WHO recommendation on zinc supplementation during pregnancy

WHO recommendation on zinc supplementation during pregnancy

 

Recommendation

Zinc supplementation for pregnant women is only recommended in the context of rigorous research.  

(Context-specific recommendation)

 

Publication history

First published: November 2016

Updated: No update planned

Assessed as up-to-date: November 2016

 

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.

 

Background

Pregnancy requires a healthy diet that includes an adequate intake of energy, protein, vitamins and minerals to meet maternal and fetal needs. However, for many pregnant women, dietary intake of vegetables, meat, dairy products and fruit is often insufficient to meet these needs, particularly in low and middle-income countries (LMICs) where multiple nutritional deficiencies often co-exist. In resource poor countries in sub-Saharan Africa, south-central and south-east Asia, maternal undernutrition is highly prevalent and is recognized as a key determinant of poor perinatal outcomes (1). However, obesity and overweight is also associated with poor pregnancy outcomes and many women in a variety of settings gain excessive weight during pregnancy. While obesity has historically been a condition associated with affluence, there is some evidence to suggest a shift in the burden of overweight and obesity from advantaged to disadvantaged populations (2).

Calcium deficiency is associated with an increased risk of pre-eclampsia (3), and deficiencies of other vitamins and minerals, such as vitamin E, C, B6 and zinc, have also been postulated to play a role in pre-eclampsia. Zinc deficiency is associated with impaired immunity (4). Vitamin C intake enhances iron absorption from the gut; however, zinc, iron and other mineral supplements may compete for absorption, and it is unclear whether such interactions have health consequences (4).

 

Methods

The ANC recommendations are intended to inform the development of relevant health-care policies and clinical protocols. These recommendations were developed in accordance with the methods described in the WHO handbook for guideline development (5). In summary, the process included: identification of priority questions and outcomes, retrieval of evidence, assessment and synthesis of the evidence, formulation of recommendations, and planning for the 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 Evaluation (GRADE) (6) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (7) approaches, for quantitative and qualitative evidence, respectively. Up-to-date systematic reviews were used to prepare evidence profiles for priority questions. The DECIDE (Developing and Evaluating Communication Strategies to support Informed Decisions and Practice based on Evidence) (8) framework, an evidence-to-decision tool that includes intervention effects, values, resources, equity, acceptability and feasibility criteria, was used to guide the formulation and approval of recommendations by the Guideline Development Group (GDG) – an international group of experts assembled for the purpose of developing this guideline – at three Technical Consultations between October 2015 and March 2016.

To ensure that each recommendation is correctly understood and applied in practice, the context of all context-specific recommendations is clearly stated within each recommendation, and the contributing experts provided additional remarks where needed.

In accordance with WHO guideline development standards, these recommendations will be reviewed and updated following the identification of new evidence, with major reviews and updates at least every five years.

 

Further information on procedures for developing this recommendation are available here.

 

Recommendation question

For this recommendation, we aimed to answer the following question:

  • For pregnant women (P), does zinc supplementation (I) compared with no intervention or placebo (C) improve maternal and perinatal outcomes (O)?

 

Evidence summary

The evidence was derived from a Cochrane review that included 21 trials involving more than 17 000 women (9). Most studies were conducted in LMICs, including Bangladesh, Chile, China, Egypt, Ghana, Indonesia, the Islamic Republic of Iran, Nepal, Pakistan, Peru and South Africa. Six trials were conducted in Denmark, the United Kingdom and the USA. Daily zinc supplementation was compared with no intervention or placebo. There was a wide variation among trials in terms of trial size (range: 56–4926 women), zinc dosage (range: 5–90 mg per day), nutritional and zinc status at trial entry, initiation and duration of supplementation (starting before conception in one trial, first or second trimester in the majority, or after 26 weeks of gestation in two trials, until delivery), and compliance with treatment.

Maternal outcomes

Moderate-certainty evidence indicates that zinc supplementation probably makes little or no difference to the risk of any maternal infections (3 trials, 1185 women; RR: 1.06; 95% CI: 0.74–1.53). The evidence on caesarean section, pre-eclampsia and side-effects (maternal taste and smell dysfunction) is of very low certainty, and the review did not include anaemia, maternal mortality or maternal satisfaction as review outcomes.

Fetal and neonatal outcomes

Moderate-certainty evidence indicates that zinc supplementation probably makes little or no difference to the risk of having SGA (8 trials, 4252 newborns; RR: 1.02; 95% CI: 0.94–1.11) or low-birthweight neonates (14 trials, 5643 neonates; RR: 0.93, 95% CI: 0.78–1.12). However, low-certainty evidence suggests that zinc supplementation may reduce preterm birth (16 trials, 7637 women; RR: 0.86, 95% CI: 0.76–0.97), particularly in women with presumed low zinc intake or poor nutrition (14 trials, 7099 women; RR: 0.87, 95% CI: 0.77–0.98). Low-certainty evidence suggests that zinc supplementation may have little or no effect on congenital anomalies (6 trials, 1240 newborns; RR: 0.67, 95% CI: 0.33–1.34) and macrosomia (defined in the review as “high birth weight”; 5 trials, 2837 neonates; RR: 1.00, 95% CI: 0.84–1.18). Evidence on perinatal mortality and neonatal sepsis is of very low certainty.

Additional considerations

The trials were clinically heterogeneous, therefore it is unclear what dose and timing of zinc supplementation, if any, might lead to a possible reduction in preterm birth. n There is little or no evidence on side-effects of zinc supplementation. In addition, it is unclear to what extent zinc might compete with iron and/or calcium for absorption. Maternal anaemia was not evaluated in the review.

 Resources

Zinc costs approximately US$ 1.30 for 100 tablets of 20 mg (i.e. less than US$ 3.00 for a 6-month supply based on a daily dose of 20 mg) (10).

Equity

Effective interventions to improve maternal nutrition in disadvantaged populations could help to address health inequalities. A WHO report shows that inequalities in neonatal, infant and child mortality, as well as stunting prevalence, can be demonstrated according to economic status, education and place of residence in LMICs. The prevalence of stunting may be a good indicator of zinc deficiency in LMICs (11).

Acceptability

Qualitative evidence suggests that women in a variety of settings tend to view ANC as a source of knowledge and information and they generally appreciate any professional advice (including dietary or nutritional) that may lead to a healthy baby and a positive pregnancy experience (high confidence in the evidence) (12).

Feasibility

It may be more feasible to fortify food with zinc rather than to provide zinc as a single supplement, particularly in settings with a high prevalence of stunting in children.

 

Further information and considerations related to this recommendation can be found in the WHO guidelines, available at:

http://apps.who.int/iris/bitstream/10665/250796/8/9789241549912-websupplement-eng.pdf?ua=1

 

Implementation considerations

  • The successful introduction of evidence-based policies related to antenatal care into national programmes and health care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of national guidelines or protocols based on this recommendation.
  • The recommendation should be adapted into locally-appropriate documents and tools that are able to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner.
  • An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health care practitioners to enable the use of evidence-based practices.
  • Local professional societies may play important roles in this process and an all-inclusive and participatory process should be encouraged.
  • Antenatal care models with a minimum of eight contacts are recommended to reduce perinatal mortality and improve women’s experience of care. Taking this as a foundation, the GDG reviewed how ANC should be delivered in terms of both the timing and content of each of the ANC contacts, and arrived at a new model – the 2016 WHO ANC model – which replaces the previous four-visit focused ANC (FANC) model. For the purpose of developing this new ANC model, the ANC recommendations were mapped to the eight contacts based on the evidence supporting each recommendation and the optimal timing of delivery of the recommended interventions to achieve maximal impact.

 

Research implications

The GDG identified these priority questions related to this recommendation

  • What is the effect of zinc supplementation on maternal outcomes (e.g. infections) and perinatal outcomes (e.g. preterm birth, SGA, neonatal infections, perinatal morbidity)?
  • What is the optimal dose of zinc supplementation in pregnancy, particularly in zinc-deficient populations with no food fortification strategy in place?

 

Related links

WHO recommendations on antenatal care for a positive pregnancy experience

(2016) - full document and evidence tables

Managing Complications in Pregnancy and Childbirth: A guide for midwives and doctors

Pregnancy, Childbirth, Postpartum and Newborn Care: A guide for essential practice

WHO Programmes: Sexual and Reproductive health

WHO Programmes: Department of Nutrition for Health and Development

Maternal Health

 

References

  1. Tang AM, Chung M, Dong K, Terrin N, Edmonds A, Assefa N et al. Determining a global midupper arm circumference cutoff to assess malnutrition in pregnant women. Washington (DC): FHI 360/Food and Nutrition Technical Assistance III Project (FANTA); 2016 (http:// www.fantaproject.org/sites/default/files/ resources/FANTA-MUAC-cutoffs-pregnantwomen-June2016.pdf, accessed 26 September 2016).
  2. Popkin S, Slining MM. New dynamics in global obesity facing low- and middle-income countries. Obes Rev. 2013;14(2):11–20. doi:10.1111/obr.12102.
  3. Guideline: calcium supplementation in pregnant women. Geneva: World Health Organization; 2013 (http://apps.who.int/iris/ bitstream/10665/85120/1/9789241505376_ eng.pdf, accessed 28 September 2016).
  4. Roohani N, Hurrell R, Kelishadi R, Schulin R. Zinc and its importance for human health: an integrative review. J Res Med Sci. 2013;18(2):144–57.
  5. WHO handbook for guideline development, 2nd edition. Geneva: World Health Organization; 2014 (http://www.who.int/kms/handbook_2nd_ ed.pdf, accessed 6 October 2016).
  6. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
  7. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016).
  8. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
  9. Ota E, Mori R, Middleton P, Tobe-Gai R, Mahomed K, Miyazaki C et al. Zinc supplementation for improving pregnancy and infant outcome. Cochrane Database Syst Rev. 2015;(2):CD000230.
  10. OneHealth Model: intervention treatment assumptions (draft 28 September). Geneva and Glastonbury (CT): United Nations InterAgency Working Group on Costing and the Futures Institute; 2013 (http://avenirhealth. org/Download/Spectrum/Manuals/ Intervention%20Assumptions%202013%20 9%2028.pdf, accessed 4 October 2016).
  11. Roohani N, Hurrell R, Kelishadi R, Schulin R. Zinc and its importance for human health: an integrative review. J Res Med Sci. 2013;18(2):144–57.
  12. Downe S, Finlayson K, Tunçalp Ö, Gülmezoglu AM. Factors that influence the use of routine antenatal services by pregnant women: a qualitative evidence synthesis. Cochrane Database Syst Rev. 2016;(10):CD012392

 

Citation: WHO Reproductive Health Library. WHO recommendation on zinc supplementation during pregnancy (November 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.