Vitamin A supplementation during pregnancy
Since the trials in the review were heterogeneous with regard to type of supplement given, duration of supplement provided and the outcomes measured, their results could not be pooled for meta-analysis. Hence, it is not known whether vitamin A supplementation has an impact on maternal mortality.
RHL Commentary by Okonofua F
1. EVIDENCE SUMMARY
All randomized or quasi-randomized trials that evaluated the effects of vitamin A supplementation in pregnant women were included in the review. However, since the trials in the review were heterogeneous with regard to type of supplement given, duration of supplement provided and the outcomes measured, their results could not be pooled for meta-analysis. Also, the review did not include studies that examined the possible beneficial effects of vitamin A supplementation in HIV pregnant women. The review is unbiased and rigorous, but owing to the limitations of the included trials, the authors could not conclude whether vitamin A supplementation had a clear impact on maternal mortality.
A large study from Nepal examined the effects of vitamin A supplementation on the reduction of pregnancy-related and direct mortality occurring within 12 weeks post partum, including injury-related deaths. The study reported a reduction in mortality for all cases in the supplementation groups (40% in the vitamin A group and 50% in the beta-carotene group). The combined effect of these two forms of supplementation was 44% reduction in pregnancy-related deaths. However, beta-carotene (pro-vitamin A) has significant anti-oxidant properties that are not present in vitamin A. As this may have implications for specific pregnancy complications such as pre-eclampsia/eclampsia, the pooling of the results may not be appropriate.
A nested case-control study within this trial found a significant reduction in night blindness. It could be speculated that this reduced prevalence of night blindness may have accounted for the observed reduction in maternal deaths from physical injuries in the trial.
Fetal or early infant survival was not improved by supplementation.
Three studies examined the effect of vitamin A supplementation on haemoglobin levels. A study from Indonesia showed that in anaemic women (Hb<11.0g/dl), supplementation reduced the proportion of pregnant women with anaemia. After supplementation, the proportion of women who became non-anaemic was 35% in vitamin A supplementation group, 68% in the iron supplemented group, 97% in the group supplemented with both vitamin A and iron, compared with 16% in the placebo group. These results suggest that vitamin A and iron combination may be more effective than either iron or vitamin A alone in treating mild anaemia in pregnancy.
Two studies from Malawi also investigated the effects of vitamin A supplementation on treatment of anaemia in pregnancy. However, rather than the factorial design used in the Indonesian study, this study compared vitamin A supplementation with placebo in a cohort of women already using iron and folic acid as part of routine antenatal care. There was no significant difference in levels of haemoglobin between women receiving vitamin A supplementation and controls. This study also reported high rates of loss to follow-up.
2. RELEVANCE TO UNDER-RESOURCED SETTINGS
2.1. Magnitude of the problem
Vitamin A deficiency is a serious public health problem in Nigeria, as it is in many sub-Saharan African countries. Nigeria has been identified by the World Health Organization as one of the category 1 countries with the highest risk of vitamin A deficiency (1). The prevalence of marginal vitamin A deficiency is reported to be 56% in Nigeria, compared with 33% in South Africa, 66% in Zambia, 57% in Senegal and 20% in Namibia (2). Although pregnant women are suspected to be at higher risk of vitamin A deficiency in these regions, few substantive data on the vitamin A status of pregnant women have been reported from African countries. Also, not known is the prevalence of night blindness as a specific complication of vitamin A deficiency in pregnant women and how it may contribute to maternal mortality.
Several countries in sub-Saharan Africa, with high levels of vitamin A deficiency also have high rates of maternal mortality. Nigeria, Africa’s most populous country, has one of the highest rates of maternal mortality in the developing world. With an estimated maternal mortality ratio of 800 per 100,000 live births and nearly 40,000 annual maternal deaths, Nigeria accounts for close to 10% of global estimates of maternal mortality(3). The leading causes of maternal mortality in Nigeria are primary postpartum haemorrhage, eclampsia and puerperal sepsis, with primary postpartum haemorrhage accounting for up to 50% of reported cases of maternal deaths (4).
2.2. Applicability of the results
The studies from Malawi showed no significant effects of vitamin A supplementation in improving haemoglobin levels, whereas the Indonesian study demonstrated such a benefit. In addition, mortality, which was reported as an outcome measure in Nepal, was not considered in the Malawi studies. Thus, it is difficult to make specific recommendations for applying the intervention in parts of Africa. The differences obtained for the effects of vitamin A supplementation on anaemia may be due to differences in baseline levels of vitamin A in the women, effects of concomitant diseases such as malaria and HIV, and the dose and intensity of vitamin A supplementation. Thus, there is a need to conduct a large multi-country trial of vitamin A supplementation among pregnant women before the results can be applied in Africa and other under-resourced settings.
2.3. Implementation of the intervention
If vitamin A supplementation is proven to be beneficial in improving maternal health in Africa, it will be possible to implement the intervention at the community level. Vitamin A supplementation is already being implemented for children in many African countries, and several food preparations are already being fortified with vitamin A. Since there is already considerable awareness about the benefits of the intervention in children, it would not take too much effort to include pregnant women in additional awareness campaigns. Furthermore, women in several parts of Africa are already used to taking folic acid and iron supplements as well as anti-malarial medications during pregnancy. Thus, in theory it would be feasible to include vitamin A supplement, especially if a once-a-day pill is developed that combines folic acid, iron and vitamin A.
However, the real challenge could be how to reach the large majority of pregnant women who do not use formal antenatal services. Less than 40% of pregnant women in Nigeria register for and use antenatal clinics, while the majority either do not attend antenatal clinics at all or visit traditional birth attendants or faith-based healers. There is therefore the need to develop strategies for involving the community in planning and implementing the intervention or to make antenatal care clinics more widespread, more user friendly and more accessible.
There are currently limited data on the vitamin A status of pregnant women in many African countries. Thus, primary research is needed to determine the prevalence of vitamin A deficiency among pregnant women in African communities and the factors that may predispose them to such deficiency. It is also important to know the prevalence of markers of vitamin A deficiency in pregnant women, such as night-blindness. Additionally, it would be relevant to identify possible associations between vitamin A deficiency in pregnant women and specific obstetric morbidities, especially anaemia, malarial parasitaemia, pre-eclampsia/eclampsia and puerperal sepsis. Any identified positive correlation will enable the generation of appropriate hypotheses linking vitamin A deficiency to specific obstetric morbidities, and provide a framework for intervening with vitamin A in pregnant women.
Finally, intervention research is needed to provide evidence for the effectiveness of vitamin A supplementation or dietary fortification in reducing maternal mortality and specific obstetric morbidities in African women. The safety of such regimens for maternal and neonatal health would also need to be determined. Such research would need to be supplemented with social science research to identify the context under which vitamin A supplementation can be provided to pregnant women in communities with high rates of deficiency.
- Adelekan DA, Adeodu OO. Dietary vitamin A intake and vitamin A status of Nigerian preschool children. Nigerian journal of nutrition and science 1998;18:1-5.
- Vitamin Information Center. Vitamin A: Durban IVACG highlights. Proceedings of XIX International Vitamin A Consultative Group (IVACG International Conference Centre, Durban March 8-1, 1999). Journal of nutrition. 2002. 132 (supplement):2934-2939S.
- Marternal Mortality in 2000: Estimates developed by WHO, UNICEF and UNFPA. http://www.who.int/reproductive- health/publications/maternal_mortality2000/executive_summary.html). Visited on 15 December 2003. .
- Harrison KA. Childbearing, health and social priorities. A survey of 22,774 consecutive hospital births in Zaria, northern Nigeria. British journal of obstetrics and gynaecology 1985;92 (Suppl 5):1-119.
- Harrison KA. Obstetric fistula: one social calamity too many. British journal of obstetrics and gynaecology 1983;90:385-389.
This document should be cited as: Okonofua F. Vitamin A supplementation during pregnancy : RHL commentary (last revised: 15 December 2003). The WHO Reproductive Health Library; Geneva: World Health Organization.