WHO recommendation on vitamin A supplementation during pregnancy

WHO recommendation on vitamin A supplementation during pregnancy

 

Recommendation

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)

 

Publication history

First published: November 2016

Updated: No update planned

Assessed as up-to-date: November 2016

 

Remarks

  • This recommendation supersedes the previous WHO recommendation found in the 2011 Guideline: vitamin A supplementation in pregnant women (1).
  • 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 (2).
  • 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 (3).
  • 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 (1).
  • 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 (1).
  • 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 (4).

 

Background

Anaemia is associated with iron, folate and vitamin A deficiencies. It is estimated to affect 38.2% of pregnant women globally, with the highest prevalence in the WHO regions of South-East Asia (48.7%) and Africa (46.3%), medium prevalence in the Eastern Mediterranean Region (38.9%) and the lowest prevalence in the WHO regions of the Western Pacific (24.3%), the Americas (24.9%) and Europe (25.8%) (2).

Major contributory factors to anaemia include parasitic infections such as malaria, hookworm and schistosomiasis, in areas where these infections are endemic. In addition, chronic infections such as tuberculosis (TB) and HIV, and haemoglobinopathies such as sickle-cell disease, contribute to the prevalence of anaemia. It is estimated that 0.8 million pregnant women globally have severe anaemia (defined as a blood haemoglobin concentration < 70 g/L) (2). In pregnancy, severe anaemia is associated with an increased risk of maternal and infant mortality (3). It is estimated that about half of the anaemia found in pregnant women is amenable to iron supplementation (5); however, this may be quite variable and is likely to be much lower in malaria-endemic areas.

In addition to causing anaemia, iron deficiency adversely affects the use of energy sources by muscles and, thus, physical capacity and work performance, and also adversely affects immune status and morbidity from infections (5). Folate (vitamin B9) deficiency, in addition to anaemia it is also linked to fetal neural tube defects (6). Vitamin A deficiency affects about 19 million pregnant women, mostly in Africa and South-East Asia, causing night blindness (7).

 

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 (8). 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) (9) and Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) (10) 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) (11) 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 vitamin A supplementation (I) compared with no intervention or placebo (C) improve maternal and perinatal outcomes (O)?

 

Evidence summary

The evidence was derived from a Cochrane systematic review of 19 trials of vitamin A (with or without other supplements) compared with no vitamin A (or placebo, or other supplements) involving over 310 000 women (12). All but one trial (conducted in the United Kingdom) were conducted in LMICs, including Bangladesh, China, Ghana, India, Indonesia, Malawi, Nepal, South Africa and the United Republic of Tanzania. Most trials were conducted in vitamin A deficient populations, with one study including only women living with HIV. Trials varied considerably in design, including in the dose and timing of the intervention. Ten trials contributed data to the comparison of vitamin A alone versus placebo or no treatment.

Maternal outcomes

Moderate-certainty evidence shows that vitamin A supplementation in vitamin A deficient populations during pregnancy probably reduces maternal anaemia (3 trials, 15 649 women; RR: 0.64, 95% CI: 0.43– 0.94), but that it probably has little or no effect on WHO recommendations on antenatal care for a positive pregnancy experience 30 maternal mortality (4 trials, 101 574 women; RR: 0.88, 95% CI: 0.65–1.20).

Low-certainty evidence on a composite outcome for maternal infection (including fever for more than one week at one week postnatally, puerperal fever greater than 38°C, subclinical mastitis and/or bacterial vaginosis) suggests that vitamin A supplementation may reduce maternal infection (5 trials, 17 313 women; average RR: 0.45, 95% CI: 0.2–0.99). Side-effects and other maternal ANC guideline outcomes were not reported in the trials.

Fetal and neonatal outcomes

High-certainly evidence shows that vitamin A supplementation makes little or no difference to perinatal mortality (76 176 women; RR: 1.01, 95% CI: 0.95–1.07), neonatal mortality (3 trials, 89 556 neonates; RR: 0.97, 95% CI: 0.90–1.05) or stillbirths (2 trials, 122 850 neonates; RR: 1.04, 95% CI: 0.98–1.10). Moderate-certainty evidence indicates that vitamin A supplementation probably has little or no effect on low birth weight (< 2500 g) (4 trials, 14 599 neonates; RR: 0. 1.02, 95% CI: 0.89–1.16), and low-certainty evidence suggests that it may have little or no effect on preterm birth (5 trials, 40 137 women; RR: 0.98, 95% CI: 0.94–1.01). Neonatal infections and congenital anomalies were not reported in the trials.

Additional considerations

Moderate-certainty evidence shows that vitamin A supplementation reduces night blindness in pregnant women living in areas with a high prevalence of this condition (2 trials, approximately 100 000 women; RR: 0.79, 95% CI: 0.64–0.98). Miscarriage and teratogenicity have been associated with high vitamin A intake within 60 days of conception; however, a WHO expert group consultation in 1998 concluded that daily doses of up to 3000 µg per day after day 60 are probably safe, especially in areas where vitamin A deficiency is common (4).

Resources

Vitamin A supplements are relatively inexpensive at approximately US$ 0.30 per woman per month (10 000 IU per day or 25 000 IU per week) (13). Vitamin A can be given as a daily or weekly supplement.

Equity

Effective nutritional interventions in disadvantaged populations could help to address health inequalities by improving nutritional status and promoting good maternal health.

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).

Feasibility

Qualitative evidence shows that where there are additional costs associated with supplements (high confidence in the evidence) or where the recommended intervention is unavailable because of resource constraints (low confidence in the evidence), women may be less likely to engage with ANC.

 

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 most effective, acceptable and feasible regimen of recommended supplements (iron, calcium and folic acid)? Could micronutrients be combined into a single, or slow-release, formulation? To what extent do iron and calcium (or zinc) supplements compete for absorption?
  • What is the most cost-effective iron compound and formulation (coated versus not) in terms of benefits and side effects?
  • Can a rapid, portable, less invasive, and field-friendly test for iron deficiency anaemia be developed?
  • Are there haemoconcentration risks associated with haemoglobin concentrations of more than 130 g/L in pregnancy?

 

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. Guideline: vitamin A supplementation in pregnant women. Geneva: World Health Organization; 2011 (http://apps.who.int/iris/bitstream/10665/44625/1/9789241501781_eng.pdf, accessed 29 September 2016).
  2. Sommer A, Davidson FR. Assessment and control of vitamin A deficiency: the Annecy Accords. J Nutr. 2002;132:2845S-50S.
  3. Healthy diet. Fact sheet No. 394. Geneva: World Health Organization; 2015 (http://www.who.int/mediacentre/factsheets/fs394/en/, accessed 1 November 2016).
  4. Safe vitamin A dosage during pregnancy and lactation. Recommendations and report of a consultation. Micronutrient series. Geneva: World Health  Organization; 1998 (WHO/NUT/98.4; http://apps.who.int/iris/bitstream/10665/63838/1/WHO_NUT_98.4_eng.pdf, accessed 29 September 2016).
  5. Guideline: intermittent iron and folic acid supplementation in non-anaemic pregnant women. Geneva: World Health Organization; 2012 http://apps.who.int/iris/bitstream/10665/75335/1/9789241502016_eng.pdf, accessed 28 September 2016).
  6. The global prevalence of anaemia in 2011.Geneva: World Health Organization; (http://apps.who.int/iris/bitstream/10665/177094/1/9789241564960_eng.pdf,... 29 September 2016).
  7. Global prevalence of vitamin A deficiency in populations at risk 1995–2005. WHO Global Database on vitamin A deficiency. Geneva: World Health Organization; 2009 (http://www. who.int/nutrition/publications/micronutrients/ vitamin_a_deficiency/9789241598019/en/, accessed 29 September 2016).
  8. 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).
  9. GRADE [website]. The GRADE Working Group; 2016 (http://gradeworkinggroup.org/, accessed 27 October 2016).
  10. GRADE-CERQual [website]. The GRADECERQual Project Group; 2016 (https://cerqual. org/, accessed 27 October 2016).
  11. The DECIDE Project; 2016 (http://www.decide-collaboration.eu/, accessed 27 October 2016).
  12. McCauley ME, van den Broek N, Dou L, Othman M. Vitamin A supplementation during pregnancy for maternal and newborn outcomes. Cochrane Database Syst Rev. 2015;(10):CD008666.
  13. 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).
  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 vitamin A supplementation during pregnancy (November 2016). The WHO Reproductive Health Library; Geneva: World Health Organization.