Rapid Responses to:

EDITORIALS: Sjúrpur F Olsen Effect of vitamin A and  carotene supplementation on women's health BMJ 1999; 318: 551-552 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Response to Editorial

Keith P West   (9 July 1999)

Response to Editorial 9 July 1999
Keith P West, Professor Johns Hopkins School of Public Health, Baltimore, MD USA Send response to journal: Re: Response to Editorial	Dear Sir, We appreciate the editorial attention given by Dr. Olsen (1) to our report on the impact of dietary vitamin A or carotene supplementation on mortality related to pregnancy in Nepal (2). The evidence from Nepal does suggest benefit and raises questions. But we think the questions of public health importance are different from those put forth by Dr. Olsen. First, it should be asked whether the effects in Nepal can be replicated to provide the scientific strength needed for nutrition policies and programs to address maternal mortality reduction in malnourished populations. Also, women were continuously supplemented in Nepal. Could a similar decrease be expected with only antenatal and postnatal supplementation, thereby decreasing a need for supplement use throughout the child-bearing years? Could other dietary or micronutrient interventions further lower risk in women or improve birth outcome in their offspring? (3) Which nutrients, how, at what cost (4) and for which groups of women? (3) Attention should be drawn to the unacceptable mortality related to pregnancy suffered by women in rural South Asia, which occurred at rates of 395 and 704 deaths per 100,000 pregnancies in our supplemented and control groups, respectively. Even among intervened women, the risk was about 30 times higher than the average maternal mortality ratio of 13 in industrialized nations (5). What else can be done? Antenatal and obstetric care are essential to reduce morbidity and death (6) but challenges persist on how best to provide these services. In our study district, 96% of all deliveries were at home; 13% were assisted by a trained health worker, and 26% by a traditional birth attendant. The rest were assisted only by family members, relatives and neighbors or, in 4%, no one. The finding from Nepal is likely irrelevant to socioeconomically advanced countries where women are better nourished, have nearly universal access to adequate antenatal and obstetric services, are exposed to fewer infections, and are at lower risk of dying from pregnancy. In such populations where diets are largely adequate in vitamin A (7) women should be cautioned to limit their supplemental vitamin A intake to levels required to meet their recommended dietary allowance (7,8) or that do not exceed limits established for antenatal supplements (4,8,9). Dr. Olsen cautions that a maternal intake of 10,000 IU daily may be teratogenic based on findings from a case-control study among Bostonian women (10). But multiple studies have failed to corroborate this finding (8,11), including our study in which we monitored both the occurrence of birth defects and measured circulating retinoic acid concentrations in women (reports in preparation). The International Vitamin A Consultative Group (IVACG) has provided policy guidance that up to 10,000 IU of vitamin A per day or 25,000 IU per week are safe during pregnancy (9). Our weekly maternal dose of 23,300 IU was within this limit and, thus, should not be construed as a high dose. We wish to address three limitations raised by Dr. Olsen: (a) As we reported, 157 (0.8%) of the 20,119 pregnant women were lost to follow-up after 2 weeks post partum, most likely because they emigrated, including back to their home of origin which may have been outside the study area, after giving birth. We think that the chances of any of these women disappearing because they had died during this lower risk post partum period was very low (ie, even a 3-fold higher risk of death in this group would have yielded a total of 1 death) (b) While there were occasional reports of carotene supplements being chewed, this did not to the knowledge of our 550 staff unmask that treatment arm. We also protected against this type of unmasking by running the trial as 270 separate arms in the field, uniquely coding bottles for each ward in Kathmandu prior to field delivery (a detail removed during editing). (c) The mortality among women with undetected pregnancies (lost early in gestation) can not be separated from non-pregnancy mortality in our study population (manuscript in preparation). The Nepal trial provides evidence that a potentially inexpensive dietary supplement with vitamin A may improve maternal survival in impoverished societies. The nutrients can be provided as low-dose supplements or in food. That carotene had such a pronounced impact should encourage women to consume adequate amounts of local carotenoid- rich vegetables and fruits more often, especially prior, during and following pregnancy. Keith P. West, Jr., Dr.P.H., R.D. for for the NNIPS-2 Study Group Johns Hopkins School of Public Health References 1. Olsen SF. Effect of vitamin A and carotene supplementation on women's health: Evidence from Nepal suggests benefits _ but raises further questions. BMJ 1999;318:551-2. 2. West KP Jr, Katz J, Khatry SK, LeClerq SC, Pradhan EK, Shrestha SR, Connor PB, Dali SM, Christian P, Pokhrel RP, Sommer A. Double blind, cluster randomised trial of low dose supplementation with vitamin A or carotene on mortality related to pregnancy in Nepal. BMJ 1999;318:370-5. 3. Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJN, McGrath N, Mwakagile D, Antelman G, Mbise R, Herrara G, Kapiga S, Willett W, Hunter DJ. Randomized trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet 1998;351:1477-82. 4. Huffman SL, Baker J, Shumann J, Zehner ER. The case for promoting multiple vitamin/mineral supplements for women of reproductive age in developing countries. The Linkages Project, Academy for Educational Development: Wash DC, November 1998. 5. Revised 1990 estimates of maternal mortality: A new approach by WHO and UNICEF. Geneva: World Health Organization, 1996. 6. Maine D. Safe motherhood programs: Options and issues. Center for Population and Family Health, School of Public Health, Faculty of Medicine, Columbia University: New York, 1991. 7. Requirements of vitamin A, iron, folate and vitamin B12. Report of a Joint FAO/WHO Expert Consultation. FAO Food and Nutrition Series No. 23. Food and Agricultural Organization of the United Nations, Rome 1988; p 21. 8. Miller RK, Hendrickx AG, Mills JL, Hummler H, Weigand U-W. Periconceptional vitamin A use: how much is teratogenic? Reproductive Toxicol 1998;12:75-88. 9. Underwood B. IVACG Statement: Safe doses of vitamin a during pregnancy and lactation. The International Vitamin A Consultative Group, ILSI Research Foundation:Washington DC, USA June 1998. 10. Rothman KJ, Moore LL, Singer MR, Nguyen UDT, Mannino S, Milunsky A. Teratogenicity of high vitamin A intake. New Engl J Med 1995;333:1369 -73. 11. Cziezel AE, Rochenbauer M. Prevention of congenital abnormalities by vitamin A. Internat J Vit Nutr Res 1998;68:219-31.