WHO recommendation on multiple micronutrient supplementation during pregnancy

WHO recommendation on multiple micronutrient supplementation during pregnancy

 

Recommendation

Multiple micronutrient supplementation is not recommended for pregnant women to improve maternal and perinatal outcomes.

(Not recommended)

 

Publication history

First published: November 2016

Updated: No update planned

Assessed as up-to-date: November 2016

 

Remarks

  • There is some evidence of additional benefit of MMN supplements containing 13–15 different micronutrients (including iron and folic acid) over iron and folic acid supplements alone, but there is also some evidence of risk, and some important gaps in the evidence. Although the GDG agreed that overall there was insufficient evidence to warrant a recommendation, the group agreed that policymakers in populations with a high prevalence of nutritional deficiencies might consider the benefits of MMN supplements on maternal health to outweigh the disadvantages, and may choose to give MMN supplements that include iron and folic acid.
  • More research is needed to determine which micronutrients improve maternal and perinatal outcomes, and how these can be optimally combined into a single supplement.

 

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), do micronutrient supplements (I) compared with iron and folic acid supplements (C) improve maternal and perinatal outcomes (O)?

 

Evidence summary

The evidence was derived from a Cochrane review that included 17 trials involving 137 791 women (9); however, only 14 trials contributed data to this comparison. These 14 trials were all conducted in LMICs: Bangladesh (2), Burkina Faso (1), China (2), Guinea-Bissau (1), Indonesia (2), Mexico (1), Nepal (2), Niger (1), Pakistan (1) and Zimbabwe (1). The trials compared supplements containing 13–15 micronutrients (including iron and folic acid) with iron and folic acid supplements only, except for one trial in which the control arm comprised iron only. Nine trials evaluated supplements with 15 micronutrients, including vitamin A, B1, B2, B6, B12, C, D and E, copper, folic acid, iodine, iron, niacin, selenium and zinc, with exactly the same dosages as the UN international MMN preparation (UNIMMAP) (10). Evidence from these UNIMMAP trials was synthesized together with trials of 13 and 14 MMN supplements, and in separate subgroup analyses using the random effects method. Subgroup analyses were performed according to the dose of iron (60 mg or 30 mg) used in the control arm.

Maternal outcomes

High-certainty evidence shows that MMN supplementation has a similar effect to iron and folic acid supplements only (standard care) on maternal anaemia (5 trials; RR: 0.98, 95% CI: 0.85–1.13). Compared to iron and folic acid only, moderate-certainty evidence indicates that MMN supplements probably make little or no difference to caesarean section rates (4 trials; RR: 1.03, 95% CI: 0.75–1.43) and low-certainty evidence suggests that they may have little or no effect on maternal mortality (3 trials; RR: 0.97, 95% CI: 0.63–1.48). There was no evidence relating to maternal satisfaction or side-effects.

Fetal and neonatal outcomes

High-certainty evidence shows that MMN supplementation reduces the risk of having a lowbirth-weight neonate compared with iron and folic acid supplements only (14 trials; RR: 0.88, 95% CI: 0.85–0.91), but moderate-certainty evidence indicates that it probably makes little or no difference to the risk of having an SGA neonate (13 trials; RR: 0.98, 95% CI: 0.96–1.00). High-certainty evidence shows that MMN supplements make little or no difference to preterm birth rates (14 trials; RR: 0.95, 95% CI: 0.88–1.03). Moderate-certainty evidence shows that MMN supplements probably make little or no difference to perinatal mortality (11 trials; RR: 1.00, 95% CI: 0.85–1.19), neonatal mortality (11 trials; RR: 0.99, 95% CI: 0.90–1.08) or stillbirths (14 trials; RR: 0.97, 95% CI: 0.86–1.09). The evidence on congenital anomalies is of low certainty and inconclusive (1 trial, 1200 women; RR: 0.99, 95% CI: 0.14–7.00). High-certainty evidence from analyses restricted to trials of UNIMMAP only are consistent with the overall findings, with the exception that it shows that UNIMMAP reduces the risk of having an SGA neonate compared with iron and folic acid supplements only (8 trials; RR: 0.85, 95% CI: 0.77–0.94). Subgroup analyses according to the iron dose in the control group are generally consistent with the overall findings. However, for the subgroup of studies that compared MMN supplements to 60 mg iron and 400 µg folic acid, a harmful effect of MMNs on neonatal mortality cannot be excluded (6 trials; RR: 1.22, 95% CI: 0.95–1.57).

Additional considerations

A separate review of the effects of MMN supplementation during pregnancy on child health benefits pooled data from nine of the trials included in the Cochrane review and found no evidence of beneficial effects on child mortality, growth or cognitive function (11).

Resources

UNIMMAP supplements cost about US$ 3 per woman per pregnancy, whereas iron and folic acid supplementation costs less than US$ 1 (12).

Equity

Effective interventions to improve maternal nutrition in disadvantaged populations could help to address maternal and neonatal health inequalities by improving maternal health and preventing illness related to nutritional deficiencies. However, the cost difference between MMNs and iron and folic acid supplementation may have an impact on affordability for disadvantaged populations, especially those in remote and rural areas, because they are often expected to pay for visits and supplements in addition to bearing greater transport costs due to the greater distance to travel to ANC services (13).

Acceptability

Qualitative evidence suggests that women in a variety of settings tend to view ANC as a source of knowledge and information and that they generally appreciate any advice (including dietary or nutritional) that may lead to a healthy baby and a positive pregnancy experience (high confidence in the evidence) (14). However, it has been noted that the lack of appropriate training on MMN supplementation has been reported by health-care providers as a major gap (13).

Feasibility

From the demand side, MMN supplementation should be as feasible as iron and folic acid supplementation if supplements are free and available, and it will face the same challenges in terms of compliance. However, on the supply side, there may be several barriers to overcome, such as changes in regulatory norms and policies (e.g. tariffs, labelling, imports, government oversight, etc.), ensuring sustainable MMN production (local or imported), product availability and quality. Great variability in feasibility across countries and within them would be expected (13).

 

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 did not identify any priority question related to this recommendation

 

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. Haider BA, Bhutta ZA. Multiple-micronutrient supplementation for women during pregnancy. Cochrane Database Syst Rev. 2015;(11):CD004905.
  10. UNICEF, WHO, United Nations University. Composition of a multi-micronutrient supplement to be used in pilot programmes among pregnancy women in developing countries: report of a United Nations Children’s Fund (UNICEF), World Health Organization (WHO) and United Nations University workshop. New York (NY): UNICEF; 1999 (http://apps.who.int/iris/handle/10665/75358, accessed 18 December 2015).
  11. Devakumar D, Fall CHD, Sachdev HS, Margetts BM, Osmond C, Wells JCK et al. Maternal antenatal multiple micronutrient supplementation for long-term health benefits in children: a systematic review and meta-analysis. BMC Med. 2016;14(1):90. doi:10.1186/s12916- 016-0633-3.
  12. 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).
  13. Technical consultation: multiple micronutrient supplements in pregnancy: implementation considerations for successful integration into existing programmes. Meeting held in collaboration with United Nations Children’s Fund (UNICEF) and the Micronutrient Initiative (MI). Geneva: World Health Organization; 18–20 August 2015 (http://www.who.int/ nutrition/events/2015_meeting_microsupp_ pregnancy_18to20aug/en/, accessed 27 October 2016).
  14. 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 multiple micronutrient supplementation during pregnancy (November 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.