, andinseparate subgroup analyses synthesized together withtrialsof13and14MMN (66). E evidence) (22). positive pregnancy experience (highconfidence inthe or nutritional)thatmay leadto ahealthy baby anda appreciate any professional advice (includingdietary of knowledge andinformation andthey generally vidence from theseUNIMMAPtrialswas Fetal and neonatal outcomes Resources High-certainty evidence shows that MMN UNIMMAP supplements cost about US$ 3 per supplementation reduces the risk of having a low- woman per pregnancy, whereas iron and folic acid birth-weight neonate compared with iron and folic supplementation costs less than US$ 1 (27). acid supplements only (14 trials; RR: 0.88, 95% CI: 0.85–0.91), but moderate-certainty evidence Equity indicates that it probably makes little or no difference Effective interventions to improve maternal nutrition to the risk of having an SGA neonate (13 trials; RR: in disadvantaged populations could help to address 0.98, 95% CI: 0.96–1.00). High-certainty evidence maternal and neonatal health inequalities by shows that MMN supplements make little or no improving maternal health and preventing illness difference to preterm birth rates (14 trials; RR: 0.95, related to nutritional deficiencies. However, the cost 95% CI: 0.88–1.03). Moderate-certainty evidence difference between MMNs and iron and folic acid shows that MMN supplements probably make little supplementation may have an impact on affordability or no difference to perinatal mortality (11 trials; RR: for disadvantaged populations, especially those 1.00, 95% CI: 0.85–1.19), neonatal mortality (11 in remote and rural areas, because they are often trials; RR: 0.99, 95% CI: 0.90–1.08) or stillbirths (14 expected to pay for visits and supplements in addition trials; RR: 0.97, 95% CI: 0.86–1.09). The evidence to bearing greater transport costs due to the greater on congenital anomalies is of low certainty and distance to travel to ANC services (68). inconclusive (1 trial, 1200 women; RR: 0.99, 95% CI: 0.14–7.00). Acceptability Qualitative evidence suggests that women in a High-certainty evidence from analyses restricted variety of settings tend to view ANC as a source to trials of UNIMMAP only are consistent with the of knowledge and information and that they overall findings, with the exception that it shows that generally appreciate any advice (including dietary UNIMMAP reduces the risk of having an SGA neonate or nutritional) that may lead to a healthy baby and compared with iron and folic acid supplements only a positive pregnancy experience (high confidence (8 trials; RR: 0.85, 95% CI: 0.77–0.94). in the evidence) (22). However, it has been noted that the lack of appropriate training on MMN Subgroup analyses according to the iron dose in supplementation has been reported by health-care the control group are generally consistent with the providers as a major gap (68). overall findings. However, for the subgroup of studies that compared MMN supplements to 60 mg iron Feasibility and 400 µg folic acid, a harmful effect of MMNs on From the demand side, MMN supplementation neonatal mortality cannot be excluded (6 trials; RR: should be as feasible as iron and folic acid 1.22, 95% CI: 0.95–1.57). supplementation if supplements are free and available, and it will face the same challenges in terms Additional considerations of compliance. However, on the supply side, there nnA separate review of the effects of MMN may be several barriers to overcome, such as changes supplementation during pregnancy on child in regulatory norms and policies (e.g. tariffs, labelling, health benefits pooled data from nine of the trials imports, government oversight, etc.), ensuring included in the Cochrane review and found no sustainable MMN production (local or imported), evidence of beneficial effects on child mortality, product availability and quality. Great variability in growth or cognitive function (67). feasibility across countries and within them would be expected (68). Values Please see “Women’s values” in section 3.A: Background (p. 15).

Chapter 3. Evidence and recommendations 33 34 WHO recommendations on antenatal care for a positive pregnancy experience n n Additional considerations evidence on congenital anomalies. but theevidence isvery uncertain. There was no weightMean birth was evaluated inonesmalltrial preterm orotherANCguidelineoutcomes. birth Trials contributed nodataon low weight, birth Fetal andneonatal outcomes the ANCguidelinewere reported inthereview. 0.85–3.45). Noothermaternal outcomes relevant to eclampsia (2trials,1197 women; RR:1.71, 95% CI: supplements may have littleornoeffect onpre- Low-certainty evidence suggests thatoral pyridoxine Maternal outcomes data to thiscomparison. treatment. Onlytwo outoffour studiescontributed to 20 mgperday) was compared withplacebo orno (100 mg) ororally ascapsulesorlozenges (2.6 mg (pyridoxine) given intramuscularly asasingledose in HICsbetween 1960and1984.Vitamin B6 pregnant1646 women (69). Studieswere conducted that includedfour trialsinvolving approximately The evidence was derived from aCochrane review with novitaminB6supplements(EBTable A.7) Effects ofvitaminB6supplements compared Summary ofevidence andconsiderations A.7: Vitamin B6(pyridoxine) supplements • • Remarks pregnant women to improve maternal andperinataloutcomes. (Notrecommended) RECOMMENDATION A.7: Vitamin B6(pyridoxine) supplementationisnotrecommended for n n

other Bvitamins(70). mostly occurs incombination with deficienciesof Vitamin B6deficiencyaloneisuncommon; it for common physiological symptoms Recommendation D.1, insectionD:Interventions during pregnancy (see evidence summaryfor B6 probably provides somerelief for nausea Moderate-certainty evidence shows thatvitamin for pregnant women onmaternal andperinataloutcomes isnotconsidered aresearch priority. supplementation inpregnancy. However, research ontheeffects of routine vitaminB6supplementation The GDGagreed thatthere isinsufficient evidence onthebenefitsandharms,if any, of routinevitaminB6 consumption ofahealthy, balanced diet,andto refer to guidelinesonhealthy eating(41) Pregnant women shouldbeencouraged to receive adequate nutrition,whichisbestachieved through ). Equity . 90 × 10 mgtablets(71) hydrochloride tablets) cancost aboutUS$ 2.50for As asinglesupplement,vitaminB6(pyridoxine Resources Background (p. 15). Please see“Women’s values” insection3.A: Values ANC services (45). evidence), women may be less likely to engage with of resource constraints (low confidence inthe recommended intervention is unavailable because (high confidence inthe evidence) orwhere the additional costs associated withsupplements Qualitative evidence shows thatwhere there are Feasibility evidence) (22) . positive pregnancy experience (highconfidence inthe or nutritional)thatmay leadto ahealthy baby anda appreciate any professional advice (includingdietary knowledge andinformation andthatthey generally variety ofsettingstend to view ANCasasource of Qualitative evidence suggests thatwomen ina Acceptability health inequalities. in disadvantaged populationscould helpto address Effective interventions to improve maternal nutrition . A.8: Vitamin E and C supplements

RECOMMENDATION A.8: Vitamin E and C supplementation is not recommended for pregnant women to improve maternal and perinatal outcomes. (Not recommended)

Remarks • The GDG noted that vitamin E and C combined supplements were evaluated mainly in the context of preventing pre-eclampsia. Vitamin C is important for improving the bioavailability of oral iron, but this was not considered within the context of the Cochrane reviews. In addition, low-certainty evidence on vitamin C alone suggests that it may prevent prelabour rupture of membranes (PROM). Therefore, the GDG agreed that future research should consider vitamin C supplements separately from vitamin E and C supplements. • Pregnant women should be encouraged to receive adequate nutrition, which is best achieved through consumption of a healthy, balanced diet, and to refer to guidelines on healthy eating (41). It is relatively easy to consume sufficient quantities of vitamin C from food sources.

Summary of evidence and considerations Fetal and neonatal outcomes High-certainty evidence indicates that vitamin E and Effects of vitamin E and C supplements C supplementation does not have an important effect compared with no vitamin E and C supplements on SGA (11 trials, 20 202 women; RR: 0.98, 95% CI: (EB Table A.8) 0.91–1.06). Moderate-certainty evidence shows that The evidence was derived from two Cochrane vitamin E and C supplements probably have little or systematic reviews that included 17 trials conducted in no effect on preterm birth (11 trials, 20 565 neonates; low-, middle- and high-income countries contributed RR: 0.98, 95% CI: 0.88–1.09), neonatal infections data (72, 73). The trials assessed vitamin E plus (5 trials, 13 324 neonates; RR: 1.10, 95% CI: 0.73–1.67) vitamin C combined supplements compared with and congenital anomalies (4 trials, 5511 neonates; placebo or no vitamin E and C supplements. The most RR: 1.16, 95% CI: 0.83–1.63). commonly used dose of vitamin E was 400 IU daily (15 trials) and vitamin C was 1000 mg daily (13 trials). Additional considerations The primary outcome of 14 trials was pre-eclampsia nnThe high-certainty evidence on abdominal pain is and nine of the trials recruited women at “high” or derived from a large, well designed trial in which “increased” risk of pre-eclampsia. Most of the trials abdominal pain occurred in 7.9% of women in the commenced supplementation in the second trimester. vitamin E and C supplement group and 4.8% of women in the placebo group. Maternal outcomes nnDespite the certainty of these effects of vitamin E Moderate-certainty evidence shows that vitamin E and C supplementation, the biological explanations and C combined supplements probably have little or for these adverse effects are not established. no effect on the risk of developing pre-eclampsia (14 nnModerate-certainty evidence indicates that studies, 20 878 women; RR: 0.91 95% CI: 0.79–1.06) vitamin E and C supplements probably reduce the and eclampsia (8 trials, 19 471 women; RR: 1.67, 95% risk of placental abruption (7 trials, 14 922 women; CI: 0.82–3.41). Moderate-certainty evidence also RR: 0.64, 95% CI: 0.44–0.93; absolute effect of 3 shows that vitamin E and C supplements probably fewer abruptions per 1000) but make little or no have little or no effect on maternal mortality (7 trials, difference to the risk of antepartum haemorrhage 17 120 women; RR: 0.60, 95% CI: 0.14–2.51) and from any cause (2 trials, 12 256 women; RR: 1.25, caesarean section (6 trials, 15 297 women; RR: 1.02, 95% CI: 0.85–1.82). 95% CI: 0.97–1.07). nnHigh-certainty evidence shows vitamin E and C supplementation increases PROM at term Side-effects: High-certainty evidence shows that (37 weeks of gestation or more) (2 trials, 2504 vitamin E and C supplementation is associated with women; RR: 1.77, 95% CI: 1.37–2.28; absolute effect an increased risk of abdominal pain during pregnancy of 52 more cases of PROM per 1000). (1 trial, 1877 women; RR: 1.66, 95% CI: 1.16–2.37; nnThe trial contributing the most data on PROM was absolute effect of 32 more per 1000 women). stopped early, based on their PROM data, when

Chapter 3. Evidence and recommendations 35 36 WHO recommendations on antenatal care for a positive pregnancy experience n LMICs (Bangladesh,Brazil, China, Indiaandthe 2833 women (76) . Ninetrialswere conducted in systematic review thatincluded 15trialsassessing The evidence was derived from aCochrane Summary ofevidence and considerations A.9: Vitamin Dsupplements could helpto address healthinequalitiesbecause Effective interventions to reduce pre-eclampsia Equity cost aboutUS$ 3for amonth’s supply(74). widely; chewable vitaminCtablets(1000mg) can US$ 8 for amonth’s supply. Costs ofvitamin Cvary Vitamin E(tocopherol) 400IUdailycancost about Resources Background (p. 15). Please see“Women’s values” insection3.A: Values • • • • • Remarks to improve maternal andperinataloutcomes. (Notrecommended) RECOMMENDATION A.9: Vitamin Dsupplementationisnotrecommended for pregnant women n

women; RR:0.55, 95% CI:0.32–0.94). 95% CI:0.48–0.91) andterm PROM (1study, 170 preterm PROM (5studies,1282 women; RR:0.66, ranging from 100 mgto 1000mg) may reduce C onlysuggests thatvitaminCalone(indoses Low- to moderate-certainty evidence onvitamin women) hadbeenaccrued. oftheplannedsample(10 000 only aquarter calcium. associated benefits orharmsofvitaminDwhen combined with othervitaminsandminerals, particularly uncertainties regarding vitamin Deffects, theeffect particularly on and preterm birth, any other supplementation inpregnancy (76). Evidence from thesetrialsshould helpto clarifythecurrent According to theCochrane review, there are 23ongoing or unpublishedstudiesonvitaminD current recommended nutrientintake (RNI)of200IU(5µg) perday. For pregnant women withdocumented vitaminDdeficiency, vitaminDsupplements may begiven atthe consumption of ahealthy, balanced diet,andto refer to guidelinesonhealthy eating(41) Pregnant women shouldbeencouraged to receive adequate nutrition,whichisbestachieved through vitamin Dthanlighter pigments) and sunscreen use(75). exposed, thetime ofday, latitudeandseason,skinpigmentation(darker skinpigmentssynthesize less of timeneededinthesunisnotknown anddependsonmany variables, suchastheamountofskin Pregnant women source shouldbeadvisedthatsunlightisthemostimportant ofvitaminD. The amount vitamin Dsupplementationinpregnant women (75). This recommendation supersedes theprevious WHOrecommendation found inthe2012 Guideline: ANC services (45). evidence), women may beless likely to engage with of resource constraints (low confidence inthe recommended intervention isunavailable because (high confidence inthe evidence) orwhere the additional costs associated withsupplements Qualitative evidence shows thatwhere there are Feasibility evidence) (22). positive pregnancy experience (highconfidence inthe or nutritional)thatmay leadto ahealthy baby anda appreciate any professional advice (includingdietary knowledge andinformation andthatthey generally variety ofsettingstend to view ANCasasource of Qualitative evidence suggests thatwomen ina Acceptability disadvantaged populations. mortality from pre-eclampsia mainlyoccurs among trials compared theeffects ofvitaminDplus calcium alone versus placebo ornosupplementation,andsix women. Ninetrialscompared the effects ofvitaminD Kingdom). Samplesizes ranged from 40to 400 HICs (France, New Zealand, Russia andtheUnited Islamic Republic ofIran) andsixwere conducted in . versus placebo or no supplementation. The dose and (< 37 weeks of gestation) (3 trials, 798 women; regimen of vitamin D varied widely among the trials. RR: 1.57, 95% CI: 1.02–2.43). Low-certainty evidence suggests that vitamin D plus calcium has little or no a) Effects of vitamin D supplements alone versus effect on neonatal mortality (1 trial, 660 women; RR: placebo or no supplement (EB Table A.9) 0.20, 95% CI: 0.01–4.14). Nine trials contributed data to this comparison. Six trials evaluated daily vitamin D with daily doses Additional considerations ranging from 400 IU to 2000 IU. Two trials evaluated nnDue to the limited evidence currently available to a single dose of 200 000 IU given at about 28 directly assess the benefits and harms of the use of weeks of gestation, one trial evaluated a weekly vitamin D supplementation alone in pregnancy for dose of 35 000 IU during the third trimester, and one improving maternal and infant health outcomes, trial administered 1–4 vitamin D doses (60 000– the use of this intervention during pregnancy as 480 000 IU in total) depending on the participants’ part of routine ANC is not recommended (75). baseline serum 25-hydroxy-vitamin D levels. nnThe moderate-certainty evidence showing that adding vitamin D to calcium supplementation Maternal outcomes probably increases preterm birth is of concern and The evidence on pre-eclampsia, GDM, maternal this potential harm needs further investigation. mortality, caesarean section and side-effects is very uncertain (i.e. all findings were assessed as very low- Values certainty evidence). Please see “Women’s values” in section 3.A: Background (p. 15). Fetal and neonatal outcomes Low-certainty evidence suggests that vitamin D Resources supplementation may reduce low-birth-weight Vitamin D supplements can cost from US$ 2 per neonates (3 trials, 493 women; RR: 0.40, 95% month, depending on the dose prescribed (74). CI: 0.24–0.67) and preterm birth (< 37 weeks of gestation) (3 trials, 477 women; RR: 0.36, 95% Equity CI: 0.14–0.93), but may have little or no effect on Effective interventions to improve maternal nutrition neonatal deaths (2 trials, 282 women, RR: 0.27; 95% in disadvantaged populations could help to address CI: 0.04–1.67) and stillbirths (3 trials, 540 women; health inequalities. RR: 0.35, 95% CI: 0.06–1.99). Acceptability b) Effects of vitamin D plus calcium supplements Qualitative evidence suggests that women in a versus placebo or no supplement (EB Table A.9) variety of settings tend to view ANC as a source of Six trials contributed data to this comparison. Vitamin knowledge and information and that they generally D doses ranged from 200 IU to 1250 IU daily and appreciate any professional advice (including dietary calcium doses ranged from 375 mg to 1250 mg daily. or nutritional) that may lead to a healthy baby and a positive pregnancy experience (high confidence in the Maternal outcomes evidence) (22). Moderate-certainty evidence shows that vitamin D plus calcium probably reduces pre-eclampsia Feasibility (3 trials, 798 women; RR: 0.51; 95% CI: 0.32–0.80), Qualitative evidence shows that where there are but low-certainty evidence suggest that it may have additional costs associated with supplements little or no effect on GDM (1 trial, 54 women, 1 event; (high confidence in the evidence) or where the RR: 0.43, 95% CI: 0.05–3.45). recommended intervention is unavailable because of resource constraints (low confidence in the Fetal and neonatal outcomes evidence), women may be less likely to engage with Moderate-certainty evidence indicates that vitamin ANC services (45). D plus calcium probably increases preterm birth

Chapter 3. Evidence and recommendations 37 38 WHO recommendations on antenatal care for a positive pregnancy experience (1153 neonates; RR:0.81, 95% CI:0.48–1.37). 20.00, 95% CI:–48.68 to 88.68) andpreterm birth 0.57–1.64), weight meanbirth (1197 neonates; MD: no effect on SGA (1150neonates; RR: 0.97, 95% CI: coffee withdecaffeinated coffee) may have littleor restricting caffeine intake (replacing caffeinated Low-certainty evidence from onetrialshows that Fetal andneonataloutcomes ANC guidelinewere reported in thereview. None ofthematernal outcomes addressed inthe Maternal outcomes caffeinated coffee group. with 317mgperday (IQR:229–461 mg) inthe (interquartile range [IQR]:56–228 mg) compared the decaffeinated coffee group was117mgper day were notrestricted. Meandailycaffeine intake in sources ofcaffeine, suchas cola, tea andchocolate was estimated to contain 65mgcaffeine. Other pregnancy. In thistrial,acupofcaffeinated coffee to assess theeffect ofcaffeine reductionduring instant caffeinated coffee (control group) in order decaffeinated coffee (intervention group) versus coffee aday were randomized to receive instant pregnant women drinkingmore thanthree cupsof Denmark, contributed evidence. Inthistrial,1207 RCTstwo (40). Onlyoneofthetrials,conducted in was derived from aCochrane review thatincluded Some evidence ontheeffects ofcaffeine intake Table A.10a) caffeinated coffee (RCT evidence) (EB a) Effects ofdecaffeinated coffee versus Summary ofevidence andconsiderations a A.10: Restricting caffeine intake

• • • Remarks 300 mg perday), RECOMMENDATION A.10: For pregnant women withhighdailycaffeine intake (more than risk ofpregnancy loss andlow-birth-weight neonates. (Context-specific recommendation) tablets). This includesany product, beverage orfood containing caffeine (i.e. brewed coffee, tea, cola-type drinks, soft caffeinated energy drinks, chocolate, caffeine

less than50 mgper250mLserving. Caffeine-containing teas (black tea andgreen drinks tea) andsoft (colas andiced tea) usually contain than 150mgofcaffeine perserving. can contain about60mgofcaffeine; however, some commercially brewed coffee brands containmore medicines. Coffee isprobably themost common source ofhighcaffeine intake. Acupofinstant coffee Caffeine isastimulant found in tea, coffee, soft-drinks, chocolate, kolanutsandsome over-the-counter associated withahigherriskofpregnancy loss andlow weight. birth Pregnant women shouldbeinformed thatahighdailycaffeine intake (>300mgperday) isprobably a lowering dailycaffeine intake during pregnancy is recommended to reduce the randomized studyevidence) (EBTable A.10b) moderate, low ornocaffeine intake (non- b) Effects ofhighcaffeine intake versus studies; RR:1.60, 95% CI:1.24–2.08) (77). 95% CI:1.18–1.62)1.38, orhighcaffeine intake (8 RR: 1.13, 95% CI:1.06–1.21), moderate (7studies;RR: fewer low-birth-weight neonates than low (5studies; that very low caffeine intake may beassociated with review was stratified according to doseandshows low- to moderate-certainty evidence from theother odds ratio [OR]: 95% CI: 1.10–1.73) 1.38, (78).Very weight thanlow ornocaffeine intake (12studies; probably associated withagreater riskoflow birth that highcaffeine intake (more than300 mg) is Moderate-certainty evidence from onereview shows Fetal andneonataloutcomes: low weight birth performed dose–response meta-analyses. adjusted datafor smokingandothervariables, and 300 mg ormore than350 mgperday. Allfour reviews and highcaffeine intake was definedasmore than was definedasless than 150 mgcaffeine per day, loss?” maternal caffeine intake andtheriskofpregnancy asked thequestion“Is there anassociation between risk oflow weight?” birth (77, 78), andtwo reviews association between maternal caffeine intake andthe Two NRSreviews asked thequestion,“Is there an non-randomized studies(NRSs) was thusevaluated. restriction andadditionalevidence from reviews of insufficient tomake a recommendation oncaffeine The GDGconsidered theevidence from RCTs to be perinatal mortality. No datawere available oncongenital anomaliesor (79, 80).Inthesereviews, low caffeine intake Fetal and neonatal outcomes: stillbirths Equity The reviews reported “pregnancy loss”, a composite Interventions to restrict coffee intake during outcome comprising stillbirths and miscarriages. pregnancy are unlikely to impact health inequalities Moderate-certainty evidence from one review (80) as coffee consumption tends to be associated shows that any caffeine intake probably increases with affluence. However, it is unclear whether the pregnancy loss compared with controls (no consumption of caffeine through other sources might exposure) (18 studies; OR: 1.32, 95% CI: 1.24–1.40). be a problem for pregnant women in disadvantaged However, pregnancy loss is probably more common populations. among pregnant women with moderate caffeine intake (18 studies; OR: 1.28, 95% CI: 1.16–1.42) and Acceptability high caffeine intake (17 studies, OR: 1.60, 1.46–1.76), Qualitative evidence indicates that women in a but not more common with low caffeine intake variety of settings generally appreciate any advice (13 studies; OR: 1.04, 95% CI: 0.94–1.15) compared (including dietary or nutritional) that may lead to a with controls. This NRS evidence was upgraded to healthy baby and a positive pregnancy experience “moderate-certainty” due to the presence of a dose– (high confidence in the evidence) (22). Evidence response relationship. A dose–response relationship on health-care providers’ views on ANC suggests was also observed in the other review but the that they may be keen to offer general health-care evidence was less certain (79). advice and specific pregnancy-related information (low confidence in the evidence) but they sometimes Values feel they do not have the appropriate training and Please see “Women’s values” in section 3.A: lack the resources and time to deliver the service in Background (p. 15). the informative, supportive and caring manner that women want (high confidence in the evidence) (45). Resources Communicating with pregnant women about Feasibility the probable risks of high caffeine intake during A lack of suitably trained staff to deliver health pregnancy is a relatively low-cost intervention. promotion interventions may limit implementation (high confidence in the evidence) (45).

Chapter 3. Evidence and recommendations 39 40 WHO recommendations on antenatal care for a positive pregnancy experience n conditions inpregnancy: information on interventions to detect thefollowing the GDGconsidered evidence and otherrelevant specifically in relation to maternal assessment, oftheANCguidelinedevelopment,As part Clinical Practice inANC. it considers to beanessential component ofGood recommendation onthisprocedure, therefore, which (57). The GDGdidnotevaluate evidence ormake a and otherpoormaternal andperinataloutcomes specific management is required to prevent eclampsia ANC contact and,upondetection ofpre-eclampsia, blood pressure andcheckingfor proteinuria ateach It isroutinely performed by measuringmaternal for pre-eclampsia ofgood isanessential part ANC. eclampsia and(9).Antenatal screening deaths andnearmisses estimated to bedueto pre- mortality, withapproximately ofmaternal aquarter causes ofmaternal andperinatalmorbidity and Hypertensive disorders ofpregnancy are important Background B.1: Maternal assessment B. Maternal andfetal assessment n matching itagainst arange ofcolours representing on speciallymadechromatography paperand is performed by placing adrop ofundiluted blood haemoglobin colour scale,alow-cost methodthat to laboratory facilities. WHOdeveloped the needed for places withnoorlimited access reliable methodofdetecting anaemiaistherefore for useinrural orLMICsettings.Alow-cost and tests may beexpensive, complex orimpractical ANC (81).However, thisandotheravailable quantifies thebloodHblevel, of ispart routine In HICs,performing afullbloodcount, which but hasbeenshown to bequite inaccurate. pallor) isacommon methodofdetecting anaemia assessment (inspectionoftheconjunctiva for pregnant women atabout38%(33).Clinical with theglobalprevalence ofanaemiaamong of themostseriousglobalpublichealthproblems, world’s second leadingcauseofdisability, andone anaemiaisthe concentration below 110 g/L, Anaemia: Definedasabloodhaemoglobin(Hb) n n n n presence of10 threshold for diagnosisusuallydefinedas the take upto seven days to get aresult, withthe stain andurinedipsticktests. Aurineculture can midstream urineculture (thegold standard), Gram (GBS) species, of isolates; otherpathogens includeKlebsiella Escherichia coli isassociated withupto 80% (cystitis andpyelonephritis) inpregnant women. with anincreased riskofurinary tract infections common urinarytract condition thatisassociated Asymptomatic bacteriuria (ASB): adversely impactsthehealthofindividuals(85). being permitted to see friendsorfamily) also subjected to controlling behaviours suchasnot (being humiliated, insulted, intimidated and by (85). theirintimate partner have experienced physical and/or sexual violence third ofallwomen whohave beeninarelationship global publichealthissue. Worldwide, almostone those intherelationship, isnow recognized asa causes physical, psychological orsexual harmto any behaviour withinanintimate relationship that violenceIntimate partner (IPV): IPV, definedas photometer) to produce areading (82). into thehaemoglobinometeris inserted (or is placed directly into amicrocuvette, which With haemoglobinometer tests, undiluted blood incrementsdifferent (82). Hb values in20 g/L section C: Preventive measures with antibiotics(see alsoRecommendation C.1 , in detected itis,therefore, usuallyactively managed with anincreased riskofpreterm once birth; pus intheurine,respectively. ASBisassociated esterase, to identifythepresence ofbacteria and which are identified by a reaction withleucocyte which are notfound innormalurine,andleucocytes, prepared glass slide.Urine dipsticks test for nitrites, (purple) andGram-negative (red) organisms ona exaggerate anddistinguishbetween Gram-positive colour stains(crystal violetandsafrinin O) to a singleorganism (84).The Gram staintest uses (83). Proteus mirabilis andgroup Bstreptococcus

Methods for diagnosing ASB include Methods for diagnosing ASBinclude 5 colony-forming units(cfu)/mL of Emotional abuse Emotional abuse ). ASB is a ASB isa

IPV is associated with chronic problems in women, Women’s values including poor reproductive health (e.g. a history of STIs including HIV, unintended pregnancy, abortion A scoping review of what women want from ANC and/or miscarriage), depression, substance use and what outcomes they value informed the ANC and other mental health problems (85). During guideline (13). Evidence showed that women from pregnancy, IPV is a potentially preventable risk high-, medium- and low-resource settings valued factor for various adverse outcomes, including having a positive pregnancy experience. Within the maternal and fetal death. Clinical enquiry about IPV context of maternal and fetal assessment, women aims to identify women who have experienced or valued the opportunity to receive screening and are experiencing IPV, in order to offer interventions tests to optimize their health and that of their baby leading to improved outcomes. Some governments as long as individual procedures were explained to and professional organizations recommend them clearly and administered by knowledgeable, screening all women for IPV rather than asking only supportive and respectful health-care practitioners women with symptoms (86). (high confidence in the evidence).

In addition to GDG recommendations on the above, recommendations on diagnosing gestational infection have been integrated into this chapter from diabetes mellitus (GDM) and screening for tobacco the respective existing WHO guidance on these smoking, alcohol and substance abuse, TB and HIV conditions.

B.1.1: Anaemia

RECOMMENDATION B.1.1: Full blood count testing is the recommended method for diagnosing anaemia during pregnancy. In settings where full blood count testing is not available, on- site haemoglobin testing with a haemoglobinometer is recommended over the use of the haemoglobin colour scale as the method for diagnosing anaemia in pregnancy. (Context-specific recommendation)

Remarks • The GDG agreed that the high recurrent costs of Hb testing with haemoglobinometers might reduce the feasibility of this method in some low-resource settings, in which case the WHO haemoglobin colour scale method may be used. • Other low-technology on-site methods for detecting anaemia need development and/or investigation.

Summary of evidence and considerations Moderate-certainty evidence shows that the sensitivity and specificity of the haemoglobinometer Test accuracy of on-site Hb testing with test in detecting anaemia (Hb < 110 g/L) are haemoglobinometer and haemoglobin colour approximately 0.85 (95% CI: 0.79–0.90) and scale (HCS) methods to detect anaemia (EB 0.80 (95% CI: 0.76–0.83), respectively, while the Table B.1.1) sensitivity and specificity of the HCS method are The evidence was derived from a test accuracy lower at approximately 0.75 (95% CI: 0.71–0.80) and review conducted to support the ANC guideline 0.47 (95% CI: 0.41–0.53), respectively. (81). Only one study (671 women) contributed data (87). The study, conducted in Malawi, assessed For severe anaemia (defined in the study as the test accuracy of on-site Hb testing with a Hb < 60 g/L), moderate-certainty evidence haemoglobinometer (HemoCue®) and the HCS shows that the sensitivity and specificity of the method in comparison to a full blood count test haemoglobinometer test are approximately 0.83 performed by an electronic counter (Coulter counter), (95% CI: 0.44–0.97) and 0.99 (95% CI: 0.98–1.00), the reference standard. respectively, while for the HCS method they are approximately 0.50 (95% CI: 0.15–0.85) and 0.98 (95% CI: 0.97–0.99), respectively.

Chapter 3. Evidence and recommendations 41 42 WHO recommendations on antenatal care for a positive pregnancy experience n n n n n Additional considerations Maternal assessment : Background (p. 41). Please see“Women’s values” insection3.B.1: Values n n n n n most user-friendly method(82). found thehaemoglobinometer methodto be the A studyofvarious Hbtesting methodsinMalawi than theability to detect Hb below 110 g/L. anaemia inpregnancy isprobably more important the accuracy ofon-site Hbtests to detect severe usually require additionaltreatment. Therefore, moderate anaemia,aswomen with severe anaemia serious thanthatofmissing women withmildor missing women withsevere anaemiaismore used by pregnant women, theconsequence of In settingswhere iron supplementationisroutinely specific thanclinicalassessment. the HCSmethodmightbemore sensitive butless Thus, 23–91) for detecting anaemia(Hb< 110 g/L). (95% CI:22–94) andaspecificity of 0.63 (95% CI: giving asensitivity for clinicalassessment of0.64 clinical assessment (4 studies,1853women), The review alsoevaluated thetest accuracy of about therelative accuracy ofthesetests. the two methodsoverlap, there issomeuncertainty confidence intervals for sensitivity andspecificityof direct comparisons intest accuracy studiesand,as accurate thantheHCSmethod.Asthere are no the haemoglobinometer test isprobably more estimates. However, theevidence suggests that anaemia, whichaffects theprecision ofthe low numberofwomen identifiedwithsevere The mainlimitationoftheevidence isthe out ofevery 1000women tested. 25 women withsevere anaemia(95% CI:3–43) whereas theHCSmethodwill probably miss about (95% CI:2–27) outofevery 1000women tested, miss aboutninewomen withsevere anaemia 5%, thehaemoglobinometer test willprobably populations withasevere anaemiaprevalence of CI: 76–110) outofevery 1000women tested. For will probably miss about95 anaemicwomen (95% 1000 women tested, whereas theHCSmethod 57 anaemicwomen (95% CI:38–80)outofevery haemoglobinometer test willprobably miss about settings withananaemiaprevalence of38%,the In absolute numbers, thedatameanthatin severe anaemia,inlow-resource settings. management ofwomen withanaemia,particularly by improving thedetection andsubsequent anaemia mighthelpto address healthinequalities Accurate, low-cost, simple-to-use tests to detect newborns andcontributes to preventable mortality. Anaemia increases perinatalrisks for mothers and infections are majorcontributory factors (33). in Africa andSouth-EastAsia, where parasitic The highestprevalence ofmaternal anaemiaoccurs Equity maintenance. (cuvettes andcontrols), equipmentcosts and haemoglobinometer tests are mainlydueto supplies swabs; however, thehighercosts associated with cotton balls,gloves andSterets® skincleansing Both methodsrequire needlesfor finger pricks, US$ 0.75 andUS$ 0.12 pertest, respectively (82). methods have beenestimated to cost approximately minimal training. The haemoglobinometer andHCS haemoglobinometer andHCSmethodsafter Any health-care provider canperform boththe Resources evidence) (45). recommended interventions (high confidence inthe to deliver theservice, may limitimplementationof treatments, aswell asthelackofsuitablytrained staff availability ofthediagnosticequipmentandpotential indicates thatalackofresources, bothinterms ofthe Qualitative evidence from providers invarious LMICs Feasibility confidence inthe evidence). may beless likely to engage withANCservices (high unavailable becauseofresource constraints, women tests, orwhere therecommended interventions are there are likely to beadditionalcosts associated with However, evidence from LMICsindicates thatwhere (moderate confidence inthe evidence) (22). theirwell-beingtests thatsupport duringpregnancy indicates thatwomen generally appreciate clinical Qualitative evidence from avariety ofsettings Acceptability B.1.2: Asymptomatic bacteriuria (ASB)

RECOMMENDATION B.1.2: Midstream urine culture is the recommended method for diagnosing asymptomatic bacteriuria (ASB) in pregnancy. In settings where urine culture is not available, on-site midstream urine Gram-staining is recommended over the use of dipstick tests as the method for diagnosing ASB in pregnancy. (Context-specific recommendation)

Remarks • This recommendation should be considered alongside Recommendation C.1 on ASB treatment (see section C: Preventive measures). • The GDG agreed that the higher resource costs associated with Gram stain testing might reduce the feasibility of this method in low-resource settings, in which case, dipstick tests may be used. • The GDG agreed that ASB is a priority research topic, given its association with preterm birth and the uncertainty around urine testing and treatment in settings with different levels of ASB prevalence. Specifically, studies are needed that compare on-site testing and treatment versus testing plus confirmation of test with treatment on confirmatory culture, to explore health and other relevant outcomes, including acceptability, feasibility and antimicrobial resistance. In addition, better on-site tests need to be developed to improve accuracy and feasibility of testing and to reduce overtreatment of ASB. Research is also needed to determine the prevalence of ASB at which targeted testing and treatment rather than universal testing and treatment might be effective.

Summary of evidence and considerations Additional considerations nnA high level of accuracy in detecting ASB is Test accuracy of on-site urine Gram staining and important to avoid treating women unnecessarily, dipsticks to detect ASB (EB Table B.1.2) particularly in view of increasing antimicrobial The evidence was derived from a test accuracy resistance. Based on the uncertain evidence above, review of on-site urine tests conducted to support and assuming a prevalence of ASB of 9%, there the ANC guideline (88). Four studies (1904 pregnant would be 18 and 118 false-positive tests per 1000 women) contributed data on urine Gram staining and women tested with Gram stain and dipstick tests, eight studies (5690 pregnant women) contributed respectively. This suggests that, in settings where data on urine dipsticks. Most of the studies were pregnant women are treated for ASB, dipstick conducted in LMICs. The average prevalence of ASB diagnosis of ASB might lead to many women in the studies was 8%. A Gram stain was positive receiving unnecessary treatment. if one or more bacteria were detected per oil- nnDipstick tests are multi-test strips that, in addition immersed field, and a dipstick test was positive if it to testing for nitrites and leucocytes, may also detected either nitrites or leucocytes. The reference include detection of urine protein and glucose. standard used was urine culture with a threshold of However, the accuracy of dipsticks to detect 105 cfu/mL. conditions associated with proteinuria (pre- eclampsia) and glycosuria (diabetes mellitus) is However, the certainty of the evidence on the considered to be low. accuracy of both Gram stain tests and dipstick tests is very low, with pooled sensitivity and specificity of Values the Gram stain test estimated at 0.86 (95% CI: 0.80– Please see “Women’s values” in section 3.B.1: 0.91) and 0.97 (95% CI: 0.93–0.99), respectively, and Maternal assessment: Background (p. 41). pooled sensitivity and specificity for urine dipsticks estimated at 0.73 (95% CI: 0.59–0.83) and 0.89 Resources (95% CI: 0.79–0.94), respectively. A positive nitrite Dipsticks are relatively low cost compared with the test alone on dipsticks was found to be less sensitive Gram stain test, as the latter requires trained staff but more specific than when urine leucocytes were and laboratory equipment and supplies (microscope, also considered. glass slides, reagents, Bunsen burner or slide warmer). Gram stain tests take longer to perform and

Chapter 3. Evidence and recommendations 43 44 WHO recommendations on antenatal care for a positive pregnancy experience test isassociated withlongwaiting timesatANC care professionals. Inaddition,iftheGram stain traditions are beingoverlooked orignored by health- properly orwhenwomen feel theirbeliefs and be limited iftests andprocedures are notexplained (22). However, engagement withANCservices may they are offered (high confidence inthe evidence) that they generally appreciate thetests andadvice knowledge, information andclinicalexpertise and suggests thatwomen view ANCasasource of Qualitative evidence from arange ofsettings Acceptability address healthinequalities. associated withpreterm mighttherefore birth helpto Timely diagnosisandtreatment ofrisk factors worldwide, withmostdeathsoccurring inLMICs. Preterm istheleadingcauseofneonataldeath birth Equity minutes vs 60seconds). to produce results thanurinedipsticktests (10–30 might bemore feasible inlow-resource settings. dipstick tests, whichare cheaperandeasy to perform, confidence inthe evidence) (45). Therefore, urine equipment, suppliesorskillsto perform tests (high that providers donothave often thediagnostic facilities discourages women from attending, and settings, thelackofdiagnosticequipmentatANC Qualitative evidence indicates that,insomeLMIC Feasibility confidence inthe evidence). (pre-eclampsia anddiabetes mellitus) (high additional information to otherconditions pertaining visits to provide theresults) andmightprovide assessment, perform tests orschedulefollow-up less effort (noneed to labelsamples for laboratory likely to prefer thedipsticktest asitisassociated with confidence inthe evidence). Healthprofessionals are cost andconvenience implicationsfor them(high acceptable to women, asitmighthave additional or having to return for test results, thismay beless B.1.3: Intimate partner violence (IPV)

RECOMMENDATION B.1.3: Clinical enquiry about the possibility of intimate partner violence (IPV) should be strongly considered at antenatal care visits when assessing conditions that may be caused or complicated by IPV in order to improve clinical diagnosis and subsequent care, where there is the capacity to provide a supportive response (including referral where appropriate) and where the WHO minimum requirements are met.a (Context-specific recommendation)

Remarks • This recommendation is consistent with the 2013 publication Responding to intimate partner violence and sexual violence against women: WHO clinical and policy guidelines (86). The evidence on clinical enquiry was indirect (strong recommendation) and the evidence on universal screening was judged as being of low to moderate quality (conditional recommendation). • “Universal screening” or “routine enquiry” (i.e. asking all women at all health-care encounters) about IPV is not recommended. However, the WHO guidelines identify ANC as a setting where routine enquiry could be implemented if providers are well trained on a first-line response and minimum requirements are met (86). • Examples of conditions during pregnancy that may be caused or complicated by IPV include (86): –– traumatic injury, particularly if repeated and with vague or implausible explanations; –– intrusive partner or husband present at consultations; –– adverse reproductive outcomes, including multiple unintended pregnancies and/or terminations, delay in seeking ANC, adverse birth outcomes, repeated STIs; –– unexplained or repeated genitourinary symptoms; –– symptoms of depression and anxiety; –– alcohol and other substance use; –– self-harm, suicidality, symptoms of depression and anxiety. • The GDG agreed that, despite a paucity of evidence, it was important to make a recommendation due to the high prevalence and importance of IPV. ANC provides an opportunity to enquire about IPV among women for whom barriers to accessing health care may exist, and also allows for the possibility for follow-up during ANC with appropriate supportive interventions, such as counselling and empowerment interventions. However, the evidence on benefits and potential harms of clinical enquiry and subsequent interventions is lacking or uncertain. • A minimum condition for health-care providers to ask women about violence is that it must be safe to do so (i.e. the partner is not present) and that identification of IPV is followed by an appropriate response. In addition, providers must be trained to ask questions in the correct way and to respond appropriately to women who disclose violence (86). • Research on IPV is needed to answer the following questions: –– Which are the most effective strategies for identifying, preventing and managing IPV in pregnancy? –– Does asking routinely about violence impact on ANC attendance? –– Can interventions targeted at partners of pregnant women prevent IPV? • Detailed guidance on responding to IPV and sexual violence against women can be found in the 2013 WHO clinical and policy guidelines (86), available at: http://www.who.int/reproductivehealth/ publications/violence/9789241548595/en/ a Minimum requirements are: a protocol/standard operating procedure; training on how to ask about IPV, and on how to provide the minimum response or beyond; private setting; confidentiality ensured; system for referral in place; and time to allow for appropriate disclosure.

Chapter 3. Evidence and recommendations 45 46 WHO recommendations on antenatal care for a positive pregnancy experience n n n Additional considerations 95% CI:1.77–10.36). through usualANC(2trials,663women; OR:4.28, pregnant women withIPVthanthoseidentified that abuseassessment screening may identifymore Low-certainty evidence from thereview suggests clusters received usualANC. the intervention clusters, whilewomen inthecontrol to women between 12and30weeks ofgestation in tool thatscreened for 15riskfactors, includingIPV, providers administered aface-to-face screening care provider. Intheothertrial(acluster-RCT), provider), priorto ANCconsultation withahealth- sheet (givingtheresults oftheassessment to the screening tool, withandwithoutaprovider cue of gestation to acomputer-based abuseassessment trial, 410 women were randomized before 26 weeks USA), involving 663pregnant women (89).Inone in urbanANCsettingsHICs(Canada andthe a Cochrane review thatincludedtwo trialsconducted The evidence onscreening for IPVwas derived from Table B.1.3) compared withnoscreening (usualcare) (EB Effects ofuniversal screening to detect IPV Summary ofevidence andconsiderations n n n inconclusive. evidence on thisandotheroutcomes islargely (306 women; RR:0.62, 95% CI:0.43–0.88), but during pregnancy period andthepostpartum may report fewer violence episodesofpartner counselling sessions) to prevent orreduce IPV who receive IPVinterventions (e.g. multiple from onestudysuggests thatpregnant women to prevent orreduce IPV(90).Uncertainevidence Another Cochrane review evaluated interventions 95% CI:1.53–3.59).2.35, screening to detect IPV(7trials,4393 women; OR: women), andthepooledeffect estimate favoured settings (involving pregnant andnon-pregnant versus noIPVscreening from otherhealth-care The review alsopooleddataonIPVscreening women (under20years old)approaches 30%, than 30%.Notably, theprevalence amongyoung against women, thelifetime prevalence ishigher foster aculture more permissive ofviolence those where economic andsociocultural factors to 6%.However, inmany settings,particularly IPV intheprevious 12monthsranged from 3% where theprevalence ofwomen experiencing Most ofthereview evidence comes from HICs n n rather thanIPVscreening. might bebesttargeted towards first response to IPV that training andresources inlow-resource settings significant cost implications. The GDG considered requires sophisticated training andcantherefore have linkedsupport to thescreening intervention, however, be relatively low. Subsequentmanagement andIPV of implementingthesemethodscanvary, they might computer-based questionnaire. Althoughthecosts to-face orby providing women withawritten or Clinical enquiryaboutIPVcanbeconducted face- Resources Maternal assessment: Background ( p. 41). Please see“Women’s values” insection3.B.1: Values nature, thoselivinginmale-dominated, particularly some women may notappreciate enquiriesofthis abusive (highconfidence inthe evidence). Inaddition, perceive to behurried,uncaringandoccasionally of information withproviders whothey sometimes unlikely to respond favourably to cursory exchanges evidence from LMICssuggests thatwomen may be (high confidence inthe evidence) (22). However, to discuss issues ofthisnature inaprivate setting supportive health-care provider whohasthetime women would like to beseenby akindand women’s views ofANCsuggests thatpregnant Qualitative evidence from arange ofsettingson Acceptability improved equity. However, more evidence isneeded. of appropriate supportive interventions leadingto related adverse outcomes, andfacilitate theprovision populations might help to identify those atriskof IPV- interventions to enquire aboutIPVindisadvantaged disadvantaged populations(92, 93). Effective IPV ishighlyprevalent inmany LMICsandamong Equity n n to respond (91). violence (2014) provides practical guidance onhow subjected violence to intimate orsexual partner WHO’s clinicalhandbookonHealthcare for women severely abusive outsideofpregnancy. who are inrelationships thathave alsobeen violence) (85)ismore common amongwomen or having aweapon usedagainst her, andsexual choked orburntonpurpose,beingthreatened with Severe IPVinpregnancy (such asbeingbeaten up, women’s relationships (85) . suggesting thatviolence commonly earlyin starts patriarchal societies, where women’s financial trusting and empathetic relationship with pregnant dependence on their husbands may influence their women (moderate confidence in the evidence) (see willingness to discuss IPV, especially if the health Recommendation E.2, in section E: Health systems professional is male (22). interventions to improve the utilization and quality of ANC). From the providers’ perspective, qualitative evidence mainly from HICs suggests that providers often Feasibility find it difficult to enquire about for IPV for the Following IPV clinical enquiry, complex, multifaceted, following reasons: they do not feel they have enough culturally specific interventions are required to knowledge, training or time to discuss IPV in a manage IPV, which could be challenging in many low- sensitive manner; the presence of the partner acts as resource settings. However, emerging evidence from a barrier; they may have experienced IPV themselves; HICs shows that medium-duration empowerment and they lack knowledge and guidance about the counselling and advocacy/support, including a safety availability of additional support services (counselling, component, offered by trained health-care providers social work, etc.) (high confidence in the evidence). could be beneficial, and the feasibility of such Providers highlight the midwife-led continuity of interventions in LMIC settings needs investigation care (MLCC) model as a way of achieving a positive, (86).

Chapter 3. Evidence and recommendations 47 48 WHO recommendations on antenatal care for a positive pregnancy experience a B.1.4: Gestational diabetes mellitus(GDM)

• • • • • • • • Remarks according to WHOcriteria. be classified aseither gestational diabetes mellitus (GDM) ordiabetes mellitusinpregnancy, RECOMMENDATION B1.4: Hyperglycaemia first detected atany timeduringpregnancy should • • • Diabetes mellitusinpregnancy shouldbediagnosedifoneormore ofthefollowing criteria are met: • • • This isnotarecommendation onroutine screening for hyperglycaemia inpregnancy. Ithasbeenadapted andintegrated from the2013 WHOpublication which states thatGDMshouldbediagnosedatany timeinpregnancy ifoneormore ofthefollowing criteria are met:

undiagnosed GDMand,ifthisisobserved, performing anOGTT could beconsidered (95) . glycosuria ondipsticktesting (2+orabove ononeoccasion, or1+ontwo ormore occasions) may indicate history ofdiabetes mellitus,andethnicity withahighprevalence ofdiabetes mellitus(95). Inaddition, en/ guideline (94), available at:http://www.who.int/diabetes/publications/Hyperglycaemia_In_Pregnancy/ Further information andconsiderations related to thisrecommendation canbefound inthe2013 WHO both require referral andincreased monitoring. whendiagnosedearlyinpregnancy;particularly however, theprinciplesofmanagement are similarand hyperglycaemia first detected inpregnancy) usuallydiffers from theapproach for womenwithGDM, The management approach for women classified withdiabetes mellitusinpregnancy (i.e. severe (OGTT). These includeaBMIofgreater than 30kg/m is usedinsomesettingsasastrategy to determine theneedfor a2-hour 75 goral glucose tolerance test The usualwindow for diagnosingGDMisbetween 24 and28weeks ofgestation. Riskfactor screening impact ofearlierdiagnosisonpregnancy outcomes (see Chapter 5:Research implications) (94). prevalence ofGDManddiabetes mellitusaccording to the2013 criteria indiverse populations,andthe There are many uncertaintiesaboutthecost–effectiveness ofdifferent screening strategies, the these pooroutcomes (94). exercise) followed by oral blood-glucose-lowering agents orinsulinifnecessary, iseffective in reducing of GDM,whichusuallyinvolves astepped approach oflifestyle changes (nutritionalcounselling and macrosomia, pre-eclampsia/hypertensive disorders inpregnancy, andshoulderdystocia. Treatment and GDM)detected duringpregnancy are atgreater riskofadverse pregnancy outcomes, including A systematic review ofcohortstudiesshows thatwomen withhyperglycaemia (diabetes mellitus resolve pregnancy after asitdoeswithGDM. Diabetes mellitusinpregnancy differs from GDMinthatthe hyperglycaemia ismore severe anddoesnot strategies for GDMare considered apriority area for research, inLMICs. particularly WHO currently doesnothave arecommendation onwhetherorhow to screen for GDM,andscreening quality oftheevidence were notstated) (94). classification of hyperglycaemia first detected in pregnancy (thestrength oftherecommendation andthe This recommendation hasbeenintegrated from the2013 WHOpublicationDiagnosticcriteria and random plasmaglucose 2-hour plasmaglucose fasting plasmaglucose 2-hour plasmaglucose 8.5–11.0 mmol/L(153–199 mg/dL) following a75 goral glucose load 1-hour plasmaglucose fasting plasmaglucose 5.1–6.9 mmol/L(92–125 mg/dL) 10.0 mmol/L(180mg/dL) following a75 goral glucose load 11.1 mmol/L(200mg/dL) following a75 goral glucose load 7.0 mmol/L(126 mg/dL) 11.1 mmol/L(200mg/dL) inthepresence ofdiabetes symptoms.. a (Recommended) 2 , previous GDM,previous macrosomia, family (94), B.1.5: Tobacco use

RECOMMENDATION B.1.5: Health-care providers should ask all pregnant women about their tobacco use (past and present) and exposure to second-hand smoke as early as possible in pregnancy and at every antenatal care visit. (Recommended)

Remarks • This strong recommendation based on low-quality evidence has been integrated from the 2013 WHO recommendations for the prevention and management of tobacco use and second-hand smoke exposure in pregnancy (96). Related recommendations from this guideline include the following: –– Health-care providers should routinely offer advice and psychosocial interventions for tobacco cessation to all pregnant women who are either current tobacco users or recent tobacco quitters (strong recommendation based on moderate quality evidence). –– All health-care facilities should be smoke-free to protect the health of all staff, patients and visitors, including pregnant women (strong recommendation based on low-quality evidence). –– Health-care providers should provide pregnant women, their partners and other household members with advice and information about the risks of second-hand smoke (SHS) exposure from all forms of smoked tobacco, as well as strategies to reduce SHS in the home (strong recommendation based on low- quality evidence). –– Health-care providers should, wherever possible, engage directly with partners and other household members to inform them of all the risks of SHS exposure to pregnant women from all forms of tobacco, and to promote reduction of exposure and offer smoking cessation support (strong recommendation based on low-quality evidence). • Further guidance on strategies to prevent and manage tobacco use and SHS exposure can be found in the 2013 WHO recommendations (96), available at: http://www.who.int/tobacco/publications/pregnancy/ guidelinestobaccosmokeexposure/en/

Chapter 3. Evidence and recommendations 49 50 WHO recommendations on antenatal care for a positive pregnancy experience B.1.6: Substance use • • • • • • Remarks at every antenatal care visit.(Recommended) use ofalcohol andothersubstances (past andpresent) asearlypossible inthepregnancy and RECOMMENDATION B.1.6: Health-care providers shouldaskallpregnant women abouttheir • • •

discrimination andstigmatization. and treatment services, respect women’s autonomy, provide comprehensive care, andsafeguard against The overarching principlesofthisguidelineaimedto prioritize prevention, ensure access to prevention substance_abuse/publications/pregnancy_guidelines/en/ disorders inpregnancy canbefound inthe2014 WHO guidelines(97), available at:http://www.who.int/ Further guidance oninterventions andstrategies to identifyand manage substance useandsubstance use of assisting anindividualto cease orreduce useofapsychoactive substance. A briefintervention isastructured therapy duration ofshort (typically 5–30minutes) offered withtheaim considered to beminimal. benefit (potential reduction ofalcohol andsubstance use)outweighed any potential harms,which were It was decidedthatdespite thelow-quality evidence oneffects ofbriefpsychosocial interventions, the – – include thefollowing: For women identifiedasbeingdependentonalcohol ordrugs, further recommendations from theguideline using alcohol and/or drugs(pastandpresent). Health-care providers shouldbeprepared to intervene orrefer allpregnant women whoare identifiedas available (refer to Annex 3ofthe2014 guidelines[97]). Validated screening instrumentsfor alcohol andothersubstance useandsubstance usedisorders are alcohol anddruguse. Pregnant women shouldbeadvisedofthepotential healthrisks to themselves andto theirbabies posedby established. as somewomen are more likely to report sensitive information atrustingrelationship onlyafter hasbeen The GDGresponsible for therecommendation noted thataskingwomen atevery ANCvisitisimportant Guidelines for theidentification andmanagementofsubstance useandsubstance usedisorders inpregnancy This strong recommendation basedonlow-quality evidence hasbeenintegrated from the2014 – – (strong recommendation basedonlow-quality evidence). Health-care providers shouldoffer abriefintervention to allpregnant women usingalcohol ordrugs evidence). medical supervision,where necessary andapplicable(strong recommendation basedonvery low-quality or drugsto cease theiralcohol ordruguseandoffer, or refer them to, detoxification services under Health-care providers shouldattheearliestopportunity advisepregnant women dependentonalcohol WHO WHO

(97). B.1.7: Human immunodeficiency virus (HIV) and syphilis

RECOMMENDATION B.1.7: In high-prevalence settings,a provider-initiated testing and counselling (PITC) for HIV should be considered a routine component of the package of care for pregnancy women in all antenatal care settings. In low-prevalence settings, PITC can be considered for pregnant women in antenatal care settings as a key component of the effort to eliminate mother-to-child transmission of HIV, and to integrate HIV testing with syphilis, viral or other key tests, as relevant to the setting, and to strengthen the underlying maternal and child health systems. (Recommended)

Remarks • This recommendation has been integrated from the 2015 WHO Consolidated guidelines on HIV testing services (98) (the strength of the recommendation and the quality of the evidence were not stated). • PITC denotes an HIV testing service that is routinely offered in a health-care facility and includes providing pre-test information and obtaining consent, with the option for individuals to decline testing. PITC has proved highly acceptable and has increased the uptake of HIV testing in LMICs (98). • The availability of HIV testing at ANC services is responsible for the high level of knowledge of HIV status among women in many countries, which has allowed women and infants to benefit from ART. • WHO recommends that ART should be initiated in all pregnant women diagnosed with HIV at any CD4 count and continued lifelong (99). This recommendation is based on evidence that shows that providing ART to all pregnant and breastfeeding women living with HIV improves individual health outcomes, prevents mother-to-child transmission of HIV, and prevents horizontal transmission of HIV from the mother to an uninfected sexual partner. • Other recommendations relevant to ANC services from the Consolidated guidelines on HIV testing services include the following (98): –– On disclosure: Initiatives should be put in place to enforce privacy protection and institute policy, laws and norms that prevent discrimination and promote tolerance and acceptance of people living with HIV. This can help create environments where disclosure of HIV status is easier (strong recommendation, low-quality evidence). –– On retesting: In settings with a generalized HIV epidemic:b Retest all HIV-negative pregnant women in the third trimester, during labour or postpartum because of the high risk of acquiring HIV infection during pregnancy (strength of recommendation and quality of evidence not stated). –– On retesting: In settings with a concentrated HIV epidemic:c Retest HIV-negative pregnant women who are in a serodiscordant couple or from a key population groupd (strength of recommendation and quality of evidence not stated). –– On retesting before ART initiation: National programmes should retest all people newly and previously diagnosed with HIV before they enrol in care and initiate ART (strength of recommendation and quality of evidence not stated). –– On testing strategies: In settings with greater than 5% HIV prevalence in the population being tested, a diagnosis of HIV-positive should be issued to people with two sequential reactive tests. In settings with less than 5% HIV prevalence in the population being tested, a diagnosis of HIV-positive should be issued to people with three sequential reactive tests (strength of recommendation and quality of evidence not stated). –– On task shifting: Lay providers who are trained and supervised can independently conduct safe and effective HIV testing using rapid diagnostic tests (strong recommendation, moderate-quality evidence). • Further guidance on HIV testing can be found in the 2015 WHO guidelines (98), available at: http://www.who.int/hiv/pub/guidelines/hiv-testing-services/en/ • In addition, the 2015 Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV (99) is available at: http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/ • To prevent mother-to-child transmission of syphilis, all pregnant women should be screened for syphilis at the first ANC visit in the first trimester and again in the third trimester of pregnancy. For further guidance

Chapter 3. Evidence and recommendations 51 52 WHO recommendations on antenatal care for a positive pregnancy experience B.1.8: Tuberculosis (TB) d c b a

• • • • • • • • • Remarks considered for pregnant women ofantenatal care. aspart (Context-specific recommendation) population is100/100 000 populationorhigher, systematic screening for active TBshouldbe RECOMMENDATION B.1.8: Insettingswhere thetuberculosis (TB) prevalence inthegeneral prevalence inthepopulationbeingtested. Low-prevalence settingsare settingswithless than5%HIVprevalence inthepopulationbeingtested (98). people whoinjectdrugs,sex workers andtransgender people(98). the general population(98). women attending antenatal clinics(98). Key populationsare definedinthe2015 WHOguidelinesasthe following groups: menwhohave sex withmen,peopleinprisonorotherclosedsettings, A concentrated HIVepidemiciswhenhasspread rapidly inadefinedsubpopulation (or key population,seenext footnote) butisnot well establishedin A generalized HIVepidemiciswhen firmly establishedinthe general population.Numericalproxy: HIVprevalence is consistently over 1%inpregnant High-prevalence settingsare definedinthe2015 WHOpublication

reproductivehealth/publications/rtis/clinical/en/ the prevention ofsexual transmission ofZika virus(101–104) , are available at:http://www.who.int/ The latest (2016) WHOguidelinesonthetreatment ofchlamydia, gonorrhoea andsyphilis, andon health/prevention_mtct_syphilis.pdf syphilis (100),available at:http://www.who.int/reproductivehealth/publications/maternal_perinatal_ on screening, pleaserefer to the2006WHOpublicationPrevention ofmother-to-child transmission of recommendations Further information andconsiderations related to thisrecommendation canbefound inthe2013 WHO pregnancy statusinregisters thattrack TBscreening andtreatment. To better understand thelocalburden ofTBinpregnancy, healthsystems may benefitfrom capturing treatment earlyisassociated withbetter maternal andinfant outcomes thanlate initiation TB increases theriskofpreterm perinataldeathandotherpregnancy birth, complications. InitiatingTB – – – Other recommendations relevant to ANCservices from thesamepublicationincludefollowing resource-constrained settings. The panelresponsible for makingthisrecommendation noted thatitmay notbepossible to implementitin detection thatmay occur asaresult ofscreening. be inplace, and there shouldbethecapacity to match to theanticipated scaletheseupfurther riseincase Before screening isinitiated, high-quality TBdiagnosis, treatment, care, management should andsupport followed poses nosignificantriskbutthenationalguidelines for theuseof radiography duringpregnancy shouldbe fever ornight sweats) orscreening withchestradiography. The use ofchestradiography inpregnant women weeks, orany symptoms compatible withTB,includingacough ofany duration, haemoptysis, weight loss, Options for initial screening includescreening for symptoms (either for cough lastinglonger thantwo predetermined target group, usingtests, examinations orotherprocedures thatcanbeapplied rapidly. Systematic screening is definedasthe systematic identificationofpeoplewithsuspected active a TBin recommendation basedonvery low-quality evidence (105). screening for active tuberculosis: principlesandrecommendations , where it was considered aconditional This recommendation hasbeenadapted andintegrated from the2013 WHOpublication – – – evidence). some indigenous populations,migrants andrefugees (conditional recommendation, very low-quality remote areas withpooraccess to healthcare, andothervulnerable ormarginalized groups including poor access to healthcare, suchaspeoplelivinginurbanslums,homeless people,peopleliving in Systematic screening for active TBmay beconsidered alsofor othersubpopulationsthathave very facility (strong recommendation, very low-quality evidence). People livingwithHIVshould besystematically screened for active TBateachvisitto ahealth-care recommendation, very low-quality evidence). Household contacts andotherclosecontacts shouldbesystematically screened for TB(strong (105). (105), available at:http://www.who.int/tb/tbscreening/en/ Consolidated guidelinesonHIVtesting services assettingswithgreater than5%HIV Systematic (105). (105): B.2: Fetal assessment

Background accurate screening tool, is resource-intensive and not widely available in LMICs. Assessment of fetal growth and well-being is an important part of ANC. The GDG considered nnRoutine antenatal cardiotocography (CTG): evidence and other relevant information on the CTG is a continuous recording of the fetal heart following interventions to assess fetal growth and rate and uterine contractions obtained via an well-being in healthy pregnant women not at risk of ultrasound transducer placed on the mother’s adverse perinatal outcomes: abdomen. CTG is widely used in pregnancy as a method of assessing fetal well-being, nnDaily fetal movement counting: Maternal predominantly in pregnancies with increased risk perception of reduced fetal movements is of complications and during labour. associated with poor perinatal outcomes, including fetal death (106). Daily fetal movement nnFetal ultrasound examination: Diagnostic counting, such as the Cardiff “count-to-ten” ultrasound examination is employed in a variety method using kick charts, is a way of screening of specific circumstances during pregnancy, such for fetal well-being, by which a woman counts as where there are concerns about fetal growth daily fetal movements to assess the condition and after clinical complications. However, because of her baby. The aim of this is to try to reduce adverse outcomes may also occur in pregnancies perinatal mortality by alerting health workers without clear risk factors, assumptions have been when the baby might be compromised (107). made that antenatal ultrasound examination in Daily fetal movement counting may be used all pregnancies will prove beneficial by enabling routinely in all pregnant women or only in women earlier detection of problems that may not be who are considered to be at increased risk of apparent (110) – such as multiple pregnancies, adverse perinatal outcomes. Early detection of IUGR, congenital anomalies, malpresentation fetal compromise could lead to timely clinical and placenta praevia – and by allowing accurate interventions to reduce poor perinatal outcomes gestational age estimation, leading to timely but might lead to maternal anxiety or unnecessary and appropriate management of pregnancy clinical interventions. It is also possible that the complications. period between decreased fetal movements and fetal death might be too short to allow effective nnFetal Doppler ultrasound examination: Doppler action to be taken (108). ultrasound technology evaluates umbilical artery (and other fetal arteries) waveforms to assess nnSymphysis-fundal height (SFH) measurement: fetal well-being in the third trimester of pregnancy. SFH measurement is a commonly-practiced It is widely used in high-risk pregnancies to method of fetal growth assessment that uses a identify fetal compromise and thus reduce tape measure to measure the SFH, in order to perinatal mortality (111, 112). Therefore, it might detect intrauterine growth restriction (IUGR). also be useful when performed as an antenatal It also has the potential to detect multiple intervention to detect fetal compromise and pregnancy, macrosomia, polyhydramnios and predict complications, particularly IUGR and oligohydramnios. For fetuses growing normally, pre-eclampsia, in apparently healthy pregnancies. from 24 weeks of gestation, the SFH measurement Doppler ultrasound is useful for distinguishing in centimetres should correspond to the number between fetuses that are growth-restricted of weeks of gestation, with an allowance of a 2-cm (IUGR) and those that are constitutionally small difference either way (109). Other methods of fetal (SGA) (113). It can be performed as part of a growth assessment include abdominal palpation of fetal ultrasound examination or separately. The fundal height in relation to anatomical landmarks examination quantifies blood flow through the such as the umbilicus and xiphisternum, abdominal umbilical artery as either a pulsatility index or a girth measurement, and serial ultrasound resistive index (114). A high resistance to blood measurement of the fetal parameters (109). flow often indicates an increased risk of IUGR and Accurate low-cost methods for detecting abnormal pre-eclampsia and indicates the need for further growth are desirable because ultrasound, the most investigation.

Chapter 3. Evidence and recommendations 53 54 WHO recommendations on antenatal care for a positive pregnancy experience RCT conducted inNorway involving 1123women that each ANCvisit.The othertrialwas amulticentre ANC group were asked aboutfetal movements at and 32weeks of gestation. Women inthestandard uncomplicated pregnancies recruited between 28 withstandardkick chart ANCinwomen with compared a“count-to-ten” fetal movement counting Sweden, theUnited Kingdom andtheUSA, which RCT (68 654women) conducted inBelgium,Ireland, comparison. Onewas alarge, multicentre, cluster (107). Two RCTs from HICscontributed datafor this counting was derived from aCochrane review The evidence ontheeffects ofdaily fetal movement Table B.2.1) counting compared withstandard ANC(EB Effects ofdailymaternal fetal movement Summary ofevidence andconsiderations B.2.1: Daily fetal movement counting • • • • Remarks RECOMMENDATION B.2.1: recommendation –research) isonlyrecommendedkick charts, inthecontext ofrigorous research. (Context-specific

the evidence). clearly andadministered by knowledgeable, supportive andrespectful health-care practitioners (highconfidence in and tests to optimize theirhealthandthatofbaby aslongindividualprocedures were explained to them experience. Within thecontext ofmaternal andfetal assessment, women valued theopportunityto receive screening Evidence showed thatwomen from high-,medium-andlow-resource settingsvalued having apositive pregnancy A scoping review ofwhatwomen want from ANCandwhatoutcomes they value informed theANCguideline(13). Women’s values trimester ofpregnancy, inLMICsettingswithahighprevalence particularly ofunexplained stillbirths. The GDGagreed thatmore research isneededontheeffects ofdaily fetal movement counting inthethird require monitoring (e.g. further withdailyfetal movement counting) and investigation, ifindicated. recommended ofgood aspart clinicalpractice. Women whoperceive poororreduced fetal movements Clinical enquiry by ANCproviders ateachANCvisitaboutmaternal perception offetal movements is movements. aware oftheimportance offetal movements inthethird trimester andofreporting reduced fetal While dailyfetal movement counting isnotrecommended, healthy pregnant women shouldbemade method) (106). 2 hours (115)orfewer than10 distinctmovements are felt within12hours (theCardiff “count to ten” indicated dependingonthemethodused,for example, iffewer thansixdistinctmovements are felt within to monitor thebaby’s health. Various methodshave monitoring variously beendescribed,withfurther Fetal movement counting iswhenapregnant woman counts andrecords herbaby’s movements inorder

Daily fetal movement counting, suchaswith“count-to-ten” little ornodifference to preterm (1trial,1076 birth Low-certainty evidence suggests thatthere may be Fetal andneonataloutcomes standardized MD : –0.22, 95% CI:–0.35 to –0.10). may reduce meananxiety scores (1trial,1013 women; evidence suggests thatdailyfetal movement counting With regard to maternal satisfaction, low-certainty (1 trial,1076 women; RR:1.04, 95% CI:0.65–1.66). 95% CI:0.60–1.44) orassisted vaginal delivery rates to caesarean section(1trial,1076 women; RR:0.93, movement counting may make littleornodifference Low-certainty evidence suggests thatdailyfetal Maternal outcomes counting protocol withstandard care. compared amodified “count-to-ten” fetal movement neonates; RR: 0.81, 95% CI: 0.46–1.46) and low birth Resources weight (1 trial, 1076 neonates; RR: 0.98, 95% CI: Fetal movement counting is a low-cost intervention 0.66–1.44) with daily fetal movement counting. on its own, but it could be resource-intensive if it leads to unnecessary additional interventions or There were no perinatal deaths in the Norwegian hospital admissions. trial (1076 women). Low-certainty evidence from the large cluster RCT, which reported the weighted mean Equity difference in stillbirth rates between intervention LMICs bear the global burden of perinatal morbidity and control clusters, suggests that fetal movement and mortality, and women who are poor, least counting may make little or no difference to stillbirth educated and residing in rural areas of LMICs have rates (weighted MD: 0.23, 95% CI: –0.61 to 1.07). lower ANC coverage and worse pregnancy outcomes than more advantaged women (29). Therefore, Additional considerations simple, effective, low-cost antenatal interventions to nnThese trials were conducted in HICs with low assess fetal well-being could help to address health stillbirth rates, therefore the findings on effects inequalities by improving detection of complications may not apply equally to settings with high in low-resource settings. stillbirth rates. nnIn the cluster RCT, despite fetal movement Acceptability counting, most fetuses detected as being Qualitative evidence shows that women generally compromised by reduced fetal movements had appreciate the knowledge and information they can died by the time the mothers received medical acquire from health-care providers during ANC visits, attention. provided this is explained properly and delivered in nnThere was a trend towards increased CTG and a consistent, caring and culturally sensitive manner antenatal hospital admissions in the intervention (high confidence in the evidence) (22). It also shows clusters of the cluster RCT. Antenatal hospital that health professionals want to give appropriate admissions were also more frequent in the information and advice to women but sometimes intervention arm of the Norwegian RCT (107). they don’t feel suitably trained to do so (high nnFindings from an additional RCT that was confidence in the evidence) (45). unpublished at the time of the Cochrane review support the Cochrane evidence that daily fetal Feasibility movement counting may reduce maternal anxiety From the perspective of women who live far from (115). ANC clinics and who may not have the resources or time to attend ANC regularly, and the perspective Values of ANC providers with limited resources, this Please see “Women’s values” in section 3.B.2: Fetal intervention may offer a practical and cost–effective assessment: Background (p. 54). approach to monitoring fetal well-being if it’s shown to be effective (high confidence in the evidence) (22, 45).

Chapter 3. Evidence and recommendations 55 56 WHO recommendations on antenatal care for a positive pregnancy experience n Additional considerations guideline outcomes were reported inthereview. 95% CI:women; 0.38–4.07). RR:1.25, NootherANC little ornodifference to perinatalmortality (1639 and low-certainty evidence suggests thatitmay make neonates 95% CI: (1639women; 0.92–1.90) RR:1.32, little ornodifference to theantenatal detection of SGA measurement versus clinicalpalpationprobably makes Moderate-certainty evidence shows thatSFH Fetal andneonataloutcomes labour (1639women; RR:0.84, 95% CI:0.45–1.58). women; RR:0.72, 95% CI:0.31–1.67) andinductionof versus clinicalpalpationoncaesarean section(1639 little ornodifference intheeffect ofSFHmeasurement Low-certainty evidence suggests thatthere may be Maternal outcomes assessments, withmeasurements plotted onachart. weeks ofgestation. Mostwomen hadatleastthree abdominal palpationwere performed from 28 weeks ofgestation (109).SFHmeasurement or 1639 pregnant women enrolled atabout14 only onetrialconducted inDenmarkinvolving was derived from aCochrane review thatincluded The evidence ontheeffects ofSFHmeasurement palpation (EBTable B.2.2) Effects ofSFHmeasurement versus abdominal Summary ofevidence andconsiderations Symphysis-fundalB.2.2: height(SFH) measurement • • • • Remarks settingisnotrecommended.in aparticular (Context-specific recommendation) outcomes. Achange from whatisusuallypracticed (abdominalpalpationorSFHmeasurement) measurement for theassessment offetal growth isnotrecommended to improve perinatal RECOMMENDATION Replacing abdominalpalpationwithsymphysis-fundal B.2.2: height(SFH) n

accuracy review regarding theaccuracy ofSFH The GDGalsoconsidered evidence from atest antenatal ultrasound isnotavailable. other riskfactors for perinatalmorbidity (e.g. multiplepregnancy, polyhydramnios) insettingswhere Research isneededto determine therole ofSFHmeasurement indetecting abnormalfetal growth and there isnoevidence ofharmwithSFHmeasurement. fromApart false reassurance, whichmightoccur withbothSFHmeasurement andclinicalpalpation, LMIC settings. The GDGagreed thatthere isalackofevidence onSFH,rather than alackofeffectiveness, in particularly does notrecommend achange ofpractice. accuracy orsuperiority ofeitherSFHmeasurement orclinicalpalpationto assess fetal growth, theGDG SFH measurement isroutinely practiced inmany ANC settings.Dueto alackofclearevidence of simple, effective, low-cost, routine antenatal than more advantaged women (29).Therefore, lower ANCcoverage andworse pregnancy outcomes educated andresiding inrural areas ofLMICshave and mortality, andwomen whoare poor, least LMICs beartheglobalburden ofperinatalmorbidity Equity training. SFHrequires tapemeasures to beavailable. low-cost interventions withthemain cost beingstaff Both abdominalpalpationandSFHmeasurement are Resources assessment: Background (p. 54). Please see“Women’s Fetal values” insection3.B.2: Values abdominal palpationisnotavailable. be missed. Comparable test accuracy evidence on examination; however, mosttrueSGA casesmay few healthy pregnancies are referred for ultrasound of ahealthy baby. Inpractice, thiscould meanthat SFH measurement may beareasonable indicator specificity (0.79–0.92), suggesting thatanormal However, there was generally ahighdegree of 73% ofpregnancies affected by SGA atbirth. to 0.76, suggesting thatitfails to identifyupto measurement hadasensitivity ranging from 0.27 measurement thresholds to detect SGA. SFH studies conducted inHICs,whichuseddifferent IUGR (116).The DTA review includedseven centile), where SGA was aproxy outcome for in predicting (birthweight SGA atbirth < 10th interventions to assess fetal well-being could help to However, in some settings women experience a sense address health inequalities by improving detection of of shame during physical examinations, and this complications in low-resource settings. needs to be addressed with sensitivity by health-care providers (low confidence in the evidence) (22). Acceptability SFH and clinical palpation are non-invasive approaches Feasibility for fetal assessment, which are widely used and not Both methods are considered equally feasible, known to be associated with acceptability issues. provided tape measures are available.

B.2.3: Antenatal cardiotocography (CTG)

RECOMMENDATION B.2.3: Routine antenatal cardiotocography is not recommended for pregnant women to improve maternal and perinatal outcomes. (Not recommended)

Remarks • CTG is the continuous recording of the fetal heart rate and uterine contractions obtained via an ultrasound transducer placed on the mother’s abdomen. • There is currently no evidence on effects or other considerations that supports the use of antenatal (prelabour) CTG as part of routine ANC. • A lack of evidence of benefits associated with CTG in high-risk pregnancies suggests that the evaluation of antenatal CTG in healthy pregnant women is not a research priority.

Summary of evidence and considerations Equity

Effects of routine antenatal CTG versus no Simple, effective, low-cost, antenatal interventions to routine antenatal CTG (EB Table B.2.3) assess fetal well-being could help to address health A Cochrane review of routine antenatal CTG for fetal inequalities by improving detection of complications assessment identified no eligible studies of routine in low-resource settings, which bear the burden of CTG and all six included studies involved women with perinatal mortality. high-risk pregnancies (117). Acceptability Additional considerations Qualitative evidence from a variety of settings nnLow-certainty evidence on antenatal CTG in high- indicates that women generally appreciate the use of risk pregnancies suggests that this intervention technology to monitor pregnancy (high confidence may have little or no effect on perinatal mortality in the evidence), and a lack of modern equipment at and caesarean section (117). ANC facilities in LMICs may discourage women from attending (moderate confidence in the evidence) Values (22). However, in some LMICs, women hold the belief Please see “Women’s values” in section 3.B.2: Fetal that pregnancy is a healthy condition and may be assessment: Background (p. 54). resistant to CTG use unless they have experienced a previous pregnancy complication (high confidence Resources in the evidence). Acceptability may be further CTG machines are costly (starting from about compromised if the reasons for using CTG are not US$ 450)4, require maintenance and supplies of properly explained (high confidence in the evidence). ultrasound gel, and require staff training in their use and interpretation. Feasibility Health-care providers in LMIC settings feel that a lack of modern equipment and training limits the implementation of this type of intervention (high confidence in the evidence) (45). 4 Crude estimate based on Internet search.

Chapter 3. Evidence and recommendations 57 58 WHO recommendations on antenatal care for a positive pregnancy experience United Kingdom andtheUSA, involving 37 505 in Australia, Norway, SouthAfrica, Sweden, the a Cochrane review thatincluded11RCTs conducted The evidence onearlyultrasound was derived from selective ultrasound scan(EBTable B.2.4a) of gestation (early ultrasound scan)versus a) Effects of an ultrasound scanbefore 24 weeks Summary ofevidence and considerations a UltrasoundB.2.4: scan

• • • • • • • • • Remarks and improve awoman’s pregnancy experience. (Recommended) of fetal anomaliesandmultiplepregnancies, reduce inductionoflabourfor post-term pregnancy, ultrasound) isrecommended for pregnant women to estimate gestational age, improve detection RECOMMENDATION Oneultrasound B.2.4: scanbefore 24 weeks ofgestation (early complications) andmonitor for potential adverse effects ondelivery ofothercriticalmaternal andnewborn healthinterventions. capacity to conduct closemonitoring andevaluation to ensure abasicstandard ofimplementation (includingadequate capacity to diagnoseandmanage Two members oftheGDG(LisaNoguchiandCharlotte Warren) indicated thatthey would prefer to recommend thisintervention inspecific contexts with

http://www.who.int/medical_devices/publications/manual_ultrasound_pack1-2/en/ For guidance, further pleaserefer to theWHOManualofdiagnosticultrasound (119),available at: criteria andindicators associated withlocallyagreed targets. equity should be monitored at thehealthservice, regional andcountry levels, basedonclearlydefined The implementationandimpactofthisrecommendation onhealthoutcomes, facility utilization and is alsousedfor otherindications(e.g. obstetric emergencies) orby othermedicaldepartments. Stakeholders mightbeableto offset/reduce the cost ofantenatal ultrasound iftheultrasound equipment training, staff retention, quality improvement activitiesandsupervisionare ensured. trained sonographers anddoctors to trained nurses, midwives andclinicalofficers, provided thatongoing The GDGnoted thatantenatal ultrasound isanintervention from thatcanpotentially betaskshifted supply andsecure storage) andresources. logistical (equipment maintenance, infrastructural supplies,technical support), (ensuring areliable power will beassociated withavariety ofchallenges thatmay include political(budgeting for fees andtariffs), The GDGacknowledges thatimplementingandscalingupthisrecommendation inlow-resource settings suspected preterm andreduce birth labourinductionfor post-term pregnancies. and theincreased accuracy ofgestational age assessment, whichwould assist management incaseof perinatal mortality. The GDGputemphasisonotherbenefitsofultrasound (mentionedinpointsabove) The GDGacknowledged thattheuseofearlypregnancy ultrasound hasnotbeenshown to reduce settings (118). health care utilization andimplementation-related information onultrasound inrural, low-resource The ongoing multicountry trialthatisunderway shouldcontribute evidence further onhealtheffects, by appropriate gestational age estimation,diagnosis,referral andmanagement. could plausiblyincrease ANCservice utilization andreduce morbidity andmortality, whenaccompanied detect pregnancy complications andconfirm fetal viability to the woman andher family inthesesettings health systems inrural, low-resource settingsare unproven. However, theintroduction ofultrasound to The GDGnoted thattheeffects ofintroducing antenatal ultrasound onpopulationhealthoutcomes and presentation andplacental location. women whohave nothadanearlyultrasound scan,for thepurposesofidentifyingnumberfetuses, ultrasound scan.However, stakeholders shouldconsider offering alate ultrasound scan to pregnant 24 weeks ofgestation (late ultrasound) isnotrecommended for pregnant women whohave hadanearly ultrasound scanwhere there hasnotbeenanearlyultrasound scan.Therefore, anultrasound scanafter The benefitsofanearlyultrasound scanare notimproved uponandcannotbe replicated withalate femur fetal length), anatomy, numberoffetuses and diameter withorwithoutheadcircumference and included assessment ofgestational age (biparietal clinicians unless requested). The scansusually scans, theresults of whichwere notshared with scans ifindicated (or, inonestudy, concealed with women inthecontrol armundergoing selective an ultrasound scanbefore 24 weeks ofgestation, women (120).The intervention inalltrialsinvolved a location of the placenta. Scans were performed in weight, amniotic fluid volume and/or placental most trials between 10 and 20 weeks of gestation, maturity. with three trials evaluating scans before 14 weeks, and three trials evaluating an intervention comprising Maternal outcomes both early (at 18–20 weeks) and late scans (at 31–33 Moderate-certainty evidence suggests that a late weeks). ultrasound scan probably has little or no effect on caesarean section (6 trials, 22 663 women; RR: 1.03, Maternal outcomes 95% CI: 0.92–1.15), instrumental delivery (5 trials, Moderate-certainty evidence suggests that an early 12 310 women; RR: 1.05, 95% CI: 0.95–1.16) and ultrasound scan probably has little or no effect on induction of labour (6 trials, 22 663 women; RR: 0.93, caesarean section rates (5 trials, 22 193 women; RR: 95% CI: 0.81–1.07). Maternal satisfaction was not 1.05; 95% CI: 0.98–1.12). However, low-certainty assessed in this review. evidence suggests that early ultrasound may lead to a reduction in induction of labour for post-term Fetal and neonatal outcomes pregnancy (8 trials, 25 516 women; RR: 0.59, 95% CI: Moderate-certainty evidence suggests that a late 0.42–0.83). ultrasound scan probably has little or no effect on perinatal mortality (8 trials, 30 675 births; RR: Regarding maternal satisfaction, low-certainty 1.01, 95% CI: 0.67–1.54) and preterm birth (2 trials, evidence suggests that fewer women may report 17 151 neonates; RR: 0.96, 95% CI: 0.85–1.08). Low- feeling worried about their pregnancy after an early certainty evidence suggests that it may have little or ultrasound scan (1 trial, 635 women; RR: 0.80, 95% no effect on SGA (4 trials, 20 293 neonates; RR: 0.98, CI: 0.65–0.99). 95% CI: 0.74–1.28) and low birth weight (3 trials, 4510 neonates; RR: 0.92, 95% CI: 0.71–1.18). Fetal and neonatal outcomes Low-certainty evidence suggests that early Additional considerations ultrasound scans may increase the detection of nnThe evidence on ultrasound is derived mainly congenital anomalies (2 trials, 17 158 women; RR: from HICs, where early ultrasound is a standard 3.46, 95% CI: 1.67–7.14). However, detection rates component of ANC to establish an accurate were low for both groups (16% vs 4%, respectively) gestational age and identify pregnancy with 346/387 neonates with abnormalities (89%) complications. The impact of ultrasound screening being undetected by 24 weeks of gestation. in low-resource settings is currently unknown but the low rates of maternal and perinatal mortality Low-certainty evidence suggests that early experienced in HICs indirectly suggests that ultrasound may make little or no difference to ultrasound is an important component of quality perinatal mortality (10 trials, 35 737 births; RR: 0.89, ANC services. 95% CI: 0.70–1.12) and low birth weight (4 trials, nnEvidence from the Cochrane review on early 15 868 neonates; RR: 1.04, 95% CI: 0.82–1.33). ultrasound suggests that multiple pregnancies may Moderate-certainty evidence also shows that it be less likely to be missed/undetected by 24–26 probably has little or no effect on SGA (3 trials, 17 105 weeks of gestation with early ultrasound (120). neonates; RR: 1.05, 95% CI: 0.81–1.35). Of 295 multiple pregnancies occurring in seven trials (approximately 24 000 trial participants), b) Effects of an ultrasound scan after 24 weeks 1% (2/153) were undetected by 24–26 weeks of gestation (late ultrasound scan) versus no late of gestation with early ultrasound screening ultrasound scan (EB Table B.2.4b) compared with 39% (56/142) in the control group This evidence on late ultrasound was derived from (RR: 0.07, 95% CI: 0.03–0.17; graded by review a Cochrane review that included 13 RCTs conducted authors as low-quality evidence). in HICs (121). Most women in these trials underwent nnThe Cochrane review also evaluated several safety early ultrasound scan and were randomized to receive outcomes in offspring and found no evidence of an additional third trimester scan or to selective or differences in school performance, vision and concealed ultrasound scan. The purpose of the late hearing, disabilities or dyslexia. scan in these trials, which was usually performed nnAn ongoing multicountry cluster RCT of antenatal between 30 and 36 weeks of gestation, variably ultrasound in the Democratic Republic of the included assessment of fetal anatomy, estimated Congo, Guatemala, Kenya, Pakistan and Zambia

Chapter 3. Evidence and recommendations 59 60 WHO recommendations on antenatal care for a positive pregnancy experience n monitored. negative impact ongender equity andneedsto be of thefetus insomelow-income countries hasa perpetuate inequalities.Inaddition,ultrasound sexing areas dueto feasibility issues, thisintervention could or ifscansare notavailable to women livinginrural women are expected to pay for ultrasound scans, perinatal mortality and improve equity. However, if care, are neededinLMICsto prevent maternal and of ANCservices, andimprove theexperience of Effective interventions to increase uptake andquality Equity resource implicationsfor LMICsettings. routine ultrasound scansmay have considerable staffing costs(allowing 15–45minutes perscan), initial andongoing stafftraining andsupervision, supplies (ultrasound gel), replacement batteries, Thus, given thecost ofequipment,maintenance, currently available atless thanUS$ 10 000(28). compact units, hasdecreased (122) , andthey are The cost ofultrasound equipment,especiallyportable Resources assessment: Background (p. 54). Please see“Women’s Fetal values” insection3.B.2: Values n and earlyultrasound isusefulfor thispurpose. and perinatalmorbidity andmortality inLMICs, preterm whichare birth, majorcausesofmaternal complications, pre-eclampsia particularly and in pregnancy, aswell asmanagement ofpregnancy appropriate delivery oftime-sensitive interventions Accurate gestational age datingiscriticalfor the enrolled.participant 18–22 weeks and32–36 weeks ofgestation ineach clinical officers) toperform ultrasound scansat course for healthworkers (e.g. midwives, nurses, involves atwo-week obstetric ultrasound training resource settings(118).The trialintervention related information onultrasound inrural, low- health care utilization, aswell asimplementation- should contribute dataonhealthoutcomes and appropriately trained andsupported. risk factors, suchasmultiplepregnancies, if gestational age estimationandto identifypotential welcome ultrasound scansto assist withaccurate evidence) (45) suitably trained to doso(highconfidence inthe and testing procedures, butsometimesdon’tfeel shows thatthey generally want to provide screening Qualitative evidence from health-care providers scans mightincrease anxiety anddistress (124). a diagnostictool, andthatadverse findingsduring that women donotunderstand thatultrasound is reassuring (123).However, there issomeevidence to seetheirbaby viaultrasound andfindthe test review indicate thatwomen value theopportunity Specific studiesnotincludedinthemainqualitative which may alsoleadto earlierANCattendance. ultrasound mightattract women to useANCfacilities, the evidence) (22). This suggests thattheoffer of some women from attending (highconfidence in ultrasound equipment)atANC facilities discourages some LMICs,thelackofmoderntechnology (like in theevidence) (22). E and culturally sensitive manner(highconfidence are explained properly anddelivered inacaring conditions, provided theinformation and procedures are willingto bescreened andtested for avariety of acquire from health-care providers andthatthey appreciate theknowledge andinformation they can Qualitative evidence shows thatwomen generally Acceptability technical support andsupervision. technical support continual suppliesofultrasound gel, andongoing equipment maintenance, maintainingadequate and or rechargeable batteries) andsecure storage, regular training, ensuringapower supply(via apower point in LMICsincludesequipmentprocurement andstaff Feasibility challenges ofantenatal ultrasound scans Feasibility . This suggests thatthey might vidence alsoshows that,in B.2.5: Doppler ultrasound of fetal blood vessels

RECOMMENDATION B.2.5: Routine Doppler ultrasound examination is not recommended for pregnant women to improve maternal and perinatal outcomes. (Not recommended)

Remarks • The GDG noted that the evidence base for the use of Doppler ultrasound of fetal blood vessels in high- risk pregnancy is already established. • The GDG agreed that the value of a single Doppler ultrasound examination of fetal blood vessels for all pregnant women in the third trimester needs rigorous evaluation, particularly in LMIC settings. Future trials should be designed to evaluate the effect of a single Doppler ultrasound on preventable perinatal deaths.

Summary of evidence and considerations Additional considerations nnSubgroup analyses according to the number Effects of Doppler ultrasound examination of of Doppler ultrasound examinations (single or fetal blood vessels compared with no Doppler multiple) are largely consistent with the overall ultrasound examination (EB Table B.2.5) findings. However, low-certainty evidence from the The evidence on Doppler ultrasound examination single examination subgroup suggests that a single was derived from a Cochrane review that included Doppler ultrasound examination might reduce five trials involving 14 624 women in HICs (Australia, perinatal mortality (1 trial, 3890 women; RR: 0.36, France and the United Kingdom) (114). One study 95% CI: 0.13–0.99). evaluated a single Doppler examination at 28–34 weeks of gestation, three studies evaluated multiple Values Doppler examinations from as early as 18 weeks, Please see “Women’s values” in section 3.B.2: Fetal and one study evaluated women undergoing single assessment: Background (p. 54). or multiple examinations from 26 to 36 weeks of gestation. Data were evaluated together and Resources separately for single and multiple examinations. The cost of ultrasound equipment, especially portable Women in the control arms received standard ANC compact units, has decreased (122), and they are with no (or concealed) Doppler examination. currently available at less than US$ 10 000 (28). Thus, given the cost of equipment, maintenance, Maternal outcomes supplies (ultrasound gel), replacement batteries, The available moderate-certainty evidence suggests initial and ongoing staff training and supervision, and that antenatal Doppler ultrasound probably makes staffing costs, routine Doppler ultrasound scans may little or no difference to caesarean section rates have considerable resource implications for LMIC (2 trials, 6373 women; RR: 0.98, 95% CI: 0.85–1.13) settings. and assisted vaginal birth (2 trials, 6884 women; RR: 1.04, 95% CI: 0.96–1.12). No other maternal Equity outcomes that were prioritized for the ANC guideline RCT evidence on maternal and perinatal effects of were reported in the trials. Doppler ultrasound examination is currently derived from HICs and high-quality research is needed on Fetal and neonatal outcomes this intervention in LMICs to determine whether, by Low-certainty evidence suggests that Doppler improving detection of pregnancy complications, it ultrasound may have little or no effect on perinatal can reduce perinatal mortality and improve health mortality (4 trials, 11 183 women; RR: 0.80, 95% CI: equity. 0.35–1.83). Moderate-certainty evidence indicates that the intervention probably has little or no effect Acceptability on preterm birth (4 trials, 12 162 women; RR: 1.02, Qualitative evidence shows that women generally 95% CI: 0.87–1.18). appreciate the knowledge and information they can acquire from health-care providers and that they

Chapter 3. Evidence and recommendations 61 62 WHO recommendations on antenatal care for a positive pregnancy experience suitably trained to doso(highconfidence inthe and testing procedures, butsometimesdon’tfeel shows thatthey generally want to provide screening Qualitative evidence from health-care providers evidence) (22). some women from attending (highconfidence inthe ultrasound equipment)atANC facilities discourages some LMICs,thelackofmoderntechnology (like in theevidence) (22). E and culturally sensitive manner(highconfidence are explained properly anddelivered inacaring conditions, provided theinformation and procedures are willingto bescreened andtested for avariety of vidence alsoshows that,in technical support andsupervision. technical support continual suppliesofultrasound gel, andongoing equipment maintenance, maintainingadequate and or rechargeable batteries) andsecure storage, regular training, ensuringapower supply(via apower point in LMICsincludeequipmentprocurement andstaff Feasibility challenges ofDopplerultrasound scans Feasibility supported. potential riskfactors, ifappropriately trained and welcome Dopplerultrasound scansto identify evidence) (45) . This suggests thatthey might C. Preventive measures

Background preventing RhD alloimmunization and HDN (129). However, Rhesus alloimmunization occurring in The GDG considered the evidence and other relevant the third trimester due to occult transplacental information to inform recommendations on antenatal haemorrhages will not be prevented by postpartum interventions to prevent the following conditions. anti-D. nnAsymptomatic bacteriuria (ASB): Defined as true nnSoil-transmitted helminthiasis: Over 50% of bacteriuria in the absence of specific symptoms pregnant women in LMICs suffer from anaemia, of acute urinary tract infection, ASB is common and helminthiasis is a major contributory cause in pregnancy, with rates as high as 74% reported in endemic areas (33). Soil-transmitted helminths in some LMICs (125). Escherichia coli is associated are parasitic infections caused mainly by with up to 80% of isolates (83). Other pathogens roundworms (Ascaris lumbricoides), hookworms include Klebsiella species, Proteus mirabilis and (Necator americanus and Ancylostoma duodenale), group B streptococcus (GBS). While ASB in non- and whipworms (Trichuris trichiura). These worms pregnant women is generally benign, in pregnant (particularly hookworms) feed on blood and women obstruction to the flow of urine by the cause further bleeding by releasing anticoagulant growing fetus and womb leads to stasis in the compounds, thereby causing iron-deficiency urinary tract and increases the likelihood of acute anaemia (130). They may also reduce the pyelonephritis. If untreated, up to 45% of pregnant absorption of iron and other nutrients by causing women with ASB may develop this complication anorexia, vomiting and diarrhoea (131). (126), which is associated with an increased risk of preterm birth. nnNeonatal tetanus: Tetanus is an acute disease caused by an exotoxin produced by Clostridium nnRecurrent urinary tract infections: A recurrent tetani. Neonatal infection usually occurs through urinary tract infection (RUTI) is a symptomatic the exposure of the unhealed umbilical cord stump infection of the urinary tract (bladder and kidneys) to tetanus spores, which are universally present in that follows the resolution of a previous urinary soil, and newborns need to have received maternal tract infection (UTI), generally after treatment. antibodies via the placenta to be protected at birth. Definitions of RUTI vary and include two UTIs Neonatal disease usually presents within the first within the previous six months, or a history of one two weeks of life and involves generalized rigidity or more UTIs before or during pregnancy (127). and painful muscle spasms, which in the absence RUTIs are common in women who are pregnant of medical treatment leads to death in most and have been associated with adverse pregnancy cases (132). Global vaccination programmes have outcomes including preterm birth and small-for- reduced the global burden of neonatal tetanus gestational-age newborns (127). Pyelonephritis deaths and continue to do so; estimates show a (infection of the kidneys) is estimated to occur in reduction from an estimated 146 000 in 2000 2% of pregnancies, with a recurrence rate of up to to 58 000 (CI: 20 000–276 000) in 2010 (133). 23% within the same pregnancy or soon after the However, because tetanus spores are ubiquitous birth (128). Little is known about the best way to in the environment, eradication is not biologically prevent RUTI in pregnancy. feasible and high immunization coverage remains essential (134). nnRhesus D alloimmunization: Rhesus (Rh) negative mothers can develop Rh antibodies if they have an In addition to GDG recommendations on the Rh-positive newborn, causing haemolytic disease above, this section of the guideline includes of the newborn (HDN) in subsequent pregnancies. two recommendations on disease prevention in Administering anti-D immunoglobulin to Rh- pregnancy that have been integrated from WHO negative women within 72 hours of giving birth guidelines on malaria and HIV prevention that are to an Rh-positive baby is an effective way of relevant to routine ANC.

Chapter 3. Evidence and recommendations 63 64 WHO recommendations on antenatal care for a positive pregnancy experience definitions were also used. than 100 000bacteria/mL on culture, butother midstream orcatheterized urine specimenwithmore was usuallydefinedasatleastoneclean-catch, treatment throughout pregnancy. Bacteriuria trials varied widelyfrom asingledose,to continuous such astetracycline. Treatment duration between are nolonger recommended for useinpregnancy, ampicillin, nitrofurantoin andsomeantibioticsthat and 1987. Types ofantibioticsincludedsulfonamides, Most trialswere conducted in HICs between 1960 14 trialsinvolving approximately 2000women (83). was derived from aCochrane review thatincluded The evidence ontheeffects ofantibiotics for ASB antibiotics orplacebo (EBTable C.1) Effects ofantibiotics for ASB versus no Summary ofevidence andconsiderations C.1: Antibioticsfor asymptomatic bacteriuria (ASB) • • • • • Remarks and low weight. birth (Recommended) women withasymptomatic bacteriuria (ASB) to prevent persistent bacteriuria, preterm birth RECOMMENDATION C.1: Aseven-day antibioticregimen isrecommended for allpregnant

deliver theseprocedures inaknowledgeable, supportive andrespectful manner(highconfidence inthe evidence). interventions to optimize pregnancy andnewborn health, andtheability ofhealth-care practitioners to explain and experience. This includedthetailored (rather thanroutine) useofbiomedicaltests andeffective preventive Evidence showed thatwomen from high-,medium-andlow-resource settingsvalued having apositive pregnancy A scoping review ofwhatwomen want from ANCandwhatoutcomes they value informed theANCguideline(13). Women’s values resistance. Preterm indicators birth shouldbemonitored withthisintervention, asshouldchanges inantimicrobial prevention andtreatment infections ofmaternal peripartum [135]). antibiotic administration to prevent earlyneonatalGBSinfection (see WHOrecommendations for GBS disease.WHOrecommends thatpregnant women withGBScolonization receive intrapartum eradicated by antibiotictreatment. GBSbacteriuria isariskfactor for having aninfant withearlyonset Studies have shown thatGBSbacteriuria isasignofheavy GBScolonization, whichmay notbe should alsoaimto evaluate theeffects ofgroup Bstreptococcus (GBS) screening andtreatment. screening andantibiotictreatment reduces preterm andperinatalmortality inLMICs.Suchtrials birth Evidence onpreterm isoflow birth certainty andlarge multicentre trialsare neededto confirm whether preterm prevalence, birth asitmay notbeappropriate insettingswithlow prevalence. Stakeholders may wishto consider context-specific ASBscreening andtreatment basedonASBand (Recommendation B.1.2). This recommendation shouldbeconsidered alongsidetherecommendation onASBdiagnosis n Additional considerations reported. 0.11–0.62). NootherANCguidelineoutcomes were preterm (2trials,142women; birth RR:0.27, 95% CI: 1437 neonates; RR:0.64, 95% CI:0.45–0.93) and ASB may reduce low-birth-weight neonates (8trials, Low-certainty evidence suggests thatantibiotics for Fetal andneonataloutcomes pyelonephritis is very uncertain. 0.18–0.53); however, theevidence ontheeffect on bacteriuria (4 trials,596 women; RR: 0.30, 95% CI: suggests thatantibioticsmay reduce persistent were infection outcomes. Low-certainty evidence The onlymaternal ANCguidelineoutcomes reported Maternal outcomes n duration (single doseversus short-course The GDGalsoevaluated evidence ontreatment [4–7 days]) from a related Cochrane review that Repeated urine testing to check for clearance of included 13 trials involving 1622 women (136). Ten ASB has cost implications for laboratory and human trials compared different durations of treatment resources, as well as for the affected women. The with the same antibiotic, and the remaining three emergence of antimicrobial resistance is of concern compared different durations of treatment with and may limit the choice of antimicrobials (125). different drugs. A wide variety of antibiotics was used. The resulting pooled evidence on bacterial Equity persistence (7 trials), recurrent ASB (8 trials) Preterm birth is the leading cause of neonatal and pyelonephritis (2 trials) was judged as death worldwide, with most deaths occurring in very uncertain. However, on sensitivity analysis LMICs; therefore, preventing preterm birth among including high-quality trials of amoxicillin and disadvantaged populations might help to address nitrofurantoin only, the high-certainty evidence inequalities. indicates that bacterial persistence is reduced with a short course rather than a single dose (2 Acceptability trials, 803 women; RR: 1.72, 95% CI: 1.27–2.33). In LMICs, some women hold the belief that High-certainty evidence from one large trial shows pregnancy is a healthy condition and may not accept that a seven-day course of nitrofurantoin is more the use of antibiotics in this context (particularly effective than a one-day treatment to reduce low if they have no symptoms) unless they have birth weight (714 neonates; RR: 1.65, 95% CI: experienced a previous pregnancy complication (high 1.06–2.57). Low-certainty evidence suggests that confidence in the evidence) (22). Others view ANC single-dose treatments may be associated with as a source of knowledge, information and medical fewer side-effects (7 trials, 1460 women; RR: 0.70, safety, and generally appreciate the interventions 95% CI: 0.56–0.88). See Web supplement (EB and advice they are offered (high confidence in the Table C.1). evidence). However, engagement may be limited if nnThe GDG also evaluated evidence on the test this type of intervention is not explained properly. In accuracy of urine Gram staining and dipstick addition, where there are likely to be additional costs testing (see Recommendation B.1.2 in section 3.B). associated with treatment, women are less likely to engage (high confidence in the evidence). Values See “Women’s values” at the beginning of section 3.C: Feasibility Background (p. 64). A lack of resources in LMICs, both in terms of the availability of the medicines and testing, Resources and the lack of suitably trained staff to provide Antibiotic costs vary. Amoxicillin and trimethoprim relevant information and perform tests, may limit are much cheaper (potentially around US$ 1–2 for a implementation (high confidence in the evidence) week’s supply) than nitrofurantoin, which can cost (45). about US$ 7–10 for a week’s supply of tablets (137).

C.2: Antibiotic prophylaxis to prevent recurrent urinary tract infections (RUTI)

RECOMMENDATION C.2: Antibiotic prophylaxis is only recommended to prevent recurrent urinary tract infections in pregnant women in the context of rigorous research. (Context-specific recommendation – research)

Remarks • Further research is needed to determine the best strategies for preventing RUTI in pregnancy, including the effects of antibiotic prophylaxis on pregnancy-related outcomes and changes in antimicrobial resistance.

Chapter 3. Evidence and recommendations 65 66 WHO recommendations on antenatal care for a positive pregnancy experience n C.3: Antenatal anti-DimmunoglobulinprophylaxisC.3: Additional considerations were reported inthestudy. No otherfetal andneonatalANCguidelineoutcomes withprophylacticbirth antibioticsisvery uncertain. Evidence ontheriskoflow weight birth andpreterm Fetal andneonatal outcomes guideline outcomes were reported inthestudy. antibiotics isvery uncertain. Noothermaternal ANC recurrent pyelonephritis andRUTI withprophylactic Evidence from thissinglestudyontheriskof Maternal outcomes surveillance only. with antibioticsonpositive culture), orto close surveillance (regular clinicvisitsandurineculture, for theremainder ofthepregnancy plusclose antibiotics (nitrofurantoin 50 mgthree timesdaily) randomized, theacute phase,to after prophylactic admitted to hospitalwithpyelonephritis were pregnant women contributed data(127). Women in whichonlyonetrialtheUSA involving 200 to prevent RUTI was derived from aCochrane review The evidence ontheeffects ofprophylactic antibiotics (EB Table C.2) prevent RUTI compared withnoantibiotics Effects ofprophylactic antibiotics to Summary ofevidence andconsiderations • • Remarks research) is recommended onlyinthecontext ofrigorous research. (Context-specific recommendation – Rh-negative pregnant women at28and 34 weeks ofgestation to prevent RhDalloimmunization RECOMMENDATION Antenatal prophylaxis C.3: withanti-Dimmunoglobulininnon-sensitized n

lack ofevidence onthispotential consequence. increased antimicrobial resistance andthere isa Antibiotic prophylaxis to prevent RUTI may leadto LMIC settings,aswell asdeveloping strategies to manage thiscondition, isconsidered aresearch priority Determining theprevalence ofRhD alloimmunization andassociated pooroutcomes amongwomen in indicated. RhD alloimmunization insubsequentpregnancies (129).Anti-Dshouldstillbegiven postnatally when practice for childbirth, whichthere ofgivinganti-Dafter ishigh-certainty evidence ofitseffect of reducing This context-specific recommendation relates to anti-D prophylaxis duringpregnancy andnotthe engage (highconfidence inthe evidence). associated withtreatment, women are less likely to addition, where there are likely to beadditionalcosts this type ofintervention isnotexplained properly. In evidence). However, engagement may belimited if and advice they are offered (high confidence inthe safety andgenerally appreciate theinterventions as asource ofknowledge, information andmedical confidence inthe evidence) (22). Others view ANC experienced aprevious pregnancy complication (high if they have nosymptoms) unless they have the useofantibioticsinthiscontext (particularly pregnancy isahealthy condition andmay notaccept In LMICs,somewomen holdthebeliefthat Acceptability Impact notknown. Equity 28 × 100 mg tablets(137). than nitrofurantoin, whichcancost aboutUS$ 5for Antibiotic costs vary. Trimethoprim ischeaper Resources 3.C See “Women’s values” atthebeginningofsection Values confidence inthe evidence) (45) and perform tests, may limitimplementation(high of suitablytrained staff to provide relevant information availability ofthemedicinesandtesting, andthelack A lackofresources inLMICs,bothterms ofthe Feasibility : Background (p. 64). . Summary of evidence and considerations nnRates of RhD alloimmunization in subsequent pregnancies were not reported in the trials. Effects of antenatal anti-D immunoglobulin nnThere is no evidence on optimal dose of antenatal prophylaxis in non-sensitized Rh-negative anti-D prophylaxis and various regimens are pregnant women compared with no intervention used. There are two ongoing studies listed in the (EB Table C.3) Cochrane review, which may help to clarify issues The evidence on the effects of antenatal anti-D around effects and dosage once completed. prophylaxis was derived from a Cochrane review that nnOnly 60% of Rh-negative primigravidas will have included two RCTs involving over 4500 Rh-negative an Rh-positive newborn, therefore 40% of Rh- pregnant women (138). Most participants were negative women will receive anti-D unnecessarily primigravidas. Both trials compared antenatal anti-D with antenatal anti-D prophylaxis (138). prophylaxis with no antenatal anti-D prophylaxis. One trial used a dose of 500 IU, the other used 250 IU, Values given at 28 and 34 weeks of gestation. Data were See “Women’s values” at the beginning of section available for 3902 pregnancies, and more than half 3.C: Background (p. 64). the participants gave birth to Rh-positive newborns (2297). All women with Rh-positive newborns Resources received postpartum anti-D immunoglobulin as per A single dose of anti-D can cost around US$ 50 usual management. The primary outcome was the (500 IU) to US$ 87 (1500 IU) (139), depending on the presence of Rh-antibodies in maternal blood (a proxy brand and local taxes; therefore, the cost of antenatal for neonatal morbidity). No maternal ANC guideline prophylaxis for two 500 IU doses could be as much outcomes (including maternal satisfaction and side- as US$ 100 per woman. Additional costs will include effects) and few perinatal guideline outcomes were screening for blood typing in settings where Rh blood reported in these trials. tests are not currently performed.

Fetal and neonatal outcomes Equity Evidence on the effect of antenatal anti-D on RhD The contribution of RhD alloimmunization to alloimmunization during pregnancy, suggesting perinatal morbidity and mortality in various LMIC little or no difference in effect, is very uncertain. In settings is uncertain and it is not known whether addition, the evidence on the effect on postpartum antenatal anti-D for non-sensitized Rh-negative RhD alloimmunization and alloimmunization up women will impact on equity. to 12 months postpartum among women giving birth to Rh-positive newborns (n = 2297 and 2048, Acceptability respectively) is very uncertain, partly because events Anti-D immunoglobulin is derived from human were rare. Evidence on the effect of antenatal anti-D plasma and is administered by injection, which may on neonatal morbidity (jaundice) from one trial (1882 not be acceptable to all women. Qualitative evidence neonates) is also very uncertain, partly because indicates that engagement may be limited if tests and events were rare. No other ANC guideline outcomes procedures are not explained properly to women, or were reported in the review. when women feel their beliefs, traditions and social support mechanisms are overlooked or ignored by Additional considerations health-care professionals (high confidence in the nnLow-certainty evidence from the Cochrane review evidence) (22). suggests that Rh-negative women who receive antenatal anti-D are less likely to register a Feasibility positive Kleihauer test (which detects fetal cells In a number of LMIC settings providers feel that a in maternal blood) during pregnancy (1 trial, 1884 lack of resources, both in terms of the availability women; RR: 0.60, 95% CI: 0.41–0.88) and at the of the medicines and the lack of suitably trained birth of a Rh-positive neonate (1 trial, 1189 women; staff to provide relevant information, may limit RR: 0.60, 95% CI: 0.46–0.79). implementation of recommended interventions nnIn the Cochrane review, the rate of RhD alloimmuni- (high confidence in the evidence) (45). Anti-D needs zation during pregnancy, the postpartum period and refrigeration at 2–8°C, which may not be feasible in up to 12 months later among women in the control some LMIC settings. group was 0.6%, 1.1% and 1.5%, respectively.

Chapter 3. Evidence and recommendations 67 68 WHO recommendations on antenatal care for a positive pregnancy experience whipworm. OnesmallUgandan trialadministered a to 65.6% for hookworm, and74.4% to 82% for ranged for from roundworm, 20%to 64.2% 46.4% respectively, andthefrequency of intestinal worms inthesetwo trialswas 56%and47%,(Hb < 110 g/L) of proven helminthiasis.The frequency ofanaemia folic acidsupplements,irrespective ofthepresence in thesecond trimester, withorwithout dailyiron and or mebendazole) was administered asasingledose Leone), theanthelminthicmedication(albendazole pregnant women (142).Intwo trials(Peru andSierra in Peru, Sierra Leone andUganda, involving 4265 Cochrane review thatincludedfour trialsconducted anthelminthic treatment was derived from a The following evidence ontheeffects ofprophylactic with nointervention orplacebo (EBTable C.4) in thesecond trimester ofpregnancy compared against soil-transmitted helminthsadministered Effects ofprophylactic anthelminthictreatment Summary ofevidence andconsiderations a C.4: Preventive anthelminthictreatment

• • • • • • Remarks RECOMMENDATION C.4: Inendemicareas, programmes. (Context-specific recommendation) recommended for pregnant women thefirst after trimesterof aspart worm infection reduction Greater than20%prevalence ofinfection withany soil-transmitted helminths.

chemotherapy to control soil-transmitted helminthinfections inhigh-riskgroups (currently inpress) (140). For guidance further onsoil-transmitted helminthinfections, refer to theWHOGuideline:preventive a prevalence of WHO recommends atreatment strategy comprising two treatments peryear inhigh-risksettingswith considered to outweigh thedisadvantages (141, 142). The safety ofthesedrugsinpregnancy hasnotbeenunequivocally established;however, thebenefitsare (500 mg) shouldbeused(140, 141). or third trimester onacase-by-case basis(140).Asingledoseofalbendazole (400 mg) ormebendazole Infected pregnant women innon-endemicareas shouldreceive anthelminthictreatment inthesecond 40% orhigher. Anaemia isconsidered asevere publichealthproblem whentheprevalence amongpregnant women is Endemic areas are areas where theprevalence ofhookworm and/or whipworm infection is20%ormore. transmitted helminthinfections inhigh-riskgroups (140),whichstates that: This recommendation isconsistent withtheWHOGuideline:preventive chemotherapy to control soil- prevalence (140). evidence).” burden ofhookworm andT. trichiura infection (conditional recommendation, moderate quality of problem, withprevalence of40%orhigheramongpregnant women, inorder to reduce the and/or T. trichiura infection is20%ormore and(2)where anaemiaisasevere publichealth thefirstafter trimester, livinginareas where both:(1)thebaselineprevalence ofhookworm mebendazole (500mg) isrecommended asapublichealthintervention for pregnant women, “Preventive chemotherapy (deworming), usingsingle-dose albendazole (400 mg) or 50%for soil-transmitted helminthiasis,andonce peryear inareas witha20–50% a preventive anthelminthictreatment is dose ofalbendazole ormebendazole inthesecond Moderate-certainty evidence indicates thatasingle Fetal andneonataloutcomes women; RR:0.94; 95% CI:0.81–1.10). anaemia (defined asHb< 11 g/dL) (4 trials,3266 of pregnancy may have littleornoeffect onmaternal albendazole ormebendazole inthesecond trimester Low-certainty evidence suggests thatasingle doseof Maternal outcomes trial entry. women were infected withanintestinal helminthat to pregnant women inthesecond trimester; all versus ivermectin only, administered assingledoses contributed dataonalbendazole plusivermectin trichuriasis, respectively. The otherUgandan RCT was 15%,38%and6%for ascariasis,hookworm and proven presence ofhelminthiasis;baselineprevalence women inthesecond trimester, irrespective ofthe single doseofalbendazole (400 mg) orplacebo to trimester of pregnancy probably has little or no effect nnPreventive helminthic treatment helps to lessen on preterm birth (2 trials, 1318 women; RR: 0.88, 95% the burden of other infections, e.g. HIV, malaria CI: 0.43–1.78) or perinatal mortality (2 trials, 3385 and TB, and contributes to a sustained reduction of women; RR: 1.09, 95% CI: 0.71–1.67). No other ANC transmission (142). guideline outcomes were reported in the review. Values Additional considerations See “Women’s values” at the beginning of section nnNone of the trials in the Cochrane review evaluated 3.C: Background (p. 64). effects of more than one dose of anthelminthics. Findings from large non-randomized studies Resources (NRSs) suggest that prophylactic anthelminthic Preventive chemotherapy against helminthic treatment may have beneficial effects for mothers infections is a cost–effective intervention. The and newborns living in endemic areas (143–145): market price of a single tablet of generic albendazole ––One NRS, including approximately 5000 (400 mg) or mebendazole (500 mg) is about pregnant women in Nepal with a 74% US$ 0.02–0.03 (141). prevalence of hookworm infection, reported a 41% reduction in six-month infant mortality Equity among women receiving two doses of Helminthic infections are widely prevalent in poverty- albendazole (one each in the second and third stricken regions and control of this disease aims to trimesters) compared with no treatment (95% alleviate suffering, reduce poverty and support equity CI: 18–57%) (143). This study also showed (141). reductions in severe maternal anaemia with albendazole. Acceptability ––A study from Sri Lanka involving approximately Affected women are often asymptomatic and may 7000 women compared mebendazole with not perceive the need for treatment. Therefore, the no treatment and found fewer stillbirths and prevalence of soil-based helminthiasis in a particular perinatal deaths among women receiving setting is likely to influence women’s and providers’ mebendazole (1.9% vs 3.3%; OR: 0.55, 95% preferences. Studies of anthelminthic programmes CI: 0.40–0.77), and little difference in the among non-pregnant cohorts, e.g. schoolchildren, in occurrence of congenital anomalies (1.8% vs endemic areas have shown high levels of acceptability 1.5%, for intervention and controls, respectively; (146). For women receiving preventive treatment in OR: 1.24, 95% CI: 0.80–1.91), even among the endemic areas, worms are often visible in the stools 407 women who had taken mebendazole in the the day after treatment, and this may reinforce the first trimester against medical advice (145). value of the intervention. However, where there nnThe WHO manual on Preventive chemotherapy in are likely to be additional costs associated with human helminthiasis stresses that every opportunity treatment (high confidence in the evidence) or where should be taken to reach at-risk populations the intervention is unavailable because of resource through existing channels (141). constraints (low confidence in the evidence) women nnCross-referencing other WHO guidelines, the may be less likely to engage with services (45). upcoming 2016 WHO Guideline: preventive chemotherapy to control soil-transmitted helminth Feasibility infections in high-risk groups recommends that a In a number of LMIC settings providers feel that a single dose of albendazole or mebendazole should lack of resources, both in terms of the availability be offered to pregnant women in the second and of the medicines and the lack of suitably trained third trimesters of pregnancy where the prevalence staff to provide relevant information, may limit of any soil-transmitted helminth infection implementation of recommended interventions (high (roundworm, hookworm and whipworm) exceeds confidence in the evidence) (45). 20% (140).

Chapter 3. Evidence and recommendations 69 70 WHO recommendations on antenatal care for a positive pregnancy experience one was conducted inColombia between 1961 and neonatal tetanus (148).Two RCTs contributed data: reproductive age orpregnant women to prevent the effect of tetanus vaccination in women of derived from aCochrane review thatassessed The evidence ontheeffects ofTT vaccination was vaccination (EB Table C.5) vaccination compared withno, otherorplacebo Effects ofantenatal tetanus toxoid (TT) Summary ofevidence and considerations C.5: Tetanus toxoid vaccination • • • • • • • • Remarks tetanus. (Recommended) depending onprevious tetanus vaccination exposure, to prevent neonatalmortalityfrom RECOMMENDATION C.5:Tetanus toxoid vaccination isrecommended for allpregnant women,

vaccine positionpapers, available at:http://www.who.int/immunization/documents/positionpapers/en reproductivehealth/publications/maternal_perinatal_health/immunization_tetanus.pdf; andinWHO’s Further information canbefound intheWHOguidance (134),available at:http://www.who.int/ vaccination scheduleto pregnant women. to explainopportunities theimportance ofinfant vaccination andcommunicate theinfant/child any vaccines thatare recommended inthenationalimmunization schedule.ANCcontacts are also ANC contacts shouldbeusedto verify thevaccination statusofpregnant women, andadminister prophylaxis exist outsideofpregnancy. among ANCinterventions ifeffective tetanus immunization programmes and good post-exposure Policy-makers inlow prevalence/high-income settingsmay choosenotto includetetanus vaccination ANC services. the vaccine, equipmentandsupplies(refrigerator, needlesandsyringes) needto bereadily available at For effective implementation,ANChealth-care providers need to betrained in tetanus vaccination and health records, whichshouldbeheldby thewoman. A monitoring system shouldincludeanimmunization register, personal vaccination cards andmaternal monitoring theimpactofinterventions. Effective surveillance iscritical for identifyingareas orpopulationsathighriskofneonatal tetanus and for maternal andneonataltetanus globally(147). Tetanus vaccination andcleandelivery practices are majorcomponents ofthestrategy to eradicate – – – the following. immunization againsttetanus (134).The GDGendorses the2006guidelineapproach, whichrecommends This recommendation isconsistent withrecommendations from the2006WHOguidelineonMaternal – – – years). each subsequentpregnancy to atotal offive doses(five doses protects throughout thechildbearing If awoman hashad1–4dosesofaTT-CV inthepast,she shouldreceive onedoseofaTT-CV during given thethird after dose,inthetwo subsequentyears orduringtwo subsequentpregnancies. Two dosesfor further women whoare first vaccinated against tetanus duringpregnancy shouldbe should extend protection to atleastfive years. for 1–3years inmostpeople.Athird dose isrecommended thesecond sixmonthsafter dose,which the second dosegiven atleasttwo weeks before delivery. Two dosesprotect against tetanus infection she shouldreceive two dosesofatetanus toxoid-containing vaccine (TT-CV) with onemonthapart If apregnant woman hasnotpreviously beenvaccinated, orifherimmunization statusisunknown, the “Additional considerations” section. additional evidence oneffects isalso considered in gestation. Dueto therelative paucity ofRCT data, in 48pregnant women between 30and32 weeks of acellular [Tdap]; pertussis 1dose)withsalineplacebo compared acombined vaccine (tetanus/diphtheria/ neonates); theotherwas conducted intheUSA and with aninfluenza vaccine (1618 women, 1182 phosphate adsorbedtetanus toxoid [10LF];3 doses) 1965 andcompared atetanus vaccine (aluminium Maternal outcomes Resources Low-certainty evidence suggests that local side- The cost of three doses of TT vaccine has been effects, such as pain, were more common with the estimated at around US$ 3 per woman (151), although Tdap vaccination than placebo (48 women; RR: 3.94, lower costs in vaccination programmes have been 95% CI: 1.41–11.01). There is no evidence on other reported (152). The need for cold-chain equipment maternal outcomes. and staff training may add to costs.

Fetal and neonatal outcomes Equity Low-certainty evidence from the Colombian trial Most deaths from neonatal tetanus occur in countries suggests that there may be fewer neonatal tetanus with low coverage of facility-based births, ANC and cases among neonates whose mothers receive tetanus vaccination (149). In addition, in LMICs, TT vaccination than among those who do not (1182 ANC coverage and infant mortality is often unequal neonates; RR: 0.20, 95% CI: 0.10–0.40). Moderate- between the most- and least-educated, urban and certainty evidence suggests that two or more doses rural, and richest and poorest populations (29). of TT probably reduce neonatal mortality from Therefore, increasing tetanus immunity in LMICs any cause (1 trial, 688 neonates; RR: 0.31, 95% CI: and among disadvantaged populations could help to 0.17–0.55). Further low-certainty evidence suggests address inequalities. that neonatal mortality from tetanus may be reduced among neonates whose mothers receive at least two Acceptability TT doses (1 trial, 688 neonates; RR: 0.02, 95% CI: Qualitative evidence indicates that most women 0.00–0.30), but not among neonates whose mothers view ANC as a source of knowledge, information receive only one dose (1 trial, 494 neonates; RR: 0.57, and medical safety, and generally appreciate the 95% CI: 0.26–1.24). Congenital anomalies and other interventions and advice they are offered. However, ANC guideline outcomes were not reported in the engagement may be limited if vaccinations are trials. not explained properly or when women feel their beliefs, traditions and social support mechanisms are Additional considerations overlooked or ignored by health-care professionals nnA systematic review that pooled data from the (high confidence in the evidence) (22). Lack of Colombian trial with that of a large cohort study engagement may be compounded if services are of antenatal TT vaccination from India found delivered in a hurried, inflexible, didactic manner moderate-certainty evidence to support a large (high confidence in the evidence). effect (94% reduction) on neonatal tetanus deaths in favour of TT vaccination with at least two doses Feasibility in pregnant women and women of childbearing Antenatal services provide a convenient opportunity age (2 trials, 2146 neonates; RR: 0.06, 95% CI: for vaccinating pregnant women, particularly in 0.02–0.20) (149). settings without effective childhood immunization nnTT vaccination has been widely used over programmes. Qualitative evidence indicates that if 40 years, leading to a substantial decrease in there are additional costs associated with vaccination neonatal tetanus and an increase in neonatal (including transport costs and loss of earnings), survival, with no sign of possible harm to pregnant uptake may be limited (high confidence in the women or their fetuses (150). The WHO strategy evidence) (22). In addition, ANC providers in many for eliminating maternal and neonatal tetanus LMIC settings feel that a lack of resources, both in includes immunization of pregnant women, terms of the availability of vaccines and the lack of supplementary immunization activities in selected suitably trained staff, may limit implementation (high high-risk areas, promotion of clean deliveries and confidence in the evidence) (45). clean cord practices, and reliable neonatal tetanus surveillance (134).

Values See “Women’s values” at the beginning of section 3.C: Background (p. 64).

Chapter 3. Evidence and recommendations 71 72 WHO recommendations on antenatal care for a positive pregnancy experience C.6: Intermittent preventive treatment ofmalariainpregnancy (IPTp) • • • • • • • Remarks the objective ofensuringthatatleast three dosesare received. (Context-specific recommendation) inthesecondshould start trimester, anddosesshouldbegiven with atleast onemonthapart, with sulfadoxine-pyrimethamine (IPTp-SP) isrecommended for allpregnant women. Dosing RECOMMENDATION C.6: Inmalaria-endemicareas inAfrica, intermittent preventive treatment •

available at:http://www.who.int/malaria/publications/atoz/9789241549127/en/ Detailed evidence andguidance related to therecommendation canbefound inthe2015 guidelines(153), most antimalarialagents inpregnancy, duringthefirst particularly trimester (153). The malariaGDGnoted thatthere isinsufficient evidence onthesafety, efficacyandpharmacokinetics of acid supplementsfor antenatal useattherecommended antenatal dosage (i.e. 0.4 mg daily). with theefficacyofSPin pregnancy (155).Countries shouldensure thatthey procure anddistribute folic There issomeevidence that highdosesofsupplemented folic acid(i.e. 5 mgdaily ormore) may interfere SP actsby interfering withfolic acidsynthesis inthemalaria parasite, thereby inhibitingitslife-cycle. taken. instructions aboutthedate (corresponding to 13 weeks ofgestation) onwhichthemedicineshouldbe Policy-makers could alsoconsider supplyingwomen withtheirfirst SP dose atthefirst ANCvisitwith trimester, policy-makers shouldensure healthsystem contact withwomen at13 weeks ofgestation. To ensure thatpregnant women inendemicareas IPTp-SP start asearlypossible inthesecond consistent withbenefit(153). however, thelimited evidence onIPTp-SP from women intheirthird andsubsequentpregnancies was The malariaGDGnoted thatmostevidence was derived from women intheirfirst andsecond pregnancies; weight infants andincreased weight meanbirth compared withtwo dosesonly(154). sulfadoxine-pyrimethamine (SP) isassociated withreduced maternal parasitaemia, fewer low-birth- of seven RCTs conducted inmalaria-endemiccountries, whichshows thatthree ormore dosesof The high-quality evidence thisrecommendation supporting was derived from asystematic review Plasmodium falciparum, administration ofIPTp-SP(153). case management withprompt, effective treatment, and,inareas withmoderate to hightransmission of malaria duringpregnancy, whichincludespromotion anduseofinsecticide-treated nets,appropriate her fetus andthenewborn. WHOrecommends apackage ofinterventions for preventing andcontrolling Malaria infection duringpregnancy isamajorpublichealthproblem, withsubstantialrisks for the mother, where itisconsidered to beastrong recommendation basedonhigh-quality evidence (153). This recommendation hasbeenintegrated from theWHOGuidelinesfor thetreatment ofmalaria(2015), C.7: Pre-exposure prophylaxis for HIV prevention

RECOMMENDATION C.7: Oral pre-exposure prophylaxis (PrEP) containing tenofovir disoproxil fumarate (TDF) should be offered as an additional prevention choice for pregnant women at substantial risk of HIV infection as part of combination prevention approaches. (Context-specific recommendation)

Remarks • This recommendation has been integrated from the WHO guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV (2015), where it is considered to be a strong recommendation based on high-quality evidence (99). The evidence and further guidance related to the recommendation can be found in this guideline. • “Substantial risk” is provisionally defined as HIV incidence greater than 3 per 100 person-years in the absence of PrEP, but individual risk varies within this group depending on individual behaviour and the characteristics of sexual partners. Local epidemiological evidence concerning risk factors and HIV incidence should be used to inform implementation. • Thresholds for offering PrEP may vary depending on a variety of considerations, including resources, feasibility and demand. • The level of protection is strongly correlated with adherence. • Detailed evidence and guidance related to this recommendation can be found in the 2015 guideline (99), available at: http://www.who.int/hiv/pub/guidelines/earlyrelease-arv/en/

Chapter 3. Evidence and recommendations 73 74 WHO recommendations on antenatal care for a positive pregnancy experience D.1: Interventions for nauseaandvomiting occur inthevulva andrectum, andmay beassociated Varicose veins usuallyoccur inthelegs,butcanalso and may beworse eatingandlyingdown after (159) . occurheartburn in two thirds ofpregnant women, experience severe disability (158).Symptoms of to occur inhalfofpregnant women, 8%ofwhom gestation (157). Low backandpelvicpainisestimated experience nauseaandvomiting beyond 20 weeks of (156); however, approximately 20%ofwomen may usually occur inthefirst trimester ofpregnancy by approximately 70% ofpregnant women and Symptoms ofnauseaandvomiting are experienced worsen aspregnancy progresses. andvaricosepelvic pain,heartburn veins, often symptoms associated withmechanicaleffects, e.g. affects theirpregnancy experience. In general, some women causesevere discomfort andnegatively varicose veins, constipation andlegcramps –thatin and vomiting, low backandpelvicpain,heartburn, to avariety ofcommon symptoms –includingnausea hormonal andmechanicaleffects. These changes lead during pregnancy, whichare brought aboutby both Women’s bodiesundergo substantialchanges Background physiological symptoms D. Interventions for common • • • Remarks options. (Recommended) for therelief ofnausea inearlypregnancy, basedonawoman’s preferences andavailable RECOMMENDATION D.1: Ginger, chamomile, vitaminB6and/or acupuncture are recommended

pharmacological options,underthesupervision ofamedicaldoctor. be reserved for thosepregnant women experiencing distressing symptoms thatare notrelieved by non- Pharmacological treatments for nauseaandvomiting, suchasdoxylamine and metoclopramide, should pregnancy. Women shouldbeinformed thatsymptoms ofnauseaandvomiting usuallyresolve inthesecond halfof to have harmfuleffects onmotherandbaby. In theabsence ofstronger evidence, theGDGagreed that these non-pharmacological optionsare unlikely other relevant information ontheseapproaches. options andtheGDGconsidered theevidence and variety ofnon-pharmacological andpharmacological manage common physiological symptoms includea and dailyactivities(162).Suggested approaches to occur atnightandcanbevery painful,affecting sleep complicated by haemorrhoids(161). Leg cramps often Constipation canbevery troublesome andmay be and worsen withlongperiodsofstanding(160). with pain,nightcramps, achingandheaviness, (moderate confidence inthe treatment ofcommon pregnancy-related symptoms or traditional approaches to thediagnosisand andrespectsupport for women’s useofalternative in theevidence). Inmany LMICs,thisalsoincluded common physiological symptoms (highconfidence included woman-centred advice andtreatment for having apositive pregnancy experience. This high-, medium-andlow-resource settingsvalued guideline (13).Evidence showed thatwomen from and whatoutcomes they value informed theANC A scoping review ofwhatwomen want from ANC Women’s values: evidence). Summary of evidence and considerations lower). Data from the studies in Thailand and the USA showed a similar direction of effect on nausea Effects of interventions for nausea and symptoms in favour of ginger. vomiting compared with other, no or placebo interventions (EB Table D.1) Lemon oil: Low-certainty evidence from one small The evidence on the effects of various interventions Iranian study suggests that lemon oil may make little for nausea and vomiting in pregnancy was derived or no difference to nausea and vomiting symptom from a Cochrane systematic review (157). The scores (100 women; MD: 0.46 lower on day 3, review included 41 trials involving 5449 women in 95% CI: 1.27 lower to 0.35 higher), or to maternal whom a wide variety of pharmacological and non- satisfaction (the number of women satisfied with pharmacological interventions were evaluated. treatment) (1 trial, 100 women; RR: 1.47, 95% CI: Trials were conducted in a variety of HICs and 0.91–2.37). LMICs, and most included pregnant women at less than 16 weeks of gestation with mild to moderate Mint oil: The evidence on mint oil’s ability to relieve nausea and vomiting. Alternative therapies and symptoms of nausea and vomiting is of very low non-pharmacological agents evaluated included certainty. acupuncture, acupressure, vitamin B6, ginger, chamomile, mint oil and lemon oil. Pharmacological Chamomile: Low-certainty evidence from one small agents included antihistamines, phenothiazines, study suggests that chamomile may reduce nausea dopamine-receptor antagonists and serotonin 5-HT3 and vomiting symptoms scores (70 women; MD: 5.74 receptor antagonists. Due to heterogeneity among lower, 95% CI: 3.17–8.31 lower). the types of interventions and reporting of outcomes, reviewers were seldom able to pool data. The primary Vitamin B6 (pyridoxine): Moderate-certainty outcome of all interventions was maternal relief evidence from two trials (one used 25 mg oral vitamin from symptoms (usually measured using the Rhodes B6 8-hourly for 3 days, the other used 10 mg oral Index), and perinatal outcomes relevant to this vitamin B6 8-hourly for 5 days) shows that vitamin guideline were rarely reported. B6 probably reduces nausea symptoms scores (388 women, trials measured the change in nausea Non-pharmacological agents versus placebo or no scores from baseline to day 3; MD: 0.92 higher score treatment change, 95% 0.4–1.44 higher), but low-certainty Ten trials evaluated non-pharmacological evidence suggests that it may have little or no effect interventions including ginger (prepared as syrup, on vomiting (2 trials, 392 women; RR: 0.76, 95% CI: capsules or powder within biscuits) (7 trials from 0.35–1.66). the Islamic Republic of Iran, Pakistan, Thailand and the USA involving 578 participants), lemon oil Acupuncture and acupressure versus placebo or no (one Iranian study, 100 participants), mint oil (one treatment Iranian study, 60 participants), chamomile (one Five studies (601 participants) evaluated P6 (inner Iranian study, 105 participants), and vitamin B6 forearm) acupressure versus placebo, one Thai study interventions (two studies in Thailand and the USA; (91 participants) evaluated auricular acupressure 416 participants) compared with no treatment or (round magnetic balls used as ear pellets) versus no placebo. treatment, one study in the USA (230 participants) evaluated P6 acustimulation therapy (nerve Ginger: Low-certainty evidence from several small stimulation at the P6 acupuncture point) versus individual studies suggests that ginger may relieve placebo, and a four-arm Australian study (593 symptoms of nausea and vomiting. A study from women) evaluated traditional Chinese acupuncture or Pakistan found that ginger reduced nausea symptom P6 acupuncture versus P6 placebo acupuncture or no scores (68 women; MD: 1.38 lower on day 3, 95% intervention. CI: 0.03–2.73 lower), and vomiting symptom scores (64 women; MD: 1.14 lower, 95% CI: 0.37–1.91 lower), Low-certainty evidence suggests that P6 acupressure and an Iranian study showed improvements in nausea may reduce nausea symptom scores (100 women; and vomiting symptom scores on day 7 in women MD: 1.7 lower, 95% CI: 0.99–2.41 lower) and reduce taking ginger supplements compared with placebo the number of vomiting episodes (MD: 0.9 lower, (95 women; MD: 4.19 lower, 95% CI: 1.73–6.65 95% CI: 0.74–1.06 lower). Low-certainty evidence

Chapter 3. Evidence and recommendations 75 76 WHO recommendations on antenatal care for a positive pregnancy experience n Additional considerations effects was uncertain. doxylamine, respectively, butevidence onrelative compared ondansetron withmetoclopramide and antagonist) withplacebo. Two smallstudies No studiescompared ondansetron (a5HT3receptor data onmetoclopramide inthereview. lower).95% CI:1.33–4.55 There was noside-effect scores (1trial,68women; MD:2.94 lower onday 3, suggests thatthisagent may reduce nauseasymptom Low-certainty evidence onmetoclopramide (10 mg) B6 andplacebo. 95% CI: 0.64–2.27) between doxylamine plus vitamin CI: 0.45–1.48) ordrowsiness (256women; RR:1.21, difference inheadache(256 women; RR: 0.81, 95% from thisstudysuggests thatthere may belittleorno 15, 95% CI:0.25–1.55 lower). Low-certainty evidence placebo (1study, 256 women; MD:0.9 lower onday and vomiting symptom scores compared with doxylamine plusvitaminB6probably reduces nausea Moderate-certainty evidence suggests that safety concerns. drugs are nolonger usedinpregnant women dueto and fluphenazine)are from oldstudiesandthese evaluated inthereview (hydroxyzine, thiethylperazine antagonist (metoclopramide). Certain otherdrugs and anotherevaluated a dopamine-receptor One studyevaluated an antihistamine(doxylamine) Pharmacological agents versus placebo 1.0 lower to 0.4 higher). acupuncture (296women; MD:0.3 lower, 95% CI: to meannauseascores compared withP6placebo that P6acupuncture may make littleornodifference 0.04–1.36 lower). Low-certainty evidence suggests acupuncture (296women; MD:0.7 lower, 95% CI: 95% CI:0.58–6.62 lower), asmay traditional Chinese nausea symptom scores (91women; MD:3.6 lower, suggests thatauricularacupressure may alsoreduce n (98 participants), andginger versus vitamin B6 (70 participants), P6acupuncture versus ginger (296 participants), ginger versus chamomile traditional acupuncture andP6acupuncture acupuncture plusplacebo (66participants), acupuncture plusvitaminB6versus P6 interventions witheachother–namely comparing different non-pharmacological Low-certainty evidence from singlestudies n n n care providers and/or policy-makers (highconfidence circumstances are ignored or overlooked by healthservices iftheirbeliefs, traditions andsocioeconomic antenatal visits,they are less likely to engage with the interventions andinformation provided during indicates thatwhilewomen generally appreciate addition, evidence from adiverse range ofsettings (moderate confidence inthe evidence) (22). In attendants (TBAs)birth to treat thesesymptoms traditional healers, herbalremedies ortraditional suggests thatwomen may bemore likely to turnto Qualitative evidence from arange ofLMICs Acceptability The impactonequity isnotknown. Equity cost aboutUS$ 2.50 for 90×10mgtablets(74) . Vitamin B6(pyridoxine hydrochloride tablets) could skills andisprobably associated withhighercosts. vary. Acupuncture requires professional training and Costs associated withnon-pharmacological remedies Resources 3.D: Background (p. 74). See “Women’s values” atthebeginningofsection Values n n n metoclopramide inthefirst trimester of gestation. exposed (3458 neonates) and notexposed to preterm orperinataldeathbetween birth neonates major congenital malformations, low weight, birth statistically significantdifferences intheriskof inIsraelbirths reported thatthey found no used (163).Astudyofover 81 700 singleton in thefirst trimester ofpregnancy, butiswidely Metoclopramide isgenerally notrecommended vomiting. various antihistaminesusedto treat nauseaand However, drowsiness isacommon side-effect of were poorlyreported intheincludedstudies. Side-effects andsafety ofpharmacological agents higher)onday theintervention. 3after to 1.35 (68 women; MD:0.33 higher, 95% CI:0.69 lower lower higher)orvomiting to symptom 3.34 scores (1 trial, 68women; MD:1.56higher, 95% 0.22 metoclopramide onnauseasymptom scores be littleornodifference between ginger and Low-certainty evidence suggests thatthere may symptoms. or nodifference ineffects on reliefofnausea (123 participants) –suggests there may belittle in the evidence). This may be particularly pertinent Feasibility for acupuncture or acupressure, which may be A lack of suitably trained staff may limit feasibility culturally alien and/or poorly understood in certain of certain interventions (high confidence in the contexts. evidence) (45).

D.2: Interventions for heartburn

RECOMMENDATION D.2: Advice on diet and lifestyle is recommended to prevent and relieve heartburn in pregnancy. Antacid preparations can be offered to women with troublesome symptoms that are not relieved by lifestyle modification. (Recommended)

Remarks • Lifestyle advice to prevent and relieve symptoms of heartburn includes avoidance of large, fatty meals and alcohol, cessation of smoking, and raising the head of the bed to sleep. • The GDG agreed that antacids, such as magnesium carbonate and aluminium hydroxide preparations, are probably unlikely to cause harm in recommended dosages. • There is no evidence that preparations containing more than one antacid are better than simpler preparations. • Antacids may impair absorption of other drugs (164), and therefore should not be taken within two hours of iron and folic acid supplements.

Summary of evidence and considerations simethicone liquid and tablets than placebo (156 women; RR: 2.04, 95% CI: 1.44–2.89). Effects of interventions for heartburn compared with other, no or placebo interventions (EB Pharmacological interventions versus advice on diet Table D.2) and lifestyle changes The evidence on the effects of various interventions for Low-certainty evidence suggests that complete heartburn in pregnancy comes from a Cochrane review relief from heartburn may occur more frequently that included nine trials involving 725 pregnant women with sucralfate than with advice on diet and lifestyle with heartburn; however, only four trials (358 women) changes (65 women; RR: 2.41, 95% CI: 1.42–4.07). contributed data (159). One of these, from the 1960s, evaluated intramuscular prostigmine, which is no Acupuncture versus no treatment longer used, therefore these data were not considered Data on relief of heartburn was not available in the for the guideline. The three remaining studies review for this comparison. Low-certainty evidence conducted in Brazil, Italy and the USA evaluated suggests that weekly acupuncture in pregnant a magnesium hydroxide–aluminium hydroxide– women with heartburn may improve the ability to simeticone complex versus placebo (156 women), sleep (36 women; RR: 2.80, 95% CI: 1.14–6.86) and sucrulfate (aluminium hydroxide and sulfated sucrose) eat (36 women; RR: 2.40, 95% CI: 1.11–5.18), a proxy versus advice on diet and lifestyle changes (66 outcome for maternal satisfaction. women), and acupuncture versus no treatment (36 women). Evidence on symptom relief was generally Additional considerations assessed to be of low to very low certainty and no nnHeartburn during pregnancy is a common problem perinatal outcomes relevant to this guideline were that can be self-treated with over-the-counter reported. Evidence on side-effects for all comparisons products containing antacids such as magnesium was assessed as being of very low certainty. carbonate, aluminium hydroxide or calcium carbonate. Pharmacological interventions versus placebo nnThe Cochrane review found no evidence on Low-certainty evidence suggests that complete prescription drugs for heartburn, such as relief from heartburn may occur more frequently omeprazole and ranitidine, which are not known to with magnesium hydroxide–aluminium hydroxide– be harmful in pregnancy (159).

Chapter 3. Evidence and recommendations 77 78 WHO recommendations on antenatal care for a positive pregnancy experience calcium withnotreatment; astudyconducted inthe One studyfrom Sweden (43 women) compared oral data onoral magnesiumcompared withplacebo. (69 women) andThailand (86women) contributed Three studiesfrom Norway (42 women), Sweden involving 390pregnant women withlegcramps Cochrane review thatincludedsixsmalltrials for legcramps inpregnancy is derived from a The evidence ontheeffects of various interventions Table D.3) with other, noorplacebo interventions (EB Effects ofinterventions for legcramps compared Summary ofevidence and considerations D.3: Interventions for legcramps symptoms (moderate confidence inthe evidence) healers, herbal remedies orTBAsto treat these that women may bemore likely to turnto traditional Qualitative evidence from arange ofLMICssuggests Acceptability relieve mightimpactinequalities. heartburn However, itisnotknown whetherinterventions to among advantaged anddisadvantaged women. treatment for inpregnancy heartburn may beunequal The prevalence ofhealth-seekingbehaviour and Equity associated withhighercosts. professional training andskillsislikely to be can berelatively low cost. Acupuncture requires Costs ofantacidsvary widely, butgeneric products Resources 3.D: Background (p. 74). See “Women’s values” atthebeginningofsection Values • • • Remarks options. (Recommended) be usedfor therelief oflegcramps inpregnancy, basedonawoman’s preferences andavailable RECOMMENDATION D.3: Magnesium,calciumornon-pharmacological treatment optionscan

magnesium andcalciuminsymptom relief, isneeded. Further research into theetiologyandprevalence oflegcramps inpregnancy, andtherole (ifany) of they are unlikely to beharmfulinthedoseschedulesevaluated inincludedstudies. The evidence onmagnesiumandcalciumisgenerally oflow certainty. However, theGDGagreed that relaxation, heattherapy, dorsiflexion ofthe foot andmassage. The review found noevidence ontheeffect ofnon-pharmacological therapies, suchasmusclestretching, (162). (high confidence inthe evidence) (45) may limittheoffer oftreatment for this condition Qualitative evidence suggests thatalackofresources Feasibility (moderate confidence inthe evidence). so may respond to lifestyle suggestions favourably health-care professionals duringantenatal visits, pregnancy-related advice andguidance given by evidence alsoindicates thatwomen welcome the or poorlyunderstood incertaincontexts. Indirect acupuncture, whichmay beculturally alienand/ for pertinent aninterventionbe particularly like makers (highconfidence inthe evidence). This may overlooked by health-care providers and/or policy- and socioeconomic circumstances are ignored or to engage withservices iftheirbeliefs, traditions provided duringantenatal visits,they are less likely appreciate theinterventions andinformation of settingsindicates thatwhilewomen generally (22). Inaddition,evidence from adiverse range ways, soresults could notbepooled.Moderate- persistence oroccurrence oflegcramps indifferent in two orthree divideddoses.Studies measured group were given 300–360 mg magnesiumperday In three smallstudies,women intheintervention Oral magnesiumversus placebo relevant to thisguidelinewere notreported. studies, andothermaternal andperinataloutcomes in different ways, was the primary outcome inthese vitamin C(30women). Symptom relief, measured conducted inSweden compared oral calcium with vitamins B6andB1withnotreatment; andanother Islamic Republic ofIran (42 women) compared oral . certainty evidence from the Thai study suggests Values that women receiving magnesium are more likely See “Women’s values” at the beginning of section to experience a 50% reduction in the number of 3.D: Background (p. 74). leg cramps (1 trial, 86 women; RR: 1.42, 95% CI: 1.09–1.86). The same direction of effect was found in Resources the Swedish study, which reported the outcome “no Magnesium and calcium supplements are leg cramps” after treatment, but the evidence was relatively low-cost interventions, particularly when of low certainty (1 trial, 69 women; RR: 5.66, 95% administered for limited periods of two to four weeks. CI: 1.35–23.68). Low-certainty evidence suggests that oral magnesium has little or no effect on the Equity occurrence of potential side-effects, including nausea, The potential etiology of leg cramps being related diarrhoea, flatulence and bloating. Evidence from the to a nutritional deficiency (magnesium) suggests third study was judged to be very uncertain. that the prevalence of leg cramps might be higher in disadvantaged populations. In theory, Oral calcium versus no treatment therefore, nutritional interventions may have equity Calcium, 1 g twice daily for two weeks, was compared implications, but evidence is needed. with no treatment in one small study. Low-certainty evidence suggests that women receiving calcium Acceptability treatment are more likely to experience no leg cramps Qualitative evidence from a diverse range of after treatment (43 women; RR: 8.59, 95% CI: settings suggests that women generally appreciate 1.19–62.07). the pregnancy-related advice given by health- care professionals during ANC, so may respond Oral calcium versus vitamin C to supplement suggestions favourably (moderate Low-certainty evidence suggests that there may be confidence in the evidence) (22). Evidence from little or no difference between calcium and vitamin C some LMICs suggests that women hold the belief in the effect (if any) on complete symptom relief from that pregnancy is a healthy condition and may turn leg cramps (RR: 1.33, 95% CI: 0.53–3.38). to traditional healers and/or herbal remedies to treat these kinds of associated symptoms (high confidence Oral vitamin B1 and B6 versus no treatment in the evidence). One study evaluated this comparison, with 21 women receiving vitamin B1 (100 mg) plus B6 (40 mg) once Feasibility daily for two weeks and 21 women receiving no Qualitative evidence suggests that a lack of resources treatment; however, the low-certainty findings are may limit the offer of treatment for this condition contradictory and difficult to interpret. (high confidence in the evidence) (45). In addition, where there are additional costs for pregnant women Additional considerations associated with treatment, women are less likely to nnThe review found no evidence on non- use it. pharmacological therapies, such as muscle stretching, massage, relaxation, heat therapy and dorsiflexion of the foot.

Chapter 3. Evidence and recommendations 79 80 WHO recommendations on antenatal care for a positive pregnancy experience 6. 5. 4. 3. 2. 1. Comparisons included: relevant to thisguidelinewere notreported. and functionaldisability, andperinataloutcomes narrative. Mainoutcomes were relief ofsymptoms individual studyfindings were describedonlyin Few trialscontributed datato analyses andseveral treatment; however, sixtrialsevaluated prevention. for low backandpelvicpain.Most trialsevaluated for pelvicpain, andin13trialstheinterventions were reducing low backpain,insixtrialsinterventions were that in15trialstheinterventions were aimedat terminology oflow backandpelvicpainvaried such involving 5121 women (165).The definitionsand from aCochrane review thatincluded34 trials for low backandpelvicpaininpregnancy was derived The evidence ontheeffects of various interventions interventions (EBTable D.4) pain compared with other, noorplacebo Effects ofinterventions for low backandpelvic Summary ofevidence andconsiderations D.4: Interventions for low back andpelvicpain • • • • • Remarks available options.(Recommended) such asphysiotherapy, beltsandacupuncture, support basedonawoman’s preferences and low backandpelvicpain.There are anumberofdifferent treatment optionsthatcanbeused, RECOMMENDATION D.4: Regular exercise throughout pregnancy isrecommended to prevent

pain inpregnancy. Standardized reporting ofoutcomes isneededfor future research ontreatment for low backand/or pelvic options dueto apaucity ofdata. Women shouldbeinformed thatitisunclearwhetherthere are side-effects to alternative treatment birth. the monthsafter Pregnant women withlow backand/or pelvicpainshouldbeinformed thatsymptoms usuallyimprove in women ofANCto prevent aspart excessive weight gain inpregnancy (see Recommendation A.9). Regular exercise isakey component oflifestyle interventions, whichare recommended for pregnant symphysis pubisdysfunction andisnotrecommended for thiscondition. exercise may alsobehelpfulto relieve low backpain,itcould exacerbate pelvicpainassociated with Exercise to prevent low backandpelvicpaininpregnancy cantake place onlandorinwater. While versus standard care osteopathic manipulation(plusstandard care) individualized physiotherapy (plusstandard care) acupuncture (plusstandard care) versus acupuncture (plusstandard care) acupuncture (plusstandard care) versus sham standard care any exercise (plusstandard care) versus multimodal interventions versus standard care. one type beltversus ofsupport anothertypee women; RR:0.76; 95% CI:0.62–0.94). related to low backandpelvic pain(2trials,1062 programme are probably less likely to take sickleave healthy pregnant women inanexercise takingpart and moderate-certainty evidence shows that (4 trials, 1176 women; RR:0.66, 95% CI:0.45–0.97) back andpelvicpaincompared withstandard care 12-week exercise programme may reduce low Low-certainty evidence suggests thatan8-to as very uncertain. (symptom scores) for low backpainwas assessed CI: 0.23–0.89 lower). Evidence onpainintensity 146 women; standardized MD:0.56 lower, 95% with exercise interventions for low backpain(2 trials, suggests thatfunctionaldisability scores are better studies isvery uncertain. Low-certainty evidence symptom relief from ameta-analysis oftheseseven visual analoguescales.However, theevidence on or intensity ofpainwas assessed inmosttrialsusing Interventions ran for 8–12 weeks andthepresence some includededucationviaCDsandbooklets. exercise, includingyoga andaqua-aerobics, and from individuallysupervisedexercise to group Africa andThailand. Exercise interventions varied in Brazil, theIslamicRepublic ofIran, Norway, South comparison for low backpain.Trials were conducted Seven women) trials(645 contributed datato this care Any exercise (plusstandard care) versus standard Acupuncture (plus standard care) versus sham Additional considerations acupuncture (plus standard care) nnIt is not clear whether the evidence on exercise Four small studies conducted in Sweden and the USA interventions applies equally to low back pain and evaluated the effects of acupuncture plus standard pelvic pain, or equally to prevention and treatment, care versus sham acupuncture plus standard care. as data from studies of prevention and treatment However, little data were extracted from these studies were pooled. Evidence from two studies on the and data could not be pooled. Low-certainty evidence effect of exercise plus education suggests that from one study suggests that acupuncture may such interventions may have little or no effect on relieve low back and pelvic pain (72 women; RR: 4.16, preventing pelvic pain (RR: 0.97; 95% CI: 0.77– 95% CI: 1.77–9.78). Evidence from other studies was 1.23). variously reported and very uncertain. nnVery low-certainty evidence on a number of other interventions, such as transcutaneous electrical Acupuncture (plus standard care) versus nerve stimulation (TENS), progressive muscle individualized physiotherapy (plus standard care) relaxation with music, craniosacral therapy, and One small study conducted in Sweden involving 46 acetaminophen (paracetamol) – which were women with low back and pelvic pain evaluated this evaluated in single small trials with apparent relief comparison. Women’s satisfaction with treatment of symptoms relative to standard care – was also was the main outcome, but the evidence was presented in the review. assessed as very uncertain. nnStandard care of low back and pelvic pain symptoms usually comprises rest, hot or cold Osteopathic manipulation therapy (OMT) (plus compresses, and paracetamol analgesia. standard care) versus no osteopathic manipulation nnThere is a paucity of evidence on potential side- (standard care) effects of alternative therapies, e.g. chiropractic Three studies evaluated OMT; however, data could and osteopathic manipulation, and further high- not be pooled and the evidence from individual quality research is needed to establish whether studies is inconsistent. The largest study involving these therapies are beneficial for low back and/or 400 women compared OMT plus standard care with pelvic pain and safe during pregnancy. placebo ultrasound plus standard care, or standard nnExercise in pregnancy has been shown to have care only. Limited data from this study suggests that other benefits for pregnant women, including OMT may relieve low back pain symptoms more reducing excessive gestational weight gain (see than standard care, and may lead to lower functional Recommendation A.9). disability scores, but may not be better than placebo ultrasound for these outcomes. Values See “Women’s values” at the beginning of section One type of support belt versus another type 3.D: Background (p. 74). One small study conducted in Australia compared two types of support belts in womewith low back Resources pain, the BellyBra® and Tubigrip® (N = 94) and the Exercise can be administered in a group setting evidence from this study was assessed as very low- and individually at home; therefore, the cost of certainty evidence. exercise interventions varies. Support belts are available commercially from under US$ 10 per item.5 Multimodal interventions versus standard care Physiotherapy and acupuncture require specialist One study in the USA reported the effect of a training and are therefore likely to be more resource multimodal intervention that included weekly manual intensive. therapy by a chiropractic specialist, combined with daily exercise at home, and education versus standard care Equity (rest, exercise, heat pads and analgesics) on low back Improving access to low back and pelvic pain and pelvic pain. Moderate-certainty evidence suggests interventions may reduce inequalities by reducing that the multimodal intervention is probably associated functional disability and sick leave related to low back with better pain scores (1 study, 169 women; MD: 2.70 and pelvic pain among disadvantaged women. lower, 95% CI: 1.86–3.54 lower) and better functional disability scores (MD: 1.40 lower; 95% CI: 0.71–2.09 lower) compared with standard care. 5 Based on Internet search.

Chapter 3. Evidence and recommendations 81 82 WHO recommendations on antenatal care for a positive pregnancy experience terminally illpeople;however, dataonstimulant is potentially carcinogenic andnow onlyusedin senna andNormax®.The latter (containing dantron) Two stimulantlaxatives were usedinthis1970s study, Stimulant laxatives versus bulk-forming laxatives stools) was assessed asbeingvery uncertain. constipation relief (reported asmeanfrequency of supplementation versus nointervention on Evidence from thesmallstudyevaluating fibre Fibre supplementationversus nointervention reported. perinatal outcomes relevant to thisguidelinewere with bulk-forming laxatives (140women). No (40 women), the othercompared stimulantlaxatives compared fibre supplementationwithnointervention among pregnant women withconstipation. One studies were conducted intheUnited Kingdom involving 180women contributed data(161) . Both a Cochrane review to whichonlytwo smallRCTs for constipation inpregnancy was derived from The evidence ontheeffects of various interventions interventions (EBTable D.5) compared withother, noorplacebo Effects ofinterventions for constipation Summary ofevidence andconsiderations D.5: Interventions for constipation forpertinent anintervention like acupuncture, which in theevidence) care providers and/or policy-makers (highconfidence circumstances are ignored oroverlooked by healthservices iftheirbeliefs, traditions andsocioeconomic antenatal visits,they are less likely to engage with the interventions andinformation provided during indicates thatwhilewomen generally appreciate Qualitative evidence from adiverse range ofsettings, Acceptability • • Remarks RECOMMENDATION D.5: on awoman’s preferences andavailable options.(Recommended) constipation inpregnancy ifthecondition fails to respond to dietarymodification,based

supplementation, stakeholders may wishto consider intermittent useofpoorlyabsorbedlaxatives. For women withtroublesome constipation thatisnotrelieved by dietarymodificationorfibre water anddietaryfibre (found in vegetables, nuts,fruitandwholegrains). Dietary advice to reduce constipation duringpregnancy shouldincludepromoting adequate intake of (22). This may beparticularly

Wheat bran orotherfibre supplementscanbeused to relieve n n this condition (highconfidence inthe evidence) A lackofresources may limittheoffer oftreatment for Feasibility 6 cost ataround US$ 1.5per375 g bagofwheatbran. region. Cereal fibre supplements canbe relatively low- Costs willvary according to theintervention and Resources 3.D: Background (p. 74). See “Women’s values” atthebeginningofsection Values Additional considerations was assessed asbeingvery uncertain. forming laxatives (sterculia withorwithoutfrangula) satisfaction for stimulantlaxatives versus bulk- (abdominal discomfort, diarrhoea),andmaternal Evidence onrelative symptom relief, side-effects laxatives were notavailable separately for senna. health services (highconfidence inthe evidence). constraints), women are less likely to engage with the treatment may beunavailable (becauseofresource be additionalcosts associated withtreatment orwhere certain contexts. Inaddition,where there are likely to may beculturally alienand/or poorlyunderstood in

n n Based onInternet sear laxatives. supplements could potentially becompromised by The absorptionofvitaminsandmineral be harmfulinpregnancy (166). medications for constipation andare notknown to laxatives (senna) are available asover-the-counter ispaghula husk),osmotic(lactulose)andstimulant fibre supplements,sterculia, methylcellulose, Various bulk-forming (wheat bran oroatbran ch. (45) 6 . Equity the interventions and information provided during It is not known whether interventions to relieve antenatal visits, they are less likely to engage with constipation might impact inequalities. services if their beliefs, traditions and socioeconomic circumstances are ignored or overlooked by health- Acceptability care providers and/or policy-makers (high confidence Qualitative evidence from a range of LMICs suggests in the evidence). that women may be more likely to turn to traditional healers, herbal remedies or TBAs to treat these Feasibility symptoms (moderate confidence in the evidence) Other qualitative evidence suggests that a lack (22). Evidence from a diverse range of settings of resources may limit the offer of treatment for indicates that while women generally appreciate constipation (high confidence in the evidence) (45).

D.6: Interventions for varicose veins and oedema

RECOMMENDATION D.6: Non-pharmacological options, such as compression stockings, leg elevation and water immersion, can be used for the management of varicose veins and oedema in pregnancy based on a woman’s preferences and available options. (Recommended)

Remarks • Women should be informed that symptoms associated with varicose veins may worsen as pregnancy progresses but that most women will experience some improvement within a few months of giving birth. • Rest, leg elevation and water immersion are low-cost interventions that are unlikely to be harmful.

Summary of evidence and considerations trial suggests that rutoside may reduce symptoms (nocturnal cramps, paraesthesia, tiredness) Effects of interventions for varicose veins and associated with varicose veins compared with oedema compared with other, no or placebo placebo (69 women; RR: 1.89, 95% CI: 1.11–3.22). interventions (EB Table D.6) However, no side-effect data were reported. The evidence on the effects of various interventions for varicose veins in pregnancy was derived from Non-pharmacological interventions versus placebo a Cochrane review that included seven small trials or no intervention involving 326 women with varicose veins and/or Low-certainty evidence suggests that reflexology oedema, and various types of interventions, including may reduce oedema symptoms compared with rest rutoside (a phlebotonic drug) versus placebo (two only (55 women; RR: 9.09, 95% CI: 1.41–58.54) trials), foot massage by a professional masseur for and that water immersion may reduce oedema five days versus no intervention (1 trial, 80 women), symptoms (leg volume) compared with leg elevation intermittent external pneumatic compression with (32 women; RR: 0.43, 95% CI: 0.22–0.83). Low- a pump versus rest (1 trial, 35 women), standing in certainty evidence suggests that there may be little water at a temperature between 29°C and 33°C for or no difference in oedema symptoms (measured 20 minutes (water immersion) versus leg elevation as lower leg circumference in centimetres) between (1 trial, 32 women) and reflexology versus rest foot massage and no intervention (80 women; MD (1 trial, 55 women) (160). Another trial comparing in cm: 0.11 less, 95% CI: 1.02 less to 0.80 more) compression stockings with rest in the left lateral and between intermittent pneumatic compression position did not contribute any data. Fetal and and rest (measured as mean leg volume, unit of neonatal outcomes relevant to the ANC guideline analysis unclear) (35 women; MD: 258.8 lower, were not reported in these studies. 95% CI: 566.91 lower to 49.31 higher). Only one study (reflexology versus rest) evaluated women’s Pharmacological interventions versus placebo or no satisfaction, but the evidence is of very low intervention certainty. Only one small trial conducted in 1975 (69 women) contributed data. Low-certainty evidence from this

Chapter 3. Evidence and recommendations 83 84 WHO recommendations on antenatal care for a positive pregnancy experience n Additional considerations varicose veins andoedemamightimpactinequalities. It isnotknown whetherinterventions to relieve Equity are, therefore, likely to bemore costly. professional massage require specialisttraining, and can cost more thanUS$ 15perpair. Reflexology and The cost ofcompression stockings varies butthey Postural interventions are low-cost interventions. Resources 3.D: Background (p. 74). See “Women’s values” atthebeginningofsection Values n generally very uncertain (167). Cochrane review ofcompression stockings was veins andtheevidence for thispractice inarelated morbidity innon-pregnant peoplewithvaricose stockings are alsowidelyusedto prevent on thispractice inpregnancy (160).Compression however, theCochrane review found noevidence management for varicose veins andoedema; elevation isthemostcommon non-surgical Compression stockings combined withleg Feasibility health services (highconfidence inthe evidence). constraints), women are less likely to engage with the treatment may beunavailable (becauseofresource additional costs associated withtreatment orwhere evidence shows that,where there are likely to be poorly understood incertain contexts. Qualitative reflexology, whichmay beculturally alienand/or for pertinent aninterventionbe particularly like makers (highconfidence inthe evidence). This may overlooked by health-care providers and/or policy- and socioeconomic circumstances are ignored or to engage withservices iftheirbeliefs, traditions provided duringantenatal visits,they are less likely appreciate theinterventions andinformation of settingsindicates thatwhilewomen generally (22). Inaddition,evidence from adiverse range symptoms (moderate confidence inthe evidence) healers, herbalremedies orTBAsto treat these that women may bemore likely to turnto traditional Qualitative evidence from arange ofLMICssuggests Acceptability oedema (highconfidence inthe evidence ) (45) may limitthe offer oftreatment for varicose veins and The evidence alsosuggests thatalackofresources . E. Health systems interventions to improve the utilization and quality of ANC

Background estimation of gestational age, which is integral to evidence-based decision-making, due to improved There is a multitude of interventions that can be continuity of fetal growth records (170). employed to improve the utilization and quality of ANC depending on the context and setting. For the nnMidwife-led continuity of care (MLCC) models: purposes of this guideline, the GDG considered the Midwives are the primary providers of care in following interventions: many ANC settings (171). In MLCC models, a 1. Women-held case notes (home-based records) known and trusted midwife (caseload midwifery), 2. Midwife-led continuity of care models or small group of known midwives (team 3. Group ANC midwifery), supports a woman throughout the 4. Community-based interventions to improve antenatal, intrapartum and postnatal period, to communication and support facilitate a healthy pregnancy and childbirth, and 5. Task shifting healthy parenting practices (172). The MLCC 6. Recruitment and retention of staff model includes: continuity of care; monitoring 7. ANC contact schedules. the physical, psychological, spiritual and social well-being of the woman and family throughout How to deliver the type and quality of ANC that the childbearing cycle; providing the woman with women want is a vast and complex field of research. individualized education, counselling and ANC; Interventions designed to increase staff competency, attendance during labour, birth and the immediate to improve staff well-being, and other interventions postpartum period by a known midwife; ongoing (e.g. financial incentives) to increase access and use support during the postnatal period; minimizing of ANC are broad topics that were considered beyond unnecessary technological interventions; and the scope of this guideline. identifying, referring and coordinating care for women who require obstetric or other specialist nnWomen-held case notes: In many countries, attention (173). Thus, the MLCC model exists women are given their own case notes (or home- within a multidisciplinary network in which based records) to carry during pregnancy. Case consultation and referral to other care providers notes may be held in paper (e.g. card, journal, occurs when necessary. The MLCC model is handbook) or electronic formats (e.g. memory usually aimed at providing care to healthy women stick), and women are expected to take them with uncomplicated pregnancies. along to all health visits. If women then move, or are referred from one facility to another, and in the nnGroup ANC: ANC conventionally takes the form case of complications where immediate access of a one-on-one consultation between a pregnant to medical records is not always possible, the woman and her health-care provider. However, practice of women-held case notes may improve group ANC integrates the usual individual the availability of women’s medical records pregnancy health assessment with tailored group (168). Women-held case notes might also be an educational activities and peer support, with effective tool to improve health awareness and the aim of motivating behaviour change among client–provider communication (169). Inadequate pregnant women, improving pregnancy outcomes, infrastructure and resources often hamper efficient and increasing women’s satisfaction (174). The record-keeping, therefore, case notes may be intervention typically involves self-assessment less likely to get lost when held personally. In activities (e.g. blood pressure measurement), addition, the practice may facilitate more accurate group education with facilitated discussion, and

Chapter 3. Evidence and recommendations 85 86 WHO recommendations on antenatal care for a positive pregnancy experience n n n n approach to ANCto improve quality ofcare and recommended afocused orgoal-orientated ANC contact schedules: In2002, theWHO and quality ofcare. they may face, may leadto improved ANCuptake in addressingpartners withsupport challenges family planning), andproviding women andtheir dialogue around newborn care andpostnatal healthy during pregnancy andbeyond (including and facilitators to utilizingANCrvices andkeeping around awareness ofawomen’s rights,barriers to doso. Interventions thatincrease thedialogue low-resource settings,may needto beempowered quality health-care services in and,particularly addition, pregnant women have arightto access affect theirsexual and reproductive health(1).In women are indecisionsthat entitledto participate A human-rights-basedapproach recognizes that isakeysupport elementofaquality ANCservice. Having access to appropriate communication and cultural, emotionalandpsychological (13). support and sociocultural refers issues; “support” to social, relevant physiological, biomedical,behavioural communication withwomen abouttimelyand the actofsharinginformation, educationand experiences. The term “communicate” refers to integral components ofpositive pregnancy communication for andsupport women as conducted for theANCguidelineidentified communication The andsupport: scoping review Community-based interventions to improve of women, withaprivate area for examinations. in aspace large enoughto accommodate agroup time to socialize. Group ANCneedsto bedelivered and E6). retention ofstaffinrural areas (Recommendations E5 andrecruitmentWHO guidelinesontaskshifting and considered existing recommendations from other ANC (Recommendations E1to E5).The GDGalso determine whetherthey shouldberecommended for other relevant information ontheseinterventions to The GDGconsidered theavailable evidence and than inANCmodelsusedHICs. number of visits in this model is considerably fewer those whodevelop pregnancy complications. The with appropriate referral ofhigh-riskwomen and healthy pregnant women (called “goal-oriented”), includes specific evidence-based interventions for between 36and38 weeks. Guidance oneachvisit between 24 and26 weeks, at32 weeks, and occurring between 8and12 weeks ofgestation, the basicANCmodel,includesfour ANCvisits The focused ANC(FANC) model,alsoknown as increase ANCcoverage, inLMICs(12). particularly Women’s values the evidence). with maternity-care providers (highconfidence in time to buildauthenticandsupportive relationships provider care where women were given privacy and of flexible appointment systems and continuity of health systems context, thisincludedtheadoption having apositive pregnancy experience. Within a high-, medium-andlow-resource settingsvalued guideline (13).Evidence showed thatwomen from and whatoutcomes they value informed theANC A scoping review ofwhatwomen want from ANC E.1: Women-held case notes

RECOMMENDATION E.1: It is recommended that each pregnant woman carries her own case notes during pregnancy to improve continuity, quality of care and her pregnancy experience. (Recommended)

Remarks • The GDG noted that women-held case notes are widely used and are often the only medical records available in various LMIC settings. • The GDG agreed that the benefits of women-held case notes outweigh the disadvantages. However, careful consideration should be given as to what personal information it is necessary to include in the case notes, to avoid stigma and discrimination in certain settings. In addition, health-system planners should ensure that admission to hospitals or other health-care facilities do not depend on women presenting their case notes. • Health-system planners should consider which form the women-held case notes should take (electronic or paper-based), whether whole sets of case notes will be held by women or only specific parts of them, and how copies will be kept by health-care facilities. • For paper-based systems, health-system planners also need to ensure that case notes are durable and transportable. Health systems that give women access to their case notes through electronic systems need to ensure that all pregnant women have access to the appropriate technology and that attention is paid to data security. • Health-system planners should ensure that the contents of the case notes are accessible to all pregnant women through the use of appropriate, local languages and appropriate reading levels.

Summary of evidence and considerations little or no effect on women’s satisfaction with ANC (2 trials, 698 women; RR: 1.09, 95% CI: 0.92–1.29). Effects of women-held case notes compared Evidence on caesarean section was very uncertain with other practices (EB Table E.1) and other guideline outcomes were not reported in The evidence on the effects of women-held case the review. notes was mostly derived from a Cochrane review that included four small trials involving 1176 women (168). Fetal and neonatal outcomes Trials were conducted in Australia, Mongolia and the Low-certainty evidence suggests that women-held United Kingdom (2 trials). In three trials, women in case notes may have little or no effect on perinatal the intervention groups were given their complete mortality (2 trials, 713 women; RR: 0.77, 95% CI: antenatal records (paper) to carry during pregnancy. 0.17–3.48). No other fetal and neonatal outcomes In the remaining trial, a cluster randomized controlled were reported in the review. trial (RCT) involving 501 women in Mongolia, women in the intervention group carried a maternal and child Coverage outcomes health handbook that included antenatal, postnatal and Low-certainty evidence suggests that women-held child health records. Antenatal records were facility- case notes may have little or no effect on ANC held in the control groups. Data on ANC coverage coverage of four or more visits (1 trial, 501 women; for the Mongolian trial were derived separately from RR: 1.25, 95% CI: 0.31–5.00). another Cochrane review (175). Additional considerations Maternal outcomes nnOther evidence from the review suggests that With regard to maternal satisfaction, moderate- there may be little or no difference in the risk of certainty evidence indicates that women who carry case notes being lost or left at home for a visit their own case notes are probably more likely to feel (2 trials, 347 women; RR: 0.38, 95% CI: 0.04– in control of their pregnancy experience than women 3.84). whose records are facility-held (2 trials, 450 women; nnA WHO multicentre cohort study of home-based RR: 1.56, 95% CI: 1.18–2.06). Low-certainty evidence maternal records (HBMR), involving 590 862 suggests that women-held case notes may have women in Egypt, India, Pakistan, Philippines,

Chapter 3. Evidence and recommendations 87 88 WHO recommendations on antenatal care for a positive pregnancy experience might perpetuate inequalities. to read andunderstand their own casenotes, which women withlower healthliteracy may beless able stigma (e.g. HIV-positive status). Less-educated information contained inthenotes isassociated with against women whodonothave them,orifthe could besubject to abuseandusedto discriminate The GDGconsidered thatwomen-held casenotes Equity may addto costs. copies. The needto adaptand/or translate journals transportable journals,aswell assystems for keeping based systems require theproduction ofdurable, Electronic systems require more resources. Paper- electronic orpaper-based systems are used. Resource implicationsdiffer dependingonwhether Resources Background (p. 86). See “Women’s values” atthebeginningofsection3.E: Values health andthatoftheirbabies.” became more involved theirown inlookingafter care personnel because,by usingit,themothers community healthworkers andotherhealth- community. The HBMRwas liked by mothers, means ofcollecting healthinformation inthe tetanus toxoid immunization, andprovided a family planningandhealtheducation,increased pregnant women andnewborn infants, improved increased thediagnosisand referral ofat-risk study reported that“The introduction oftheHBMR conducted between 1984and1988(176). The Senegal, Sri Lanka, Yemen andZambia,was fragmented systems. and thepotential for datato belostbecauseof data security, sensitivity oftheshared information, responsibilities. Providers alsoraised concerns about the approach may generate additionaladministrative their own casenotes, butfeel theimplementationof providers are generally happy for women to carry (36 outof37 studies). Findings alsosuggest that were derived primarilyfrom high-income settings GRADE-CERQual assessments ofconfidence, and (177). These review findings were notsubject to they carry, orhave access to, theirown casenotes RCT evidence thatwomen feel more satisfiedwhen evidence from amixed-methods review supports (moderate confidence inthe evidence). Further where maternity services are under-resourced for women whodonothave casenotes, particularly settings, for example, by limitingaccess to hospitals be potential for abuseofthesystem insomeLMIC (high confidence inthe evidence) (22). There may and theassociated senseofempowerment thisbrings acquire pregnancy andhealth-related information case notes becauseoftheincreased opportunity to variety ofsettingsare likely to favour carryingtheir Qualitative evidence suggests thatwomen from a Acceptability resources (45) records may require little intheway ofextra cost or confidence inthe evidence), althoughpaper-based software packages, etc.) insomeLMICsettings(high with usinganelectronic system (USBmemorysticks, There may beprohibitive additionalcosts associated Feasibility . E.2: Midwife-led continuity of care (MLCC)

RECOMMENDATION E.2: Midwife-led continuity-of-care models, in which a known midwife or small group of known midwives supports a woman throughout the antenatal, intrapartum and postnatal continuum, are recommended for pregnant women in settings with well functioning midwifery programmes. (Context-specific recommendation)

Remarks • MLCC models are models of care in which a known and trusted midwife (caseload midwifery), or small group of known midwives (team midwifery), supports a woman throughout the antenatal, intrapartum and postnatal period, to facilitate a healthy pregnancy and childbirth, and healthy parenting practices. • MLCC models are complex interventions and it is unclear whether the pathway of influence producing these positive effects is the continuity of care, the midwifery philosophy of care or both. The midwifery philosophy inherent in MLCC models may or may not be enacted in standard midwife practice in other models of care. • Policy-makers in settings without well functioning midwife programmes should consider implementing this model only after successfully scaling up of the number and quality of practising midwives. In addition, stakeholders may wish to consider ways of providing continuous care through other care providers, because women value continuity of care. • The panel noted that with this model of care it is important to monitor resource use, and provider burnout and workload, to determine whether caseload or team care models are more sustainable in individual settings. • MLCC requires that well trained midwives are available in sufficient numbers for each woman to see one or only a small group of midwives throughout pregnancy and during childbirth. This model may therefore require a shift in resources to ensure that the health system has access to a sufficient number of midwives with reasonable caseloads. • The introduction of MLCC may lead to a shift in the roles and responsibilities of midwives as well as other health-care professionals who have previously been responsible for antenatal and postnatal care. Where this is the case, implementation is likely to be more effective if all relevant stakeholders are consulted and human resources departments are involved. In some settings, government-level consultation with professional organizations could also aid implementation processes. • The need for additional one-off or continuing training and education should be assessed, and should be provided where necessary.

Summary of evidence and considerations visits to an obstetrician and/or family doctor. Eight trials included women with “low-risk” pregnancies Effects of MLCC models compared with other only; six also included women with “high-risk” models of care (EB Table E.2) pregnancies. Four trials evaluated one-to-one The evidence on the effects of MLCC models of care (caseload) MLCC and 10 trials evaluated team MLCC. was derived from a Cochrane review that included Caseload sizes for one-to-one models ranged from 32 15 trials involving 17 674 women, in which pregnant to 45 pregnant women per midwife per year. Levels of women were randomized to receive ANC either by continuity of care were measured (as the proportion MLCC models or by other models of care (172). All of births attended to by a known carer), and were the studies included were conducted in public health in the ranges of 63–98% for MLCC and 0–21% for systems in HICs (Australia, Canada, Ireland and other models. A random effects model was used in all the United Kingdom) and 14 out of 15 contributed meta-analyses. data. Eight trials compared an MLCC model with a shared care model, three trials compared MLCC Maternal outcomes with medical-led care, and three compared MLCC Moderate-certainty evidence shows that MLCC with “standard care” (mixed-care options, including compared with other models of care probably slightly midwife-led non-continuous care, medical-led, and increases the chance of a vaginal birth (12 trials, shared care). Some MLCC models included routine 16 687 participants; RR: 1.05, 95% CI: 1.03–1.07).

Chapter 3. Evidence and recommendations 89 90 WHO recommendations on antenatal care for a positive pregnancy experience n a shift inresourcesa shift may benecessary to ensure In settingswithwell functioningmidwife programmes, Resources Background (p. 86). See “Women’s values” atthebeginningofsection3.E: Values Additional considerations outcomes was notavailable inthereview. 95% CI:0.82–1.13) . Evidence onotherANCguideline on low weight birth (7trials,11 458women; RR:0.96, evidence suggests thatitmay have littleornoeffect 0.84, 95% CI:0.71–0.99). However, low-certainty and neonataldeath)(13trials,17 561 women; RR: the review asfetal 24 loss after weeks ofgestation and probably reduces perinatalmortality (defined in RR:0.76,13 338 participants; 95% CI:0.64–0.91) probably reduces theriskofpreterm (8trials, birth Moderate-certainty evidence indicates thatMLCC Fetal andneonatal outcomes 95% CI:1.11–1.54;RR: 1.31, low-certainty evidence). compared withothermodels(4 trials,5419 women; reporting highlevels ofsatisfaction withtheANC models may increase theproportion ofwomen Table E.2), thefindingsofwhichsuggest thatMLCC performed for thepurposesofthisguideline(see EB A meta-analysis onsatisfaction withANConlywas aspects ofantenatal, intrapartum andpostnatalcare. data onwomen’s satisfaction to various pertaining Maternal satisfaction: The Cochrane review tabulated 95% CI:0.83–0.97). RR:0.90,other models(13trials,17 501 participants; lower rates ofinstrumentalvaginal delivery than suggests thatMLCC modelsmay beassociated with the possibility ofnoeffect. Low-certainty evidence however, thisevidence isoflow certainty 17 674 RR:0.92, participants; 95% CI:0.84–1.00), MLCC may reduce caesarean sections(14trials, n important. of theresults andtheabsence ofharmto be is unclear, theGDGconsidered theconsistency reduction inpreterm andperinataldeath birth Although themechanismfor theprobable andincludes the evidence). not have theresources to doso(low confidence in opportunity to useanMLCC modelbutfeel they do locations suggests thatthey would welcome the However, indirect evidence from providers inthese is very littleevidence onMLCC modelsfrom LMICs. desire (moderate confidence inthe evidence). There the authentic,supportive relationships thatwomen indicates thatthey view MLCC asaway ofachieving (22). Evidence from providers, mainlyinHICs, during ANCvisits(highconfidence inthe evidence) a consistent, unhurried,woman-centred approach (high confidence inthe evidence) andappreciate number ofmidwives duringthematernity phase caring relationships withamidwife orasmall welcome theopportunity to buildsupportive, of settingsandcontexts indicates thatwomen Qualitative evidence synthesized from awidevariety Acceptability outcomes, violence. suchasintimate partner may facilitate theidentificationofrisk factors for poor disadvantaged women to discloseinformation that example, by providing amore supportive settingfor potential to helpto address healthinequalities,for . MLCCLMICs (171) models inany settinghave the of midwifery practice are majorchallenges inmany Equitable coverage andimprovements inthequality Equity confidence inthe evidence) (45) delivery ofcaseloadorone-to-one approaches (high providers aboutpotential staffing issues, e.g. for the low-resource settingshighlightsconcerns among Qualitative evidence from high-,medium-and Feasibility in staff costs (178). model thanothermidwife-led care dueto differences provider costs were 20–25% lower withtheMLCC one studyintheCochrane review found thatANC associated withchangingto anMLCC model.However, reasonable caseloads.There may alsobetraining costs that thehealthsystem hassufficientmidwives with . E.3: Group antenatal care

RECOMMENDATION E.3: Group antenatal care provided by qualified health-care professionals may be offered as an alternative to individual antenatal care for pregnant women in the context of rigorous research, depending on a woman’s preferences and provided that the infrastructure and resources for delivery of group antenatal care are available. (Context-specific recommendation – research)

Remarks • With the group ANC model, the first visit for all pregnant women is an individual visit. Then at subsequent visits, the usual individual pregnancy health assessment, held in a private examination area, is integrated into a group ANC session, with facilitated educational activities and peer support. • Health-care facilities need to be seeing sufficient numbers of pregnant women, as allocation to groups is ideally performed according to gestational age. • Health-care providers need to have appropriate facilities to deal with group sessions, including access to large, well ventilated rooms or sheltered spaces with adequate seating. A private space should be available for examinations, and opportunities should be given for private conversations. • Group ANC may take longer than individual ANC, and this may pose practical problems for some women in terms of work and childcare. Health-care providers should be able to offer a variety of time slots for group sessions (morning, afternoon, evening) and should consider making individual care available as well. • The GDG noted that group ANC may have acceptability and feasibility issues in settings where perceived differences keep people apart, e.g. women from different castes in India may not wish to be in a group together. • Group ANC studies are under way in Nepal, Uganda and five other low-income countries, and the GDG was informed by a GDG member that some of these studies are due to report soon. Core outcomes of studies of group ANC should include maternal and perinatal health outcomes, coverage, and women's and providers' experiences.

Summary of evidence and considerations Maternal outcomes Moderate-certainty evidence indicates that group Effects of group ANC compared with individual ANC probably does not have an important effect on ANC (EB Table E.3) vaginal birth rates compared with individual ANC The evidence on the effects of group ANC was (1 trial, 322 women; RR: 0.96, 95% CI: 0.80–1.15). derived from a Cochrane review that included But low-certainty evidence suggests that it may lead four trials involving 2350 women (174). Two trials to higher women’s satisfaction scores (1 trial, 993 from the USA used a group ANC model known as women; MD: 4.9, 95% CI: 3.10–6.70). CenteringPregnancy®, in which group ANC was conducted in circles of 8–12 women of similar Fetal and neonatal outcomes gestational age, meeting for 8–10 sessions during Moderate-certainty evidence indicates that group pregnancy, with each session lasting 90–120 minutes. ANC probably has little or no effect on low birth ssions included self-assessment activities (blood weight (3 trials, 1935 neonates; RR: 0.92, 95% CI: pressure measurement), facilitated educational 0.68–1.23) and low-certainty evidence suggests that discussions and time to socialize, with individual it may have little or no effect on perinatal mortality examinations performed in a private/screened- (3 trials, 1943 neonates; RR: 0.63, 95% CI: 0.32–1.25). off area. One trial conducted in Sweden used a However, low-certainty evidence also suggests that group model similar to the USA model but mainly group ANC may reduce preterm birth (3 trials, 1888 assessed provider outcomes and contributed little women; RR: 0.75, 95% CI: 0.57–1.00); this evidence data to the review. The fourth trial, conducted in the includes the possibility of no effect. Evidence on Islamic Republic of Iran, was a cluster-RCT in which the risk of having an SGA neonate is of a very low group ANC was described as being similar to the certainty. CenteringPregnancy® approach.

Chapter 3. Evidence and recommendations 91 92 WHO recommendations on antenatal care for a positive pregnancy experience n n Additional considerations ANC visits,there may begreater cost implications where group ANCsessions take longer thanstandard networks.peer support However, incertain settings, reduce inequalities by facilitating thedevelopment of disadvantaged women andgroup ANC may helpto women. lackingfor isoften Inaddition,socialsupport maternal healthliteracy amongdisadvantaged impact onreducing healthinequalitiesby improving and useeducationalmaterials could have apositive aim to improve women’s ability to access, understand (179). Therefore, interventions suchasgroup ANCthat maternal healthliteracy thanmore-educated women Less-educated women are more likely to have poor Equity appointment could represent areduced visittime. times are thenorm,sogroup ANCwithascheduled off work. However, inmany settings,long waiting with thetimeeachpregnant woman needsto take perspective, there may beadditionalcosts associated longer thanindividualvisits,therefore, from auser also associated withcost. Group ANCvisitstake based counselling discussions is andparticipatory supervising health-care providers to conduct group- waiting to beseen(181,182).However, training and likely to feel overwhelmed by longqueuesofwomen to eachwoman individually, andthey may beless health-care providers donotneedto repeat advice to increased staffproductivity andefficiency;e.g. associated withlower health-care provider costs due It hasbeensuggested thatgroup ANCmay be Resources Background (p. 86). See “Women’s values” atthebeginningofsection3.E: Values n n engagement ofpregnant women withANC(179). due to improved healthliteracy andbetter improve healthoutcomes inlow-income settings, and providers’ experiences, andpotentially might improve women’s pregnancy experiences, conducted inGhanasuggests thatgroup ANC ANC from LMICs.However, afeasibility study There islittleevidence ontheeffects ofgroup potential effects islimited (180). healthy behaviours; buttheevidence onthese communication related andsocialsupport to these and postnatalcontraception, by improving ANC guideline,suchasbreastfeeding initiation on otheroutcomes outsidethescope ofthe It isplausiblethatgroup ANCmay have animpact in theevidence). of providing continuity ofcare (moderate confidence Providers alsoidentifiedthegroup approach asa way time (moderate confidence inthe evidence) (45) and satisfyingamore efficientuseoftheir suggests they findgroup sessions to beenjoyable in theevidence). Evidence from providers inHICs husbands includedvaries (moderate confidence the evidence) andthedesire to have partners/ during physical examinations (low confidence in lack ofprivacy duringthegroup sessions, particularly evidence). Somewomen have reservations aboutthe time commitments (moderate confidence inthe attend group sessions becauseoftheadditional in theevidence), althoughsomewomen donot time inherent inthegroup approach (highconfidence evidence). Mostwomen appreciate theadditional and informal manner(highconfidence inthe discuss pregnancy-related concerns inarelaxed exchange valuable information witheachotherand (22). The flexibility ofthe format allows women to professionals (highconfidence inthe evidence) with otherpregnant women andhealth-care opportunity to buildsociallysupportive relationships that women enjoy thegroup format andusethe Qualitative evidence from several HICssuggests Acceptability that group ANCmay beafeasible way ofimproving feasible inthesesettings(181).Ithasbeensuggested Republic ofTanzania suggest that group ANCis pilot studiesinGhana,Malawi andtheUnited resource research; settingsneedsfurther however, evidence). The feasibility ofgroup ANCinlow- with adequate seating(moderate confidence inthe sessions, i.e. clinicsneedto have large enoughrooms clinics needto bebetter equippedto deliver group in theevidence) (45) and provider commitment (moderate confidence requiring additionalinvestment interms oftraining facilitative components ofgroup ANCasaskill suggests thathealth-care professionals view the Qualitative evidence from high-resource settings Feasibility prefer amore private approach to ANC. personal information inagroup settingandmight disadvantaged women mightfinditharder to disclose for women livinginremote areas. Furthermore, some suitable andmay have anegative impactonequity appointment system withgroup ANCmay notbe with poortransport systems orvariable weather, the for disadvantaged women. Inaddition,insettings . Someproviders alsofeel that . ANC quality in settings where relatively few providers can be challenging (182). Others have suggested attend to relatively large numbers of women in a that the group approach may be a sustainable way of limited time and, as such, effective communication providing continuity of care (181).

E.4: Community-based interventions to improve communication and support

E.4.1: Facilitated participatory learning and action (PLA) cycles with women’s groups

RECOMMENDATION E.4.1: The implementation of community mobilization through facilitated participatory learning and action (PLA) cycles with women’s groups is recommended to improve maternal and newborn health, particularly in rural settings with low access to health services. Participatory women’s groups represent an opportunity for women to discuss their needs during pregnancy, including barriers to reaching care, and to increase support to pregnant women. (Context-specific recommendation)

Remarks • Part of this recommendation was integrated from WHO recommendations on community mobilization through facilitated participatory learning and action cycles with women’s groups for maternal and newborn health (2014) (183). • The pathways of influence of this multifaceted, context-specific intervention on maternal and newborn outcomes are difficult to assess. Women meeting to identify their needs and seek solutions plays an important role; mechanisms related to additional activities that are organized based on the solutions identified at the meetings may also play a role. • Detailed information and guidance related to the recommendation, including important implementation considerations, can be found in the 2014 WHO recommendations on PLA cycles (183), available at: http://www.who.int/maternal_child_adolescent/documents/community-mobilization-maternal- newborn/en/

Summary of evidence and considerations Meetings were usually held on a monthly basis and specific activities were prioritized according to the Effects of community mobilization through local context and conditions. Coverage of women’s facilitated PLA cycles and women’s groups group meetings ranged from one group per 309 to versus standard care (EB Table E.4.1) one group per 1414 people in the population among The evidence on the effects of community included trials, with the proportion of pregnant mobilization interventions was synthesized for this women attending groups ranging from 2% to 51%. guideline from data derived from a Cochrane review Five out of seven trials were conducted against of health system and community-level interventions a backdrop of context-specific health system for improving ANC coverage and health outcomes strengthening in both intervention and control (175). Seven cluster-RCTs conducted between 1999 arms; these included training of TBAs and provision and 2011, involving approximately 116 805 women, of basic equipment to TBAs and/or primary care contributed data to this comparison. Trials were facilities in four trials. Random effects models were conducted in Bangladesh (2), India (2), Malawi (2) used and sensitivity analyses were performed by and Nepal (1), and six out of seven were conducted including only those trials in which pregnant women in low-resource, rural settings (184–190). The comprised more than 30% of the women’s groups. intervention consisted of involving women (pregnant and non-pregnant) in PLA cycles facilitated by Maternal outcomes trained facilitators, with the aim of identifying, Low-certainty evidence suggests that participatory prioritizing and addressing problems women face women’s groups (PWGs) may reduce maternal around pregnancy, childbirth and after birth, and mortality (7 trials; RR: 0.78, 95% CI: 0.60–1.03). This empowering women to seek care and choose healthy interpretation is confirmed by the sensitivity analysis pregnancy and newborn care behaviours (191). that included only those trials in which the women’s

Chapter 3. Evidence and recommendations 93 94 WHO recommendations on antenatal care for a positive pregnancy experience recommendation onPWGs (183). review formed theevidence basefor the2014 WHO mortality (OR: 0.77, 95% CI:0.65–0.90). The latter evidence thatwomen’s groups reduced neonatal 0.63, 95% CI:0.32–0.94) andmoderate-quality women’s groups reduced maternal mortality (OR: (191), whichprovided low-quality evidence that Findings are consistent witha2013 review ofPWGs Additional considerations visit (3trials;RR:1.77, 95% CI:1.21–2.58). PWGs may increase ANCcoverage ofatleastone more than30%ofthewomen’s groups, suggests that only thosetrialsinwhichpregnant women comprised evidence from thesensitivity analysis, whichincluded (6 trials; RR:1.43, 95% CI:0.81–2.51). However, 0.89–1.22) andANCcoverage ofatleastonevisit facility-based delivery (5trials;RR:1.04, 95% CI: four visits(3trials;RR:1.05, 95% CI:0.78–1.41), have littleornoeffect onANC coverage ofatleast Low-certainty evidence suggests thatPWGs may Coverage outcomes 0.77–0.94). of thewomen’s groups (4 trials;RR:0.85, 95% CI: which pregnant women comprised more than30% sensitivity analysis thatincludedonlythosetrialsin 0.82–1.01). This interpretation isconfirmed by the reduce perinatalmortality (6trials;RR:0.91, 95% CI: Low-certainty evidence suggests thatPWGs may Fetal andneonataloutcomes (4 trials; RR:0.67, 95% CI:0.47–0.95). groups includedmore than30%pregnant women n for Recommendation E.4.2. See the“Summaryofevidence andconsiderations” Resources, Equity, Acceptability andFeasibility 3.E: Background (p. 86). See “Women’s values” atthebeginningofsection Values n as follows: The existing WHOrecommendation onPWGs is local context. high quality implementationadapted to the for closemonitoring andevaluation to ensure different contexts, and recommended theneed mobilization oncare-seeking outcomes in to understand theeffects of community also highlighted theneedfor more research improve thequality ofthehealthservices. It implemented intandemwithstrategies to increase access to healthservices shouldbe advised thatany intervention designedto The GDGthatdeveloped thisrecommendation outcomes)” (183). for maternal mortality andcare-seeking on neonatalmortality, low-quality evidence recommendation; moderate-quality evidence with low access to healthservices (strong newborn inrural health,particularly settings is recommended to improve maternal and learning andactioncycles withwomen’s groups mobilization through facilitated participatory “The implementationofcommunity E.4.2: Community mobilization and antenatal home visits

RECOMMENDATION E.4.2: Packages of interventions that include household and community mobilization and antenatal home visits are recommended to improve antenatal care utilization and perinatal health outcomes, particularly in rural settings with low access to health services. (Context-specific recommendation)

Remarks • The GDG agreed that the extent to which these packages improve communication and support for pregnant women is not clear. • As a stand-alone intervention, the evidence does not support the use of antenatal home visits by lay health workers during pregnancy to improve ANC utilization health outcomes. While the quality and effectiveness of communication during home visits, and the extent to which they increase support for women, is not clear, antenatal home visits may be helpful in ensuring continuity of care across the antenatal, intrapartum and postnatal periods and in promoting other healthy behaviour. • Stakeholders need to be clear that antenatal home visits by lay health workers do not replace ANC visits. • Stakeholders should implement health system strengthening interventions alongside these community- based interventions. • Health-care providers need initial and ongoing training in communication with women and their partners. For women’s groups and community mobilization, providers also need training on group facilitation, in the convening of public meetings and in other methods of communication. • Information for women and community members should be provided in languages and formats accessible to them and programme planners need to ensure that health-care providers/facilitators have reliable supplies of appropriate information materials. • Programme planners should be aware of the potential for additional costs associated with home visits and community mobilization initiatives, including the potential need for extra staff and travel expenses. • When considering the use of antenatal home visits, women’s groups, partner involvement or community mobilization, programme planners need to ensure that these can be implemented in a way that respects and facilitates women’s needs for privacy as well as their choices and their autonomy in decision-making. By offering pregnant women a range of opportunities for contact, communication and support, their individual preferences and circumstances should also be addressed. • Further research is needed on the acceptability and feasibility of mixed-gender communication, the optimal methods for community mobilization, the best model for integration with health systems, continuity elements of home visits, and the mechanisms of effect of these interventions.

Summary of evidence and considerations strengthening occurred in both the intervention and control groups in two of the trials. The focus of Effects of communication and support provided these packages was generally to promote maternal to women through community mobilization and health education, ANC attendance and other care- home visits during pregnancy versus standard seeking behaviour, tetanus toxoid vaccinations care (EB Table E.4.2) and iron and folic acid supplements, and birth and The evidence on the effects of community newborn-care preparedness. Household visits mobilization and antenatal home visits was were performed by trained lay health workers and synthesized from data derived from a Cochrane consisted of at least two visits during pregnancy. review of health system and community-level In two trials, these visits were targeted to occur at interventions for improving ANC coverage and health 12–16 weeks of gestation and 32–34 weeks; in one outcomes (175). Four large cluster-RCTs conducted trial, these visits both occurred in the third trimester; in rural Bangladesh, India and Pakistan contributed and in the fourth trial the timing of the visits was data on packages of interventions involving not specified. Multilevel community mobilization community mobilization and antenatal home visits strategies included advocacy work with community versus no intervention (192–195). Health system stakeholders (community leaders, teachers, and

Chapter 3. Evidence and recommendations 95 96 WHO recommendations on antenatal care for a positive pregnancy experience n Additional considerations CI: 0.87–2.46). 4.59) orfacility-based (3trials;RR:1.46, birth 95% of atleastfour visits(1 trial;RR:1.51, 95% CI:0.50– probably have littleornoeffect onANC coverage moderate-certainty evidence indicates thatthey visit (4 trials;RR:1.76, 95% CI:1.43–2.16). However, home visitsimprove ANCcoverage of atleastone packages withcommunity mobilization andantenatal High-certainty evidence shows thatintervention Coverage outcomes mortality (3trials;RR: 0.65, 95% CI:0.48–0.88). and antenatal homevisitsprobably reduce perinatal intervention packages withcommunity mobilization Moderate-certainty evidence indicates that Fetal andneonatal outcomes CI: 0.44–1.31). effect onmaternal mortality (2trials;RR: 0.76, 95% and antenatal homevisitsprobably have littleorno intervention packages withcommunity mobilization Moderate-certainty evidence indicates that Maternal outcomes women’s meetings. in additionto advocacy work, householdvisitsand emergency transport fundanduselocalvehicles, health committees were encouraged to establishan the intervention package. Inanothertrial,community with transport linkages were of alsosetupaspart packages. Inonetrial,telecommunication systems emergencies was acomponent ofthree intervention to recognize common obstetric andnewborn via bookletsandaudiocassettes. Training ofTBAs intervention package includedhusbandeducation promotion ofANCandother healtheducation.One around pregnancy andearlyneonatalcare, including women focusing onkey knowledge andbehaviour packages includedgroup educationsessions for women, andotherfamily members). Two intervention partners, andhouseholds(husbandsor other respected members), TBAs,husbandsor n of atleastfour visits(4 trials;RR:1.09, 95% CI: have littleornoeffect onANCvisit coverage suggests thatstand-alone antenatal homevisits In brief, evidence ofmoderate- to high-certainty benefits related to theANCguidelineoutcomes. this intervention dueto thelackofevidence of did notmake aseparate recommendation on home visitsasastand-aloneintervention, but The GDGalsoconsidered evidence onantenatal n n n there was reasonably strong evidence for the lower-middle-income countries reported that of maternal andnewborn healthcare inlow- and strategies to improve the utilization and provision A systematic review ofthecost–effectiveness of Resources Background (p. 86). See “Women’s values” atthebeginningofsection3.E: Values n n n childbirth andpostnatalcarechildbirth amongadolescents”: outcome “Increase useofskilledantenatal, recommend thefollowing inrelation to the adolescents indeveloping countries strongly pregnancy andpoorreproductive outcomes among The 2011 WHOguidelinesonPreventing early recommendation: of themotherandnewborn includethefollowing The 2013 WHOrecommendations onpostnatal care Box 3. during pregnancy (198)–theseare presented in improve communication for andsupport women are relevant to community-based interventions to interventions for maternal and newborn health 2015 WHOrecommendations onhealthpromotion Several WHOrecommendations includedinthe – – – supplement). (1 trial;RR:0.88, 95% CI:0.54–1.44) (see Web RR: 0.91, 95% CI:0.79–1.05) andpreterm birth 95% CI:0.87–1.35), perinatalmortality(4 trials; 0.99–1.22), facility-based (4 birth trials;RR:1.08, – – – health facility settings)” (197). adolescents (in household,community and in antenatal care strategies for pregnant “Promote andemergency birth preparedness care.”utilizing skilledchildbirth and otherstakeholders abouttheimportance of “Provide information to allpregnant adolescents utilizing skilledantenatal care.” and otherstakeholders abouttheimportance of “Provide information to allpregnant adolescents CHWs [community healthworkers]” (196). providers orwell trained andsupervised visits canbemadeby midwives, otherskilled system indifferent settings,thesehome remark “Depending ontheexisting health recommendation isaccompanied by the low-quality evidence for mothers).” This on high-quality evidence for newborns and newborn (strong recommendation based recommended for care ofthemotherand “Home visitsinthefirst are birth week after Box 3: Relevant recommendations from the 2015 WHO recommendations on health promotion interventions for maternal and newborn health

Recommendation 1: Birth preparedness and complication readiness interventions are recommended to increase the use of skilled care at birth and to increase the timely use of facility care for obstetric and newborn complications. (Strong recommendation, very low-quality evidence.)

Recommendation 2: Interventions to promote the involvement of men during pregnancy, childbirth and after birth are recommended to facilitate and support improved self-care of women, improved home care practices for women and newborns, and improved use of skilled care during pregnancy, childbirth and the postnatal period for women and newborns. (Strong recommendation, very low-quality evidence.) These interventions are recommended provided that they are implemented in a way that respects, promotes and facilitates women’s choices and their autonomy in decision-making, and supports women in taking care of themselves and their newborns. In order to ensure this, rigorous monitoring and evaluation of implementation is recommended.

Recommendation 3 on interventions to promote awareness of human, sexual and reproductive rights and the right to access quality skilled care: Because of the paucity of evidence available, additional research is recommended. The GDG supports, as a matter of principle, the importance for MNH programmes to inform women about their right to health and to access quality skilled care, and to continue to empower them to access such care.

Recommendation 6 on partnership with traditional birth attendants (TBAs): Where TBAs remain the main providers of care at birth, dialogue with TBAs, women, families, communities and service providers is recommended in order to define and agree on alternative roles for TBAs, recognizing the important role they can play in supporting the health of women and newborns. (Strong recommendation, very low-quality evidence.)

Recommendation 7: Ongoing dialogue with communities is recommended as an essential component in defining the characteristics of culturally appropriate, quality maternity care services that address the needs of women and newborns and incorporate their cultural preferences. Mechanisms that ensure women’s voices are meaningfully included in these dialogues are also recommended. (Strong recommendation, very low-quality evidence.)

Recommendation 11: Community participation in quality-improvement processes for maternity care services is recommended to improve quality of care from the perspectives of women, communities and health-care providers. Communities should be involved in jointly defining and assessing quality. Mechanisms that ensure women’s voices are meaningfully included are also recommended. (Strong recommendation, very low-quality evidence.)

Recommendation 12: Community participation in programme planning, implementation and monitoring is recommended to improve use of skilled care during pregnancy, childbirth and the postnatal period for women and newborns, increase the timely use of facility care for obstetric and newborn complications and improve maternal and newborn health. Mechanisms that ensure women’s voices are meaningfully included are also recommended. (Strong recommendation, very low-quality evidence.)

Source: WHO, 2015 (198).

cost–effectiveness of the use of PLA cycles (199). Equity Estimated costs per life saved for PLA cycle Interventions such as PLA cycles, community interventions alone was US$ 268 and for community mobilization and home visits during pregnancy are mobilization combined with home visits during a way of facilitating dialogue and action with, and pregnancy and/or health system strengthening, empowering, disadvantaged populations to engage in costs ranged from US$ 707 to US$ 1489 per death efforts to improve health and to strengthen broader averted. However, costs of these interventions community support. The women’s groups PLA cycles, are difficult to estimate and depend on context. in particular, were conducted in marginalized areas Costing must also take into account the facilitators’ where other support mechanisms often do not exist. time, training and supervision; these elements are Interventions to engage male partners/husbands and considered key to the quality of implementation and others in the community to support women to make the success of the intervention. healthy choices for themselves and their children

Chapter 3. Evidence and recommendations 97 98 WHO recommendations on antenatal care for a positive pregnancy experience (moderate confidence in the evidence). Qualitative beliefs may differ from conventional understandings services, especially incommunities where traditional in thedesignanddelivery ofinformational-based the importanceofactive community engagement from women andproviders inLMICsalsohighlighted providers (highconfidence inthe evidence). Evidence relationships withotherwomen andhealth-care information andtheopportunityto develop supportive – theopportunityto receive andshare relevant key requirements ofANCfrom awoman’s perspective (22). The useofwomen’s groups islikely to fulfil two respectful manner(highconfidence inthe evidence) providedsupport, they are delivered inacaringand interventions designedto increase communication and variety ofsettingsandcontexts readily engage with Qualitative evidence suggests thatwomen ina Acceptability their partner’s involvement. discuss pregnancy-related andothermatters without have anegative effect for women who would prefer to preferences, asincludingmalepartners could also toengaging consider men,itisimportant women’s may helpto address inequalities.However, when based interventions (200). feasible andmore likely to succeed thanproject- workers andlocalhealthsystems may bemore introduced through existing publicsector health been suggested thatcommunity-based interventions LMICs (highconfidence inthe evidence) (45) extra resources may limitimplementationinsome with homevisitsinterms ofadditionalstaffand the evidence). Similarly, theextra costs associated in someresource-poor settings(highconfidence in facilitative components andthismay beabarrier they may needadditionaltraining to helpwiththe providers are involved infacilitating women’s groups, Qualitative evidence suggests that,where health-care Feasibility evidence) managerial (moderate support confidence inthe a coordinated, organized mannerwithappropriate in theevidence) andtheservices are delivered in provided thatresources are available (highconfidence and offer psychological/emotional to support women willingness to supplypregnancy-related information evidence from providers suggests thatthere isa (45) . . Ithas E.5: Task shifting components of antenatal care delivery

RECOMMENDATION E.5.1: Task shifting the promotion of health-related behaviours for maternal and newborn healtha to a broad range of cadres, including lay health workers, auxiliary nurses, nurses, midwives and doctors is recommended. (Recommended)

RECOMMENDATION E.5.2: Task shifting the distribution of recommended nutritional supplements and intermittent preventive treatment in pregnancy (IPTp) for malaria prevention to a broad range of cadres, including auxiliary nurses, nurses, midwives and doctors is recommended. (Recommended)

Remarks • Recommendations E.5.1 and E.5.2 have been adapted and integrated from Optimizing health worker roles to improve access to key maternal and newborn health interventions through task shifting (OptimizeMNH) (2012) (201). • The GDG noted that, while task shifting has an important role to play in allowing flexibility in health-care delivery in low-resource settings, policy-makers need to work towards midwife-led care for all women. • Lay health workers need to be recognized and integrated into the system, and not be working alone, i.e. task shifting needs to occur within a team approach. • The mandate of all health workers involved in task shifting programmes needs to be clear. • In a separate guideline on HIV testing services (98), WHO recommends that lay providers who are trained and supervised can independently conduct safe and effective HIV testing using rapid tests (see Recommendation B.1.8). • The GDG noted that it may be feasible to task shift antenatal ultrasound to midwives with the appropriate training, staffing, mentoring and referral systems in place. • Further research is needed on the mechanism of effect of MLCC and whether continuity of care can be task shifted. • Further information on this recommendation can be found in the OptimizeMNH guideline (201), available at: http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/978924504843/en/ a Including promotion of the following: care-seeking behaviour and ANC utilization; birth preparedness and complication readiness; sleeping under insecticide- treated bednets; skilled care for childbirth; companionship in labour and childbirth; nutritional advice; nutritional supplements; HIV testing during pregnancy; exclusive breastfeeding; postnatal care and family planning; immunization according to national guidelines.

Chapter 3. Evidence and recommendations 99 100 WHO recommendations on antenatal care for a positive pregnancy experience E.6: Recruitment andretention ofstaff inrural and remote areas • • • Remarks rural andremote areas. (Context-specific recommendation) personal andprofessional interventions support to recruit andretain qualifiedhealth workers in RECOMMENDATION E.6: Policy-makers shouldconsider educational,regulatory, financial,and

retention/guidelines/en/ in theWHOglobalpolicyrecommendations document(202), availablehttp://www.who.int/hrh/ at: Conditional educational,regulatory andfinancial recommendations from thisguidelinecanbe found – – – – – – – – the following. Strong recommendations (abridged) onrecruitment andstaff retention from theabove guidelineinclude policy recommendations (202). publication Increasing access to healthworkers inremote andrural areas through improved retention: global Recommendation E.6 hasbeenadapted andintegrated for theANCguidelinefrom the2010 WHO – – – – – – – – international levels theprofile to lift of working inrural areas. Adopt publicrecognition measures suchasrural healthdays, awards andtitlesatlocal,national professional isolation. rural healthjournals,etc., to improve themorale andstatusof rural providers andreduce feelings of thedevelopmentSupport ofprofessional networks, rural health-care professional associations, necessarily leaving rural areas. health workers canmove upthecareer pathasaresult ofexperience, educationandtraining, without Develop career andsupport development programmes andprovide seniorpostsinrural areas sothat to provide additionalsupport. workers from better-served areas andthoseinunderserved areas, and,where feasible, usetele-health Identify andimplementappropriate outreach activitiesto facilitate cooperation between health supportive supervisionandmentoring. Provide agood andsafe working environment, includingappropriate equipmentandsupplies, (sanitation, electricity, telecommunications, schools,etc.). Improve livingconditions for healthworkers andtheirfamilies andinvest ininfrastructure andservices rural areas soasto enhance thecompetencies ofhealth-care professionals working inrural areas. Revise undergraduate andpostgraduate curriculato includerural healthtopics andclinicalrotations in for various healthdisciplinesand/or establishahealth-care professional schooloutsideofmajorcities. Use targeted admission policiesto enrol studentswitharural background ineducationprogrammes E.7: Antenatal care contact schedules

RECOMMENDATION E.7: Antenatal care models with a minimum of eight contacts are recommended to reduce perinatal mortality and improve women’s experience of care. (Recommended)

Remarks • The GDG stresses that the four-visit focused ANC (FANC) model does not offer women adequate contact with health-care practitioners and is no longer recommended. With the FANC model, the first ANC visit occurs before 12 weeks of pregnancy, the second around 26 weeks, the third around 32 weeks, and the fourth between 36 and 38 weeks of gestation. Thereafter, women are advised to return to ANC at 41 weeks of gestation or sooner if they experience danger signs. Each ANC visit involves specific goals aimed at improving triage and timely referral of high-risk women and includes educational components (12). However, up-to-date evidence shows that the FANC model, which was developed in the 1990s, is probably associated with more perinatal deaths than models that comprise at least eight ANC visits. Furthermore, evidence suggests that more ANC visits, irrespective of the resource setting, is probably associated with greater maternal satisfaction than less ANC visits. • The GDG prefers the word “contact” to “visit”, as it implies an active connection between a pregnant woman and a health-care provider that is not implicit with the word “visit”. In terms of the operationalization of this recommendation, “contact” can be adapted to local contexts through community outreach programmes and lay health worker involvement. • The decision regarding the number of contacts with a health system was also influenced by the following: –– evidence supporting improving safety during pregnancy through increased frequency of maternal and fetal assessment to detect problems; –– evidence supporting improving health system communication and support around pregnancy for women and families; –– evidence from HIC studies indicating no important differences in maternal and perinatal health outcomes between ANC models that included at least eight contacts and ANC models that included more (11–15) contacts (203); –– evidence indicating that more contact between pregnant women and knowledgeable, supportive and respectful health-care practitioners is more likely to lead to a positive pregnancy experience. • Implementation considerations related to this recommendation and the mapping of guideline recommendations to ANC contacts are presented in Chapter 4: Implementation of the ANC guideline and recommendations.

Summary of evidence and considerations RCTs involving more than 50 000 women contributed data. The median number of visits achieved in the Effects of the FANC model (with four visits) FANC arms of these trials ranged from four to five compared with “standard” ANC (with at least visits and the median number of visits achieved in the eight ANC visits planned) (EB Table E.7) standard ANC arms ranged from four to eight visits. The evidence on the effects of FANC (the four-visit ANC model) was derived from a Cochrane review Maternal outcomes on “reduced-visit” ANC models versus “standard” High-certainty evidence shows that FANC had little care models (with at least eight ANC visits planned) or no effect on caesarean section rates (1 trial, 24 526 that included seven RCTs (203). Four individual RCTs women; RR: 1.00, 95% CI: 0.89–1.11), and low- were conducted in HICs (the United Kingdom and the certainty evidence suggests that it may make little or USA) and three large cluster-RCTs were conducted in no difference to maternal mortality (3 trials, 51 504 LMICs, including one conducted in Argentina, Cuba, women; RR: 1.13, 95% CI: 0.5–2.57). Saudi Arabia and Thailand (204), and two conducted in Zimbabwe. The LMIC trials evaluated the FANC With regard to maternal satisfaction, outcomes model compared with “standard” ANC models that were reported narratively in the review, as data were planned for at least eight visits (12). Three cluster- sparse. In a survey conducted among a subset of

Chapter 3. Evidence and recommendations 101 102 WHO recommendations on antenatal care for a positive pregnancy experience n n Additional considerations 95% CI:0.88–1.17). difference to SGA (3trials,43094 women; RR:1.01, suggests thatFANC probably makes littleorno “standard” ANC.Inaddition,low-certainty evidence RR: 1.04, 95% CI:0.97–1.12) compared with and low weight birth (3 trials,46220 women; (3 trials, 47 094 women; RR:0.99, 95% CI: 0.91–1.08) probably haslittleornoeffect onpreterm birth Moderate-certainty evidence indicates thatFANC shown inBox 4. the illustrative impactonperinatalmortality rates are women; RR:1.15, 95% CI:1.01–1.32). BasedonthisRR, with “standard” ANCwithmore visits(3trials,51 323 probably increases perinatalmortality compared Moderate-certainty evidence indicates thatFANC Fetal andneonataloutcomes due to insufficientdata. versus 81%).This evidence was notformally graded visits compared withthestandard model(72.7% less likely to besatisfiedwiththespacingbetween versus 87.2%) andwomen intheFANC modelwere FANC modelthaninthestandard model(77.4% were satisfiedwiththefrequency ofvisitsinthe women intheWHOtrial,fewer participating women n n high-risk populations. compared with“standard” ANCinbothlow- and between 32and36 weeks ofgestation withFANC an increase intheoverall riskofperinatalmortality 18 365 low-risk and6160 high-riskwomen, found trial of perinatalmortality datafrom theWHOFANC asecondaryIn 2012, theWHOundertook analysis the effect persisted in various exploratory analyses. reasons for theeffect onperinatalmortality and The GDGnoted thatthereview authors explored a Based onRR:1.15, 95% CI:1.01–1.32. Box 4:Illustration oftheimpactfocused ANC (FANC) onperinatalmortalityrates (PMR) 50 deathsper1000births 25 deathsper1000births 10 deathsper1000births (“Standard” ANC) Assumed PMR (205). This secondary analysis, which included Illustrative PMR (FANC model) (50–66 deaths) 58 deathsper1000births (25–33 deaths) 29 deathsper1000births (10–13 deaths) 12 deathsper1000births a n n n n n n stillbirths. additional visitsinthethird trimester may prevent analysis ofthe WHOtrialandsuggest that data are consistent withthose from thesecondary i.e. noadditional peaks at30and37 weeks. These a single(andlower) peakat40 weeks ormore, rise intheoverall riskfrom stillbirth 28 weeks, with 28 weeks ofgestation, thelatter showed agradual of ANCthatincludesfortnightly ANCvisitsfrom another SouthAfrica province, whichusesamodel data were compared datafrom withstillbirth third occurring at40 weeks ormore. Whenthese of gestation, anotherataround 37 weeks, andthe wereof stillbirths noted, oneataround 31 weeks gestational age andthree peaks intheoccurrence births). riskwas Stillbirth plotted according to perinatal deaths(givingaPMR of24.8 per1000 more than1000 g,amongwhich there were 3893 data of149 308 ofneonates weighing births from September 2013 to August 2015 comprised implemented theFANC model(206).The audit the Mpumalanga region ofSouthAfrica thathas of atwo-year auditofperinatalmortality from The GDGpanelconsidered unpublishedfindings complications, andto address women’s concerns. a reduced opportunity to detect riskfactors and represent reduced healthprovider contact, and a poorlyexecuted FANC modelmay thensimply in thetrials.However, ifthiselementisneglected, at eachANCvisit,was implemented effectively approach, withregard to improving quality ofcare It isnotclearwhetherthephilosophy oftheFANC may beassociated withincreased preterm birth reduced-visit model(with atleasteightvisits) (203). Low-certainty evidence suggested thatthe models with11–15 visitsfrom four RCTs inHICs of atleasteightvisitsversus “standard” ANC Cochrane review onreduced visitANCmodels The GDGalsoconsidered theevidence from the perinatal deaths Absolute increase in (0–16 deaths) 8 deathsper1000births (0–8 deaths) 4 deathsper1000births (0–3 deaths) 2 deathsper1000births (3 trials; RR: 1.24, 1.01–1.52), but no other important Values effects on health outcomes were noted. In general, See “Women’s values” at the beginning of section however, evidence from these individual studies 3.E: Background (p. 86). also suggests that the reduced-visit models may be associated with lower women’s satisfaction. Resources nnThe GDG considered unpublished evidence from Two trials evaluated cost implications of two four country case studies (Argentina, Kenya, models of ANC with reduced visits, one in the Thailand and the United Republic of Tanzania) United Kingdom and one in two LMICs (Cuba and where the FANC model has been implemented Thailand). Costs per pregnancy to both women and (207). Provider compliance was noted to be providers were lower with the reduced visits models problematic in some settings, as were shortages in both settings. Time spent accessing care was also of equipment, supplies and staff. Integration of significantly shorter with reduced visits models. In the services was found to be particularly challenging, United Kingdom trial, there was an increase in costs especially in settings with a high prevalence of related to neonatal intensive care unit stays in the endemic infections (e.g. malaria, TB, sexually reduced visit model. transmitted infections, helminthiasis). Guidance on implementation of the FANC model in such Equity settings was found to be inadequate, as was the Preventable maternal and perinatal mortality is amount of time allowed within the four-visit model highest among disadvantaged populations, which to provide integrated care. are at greater risk of various health problems, such nnFindings on provider compliance from these case as nutritional deficiencies and infections, that studies are consistent with published findings from predispose women to poor pregnancy outcomes. rural Burkina Faso, Uganda and the United Republic This suggests that, in LMICs, more and better quality of Tanzania (208). Health-care providers in this contact between pregnant women with health-care study were found to variably omit certain practices providers would help to address health inequalities. from the FANC model, including blood pressure measurement and provision of information on Acceptability danger signs, and to spend less than 15 minutes Evidence from high-, medium- and low-resource per ANC visit. Such reports suggest that fitting all settings suggests that women do not like reduced the components of the FANC model into four visits visit schedules and would prefer more contact with is difficult to achieve in some low-resource settings antenatal services (moderate confidence in the where services are already overstretched. In evidence) (22). Women value the opportunity to build addition, in low-resource settings, when the target supportive relationships during their pregnancy (high is set at four ANC visits, due to the various barriers confidence in the evidence) and for some women, to ANC use, far fewer than four visits may actually especially in LMIC settings, the reduced visit schedule be achieved. may limit their ability to develop these relationships, nnProgrammatic evidence from Ghana and Kenya both with health-care professionals and with other indicates similar levels of satisfaction between pregnant women (low confidence in the evidence). FANC and standard ANC, with sources of In some low-income settings where women rely on dissatisfaction with both models being long husbands or partners to financially support their waiting times and costs associated with care (209, antenatal visits, the reduced visit schedule limits 210). their ability to procure additional finance (low nnEmotional and psychosocial needs are variable confidence in the evidence). However, the reduced and the needs of vulnerable groups (including visit schedule may be appreciated by some women adolescent girls, displaced and war-affected in a range of LMIC settings because of the potential women, women with disabilities, women with for cost savings, e.g. loss of domestic income from mental health concerns, women living with HIV, extra clinic attendance and/or associated travel costs sex workers, ethnic and racial minorities, among (low confidence in the evidence). Indirect evidence others) can be greater than for other women. also suggests that women are much more likely to Therefore, the number and content of visits should engage with antenatal services if care is provided be adaptable to local context and to the individual by knowledgeable, kind health-care professionals woman. who have the time and resources to deliver genuine woman-centred care, regardless of the number of

Chapter 3. Evidence and recommendations 103 104 WHO recommendations on antenatal care for a positive pregnancy experience in LMICsfeel thatthereduced visitscheduleisa Qualitative evidence suggests thatsomeproviders Feasibility resource settings. are to allmodelsofANCdelivery pertinent inlow- shortages andinadequate training –issues that availability ofequipmentandresources, staff in someLMICs,highlightsconcerns around the schedules ortheadoptionofFANC issparse and, evidence from providers relating to reduced visit visits (highconfidence inthe evidence). Specific already stretched (208,211). United Republic ofTanzania) where services are especially inLMICs(BurkinaFaso, Uganda andthe components into relatively appointments, short the difficulty ofincorporating allofthe FANC 210). Providers have alsoraised concerns about and training may hamperimplementation(209, that inadequate equipment,supplies,infrastructure Programme reports from GhanaandKenya stress (moderate confidence inthe evidence) (45) deplete limited suppliesofequipmentandmedicine more efficientuseofstaff timeandis less likely to . 4. Implementation of the ANC guideline and recommendations: introducing the 2016 WHO ANC model

The ultimate goal of this guideline and its local context, to allow flexibility in the delivery of the recommendations is to improve the quality recommended interventions. Different to the FANC of ANC and to improve maternal, fetal and model, an additional contact is now recommended newborn outcomes related to ANC. These ANC at 20 weeks of gestation, and an additional three recommendations need to be deliverable within an contacts are recommended in the third trimester appropriate model of care that can be adapted to (defined as the period from 28 weeks of gestation different countries, local contexts and the individual up to delivery), since this represents the period of woman. With the contributions of the members of greatest antenatal risk for mother and baby (see the Guideline Development Group (GDG), WHO Box 5). At these third-trimester contacts, ANC reviewed existing models of delivering ANC with providers should aim to reduce preventable morbidity full consideration of the range of interventions and mortality through systematic monitoring of recommended within this guideline (Chapter 3). maternal and fetal well-being, particularly in relation Recommendation E.7 states that “Antenatal care to hypertensive disorders and other complications models with a minimum of eight contacts are that may be asymptomatic but detectable during this recommended to reduce perinatal mortality and critical period. improve women’s experience of care”; taking this as a foundation, the GDG reviewed how ANC should Box 5: Comparing ANC schedules be delivered in terms of both the timing and content of each of the ANC contacts, and arrived at a new WHO FANC 2016 WHO ANC model – the 2016 WHO ANC model – which replaces model model the previous four-visit focused ANC (FANC) model. For the purpose of developing this new ANC model, First trimester the ANC guideline recommendations were mapped to Visit 1: 8–12 weeks Contact 1: up to 12 weeks the eight contacts based on the evidence supporting Second trimester each recommendation and the optimal timing of delivery of the recommended interventions to achieve Contact 2: 20 weeks Visit 2: 24–26 weeks Contact 3: 26 weeks maximal impact. Third trimester

The 2016 WHO ANC model recommends a minimum Visit 3: 32 weeks Contact 4: 30 weeks of eight ANC contacts, with the first contact Contact 5: 34 weeks scheduled to take place in the first trimester (up to Visit 4: 36–38 weeks Contact 6: 36 weeks 12 weeks of gestation), two contacts scheduled in the Contact 7: 38 weeks Contact 8: 40 weeks second trimester (at 20 and 26 weeks of gestation) and five contacts scheduled in the third trimester (at Return for delivery at 41 weeks if not given birth. 30, 34, 36, 38 and 40 weeks). Within this model, the word “contact” has been used instead of “visit”, as it implies an active connection between a pregnant woman and a health-care provider that is not implicit If the quality of ANC is poor and women’s experience with the word “visit”. It should be noted that the list of it is negative, the evidence shows that women of interventions to be delivered at each contact and will not attend ANC, irrespective of the number of details about where they are delivered and by whom recommended contacts in the ANC model. Thus, (see Table 2) are not meant to be prescriptive but, the overarching aim of the 2016 WHO ANC model rather, adaptable to the individual woman and the is to provide pregnant women with respectful,

Chapter 4. Implementation of the ANC guideline and recommendations 105 106 WHO recommendations on antenatal care for a positive pregnancy experience schedule ofcontacts. for implementationhave notbeenmappedto the research isrequired before they canbeconsidered Context-specific recommendations for whichrigorous for informational purposesandhighlighted ingrey. not recommended have beenincludedinthetable manual aimedatpractitioners. Practices thatare would ofanimplementation beincludedaspart and weight, checkingfor fetal sounds,which heart such asmeasuringbloodpressure, proteinuria table doesnotincludegood clinicalpractices, ofapositivesupport pregnancy experience. This framework for the2016 WHOANCmodelin recommended contacts, thuspresenting asummary recommendations mappedto theeight Table 2shows theWHOANCguideline local context. eight ANCcontacts inways thatare feasible inthe system planners to operationalize therecommended recommendations are intended to encourage health to improving thequality ofcare, thesehealthsystem provision ofquality midwifery care (212).Inaddition shown to besignificantinLMICs,andcanprevent the implement thisguideline.Suchbarriers have been satisfaction willneedto beaddressed to successfully quality ANC;barriers to provider recruitment andjob an impactonthecapacity ofhealthsystems to deliver asproviderimportant, experience andattitudeshave staff (Recommendations E.5.1, andE.6) are E.5.2 also recommendations andrecruitment ontaskshifting of for,support women (Recommendations E.1–E.4). The of care, andimprove communication with,and mainly onthosestrategies thataddress continuity recommendations inthisguidelinehave focused utilization andquality ofANC.The healthsystem a range ofstrategies thatcanimprove the planners to optimize ANCdelivery by employing There are many different ways for health system commodities andempowered health-care providers. integrated service delivery, availability ofsuppliesand strengthening focusing oncontinuity ofcare, of ANCrequires ahealthsystems approach and functioning healthsystem. Effective implementation good clinicalandinterpersonal skillswithinawell byand emotionalsupport, practitioners with relevant andtimelyinformation, andpsychosocial practices (interventions andtests), andprovision of contact, withimplementationofeffective clinical individualized, person-centred care atevery be remembered thatthefour-visit modelhas to ongoing monitoring andevaluation. Itshould implementation ofthemodel, itshouldbesubject equity andtheotherdomains;rather, following ultrasound, onpregnancy outcomes, resources, additional recommended interventions, suchas optimal numberofcontacts, ortheimpactof multicentre trialto beconducted to determine the WHO ANCmodelshouldnotwait for alarge The GDGagreed thatimplementationofthe2016 2016 WHOANCmodel. to theadoption,scale-upandimplementationof at theendofthischapter for considerations related population andhealthsystem. Pleaserefer to Box 6 – may needto beadapted, basedonthelocalcontext, especially related to malaria,tuberculosis andHIV some oftheseANCpractices andinterventions – to highlightthatthefrequency andexact timingof as preterm andpre-eclampsia). birth Itisimportant diagnosis and/or management ofcomplications (such gestational age assessment cancompromise the ANC utilization ishistorically low; lackofaccurate age assessments, especiallyinsettingswhere proportion of pregnancies withaccurate gestational this pragmatic approach inorder to increase the the second contact (20weeks). The GDGsuggests the first contact (up to 12 weeks of gestation) orat scan (i.e. before 24 weeks ofgestation): eitherat to arrangeopportunities asingleearlyultrasound Within the2016 WHOANCmodel,there are two model. transport are alsoessential components ofthisANC way. Aneffective referral system andemergency in arespectful, individualized andperson-centred test results andretests. Communication shouldoccur symptoms, malariaandHIVprevention, andblood tobacco, substance use,caffeine intake, physiological can includehealthy eating,physical activity, nutrition, contacts. Topics for individualized advice andsupport planning options;andthetimingpurposeofANC complication-readiness planning;postnatalfamily supplements andtreatments; birth-preparedness and advice timelyinformation andsupport; ontests, newborns through lifestyle choices; individualized any symptoms; promotion ofhealthy pregnancies and facilitated atallANCcontacts, to cover: presence of next contact. Effective communication shouldbe for any reason, shouldinprinciplebeincludedatthe Any intervention thatismissed atanANCcontact, significantly increased stillbirth risk compared sexual and reproductive health (1). Ensuring that to standard models with eight or more contacts. women’s rights to sexual and reproductive health are Understandably, policy-makers and health-care supported requires meeting standards with regard providers might feel that an increase in the number of to the availability, accessibility, acceptability and ANC contacts with an emphasis on quality of care will quality of health-care facilities, supplies and services increase the burden on already overstretched health (1). Specifically, in addition to other health system systems. However, the GDG agreed that there is likely strengthening initiatives, investment is urgently to be little impact on lives saved or improved without needed to address the shortage and training of substantial investment in improving the quality midwives and other health-care providers able to of ANC services provided in LMICs. International offer ANC. Such investment should be considered a human rights law requires that States use “maximum top priority as quality health care around pregnancy available resources” to realize economic, social and and childbirth has far-reaching benefits for cultural rights, which includes women’s rights to individuals, families, communities and countries.

Chapter 4. Implementation of the ANC guideline and recommendations 107 108 WHO recommendations on antenatal care for a positive pregnancy experience

Table 2: The 2016 WHO ANC model for a positive pregnancy experience: recommendations mapped to eight scheduled ANC contacts

Overarching aim: To provide pregnant women with respectful, individualized, person-centred care at every contact, with implementation of effective clinical practices (interventions and tests), and provision of relevant and timely information, and psychosocial and emotional support, by practitioners with good clinical and interpersonal skills within a well functioning health system. Notes: • These recommendations apply to pregnant women and adolescent girls within the context of routine ANC. • This table does not include good clinical practices, such as measuring blood pressure, proteinuria and weight, and checking for fetal heart sounds, which would be included as part of an implementation manual aimed at practitioners. • Remarks detailed in the shaded box with each recommendation should be taken into account when planning the implementation of these recommendations.

A. Nutritional interventions

Dietary A.1.1: Counselling about healthy eating and keeping physically active Recommended X X X X X X X X interventions during pregnancy is recommended for pregnant women to stay healthy and to prevent excessive weight gain during pregnancy.a A.1.2: In undernourished populations, nutrition education on Context-specific X X X X X X X X increasing daily energy and protein intake is recommended for recommendation pregnant women to reduce the risk of low-birth-weight neonates. A.1.3: In undernourished populations, balanced energy and protein Context-specific X X X X X X X X dietary supplementation is recommended for pregnant women to recommendation reduce the risk of stillbirths and small-for-gestational-age neonates. A.1.4: In undernourished populations, high-protein supplementation Not recommended is not recommended for pregnant women to improve maternal and perinatal outcomes. Iron and folic acid A.2.1: Daily oral iron and folic acid Recommended X X X X X X X X supplements supplementation with 30 mg to 60 mg of elemental ironb and 400 µg (0.4 mg) of folic acidc is recommended for pregnant women to prevent maternal anaemia, puerperal sepsis, low birth weight, and preterm birth.d

a. A healthy diet contains adequate energy, protein, vitamins and minerals, obtained through the consumption of a variety of foods, including green and orange vegetables, meat, fish, beans, nuts, whole grains and fruit. b. The equivalent of 60 mg of elemental iron is 300 mg of ferrous sulfate hepahydrate, 180 mg of ferrous fumarate or 500 mg of ferrous gluconate. c. Folic acid should be commenced as early as possible (ideally before conception) to prevent neural tube defects. d. This recommendation supersedes the previous recommendation found in the 2012 WHO publication Guideline: daily iron and folic acid supplementation in pregnant women (36). 8 X X X (40 (40 weeks) 7 X X X (38 weeks) 6 X X X (36 weeks) 5 X X X (34 weeks) 4 X X X (30 weeks) (weeks of gestation) (weeks 3 X X X (26 (26 weeks) Eight scheduled ANC contacts Eight scheduled ANC contacts 2 X X X (20 weeks) 1 X X X (12 weeks) Type of Type (research) Context-specific Context-specific Context-specific Context-specific Context-specific Context-specific recommendation recommendation recommendation recommendation recommendation Not recommended Not recommended recommendation i 5% of women in a population have a history of night blindness in their most recent pregnancy in the previous 3–5 years that ended in a live birth, or if that ended in a live 3–5 years in the previous pregnancy in their most recent of night blindness a history in a population have 5% of women f Recommendation g (2.8 mg) of folic acid once weekly weekly acid once of folic and 2800 µ g (2.8 mg) e g to prevent night blindness. prevent to h In populations with low dietary calcium intake, daily calcium A.3: dietary calcium intake, In populations with low elemental calcium) oral supplementation (1.5–2.0 g the risk of reduce to women pregnant for is recommended pre-eclampsia. pregnant for A supplementation is only recommended Vitamin A.4: public health vitamin A deficiency is a severe where in areas women problem, is only recommended women pregnant A.5: Zinc supplementation for research. of rigorous in the context for supplementation is not recommended Multiple micronutrient A.6: and perinatal outcomes. maternal improve to women pregnant supplementation is not recommended B6 (pyridoxine) Vitamin A.7: and perinatal outcomes. maternal improve to women pregnant for Intermittent oral iron and folic acid supplementation with 120 and folic A.2.2: iron oral Intermittent mg of elemental iron is recommended for pregnant women to improve maternal and maternal improve to women pregnant for is recommended side-effects, due to is not acceptable if daily iron neonatal outcomes among pregnant and in populations with an anaemia prevalence than 20%. of less women mol/L. Determination of vitamin A deficiency as a public health problem involves estimating the prevalence of deficiency in a population by using of deficiency in a population estimating the prevalence involves of vitamin A deficiency as a public health problem µ mol/L. Determination < 0.70 level a serum retinol have women 20% of pregnant The equivalent of 120 mg of elemental iron equals 600 mg of ferrous sulfate heptahydrate, 360 mg of ferrous fumarate or 1000 mg of ferrous gluconate. or 1000 mg of ferrous fumarate 360 mg of ferrous heptahydrate, sulfate equals 600 mg of ferrous of 120 mg elemental iron equivalent The (55) . women in non-anaemic pregnant acid supplementation and folic iron WHO publication Guideline: intermittent in the 2012 recommendation the previous supersedes recommendation This WHO in the 2013 found recommendation the previous and supersedes and eclampsia (57) of pre-eclampsia and treatment prevention for WHO recommendations with the 2011 is consistent recommendation This (38) . women in pregnant supplementation publication Guideline: calcium if public health problem A deficiency is a severe Vitamin (60) . women in pregnant A supplementation WHO publication Guideline: vitamin in the 2011 found recommendation the previous supersedes recommendation This specific biochemical and clinical indicators of vitamin A status. specific biochemical and clinical indicators

Calcium supplements A Vitamin supplements Zinc supplements Multiple micronutrient supplements B6 Vitamin (pyridoxine) supplements Iron and folic acid and folic Iron supplements

Type of Type intervention e. f. g. h. i.

Chapter 4. Implementation of the ANC guideline and recommendations 109 110 WHO recommendations on antenatal care for a positive pregnancy experience

Type of Recommendation Type of Eight scheduled ANC contacts intervention recommendation (weeks of gestation) 1 2 3 4 5 6 7 8 (12 (20 (26 (30 (34 (36 (38 (40 weeks) weeks) weeks) weeks) weeks) weeks) weeks) weeks) Vitamin E and C A.8: Vitamin E and C supplementation is not recommended for Not recommended supplements pregnant women to improve maternal and perinatal outcomes.

Vitamin D A.9: Vitamin D supplementation is not recommended for pregnant Not recommended supplements women to improve maternal and perinatal outcomes.j

Restricting A.10.1: For pregnant women with high daily caffeine intake (more than Context-specific X X X X X X X X caffeine intake 300 mg per day),k lowering daily caffeine intake during pregnancy recommendation is recommended to reduce the risk of pregnancy loss and low-birth- weight neonates.

B. Maternal and fetal assessment l

Anaemia B.1.1: Full blood count testing is the recommended method for Context-specific X X X diagnosing anaemia in pregnancy. In settings where full blood recommendation count testing is not available, on-site haemoglobin testing with a haemoglobinometer is recommended over the use of the haemoglobin colour scale as the method for diagnosing anaemia in pregnancy.

Asymptomatic B.1.2: Midstream urine culture is the recommended method for Context-specific X X X bacteriuria (ASB) diagnosing asymptomatic bacteriuria (ASB) in pregnancy. In settings recommendation where urine culture is not available, on-site midstream urine Gram- staining is recommended over the use of dipstick tests as the method for diagnosing ASB in pregnancy.

j. This recommendation supersedes the previous recommendation found in the 2012 WHO publication Guideline: vitamin D supplementation in pregnant women (75). k. This includes any product, beverage or food containing caffeine (i.e. brewed coffee, tea, cola-type soft drinks, caffeinated energy drinks, chocolate, caffeine tablets). l. Evidence on essential ANC activities, such as measuring maternal blood pressure, proteinuria and weight, and checking for fetal heart sounds, was not assessed by the GDG as these activities are considered to be part of good clinical practice. 8 X X X X (40 (40 weeks) 7 X X X X (38 weeks) 6 X X X X (36 weeks) 5 X X X X (34 weeks) 4 X X X X (30 weeks) (weeks of gestation) (weeks 3 X X X X (26 (26 weeks) Eight scheduled ANC contacts Eight scheduled ANC contacts 2 X X X X (20 weeks) 1 X X X X (12 weeks) Type of Type Recommended Recommended Recommended Context-specific Context-specific recommendation recommendation o q Recommendation m n p 11.1 mmol/L (200 mg/dL) in the presence of diabetes symptoms. of diabetes in the presence mmol/L (200 mg/dL) 11.1 7.0 mmol/L (126 mg/dL) mmol/L (126 7.0 11.1 mmol/L (200 mg/dL) following a 75 g oral glucose load glucose g oral a 75 following mmol/L (200 mg/dL) 11.1 10.0 mmol/L (180 mg/dL) following a 75 g oral glucose load glucose g oral a 75 following mmol/L (180 mg/dL) 10.0 Hyperglycaemia first detected at any time during pregnancy time during pregnancy at any detected first Hyperglycaemia B.1.4: (GDM) or mellitus gestational diabetes as either, should be classified criteria. WHO 2013 to according mellitus in pregnancy, diabetes Health-care providers should ask all pregnant women about women should ask all pregnant providers Health-care B.1.5: second-hand to and exposure use (past and present) their tobacco antenatal and at every in the pregnancy as early possible smoke visit. care about women should ask all pregnant providers Health-care B.1.6: as early (past and present) and other substances their use of alcohol visit. care antenatal and at every in the pregnancy as possible Clinical enquiry about the possibility of intimate partner of intimate enquiry about the possibility Clinical B.1.3: visits care at antenatal considered (IPV) should be strongly violence by be caused or complicated that may conditions when assessing clinical diagnosis and subsequent care, improve to IPV in order response a supportive provide to is the capacity there where the WHO minimum and where appropriate) where (including referral met. are requirements Minimum requirements are: a protocol/standard operating procedure; training on how to ask about IPV, and on how to provide the minimum response or beyond; private setting; confidentiality ensured; system for system ensured; setting; confidentiality private or beyond; the minimum response provide to and on how ask about IPV, to on how training procedure; operating a protocol/standard are: Minimum requirements disclosure. appropriate for allow and time to in place; referral and policy guidelines (86) . WHO clinical against women: violence partner and sexual intimate to violence publication Responding with the 2013 is consistent recommendation This hyperglycaemia of and classification WHO publication Diagnostic criteria the 2013 from and integrated It has been adapted in pregnancy. hyperglycaemia for screening on routine is not a recommendation This met: are criteria of the following if one or more time in pregnancy that GDM should be diagnosed at any , which states (94) in pregnancy detected first mg/dL) mmol/L (92–125 5.1–6.9 plasma glucose • fasting • 1-hour plasma glucose (96) . in pregnancy exposure smoke use and second-hand of tobacco and management the prevention for publication WHO recommendations the 2013 from Integrated . (97) in pregnancy use disorders use and substance and management of substance the identification WHO publication Guidelines for the 2014 from Integrated • 2-hour plasma glucose 8.5–11.0 mmol/L (153–199 mg/dL) following a 75 g oral glucose load. glucose g oral a 75 following mg/dL) mmol/L (153–199 8.5–11.0 plasma glucose • 2-hour met: are criteria of the following should be diagnosed if one or more mellitus in pregnancy Diabetes plasma glucose • fasting plasma glucose • random • 2-hour plasma glucose plasma glucose • 2-hour

Gestational Gestational mellitus diabetes (GDM) Tobacco use Tobacco use Substance Intimate partnerIntimate (IPV) violence Type of Type intervention m. n. o. p. q.

Chapter 4. Implementation of the ANC guideline and recommendations 111 112 WHO recommendations on antenatal care for a positive pregnancy experience

Type of Recommendation Type of Eight scheduled ANC contacts intervention recommendation (weeks of gestation) 1 2 3 4 5 6 7 8 (12 (20 (26 (30 (34 (36 (38 (40 weeks) weeks) weeks) weeks) weeks) weeks) weeks) weeks) Human B.1.7: In high prevalence settings,r provider-initiated testing and Recommended X immunodeficiency counselling (PITC) for HIV should be considered a routine component virus (HIV) and of the package of care for pregnant women in all antenatal care syphilis settings. In low-prevalence settings, PITC can be considered for pregnant women in antenatal care as a key component of the effort to eliminate mother-to-child transmission of HIV, and to integrate HIV testing with syphilis, viral or other key tests, as relevant to the setting, and to strengthen the underlying maternal and child health systems.s

Tuberculosis (TB) B.1.8: In settings where the tuberculosis (TB) prevalence in the Context-specific X general population is 100/100 000 population or higher, systematic recommendation screening for active TB should be considered for pregnant women as part of antenatal care.t

Symphysis-fundal B.2.2: Replacing abdominal palpation with symphysis-fundal height Context-specific X X X X X X X X height (SFH) (SFH) measurement for the assessment of fetal growth is not recommendation measurement recommended to improve perinatal outcomes. A change from what is usually practiced (abdominal palpation or SFH measurement) in a particular setting is not recommended.

Antenatal cardio- B.2.3: Routine antenatal cardiotocographyu is not recommended for Not recommended tocography pregnant women to improve maternal and perinatal outcomes.

r. High-prevalence settings are defined in the 2015 WHO publication Consolidated guidelines on HIV testing services as settings with greater than 5% HIV prevalence in the population being tested (98). Low-prevalence settings are those with less than 5% HIV prevalence in the population being tested. In settings with a generalized or concentrated HIV epidemic, retesting of HIV-negative women should be performed in the third trimester because of the high risk of acquiring HIV infection during pregnancy; please refer to Recommendation B.1.7 for details. s. Adapted and integrated from the 2015 WHO publication Consolidated guidelines on HIV testing services (98). t. Adapted and integrated from the 2013 WHO publication Systematic screening for active tuberculosis: principles and recommendations (105). u. Cardiotocography (CTG) is a continuous recording of the fetal heart rate and uterine contractions obtained via an ultrasound transducer placed on the mother’s abdomen. 8 (40 (40 weeks) 7 (38 weeks) 6 (36 weeks) 5 X (34 weeks) 4 (30 weeks) (weeks of gestation) (weeks 3 X (26 (26 weeks) Eight scheduled ANC contacts Eight scheduled ANC contacts 2 X X (20 weeks) 1 X X (12 weeks) Type of Type (research) (research) Recommended Recommended Context-specific Context-specific Context-specific Context-specific Context-specific recommendation recommendation recommendation recommendation Not recommended recommendation v x Recommendation , preventive anthelminthic treatment is anthelminthic treatment , preventive w One ultrasound scan before 24 weeks of gestation (early (early of gestation weeks 24 scan before B.2.4: One ultrasound estimate to women pregnant for is recommended ultrasound) anomalies and multiple of fetal detection improve age, gestational and pregnancy, post-term induction of labour for reduce pregnancies, experience. pregnancy a woman’s improve Routine Doppler ultrasound examination is not recommended is not recommended examination B.2.5: Doppler ultrasound Routine and perinatal outcomes. maternal improve to women pregnant for recommended for pregnant women after the first trimester as part trimester after of the first women pregnant for recommended programmes. reduction infection worm A seven-day antibiotic regimen is recommended for all pregnant all pregnant for is recommended antibiotic regimen A seven-day C.1: persistent prevent to (ASB) bacteriuria with asymptomatic women birth birth weight. and low preterm bacteriuria, Antibiotic prophylaxis is only recommended to prevent recurrent recurrent prevent to is only recommended C.2: Antibiotic prophylaxis of rigorous in the context women in pregnant infections urinary tract research. with anti-D immunoglobulin in non- C.3: prophylaxis Antenatal of at 28 and 34 weeks women pregnant Rh-negative sensitized in is only recommended RhD alloimmunization prevent to gestation research. of rigorous the context In endemic areas C.4: Doppler ultrasound technology evaluates umbilical artery (and other fetal arteries) waveforms to assess fetal well-being in the third trimester of pregnancy. trimester in the third well-being fetal assess to waveforms arteries) umbilical artery (and other fetal evaluates technology Doppler ultrasound helminths. soil-transmitted with any of infection than 20% prevalence with greater Areas (140) . in high-risk groups helminth infections soil-transmitted control to chemotherapy WHO publication Guideline: preventive with the 2016 Consistent

Ultrasound scan Ultrasound Doppler of fetal ultrasound blood vessels C. Preventive measures C. Preventive Antibiotics for asymptomatic (ASB) bacteriuria Antibiotic to prophylaxis recurrent prevent urinary tract infections anti-D Antenatal immunoglobulin administration Preventive anthelminthic treatment Type of Type intervention v. w. x.

Chapter 4. Implementation of the ANC guideline and recommendations 113 114 WHO recommendations on antenatal care for a positive pregnancy experience

Type of Recommendation Type of Eight scheduled ANC contacts intervention recommendation (weeks of gestation) 1 2 3 4 5 6 7 8 (12 (20 (26 (30 (34 (36 (38 (40 weeks) weeks) weeks) weeks) weeks) weeks) weeks) weeks) Tetanus toxoid C.5: Tetanus toxoid vaccination is recommended for all pregnant Recommended X vaccination women, depending on previous tetanus vaccination exposure, to prevent neonatal mortality from tetanus.y

Malaria C.6: In malaria-endemic areas in Africa, intermittent preventive Context-specific X X X X X X prevention: treatment with sulfadoxine-pyrimethamine (IPTp-SP) is recommendation (13 Intermittent recommended for all pregnant women. Dosing should start in the weeks) preventive second trimester, and doses should be given at least one month apart, treatment in with the objective of ensuring that at least three doses are received.z pregnancy (IPTp)

Pre-exposure C.7: Oral pre-exposure prophylaxis (PrEP) containing tenofovir Context-specific X prophylaxis for disoproxil fumarate (TDF) should be offered as an additional recommendation HIV prevention prevention choice for pregnant women at substantial risk of HIV infection as part of combination prevention approaches.aa

D. Interventions for common physiological symptoms

Nausea and D.1: Ginger, chamomile, vitamin B6 and/or acupuncture are Recommended X X X vomiting recommended for the relief of nausea in early pregnancy, based on a woman’s preferences and available options.

Heartburn D.2: Advice on diet and lifestyle is recommended to prevent and Recommended X X X X X X X X relieve heartburn in pregnancy. Antacid preparations can be used to women with troublesome symptoms that are not relieved by lifestyle modification.

y. This recommendation is consistent with the 2006 WHO guideline on Maternal immunization against tetanus (134). The dosing schedule depends on the previous tetanus vaccination exposure; please refer to Recommendation C.5 for details. z. Integrated from the 2015 WHO publication Guidelines for the treatment of malaria, which also states: “WHO recommends that, in areas of moderate-to-high malaria transmission of Africa, IPTp-SP be given to all pregnant women at each scheduled antenatal care visit, starting as early as possible in the second trimester, provided that the doses of SP are given at least 1 month apart. WHO recommends a package of interventions for preventing malaria during pregnancy, which includes promotion and use of insecticide-treated nets, as well as IPTp-SP” (153). To ensure that pregnant women in endemic areas start IPTp-SP as early as possible in the second trimester, policy-makers should ensure health system contact with women at 13 weeks of gestation. aa. Integrated from the 2015 WHO publication Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV (99). Substantial risk of HIV infection is defined by an incidence of HIV infection in the absence of PrEP that is sufficiently high (> 3% incidence) to make offering PrEP potentially cost-saving (or cost–effective). Offering PrEP to people at substantial risk of HIV infection maximizes the benefits relative to the risks and costs. 8 X X X X X X (40 (40 weeks) 7 X X X X X X (38 weeks) 6 X X X X X X (36 weeks) 5 X X X X X X (34 weeks) 4 X X X X X X (30 weeks) (weeks of gestation) (weeks 3 X X X X X X (26 (26 weeks) Eight scheduled ANC contacts Eight scheduled ANC contacts 2 X X X X X X (20 weeks) 1 X X X X X X (12 weeks) Type of Type (research) Recommended Recommended Recommended Recommended Recommended Context-specific Context-specific Context-specific Context-specific recommendation recommendation recommendation recommendation Recommendation Group antenatal care provided by qualified health-care qualified health-care by provided care antenatal Group Non-pharmacological options, such as compression stockings, stockings, options, such as compression Non-pharmacological D.6: the management can be used for immersion, and water leg elevation based on a woman’s and oedema in pregnancy, veins of varicose options. and available preferences Wheat bran or other fibre supplements can be used to relieve relieve to supplements can be used or other fibre Wheat bran D.5: dietary to respond to fails if the condition in pregnancy constipation options. available and preferences woman’s modification, based on a E.3: Regular exercise throughout pregnancy is recommended to to is recommended pregnancy throughout exercise Regular D.4: a number of different are back and pelvic pain. There low prevent support options that can be used, such as physiotherapy, treatment and available preferences based on a woman’s belts and acupuncture, options. Midwife-led continuity of care models, in which a known midwife midwife models, in which a known of care E.2: continuity Midwife-led the throughout supports a woman midwives of known or small group recommended are and postnatal continuum, intrapartum antenatal, functioning midwifery in settings with well women pregnant for programmes. Magnesium, calcium or non-pharmacological treatment options treatment Magnesium, calcium or non-pharmacological D.3: based on a in pregnancy, of leg cramps the relief can be used for options. and available preferences woman’s It is recommended that each pregnant woman carries her own carries her own woman that each pregnant It is recommended E.1: and of care quality continuity, improve to during pregnancy case notes experience. her pregnancy professionals may be offered as an alternative to individual antenatal as an alternative be offered may professionals depending research, of rigorous in the context women pregnant for care and that the infrastructure and provided preferences on a woman’s available. are care antenatal of group delivery for resources Varicose veins and veins Varicose oedema Constipation Group antenatal antenatal Group care Low back and Low pelvic pain Midwife-led Midwife-led of care continuity Leg cramps Leg E: Health systems interventions to improve utilization and quality of antenatal care of antenatal and quality utilization improve to interventions E: Health systems case Woman-held notes Type of Type intervention

Chapter 4. Implementation of the ANC guideline and recommendations 115 116 WHO recommendations on antenatal care for a positive pregnancy experience

Type of Recommendation Type of Eight scheduled ANC contacts intervention recommendation (weeks of gestation) 1 2 3 4 5 6 7 8 (12 (20 (26 (30 (34 (36 (38 (40 weeks) weeks) weeks) weeks) weeks) weeks) weeks) weeks) Community-based E.4.1: The implementation of community mobilization through Context-specific X X X X X X X X interventions to facilitated participatory learning and action (PLA) cycles with women’s recommendation improve groups is recommended to improve maternal and newborn health, communication particularly in rural settings with low access to health services.ab and support Participatory women’s groups represent an opportunity for women to discuss their needs during pregnancy, including barriers to reaching care, and to increase support to pregnant women.

E.4.2: Packages of interventions that include household and Context-specific X X X X X X X X community mobilization and antenatal home visits are recommended recommendation to improve antenatal care utilization and perinatal health outcomes, particularly in rural settings with low access to health services.

Task shifting E.5.1: Task shifting the promotion of health-related behaviours for Recommended X X X X X X X X components of maternal and newborn healthad to a broad range of cadres, including antenatal care lay health workers, auxiliary nurses, nurses, midwives and doctors is deliveryac recommended.

E.5.2: Task shifting the distribution of recommended nutritional Recommended X X X X X X X X supplements and intermittent preventive treatment in pregnancy (IPTp) for malaria prevention to a broad range of cadres, including auxiliary nurses, nurses, midwives and doctors is recommended.

Recruitment and E.6: Policy-makers should consider educational, regulatory, financial, Context-specific X X X X X X X X retention of staff and personal and professional support interventions to recruit and recommendation in rural and remote retain qualified health workers in rural and remote areas. areasae

Antenatal care E.7: Antenatal care models with a minimum of eight contacts are Recommended X X X X X X X X contact schedules recommended to reduce perinatal mortality and improve women’s experience of care.

ab. Integrated from the 2014 publication WHO recommendations on community mobilization through facilitated participatory learning and action cycles with women’s groups for maternal and newborn health (183). ac. Including promotion of the following: care-seeking behaviour and ANC utilization; birth preparedness and complication readiness; sleeping under insecticide-treated bednets; skilled care for childbirth; companionship in labour and childbirth; nutritional advice; nutritional supplements; other context-specific supplements and interventions; HIV testing during pregnancy; exclusive breastfeeding; postnatal care and family planning; immunization according to national guidelines. ad. Recommendations adapted and integrated from the 2012 WHO guideline on Optimizing health worker roles to improve access to key maternal and newborn health interventions through task shifting (OptimizeMNH) (201). ae. Adapted and integrated from the 2010 WHO publication Increasing access to health workers in remote and rural areas through improved retention: global policy recommendations (202). Box 6: Considerations for the adoption, scale-up and implementation of the 2016 WHO ANC model

Health policy considerations for adoption and scale-up of the model nnThere needs to be a firm government commitment to scale up implementation of ANC services to achieve national coverage at health-care facilitates; national support must be secured for the whole package rather than for specific components, to avoid fragmentation of services. nnIn low-income countries, donors may play a significant role in scaling up the implementation of the model. Sponsoring mechanisms that support domestically driven processes to scale up the whole model are more likely to be helpful than mechanisms that support only a part of the package. nnTo set the policy agenda, to secure broad anchoring and to ensure progress in policy formulation and decision-making, stakeholders should be targeted among both elected and bureaucratic officials. In addition, representatives of training facilities and the relevant medical specialties should be included in participatory processes at all stages, including prior to an actual policy decision, to secure broad support for scaling-up. nnTo facilitate negotiations and planning, information on the expected impact of the model on users, providers (e.g. workload, training requirements) and costs should be assessed and disseminated. nnThe model must be adapted to local contexts and service-delivery settings.

Health system or organizational-level considerations for implementation of the model nnIntroduction of the model should involve pre-service training institutions and professional bodies, so that training curricula for ANC can be updated as quickly and smoothly as possible. nnLong-term planning is needed for resource generation and budget allocation to strengthen and sustain high-quality ANC services. nnIn-service training and supervisory models will need to be developed according to health-care providers’ professional requirements, considering the content, duration and procedures for the selection of providers for training. These models can also be explicitly designed to address staff turnover, particularly in low-resource settings. nnStandardized tools will need to be developed for supervision, ensuring that supervisors are able to support and enable health-care providers to deliver integrated, comprehensive ANC services. nnA strategy for task shifting may need to be developed to optimize the use of human resources. nnTools or “job aids” for ANC implementation (e.g. ANC cards) will need to be simplified and updated with all key information in accordance with the model. nnStrategies will need to be devised to improve supply chain management according to local requirements, such as developing protocols for the procedures of obtaining and maintaining the stock of supplies, encouraging providers to collect and monitor data on the stock levels and strengthening the provider- level coordination and follow-up of medicines and health-care supplies required for implementation of the ANC model.

User-level considerations for implementation of the model nnCommunity-sensitizing activities should be undertaken to disseminate information about the importance of each component of ANC, and pregnant women’s right to attend ANC for their health and the health of their unborn baby. This information should provide details about the timing and content of the recommended ANC contacts, and about the expected user fees. nnIt may be possible to reduce waiting times by reorganizing ANC services and/or client flow.

For specific implementation considerations related to the individual recommendations, see Annex 4.

Chapter 4. Implementation of the ANC guideline and recommendations 117 118 WHO recommendations on antenatal care for a positive pregnancy experience an impactonfuture certainty andsubsequent evidence foroutcomes important islikely to have on interventions with“low” or“very low” certainty methodology interventions evaluated. According to GRADE was rated as“low” or“very low” for anumber of through primaryresearch. The certainty ofevidence knowledgeimportant gaps thatneedto beaddressed Guideline Development Group (GDG) identified During theguidelinedevelopment process, the 5. Research implications Box 7: Priority research questions, by type ofintervention • • • B. Maternal andfetal assessment • • • • • • • • • • • • A. Nutritionalinterventions •

rather thanuniversal testing andtreatment mightbeamore effective strategy? reduce overtreatment ofASB?What isthethreshold prevalence ofASBatwhichtargeted testing andtreatment Can better on-site tests to diagnoseASBbedeveloped to improve accuracy andfeasibility ofASBtesting and other relevant outcomes, includingequity, acceptability, feasibility andantimicrobial resistance? urine testing plusculture confirmation ofurine test, followed by ASBtreatment ifindicated, onpregnancy and What are theeffects ofon-site urine testing (dipsticks or Gram stain)withantibiotic treatment for ASB versus Can better andmore cost–effective on-site tests to diagnoseanaemiabedeveloped? Does vitaminDincrease theriskofpreterm whenit’s birth combined withcalcium? Does vitaminCreduce PROM andimprove maternal andperinataloutcomes? in pregnancy, inzinc-deficientpopulationswithno particularly food strategyfortification in place? preterm SGA, neonatalinfections, birth, perinatalmorbidity)? Whatistheoptimaldoseofzincsupplementation What istheeffect ofzincsupplementationonmaternal outcomes (e.g. infections) andperinataloutcomes (e.g. positive effect onpre-eclampsia andpreterm birth? What istheminimaldoseandoptimalcommencement schedulefor calciumsupplementationto achieve a eclampsia, HELLPsyndrome (haemolysis, elevated liver enzymes,low platelet count) andpreterm birth? What are thebiologicalmechanisms underlyingtherelationships amongcalciumsupplementation,pre- pregnancy? Are there haemoconcentration risks associated withhaemoglobinconcentrations in ofmore than130 g/L Can arapid, less invasive, portable, andfield-friendly test for iron deficiency anaemiabe developed? effects? What isthemostcost-effective iron compound and formulation (coated versus not)in terms ofbenefitsandside- and calcium(or zinc)supplementscompete for absorption? folic acid)?Could micronutrients becombined into asingle,orslow-release, formulation? To whatextent doiron What isthemosteffective, acceptable and feasible regimen of recommended supplements(iron, calciumand and nationalfood production anddistribution,leadto improved maternal andperinatal outcomes? alternatives to energy andprotein supplements,suchascashorvouchers for pregnant women, orimproved local Research isneededatcountry level to better understand thecontext-specific etiologyofunder-nutrition. Do sustainable, reproducible, accessible andadaptableto different cultural settings? Can anintervention package withstandardized guidance onnutritionbedeveloped thatisevidence-based, in LMICs? What are theeffects, feasibility, acceptability andequity implicationsofhealthy eatingand exercise interventions IPV (with appropriate referral) have animpactonmaternal andperinataloutcomes? have animpactonANCattendance? Caninterventions focusing onpartners prevent IPV?Doesenquiryabout Which strategies to enquire aboutandmanage IPVare themosteffective? Dointerventions to enquire aboutIPV , this implies that further research(15), thisimpliesthatfurther listed inasimilarorder to therecommendations. this ANCguideline(i.e. types ofinterventions) andare according to thegrouping oftherecommendations in In improvements inthepregnancy experience ofwomen. equity, befeasible to implement,andcontribute to researchwhether further would belikely to promote and prioritized related research questionsaccording to GDG identifiedknowledge gaps basedonthis concept recommendations related to theseinterventions. The Box 7 , priority research questionsare grouped • What is the prevalence of GDM and diabetes mellitus in pregnancy, according to the new criteria, in various populations and ethnic groups? What are the best screening strategies for GDM and what are the prevalence thresholds at which these are cost-effective? • What is the effect of daily fetal movement counting, such as the use of “count-to-ten” kick charts, in the third trimester of pregnancy on perinatal outcomes in LMICs? • What are the effects and accuracy of SFH measurement to detect abnormal fetal growth and other risk factors for perinatal morbidity (e.g. multiple pregnancy, polyhydramnios) in settings without routine ultrasound? • Can a single routine Doppler ultrasound examination of fetal blood vessels for all pregnant women in the third trimester accurately detect or predict pregnancy complications, particularly IUGR and pre-eclampsia, and lead to improved pregnancy outcomes?

C. Preventive measures

• What are the effects of prophylactic antibiotics to prevent RUTI in pregnancy, compared to monitoring with use of antibiotics only when indicated, on maternal infections, perinatal morbidity and antimicrobial drug resistance? • What is the prevalence of Rh alloimmunization and associated poor outcomes among pregnant women in LMIC settings? Can cost-effective strategies be developed to manage this condition in LMICS and improve equity?

D. Interventions for common physiological symptoms

• What is the prevalence of common physiological symptoms among pregnant women in low-resource settings, and can the offer of treatment of these symptoms reduce health inequality, improve ANC coverage and improve women’s pregnancy experiences? • What is the etiology of leg cramps in pregnancy, and does treatment with magnesium and/or calcium relieve symptoms?

E. Health systems interventions to improve utilization and quality of ANC

• What should be included in women-held case notes, and how can discrepancies across different records be reduced to improve quality of care? • What is the pathway of influence of midwife-led continuity of care (MLCC)? Is it specifically the continuity, the provider–client relationship or the midwifery philosophy that leads to better health outcomes and maternal satisfaction? Can this effect be replicated with other cadres of health-care providers, e.g. auxiliary nurse midwives, nurses, family doctors, etc.? How can ANC in LMICs be structured to incorporate the active ingredients of MLCC, particularly in settings where the number of midwives is very limited? • What are the effects, feasibility and resource implications of MLCC in LMICs? Which models are most feasible (i.e. caseload or team models)? Can a continuity model for group ANC be developed for settings where other MLCC models are not feasible? • Can a group ANC model be developed for LMICs, to provide guidance on the optimal group size, frequency and content of group ANC contacts? • Is group ANC acceptable (data should include the views of women who decline to participate), feasible and cost-effective in LMIC settings? • Are mixed models (group and individual ANC) feasible and acceptable, and are there benefits to mixed models? • What are the effects of group ANC on maternal and perinatal health outcomes, coverage outcomes (ANC contacts and facility-based births), and women’s and providers’ experiences? • Should women with complicated pregnancies also be offered group ANC, for the communication and social support aspects, in addition to receiving specialist care? • How acceptable and feasible are mixed-gender community mobilization groups? What are the optimal methods for community-based interventions to improve communication and support for pregnant women and adolescent girls; to improve integration of community-based mobilization efforts with health systems; and to ensure continuity of care with home visits? What are the mechanisms of effect of these interventions? • Can the 2016 WHO ANC model with a minimum of eight contacts impact the quality of ANC in LMICs, and what is the effect on health, values, acceptability, resources, feasibility and equity parameters?

ANC: antenatal care; ASB: asymptomatic bacteriuria; GDM: gestational diabetes mellitus; IPV: intimate partner violence; LMICs: low- and middle-income countries; MLCC: midwife-led continuity of care; PROM: prelabour rupture of membranes; RUTI: recurrent urinary tract infections; SFH: symphysis-fundal height; SGA: small for gestational age

5. Research implications 119 120 WHO recommendations on antenatal care for a positive pregnancy experience 7 (RHL). and through theWHOReproductive HealthLibrary Newborn, Child andAdolescent Health(MCA), for HealthandDevelopment (NHD) andMaternal, of Reproductive HealthandResearch (RHR),Nutrition available viathewebsites oftheWHODepartments also asaprinted publication.Onlineversions willbe This guidelinewillbeavailable onlinefor download and 6.1 Dissemination recommendations and updatingoftheguideline 6. Dissemination, applicability UN languages for dissemination through theWHO from thispublicationwillbetranslated into thesix The executive summaryandrecommendations accordingly to partners. derivative products to betailored anddisseminated assessment or preventive measures to allow for for example focusing onnutrition,maternal andfetal alignment withthedifferent sectionsoftheguideline, USAID, FIGOand ICM.The briefs willbeorganized in be developed anddisseminated incollaboration and implementation-related contextual issues, will briefs, whichwillhighlighttherecommendations other setfor health-care professionals. These evidence for policy-makers andprogramme managers andthe Two setsofevidence briefs willbedeveloped: oneset implementation. with theteams responsible for policyandprogramme implementation ofthenew 2016 WHOANCmodel, products, whichwillincludeapractical manualfor MCA to share therecommendations andderivative ofRHR,NHDand within theWHODepartments Evaluation) instrument (Appraisal ofGuidelinesfor Research & independent criticalappraisal basedontheAGREE (FANC). The guidelinewillbeaccompanied by an developed for theimplementationoffocused ANC associations, usingthesamedistributionlistthatwas collaborating centres, NGOpartnersandprofessional regional and country offices, ministries of health, WHO

RHL isavailable at: 7 Print versions willbedistributed to WHO (213). Technical meetingswillbeheld http://apps.who.int/rhl/en/ has beencreated andrecently launchedby database ofWHOguidelines andrecommendations rights, asearch function withtheability to search the guidelines onsexual andreproductive healthand In aneffort to increase dissemination ofWHO dissemination process. & Child Health(PMNCH) ofthis willalsobepart (IVR) andthePartnership for Maternal, Newborn and Malaria,theInitiative for Vaccine Research and partnerships, suchasHIV/AIDS, Tuberculosis policies. Relevant WHOclusters, departments compliance withWHO’s openaccess andcopyright implementation considerations willbepublished,in presentingarticles therecommendations andkey from allaround theworld. Inaddition,anumberof managers, policy-makers andhealthservice users 3000 subscribers includingclinicians,programme monthly "HRPNews”. This site currently hasover ofRHRofficialDepartment ofthe website aspart The guidelinewillalsobelaunchedontheWHO versions are plannedandhave beenbudgeted for. American HealthOrganization [PAHO]) web-based with theWHORegional Office fortheAmericas/Pan Portuguese andSpanish(thelatter incollaboration and products to bedeveloped. English,French, topics (e.g. nutrition)andallow for focused activities would allow for products to beorganized by different recommendations are upto date. Furthermore, this updated onanongoing basisto ensure thatthe for cross-referenced recommendations to be in auser-friendly format, andwillallow aplatform recommendations by makingthemavailable online the dissemination anduptake oftheguideline professional infographics group. This willfacilitate is planned,whichwillbedeveloped by a guideline, aninteractive web-based version In additionto onlineandprintversions ofthis MCA andNHD. attended by, ofRHR, staffoftheWHODepartments regional offices andduringmeetings organized by, or the Department of RHR.8 The ANC guideline nnlack of effective referral mechanisms and care recommendations will be made available via this new pathways for women identified as needing search function. additional care; nnlack of understanding of the value of newly The Maternal and Perinatal Health and Preventing recommended interventions among health-care Unsafe Abortion team of the WHO Department providers and system managers. of RHR, in collaboration with the Departments of nnlack of health information management systems NHD and MCA and other partners, will support (HMISs) designed to document and monitor national and subnational working groups to adapt recommended practices (e.g. client cards, and implement the guideline. This process will registers, etc.). include the development or revision of existing national guidelines or protocols in line with the WHO Given the potential barriers noted above, a guideline. The GREAT Network (Guideline-driven, phased approach to adoption, adaptation and Research priorities, Evidence synthesis, Application implementation of the guideline recommendations of evidence, and Transfer of knowledge) will be used may be prudent. Various strategies for addressing to bring together relevant stakeholders to identify these barriers and facilitating implementation have and assess the priorities, barriers and facilitators to been suggested in the list of considerations at the end guideline implementation, and to support the efforts of Chapter 4. of stakeholders to develop adaptations and guideline implementation strategies tailored to the local Monitoring and evaluating the impact of context (214). This includes technical support for the guideline local guideline implementers in the development of training manuals, flow charts and quality indicators, The implementation and impact of these as well as participation in stakeholder meetings. recommendations will be monitored at the health- service, regional and country levels, based on clearly defined criteria and indicators that are associated 6.2 Applicability issues with locally agreed targets. In collaboration with the monitoring and evaluation teams of the Anticipated impact of the guideline on the WHO Departments of RHR and MCA, data on organization of ANC country- and regional-level implementation of the recommendations will be collected and evaluated in Effective implementation of the recommendations the short to medium term to evaluate their impact on in this guideline will likely require reorganization of national policies of individual WHO Member States. care and redistribution of health-care resources, Interrupted time series, clinical audits or criterion- particularly in low- and middle-income countries based audits could be used to obtain the relevant (LMICs). The potential barriers to implementation data on the interventions contained in this guideline. include the following: nnlack of human resources with the necessary expertise and skills to implement, supervise and 6.3 Updating the guideline support recommended practices, including client counselling; In accordance with the concept of WHO’s GREAT nnlack of infrastructure to support interventions, e.g. Network, which employs a systematic and continuous lack of power to support ultrasound equipment; process of identifying and bridging evidence gaps nnlack of physical space to conduct individual or following guideline implementation (214), the group-based counselling; proposed guideline will be updated five years nnlack of community understanding of the new after publication unless significant new evidence model of care, particularly around the contact emerges that necessitates earlier revision. The WHO schedule and potentially longer wait times; Steering Group will continue to follow the research nnlack of physical resources, e.g. equipment, test kits, developments in the area of ANC, particularly for supplies, medicines and nutritional supplements; those questions for which no evidence was found and those that are supported by low-quality evidence, where new recommendations or a change in the 8 This can be accessed at: search.optimizemnh.org published recommendation may be warranted,

Chapter 6. Dissemination, applicability and updating 121 122 WHO recommendations on antenatal care for a positive pregnancy experience needed. areas where evidence-based further guidance may be and service users to identifycontroversial orpriority technical experts, healthprofessionals, researchers achieved by performing ascoping exercise among the needfor new guidance onthetopic. This willbe assess thecurrency oftherecommendations and in conjunction withtheWHOSteering Group, will officer (oranotherdesignated WHOstaff person), five-year validity period,the responsible technical As theguidelinenears theendofproposed who.int). ofRHRbyDepartment email(reproductivehealth@ in theupdated version oftheguidelineto theWHO suggestions for additionalquestionsfor inclusion WHO MemberStates. Stakeholders canaddress for additionalguidance may alsobereceived from feedback relevant to future modifications. Requests decisions. This survey willalsohelpingathering guideline have beenimplemented orinfluenced policy adaptation, andwhetherany recommendations inthe status andextent ofin-country utilization and (e.g. professional societies,NGOs) to gauge the through selected respondents ofotheruser groups through WHOregional andcountry offices and the guideline,anonlinesurvey willbeconducted Two years publicationanddissemination of after needed. will bemadeto update therecommendation, as 9 the interactive website for theguideline, recommendation willbepromptly communicated via respectively. Any concern aboutthevalidity ofany

Available at: en/ maternal_perinatal_health/anc-positive-pregnancy-experience/ www.who.int/reproductivehealth/publications/ 9 andplans (RevMan) and dates ofsearches, Cochrane Review Manager systematic reviews, corresponding search strategies of developing thisguideline–includingfullreports of All technical products developed duringtheprocess 10 the antenatal, intrapartum andpostnatalcontinuum. guidance onimproving thequality ofcare throughout delivery, whichwillbeinformed by new WHO on how to improve ANCutilization, quality and updates willaimto includemore recommendations included inupdated ANCguidance. Inaddition,future so thattheappropriate recommendations canbe to develop guidance further around thesetopics GDM, syphilis andhaemoglobinopathies.WHOaims knowledge gaps related to antenatal screening of The guidelinedevelopment process exposed several development. in accordance withtheWHOstandards for guideline process of evidence retrieval, synthesis andgrading exercise attheendoffive years willundergo asimilar Any new questionsidentified following thescoping available. or anotherteam iftheinitialreview team isnolonger applied, possibly by thesamesystematic review team search strategy usedfor theinitialreview willbe question willbeupdated. To update thereview, the the systematic review addressing theprimary recommendationparticular basedonnew evidence, use. Where there are concerns aboutthevalidity ofa shareddepartmental folder for future reference and the GRADEprocess –willbearchived inthe and thebasisfor quality rating ofoutcomes within

For information, further see: 10 filescustomized for priority outcomes, http://www.cochrane.org/revman References

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WHO Steering Group (Geneva, Switzerland) Luz Maria De-Regil Director, Research and Evaluation & Chief Technical A. Metin Gülmezoglu Advisor Coordinator Micronutrient Initiative Department of Reproductive Health and Research Ottawa, Canada Maternal and Perinatal Health & Preventing Unsafe Abortion Team Atf Ghérissi Assistant Professor Matthews Mathai Ecole Supérieure des Sciences et Techniques de la Coordinator Santé de Tunis (ESSTST) Department of Maternal, Newborn, Child and El Manar, Tunisia Adolescent Health Epidemiology, Monitoring and Evaluation Team Gill Gyte Patient Representative Olufemi T. Oladapo Cochrane Pregnancy and Childbirth Group Medical Officer Liverpool Women’s NHS Foundation Trust Department of Reproductive Health and Research Liverpool, United Kingdom Maternal and Perinatal Health & Preventing Unsafe Abortion Team Rintaro Mori Director Juan Pablo Peña-Rosas Department of Health Policy Coordinator National Research Institute for Child Health and Department Nutrition for Health and Development Development Evidence and Programme Guidance Team Tokyo, Japan

Özge Tunçalp Lynnette Neufeld Scientist Director Department of Reproductive Health and Research Monitoring, Learning and Research Maternal and Perinatal Health & Preventing Unsafe Global Alliance for Improved Nutrition (GAIN) Abortion Team Geneva, Switzerland

Lisa M. Noguchi Guideline Development Group (GDG) Senior Maternal Health Advisor Maternal and Child Survival Program Jim Neilson (CHAIR) Washington, DC, USA Dundee, United Kingdom Nafissa Osman Mohammed Ariful Alam Head Programme Coordinator Academic Department of Obstetrics and Gynaecology BRAC Health Nutrition & Population Program Faculty of Medicine BRAC Center Eduardo Mondlane University Dhaka, Bangladesh Maputo, Mozambique

Françoise Cluzeau Erika Ota Associate Director Researcher NICE International National Center for Child Health and Development National Institute for Health and Care Excellence (NICE) Tokyo, Japan London, United Kingdom

Annex 1: External experts and WHO staff 137 138 WHO recommendations on antenatal care for a positive pregnancy experience Cape Town, SouthAfrica Stellenbosch University Faculty ofMedicineandHealthSciences Centre for Evidence-based HealthCare Professor ofClinical Epidemiology&Deputy Director Charles Wisonge Washington, DC,USA Population Council Senior Associate Charlotte Warren Putrajaya, Malaysia Ministry ofHealthMalaysia Nutrition Division Deputy Director (Operations) Rusidah Selamat New Delhi,India Sitaram Institute ofScience Bhartia andResearch Professor Harshpal SinghSachdev West BankandGaza Strip Birzeit University Institute ofCommunity andPublic Health Director Niveen AbuRmeileh Ithaca, NY, USA Cornell University Division ofNutritionalSciences Professor Kathleen Rasmussen Arcadia, SouthAfrica Unit for Maternal andInfant HealthCare Strategies Medical Research Council University ofPretoria Professor Robert Pattinson Santiago, Chile Pontificia Universidad Católica de Chile Faculty ofMedicine ofFamilyDepartment Medicine Family Physician Tomas Pantoja Mumbai, India Obstetrics (FIGO) International Federation ofGynecology and President Chittaranjan Narahari Purandare New York, NY, USA United NationsChildren’s Fund (UNICEF) Nutrition Section Senior Adviser, Micronutrients Roland Kupka Washington, DC,USA USAID Bureau for GlobalHealth Maternal andChild HealthDivision Karen Fogg Seattle, WA, USA Bill &MelindaGates Foundation Senior Program Officer France Donnay Geneva, Switzerland United NationsPopulation Fund (UNFPA) Senior Maternal HealthAdviser Luc deBernis Msida, Malta University ofMalta Faculty ofHealthSciences ofMidwiferyHead ofDepartment International Confederation ofMidwives Rita Borg-Xuereb Porto, Portugal University ofPorto Faculty ofMedicine ofObstetrics andGynaecologyDepartment Associate Professor Diogo Ayres-De-Campos Washington, DC,USA (USAID) United States Agency for International Development Bureau for GlobalHealth Maternal andChild HealthDivision Senior Maternal HealthAdvisor Debbie Armbruster Observers Technical Working Group Ewelina Rogozinska Edgardo Abalos Project Coordinator Vice Director Women’s Health Research Unit Centro Rosarino de Estudios Perinatales (CREP) Queen Mary University of London Rosario, Argentina Barts and The London School of Medicine and Dentistry London, United Kingdom Monica Chamillard Obstetrician and Gynecologist Inger Scheel CREP Senior Researcher Rosario, Argentina Global Health Unit, Norwegian Public Health Institute Oslo, Norway Virginia Diaz Obstetrician and Gynecologist CREP WHO regional offices Rosario, Argentina Regional Office for Africa Soo Downe Leopold Ouedraogo Professor in Midwifery Studies Regional Advisor University of Central Lancashire Research and Programme Development in Preston, Lancashire, United Kingdom Reproductive Health Health Promotion Cluster Kenneth Finlayson Senior Research Assistant Regional Office for the Americas/Pan American Midwifery Studies Health Organization (PAHO) University of Central Lancashire Susan Serruya Preston, Lancashire, United Kingdom Director Latin American Center for Perinatology, Women and Claire Glenton Reproductive Health (CLAP/WR) Senior Researcher Global Health Unit, Norwegian Public Health Institute Regional Office for Europe Oslo, Norway Gunta Lazdane Programme Manager Ipek Gurol-Urganci Sexual and Reproductive Health Division Lecturer in Health Services Research Noncommunicable Diseases and Promoting Health London School of Hygiene & Tropical Medicine through the Life-course London, United Kingdom Regional Office for the Western Pacific Khalid S. Khan Mari Nagai Professor of Women’s Health and Clinical Technical Officer Epidemiology Reproductive and Maternal Health The Blizard Institute Reproductive, Maternal, Newborn, Child and London, United Kingdom Adolescent Health Unit

Theresa Lawrie Regional Office for the Eastern Mediterranean Consultant Karima Gholbzouri Evidence-based Medicine Consultancy Medical Officer Bath, United Kingdom Women’s Reproductive Health

Simon Lewin Regional Office for South-East Asia Senior Researcher Neena Raina Global Health Unit, Norwegian Public Health Institute Coordinator Oslo, Norway Maternal, Child and Adolescent Health

Annex 1: External experts and WHO staff 139 140 WHO recommendations on antenatal care for a positive pregnancy experience Evidence andProgramme Guidance Team NutritionforDepartment HealthandDevelopment Technical Officer Zita Weise Preventing Unsafe Team Abortion Maternal andPerinatal Health& ofReproductiveDepartment HealthandResearch Technical Officer Joshua Vogel Evidence andProgramme Guidance Team NutritionforDepartment HealthandDevelopment Technical Officer Lisa Rogers Evidence andProgramme Guidance Team NutritionforDepartment HealthandDevelopment Epidemiologist Pura Rayco-Solon Preventing Unsafe Team Abortion Maternal andPerinatal Health& ofReproductiveDepartment HealthandResearch Technical Officer Sarah deMasi Policy, PlanningandProgramme Unit Adolescent Health ofMaternal, Newborn,Department Child and Medical Officer, Maternal HealthServices Maurice Bucagu Preventing Unsafe Team Abortion Maternal andPerinatal Health& ofReproductiveDepartment HealthandResearch Consultant Emma Allanson WHO headquarters (Geneva, Switzerland) Montevideo, Uruguay Reproductive Health (CLAP/WR) Latin AmericanCenter for Perinatology, Women and Reproductive Health Advisor Rodolfo Gomez Prague, Czech Republic Mother andChild Perinatal Centre oftheInstitute for theCare of Obstetrician Petr Velebil Beirut, Lebanon American University ofBeirut Faculty ofHealthSciences Department Health Promotion andCommunity Health Associate Professor Tamar Kabakian Ouagadougou, BurkinaFaso Economic andSocialDevelopment (CERFODES) Center for Studies,Research andTraining for Director General Yacouba Yaro External reviewers Approach Recommendation relevant to ANC was adapted for, and for, adapted ANC was to relevant Recommendation the ANC guideline. into, integrated in the ANC guideline supersedes recommendation New guideline. in this 2011 the recommendation consistency for Cross-checked Referenced and for, adapted ANC was to relevant Recommendation the ANC guideline. into, integrated in the ANC guideline supersedes recommendation New guideline. in this 2012 the recommendation in the ANC guideline supersedes recommendation New guideline. in this 2012 the recommendation in the ANC guideline supersedes recommendation New guideline. in this 2012 the recommendation the into integrated ANC was to relevant Recommendation ANC guideline. consistency for Cross-checked in the ANC guideline supersedes recommendation New guideline. in this 2013 the recommendation WHO department responsible Department of Nutrition for Health and Department of Nutrition for (NHD) Development Health and Department of Reproductive (RHR) Research and Child Department Newborn, of Maternal, Health (MCA) Adolescent RHR, MCA RHR, Departmentand Adolescent MCA, of Child Safer Making Pregnancy Health (CAH), RHR RHR, MCA NHD, RHR, MCA NHD, RHR, MCA NHD, Various WHO departments and regional WHO departments and regional Various representatives. and Management, Diseases Prevention Chronic RHR RHR NHD 2011 2011 2011 2013 2013 2013 2012 2012 2012 2012 2010 Year of Year publication Increasing access to health workers in remote and in remote health workers to access Increasing global policy retention: improved through areas rural recommendations women Guideline: vitamin A supplementation in pregnant of and treatment prevention for WHO recommendations and eclampsia pre-eclampsia and poor reproductive early pregnancy Preventing outcomes roles optimizing health worker WHO recommendations: health and newborn maternal key to access improve to task shifting (OptimizeMNH) through interventions women Guideline: vitamin D supplementation in pregnant acid supplementation and folic iron Guideline: intermittent women in non-anaemic pregnant acid supplementation in and folic Guideline: daily iron women pregnant hyperglycaemia of and classification Diagnostic criteria in pregnancy detected first and sexual partner intimate to violence Responding women against violence women Guideline: calcium supplementation in pregnant

WHO guideline title 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Annex 2: Other WHO guidelines with recommendations relevant to routine ANC routine to relevant 2: Other WHO guidelines with recommendations Annex

Annex 2: Other WHO guidelines 141 142 WHO recommendations on antenatal care for a positive pregnancy experience

WHO guideline title Year of WHO department responsible Approach publication 12. Systematic screening for active tuberculosis: principles and 2013 Strategic and Technical Advisory Group for Recommendation relevant to ANC was integrated into the recommendations Tuberculosis ANC guideline.

13. WHO recommendations for the prevention and 2013 Department of Prevention of Noncommunicable Recommendations relevant to ANC were integrated into management of tobacco use and second-hand smoke Diseases the ANC guideline. exposure in pregnancy

14. Guidelines for the identification of substance use and 2014 Department of Mental Health and Substance Recommendation relevant to ANC was integrated into the substance use disorders in pregnancy Abuse ANC guideline.

15. WHO recommendations on community mobilization 2014 MCA Referenced through facilitated participatory learning and action cycles with women’s groups for maternal and newborn health

16. Guidelines for the treatment of malaria 2015 Global Malaria Programme Recommendation relevant to ANC was integrated into the ANC guideline.

17. Guideline on when to start antiretroviral therapy and on 2015 Department of HIV Recommendation relevant to ANC was integrated into the pre-exposure prophylaxis for HIV ANC guideline.

18. Consolidated guidelines on HIV testing services 2015 Department of HIV Recommendation relevant to ANC was integrated into the ANC guideline.

19. WHO recommendations for prevention and treatment of 2015 RHR Referenced maternal peripartum infections

20. WHO recommendations on health promotion interventions 2015 MCA Referenced and cross-checked for consistency for maternal and newborn health

21. Guideline: preventive chemotherapy to control soil- 2016 WHO Evidence and Programme Guidance Referenced and cross-checked for consistency transmitted helminths in high-risk groups Unit, NHD, Preventive Chemotherapy and Transmission Control, Department of Control of Neglected Tropical Diseases Annex 3: Summary of declarations of interest from the Guideline Development Group (GDG) members and how they were managed

Name Expertise Disclosure of interest Conflict of interest and management Dr Ariful Alam Nutrition, health systems None declared Not applicable

Dr Françoise Cluzeau Evidence synthesis and guideline None declared Not applicable development using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach

Dr Luz Maria De-Regil Nutrition, epidemiology, Full staff employee of the The conflict was not systematic reviews, programme Micronutrient Initiative considered serious enough implementation and part of the working to affect GDG membership group that advised on the or participation in the International Federation of Technical Consultation. Gynecology and Obstetrics (FIGO) recommendations on nutrition.

Dr Atf Ghérissi Systematic reviews, qualitative None declared Not applicable evidence, maternal and perinatal health, community health

Mrs Gill Gyte Patient representative, pregnancy Voluntary work for the The conflict was not and childbirth Cochrane Pregnancy and considered serious enough Childbirth Group, which is to affect GDG membership funded by United Kingdom or participation in the Department of Health. Technical Consultation.

Dr Rintaro Mori Perinatology, neonatology, None declared Not applicable systematic reviews, evidence synthesis and guideline development using GRADE

Prof. Jim Neilson General obstetrics, perinatology, None declared Not applicable gynaecology, systematic reviews, evidence synthesis and guideline development using GRADE

Dr Lynnette Neufeld Micronutrients, programmes, Previous employer received The conflict was not epidemiology funding from the Canadian considered serious enough Government to design and to affect GDG membership implement iron/folic acid or participation in the and other programmes Technical Consultation. related to nutrition during pregnancy; designed demonstration projects with local partners and academic institutions to integrate nutrition actions into antenatal care (ANC).

Prof. Nafissa Osman Obstetrics and gynaecology, None declared Not applicable implementation research

Prof. Bob Pattinson Obstetrics and gynaecology, None declared Not applicable delivery of care, evidence synthesis

Annex 3: Summary of declarations of interest 143 144 WHO recommendations on antenatal care for a positive pregnancy experience Prof. Charles Wisonge Dr Charlotte Warren Dr Tomas Pantoja Dr LisaNoguchi Ms RusidahSelamat Prof. H.P.S. Sachdev Dr Niveen AbuRmeileh Dr KathleenRasmussen Dr Erika Ota delivery ofcare Health systems, systematic reviews, research systematic reviews, implementation Maternal andperinatalhealth, systems Obstetrics andgynaecology, health implementation science Midwifery, delivery ofcare, implementation research community-based programmes, Maternal andinfant nutrition, reviews Paediatrics, nutrition,systematic statistical epidemiology Community andpublichealth, Maternal andchildnutrition guideline development Nutrition, evidence synthesis, None declared None declared None declared and Child Survival Program. supplied by theMaternal delivery; travel costs ANC for increasing facility funded studyongroup Melinda Gates Foundation- Technical advisorto Bill& None declared None declared None declared None declared None declared Not applicable Not applicable Not applicable Technical Consultation. inthe or participation to affect GDGmembership considered seriousenough The conflict was not Not applicable Not applicable Not applicable Not applicable Not applicable Consider Gender issues and cultural and cultural Gender issues of women expectations security food Local on ANC providers for Capacity-building nutrition counselling shifting Task counselling Group-based on ANC providers for Capacity-building nutrition counselling shifting Task counselling Group-based N/A calcium dosing vs of iron Timing dispensing Community-based shifting Task counselling Group-based calcium dosing vs of iron Timing dispensing Community-based shifting Task counselling Group-based guideline existing Referencing dispensing Community-based shifting Task counselling Group-based

• • • • • • • • • • • • • • • • • • • • • Need to have Need to Counselling skills Counselling counselling for and space Time counsel to Time skills Counselling counsel to Time skills Counselling N/A counsel to Time skills Counselling management Commodities counsel to Time skills Counselling management Commodities counsel to Time skills Counselling management Commodities

• • • • • • • • • • • • • • • • Need to do Need to ations for ANC guideline recommendations ations for Counselling Counselling Counselling high If in use, advise against supplementation protein during pregnancy Counselling Dispensing Counselling Dispensing Counselling Dispensing

• • • • • • • • • • Implementation considerations for ANC guideline recommendations for Implementation considerations Need to know Need to Healthy diet and exercise in diet and exercise Healthy local context of overweight Prevalence setting has an If your undernourished population do counselling to How and energy What balanced supplementation protein means locally that What is available this provides If this is in use acid is still and folic iron That recommended in the If dietary calcium is low local population is endemic If night blindness

• • • • • • • • • • Implementation consider

A.1.2. Nutritional education A.1.2. and daily energy on increasing intake protein and energy Balanced A.1.3. supplementation in protein undernourished populations High protein A.1.4 supplementation in undernourished populations acid A.2. and folic Iron supplements A.3. Calcium supplements A supplements Vitamin A.4. A. Nutritional interventions on a Nutritional counselling A.1.1. activity diet and physical healthy Annex 4: Annex

Annex 4: Implementation considerations 145 146 WHO recommendations on antenatal care for a positive pregnancy experience

Implementation considerations for ANC guideline recommendations

Need to know Need to do Need to have Consider

A.10.a Restricting caffeine intake • Whether local women typically • Counselling • Counselling skills • Gender issues and cultural norms for have caffeine in their diet • Time and space for counselling and expectations of women • Task shifting

B. Maternal and fetal assessment

B.1. Maternal assessment

B.1.1. Diagnosing anaemia • What method is in place to • Collect specimens • Capacity to conduct • Switching to full blood count or diagnose anaemia • Follow kit instructions • Kits haemoglobinometer method, if feasible • What method is feasible to • Maintain infection control • Quality assurance/quality control start with standards (QA/QC) for any lab testing • How to interpret and manage • Commodities for treatment

B.1.2. Diagnosing asymptomatic • What method is in to diagnose • Collect specimens • Capacity to conduct • What levels of care are feasible for bacteriuria (ASB) ASB • Follow kit instructions • Kits each type of test, with urine culture and • What method is feasible to • Maintain infection control • QA/QC for any lab testing sensitivity (C&S) being gold standard start standards • Commodities for treatment but dipstick sufficient in facilities • How to interpret and manage without capacity

B.1.3. Enquiry about intimate • Local resources available to • Ask about IPV • Well trained providers on first-line • Forming linkages to supportive and partner violence (IPV) address IPV if identified during • Counselling response social services if not already in place ANC • Resources and referral mechanisms in • How to enquire if WHO place minimum requirements are in • Time to counsel placeb • Sufficient confidential counselling • Country-level guidelines and space policies • Counselling skills

B.1.4. Diagnosing gestational • National guidance/standard • Counselling and testing • Mechanisms and systems for testing • Reference existing guideline diabetes mellitus (GDM) of care and receiving results • Feasibility and acceptability of • Guidelines for management of • Time and space to counsel screening strategies abnormal results • Counselling skills • Information on local context • Commodity management for oral glucose solution and testing supplies • QA/QC • Clinical algorithm

a. Recommendations A.5–A.9 are not included because interventions that are not recommended are excluded from the implementation considerations table. b. Minimum requirements are: a protocol/standard operating procedure; training on how to ask about IPV, and on how to provide the minimum response or beyond; a private setting; confidentiality ensured; system for referral in place; and time to allow for appropriate disclosure. Consider Gender issues and cultural norms for norms for and cultural Gender issues of women and expectations shifting Task guideline existing Referencing and local norms, context Cultural impact of gender questioning in Impact of routine specific settings shifting Task counselling Group-based shifting Task TB clinics track having Consider in the register, as a column pregnancy estimation of the better for allow to of TB in pregnancy. local burden N/A to switching to benefit No proven in settings fundal height measurement in place. not currently where

• • • • • • • • • • • Need to have Need to d Counselling skills Counselling counsel to Time counsel to and space Time skills Counselling testing for Commodities counsel to Time skills Counselling treatment to Linkage N/A N/A

• • • • • • • • • • Need to do Need to Counselling and testing Counselling and testing Counselling the specific WHO guidance to Refer advising are If ANC providers in routine counting daily FM instruct ANC counselling, lack of omit it, due to them to evidence. include GA to Continue growth and fetal assessment SFH or clinical (by assessment palpation) in ANC contacts and documentation

• • • • • • Implementation considerations for ANC guideline recommendations for Implementation considerations c Need to know Need to How to screen/enquire to How on local context Information norms and behaviours Local these risks around the specific WHO to Refer guideline in high women Retest settings or in key prevalence high-risk groups of TB prevalence Population is counting daily FM If routine being advised being used What methods are and gestational growth fetal for assessment (GA) age

• • • • • • • • WHO guidelines for the identification and management of substance use and substance use disorders in pregnancy. Geneva: World Health Organization; 2014 (http://apps.who.int/iris/ 2014 World Health Organization; Geneva: in pregnancy. use disorders use and substance of substance the identification and management WHO guidelines for 2016). 28 September accessed bitstream/10665/107130/1/9789241548731_eng.pdf, accessed (http://apps.who.int/iris/bitstream/10665/84971/1/9789241548601_eng.pdf, 2013 Health Organization; World Geneva: principles and recommendations tuberculosis: active for screening Systematic 2016). 28 September

Screening for alcohol and alcohol for Screening B.1.6. abuse substance HIV testing B.1.7. (TB) Tuberculosis B.1.8. screening height B.2.2. Symphysis-fundal measurement (SFH) Screening for tobacco use tobacco for Screening B.1.5. assessment B.2. Fetal daily fetal Routine B.2.1. counting (FM) movement c. d.

Annex 4: Implementation considerations 147 148 WHO recommendations on antenatal care for a positive pregnancy experience

Implementation considerations for ANC guideline recommendations

Need to know Need to do Need to have Consider

B.2.3. Routine antenatal • If routine antenatal CTG is • If being conducted, instruct • N/A • N/A cardiotocography (CTG) being conducted providers to omit this from practice, due to lack of evidence.

B.2.4. Routine ultrasound scans • Health system level • Health system level • Health system level • Cost – of purchase, maintenance, ––Number and capacity of ––Determine appropriate ––Transportation for women if services training, impact of shifting resources to ultrasound providers to act settings and timeline for are not sufficiently decentralized ultrasound from other key costs as providers and trainers/ introduction of ultrasound ––Cadres with skills to provide quality • Local availability/feasibility of mentors ––Obtain machines services service contracts to support machine ––Number of functional ––Capacity-building plan • Facility level maintenance, especially in areas not machines available and • Provider level ––Machines previously prioritized for ultrasound geographic distribution ––Conduct or refer ––Mechanism to review results and get market development ––Regulations around ––Document results reports • Power supply – availability and stability ultrasound use ––Provide guidance on how to ––Service contracts for machines • Protection from power surges, which ––Cadres – who can perform? estimate GA and delivery ––Surge protection can permanently damage machines ––Available pre-service date (EDD), depending on ––Power supply • Extreme fragility of ultrasound education and other certainty of last menstrual ––Counselling skills transducers (one drop on a concrete certification period (LMP) and estimated ––Security and environmental floor may necessitate purchase of a • Provider level GA at time of ultrasound, protection for costly machine new transducer, costing thousands of ––Training to do anatomy scan e.g. WHO’s Manual of ––Space for machine dollars) or on referral diagnostic ultrasounde and ––Ultrasound gel supply • Relative benefits compared to other ––How to interpret results and the American Institute of ––Staff and supplies to keep equipment interventions do counselling Ultrasound in Medicine clean • Burden to mother (AIUM) guidelinesf • Burden to providers and facility • Creative, alternative models of service delivery that do not burden women with travel and related costs • Feasibility studies in settings without widely available ultrasonography • Studies on quality of ultrasound

B.2.5. Routine Doppler • If routine Doppler ultrasound is • If being conducted, instruct • N/A • Research context ultrasound being conducted providers to omit or consider in the context of research

e. Manual of diagnostic ultrasound, second edition. Geneva: World Health Organization; 2013 (http://www.who.int/medical_devices/publications/manual_ultrasound_pack1-2/en/, accessed 21 October 2016). f. AIUM practice parameter for the performance of obstetric ultrasound examinations. Laurel (MD): American Institute of Ultrasound in Medicine (AIUM); 2013 (http://www.aium.org/resources/guidelines/ obstetric.pdf, accessed 21 October 2016). g Consider Capacity-building for providers in providers for Capacity-building this is an unfamiliar where contexts of – value and practice concept risk of non-treatment, treatment, of antibiotic stewardship/avoidance resistance context Research context Research is routine that this practice Recognize settings; high-resource in many be may evidence more however, needed shifting Task distribution Community-based (QI) improvement quality Consider in coverage activities if gaps dosing schedule in to Refer NOTE: WHO 2006 guideline on maternal tetanus against immunization on task shifting to evidence Emerging distribution community-based receive of ensuring that women Ways gestation of weeks dose at 13 the first

• • • • • • • • • • Need to have Need to h Commodity management Commodity skills Counselling counselling for and space Time of blood-typing Availability management Commodities management Commodities

• • • • • • Need to do Need to Prescribing Counselling omit, if necessary Instruct to Context-specific or omit, depending on Provide context to according vaccine Provide established guidance

• • • • • • Implementation considerations for ANC guideline recommendations for Implementation considerations Need to know Need to What ASB is and how to to What ASB is and how diagnose it being Whether currently performed in the What is practised context of helminth endemicity Local infections status of worm Local infestation-reduction programmes is still this practice That recommended of neonatal prevalence Local tetanus in the specific WHO guideline on malaria See detailed implementation guidance

• • • • • • • • Maternal immunization against tetanus: integrated management of pregnancy and childbirth (IMPAC). Standards for maternal and neonatal care 1.1. Geneva: Department of Making Pregnancy Safer, World Health World Safer, Department of Making Pregnancy Geneva: 1.1. and neonatal care maternal for Standards and childbirth (IMPAC). of pregnancy management integrated tetanus: against immunization Maternal 2016). 28 September accessed 2016). 10 October accessed 2006 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/immunization_tetanus.pdf, Organization; (http://www.who.int/malaria/publications/atoz/9789241549127/en/, 2015 Health Organization; World edition. Geneva: of malaria, third the treatment Guidelines for

Antibiotic prophylaxis to to C.2. Antibiotic prophylaxis urinary tract recurrent prevent infections C.3. anti-D Antenatal immunoglobulin administration anthelminthic Preventive C.4. treatment vaccination toxoid C.5. Tetanus C. Preventive measures C. Preventive ASB Antibiotics for C.1. preventive Intermittent C.6. in pregnancy treatment g. h.

Annex 4: Implementation considerations 149 150 WHO recommendations on antenatal care for a positive pregnancy experience

Implementation considerations for ANC guideline recommendations

Need to know Need to do Need to have Consider

C.7. Pre-exposure prophylaxis • Health system level: status • Health system: capacity- • Commodities management • Best mechanisms for the setting (ANC (PrEP) for HIV prevention of national PrEP guidelines building plan • Time and space for counselling, vs other) and whether they include • Provider level: prescribe and/ confidential dispensing • Stigma associated with ARV use pregnant women, who to or dispense; counselling • Potential social harms to pregnant consider at substantial risk of about the risks, benefits and women, including IPV HIV infection, sociocultural alternatives to continuing to • Pending evidence from the National barriers to antiretroviral use PrEP during pregnancy and Institute of Child Health and Human (ARV) use by HIV-uninfected breastfeeding Development (NICHD) study on safety pregnant women, availability of and feasibility of PrEP in pregnancy providers to counsel and train, • Additional research recommended by availability of ARVs, cost to WHO and others patients, capacity of laboratory • Cost and frequency of stock-outs – to conduct recommended distribution of drug for treatment vs baseline and follow-up renal PrEP function tests • Provider level: how to initiate and follow up, how to recognize renal toxicity, when to discontinue PrEP

D. Interventions for common physiological symptoms

D.1–6 • Cultural norms around • Counselling • Time to counsel • Building ANC providers’ capacity for treatment, harmful vs non- • Counselling skills counselling and listening, woman- harmful practices centered care, etc.

E. Health system interventions to improve utilization and quality of antenatal care

E.1. Woman-held case notes • What is currently being used • Ensure case notes are available • Commodities management • What format is appropriate in the appropriate language • Resources for production • Whether it is necessary to exclude and at the appropriate • Method for retaining a facility copy certain personal information to avoid education level for setting stigmatization • Adapt the case notes according to context • Ensure durable product Consider Strategies to scale up the quality and scale up the quality to Strategies midwives number of practising of care continuity of providing Ways e.g. lay providers, other care through health workers MLCC Whether a caseload or team appropriate model is more context Research of and language format Appropriate communication Whether meetings should include men or separately together and women of range women a Offering communication opportunities for and support, so that their individual can be and circumstances preferences for catered Implementing health system such interventions, strengthening and improving as staff training, supplies, etc. equipment, transport,

• • • • • • • • Need to have Need to A well functioning midwifery functioning midwifery A well programme deal with group to facilities Appropriate well large, to including access sessions, spaces or sheltered rooms, ventilated seating, and a private and adequate individual examination for area facilitation in group trained Providers and communication hold meetings to spaces Group and educationally Culturally e.g. educational material, appropriate videos, flip charts, booklets pictorial cards and/or of supervision and monitoring Ongoing facilitators e.g. additional staff, Resources, for material, for and budget transport initiatives mobilization community

• • • • • • • Need to do Need to Consult all relevant all relevant Consult including human stakeholders, departments and resource bodies professional additional the need for Assess in MLCC training is a well- that there Ensure in system functioning referral place and workload midwife Monitor burnout in evaluating Consider context research in group facilitators Train public convening facilitation, meetings, and communication techniques facilitators sufficient Ensure support to them and resources volunteers/ community Train identify to health workers lay in the women pregnant their and enourage community attendance that the individual Ensure are preferences woman’s to e.g. with regard respected, partner involvment

• • • • • • • • • Implementation considerations for ANC guideline recommendations for Implementation considerations Need to know Need to What model of care is What model of care being used currently sufficient are Whether there midwives of trained numbers are Whether resources or can be shifted to available this model facilitate norms and women’s Cultural group regarding preferences ANC and demographics Community norms cultural stakeholders the key Who are in the community

• • • • • • E.3. ANC Group Community-based E.4. improve to interventions and support communication Midwife-led continuity of E.2. continuity Midwife-led (MLCC) care

Annex 4: Implementation considerations 151 152 WHO recommendations on antenatal care for a positive pregnancy experience

Implementation considerations for ANC guideline recommendations

Need to know Need to do Need to have Consider

E.5. Task shifting components of • Task shifting allows flexibility • Give health workers involved in • Ongoing supervision and monitoring • Refer to specific WHO guideline on ANC delivery in certain contexts, but policy- task shifting a clear mandate • Commodities management task shiftingi makers need to work towards • Ensure that lay health workers MLCC for all women are integrated into the health system and given appropriate supervision

E.6. Recruitment and retention of • Refer to specific WHO guideline on recruitment and retentionj • Many pregnant women prefer receiving staff in rural and remote areas care from women health workers • Personal safety can impact a woman health worker’s decision to apply for, and remain in, rural positions • Rotation of health workers from urban to rural areas and vice versa • Agreeing the terms and period of rural deployment upfront

E.7. ANC contact schedules • Timing and content and of • Secure national support for • Long-term planning and resource • Reorganizing services to reduce waiting ANC contacts increased number of ANC generation times • How to adapt to local settings, contacts • Provider training and supervision for • Other considerations can be found e.g. which context-specific • Conduct community newly introduced interventions in Chapter 4 of the ANC guideline recommendations apply?, sensitizing activities • Updated “job aids” (e.g. ANC case (Implementation of the ANC guideline what can be task shifted? • Involve pre-service training notes) that reflect changes and recommendations) institutions and professional • Updated ANC training curricula and bodies clinical manuals • Assess context-specific • Ongoing supervision and monitoring implications for resources, including staff, infrastructure, equipment, etc.

i. WHO recommendations: optimizing health worker roles to improve access to key maternal and newborn health interventions through task shifting. Geneva: World Health Organization; 2012 (www.optimizemnh. org, accessed 10 October 2016). j. Increasing access to health workers in remote and rural areas through improved retention: global policy recommendations. Geneva: World Health Organization; 2010 (http://www.who.int/hrh/retention/ guidelines/en/, accessed 10 October 2016).