Kawai K, Kupka R, Mugusi F, Aboud S, Okuma J, Villamor E, Spiegelman D, Fawzi WW. A randomized trial to determine the optimal dosage of multivitamin supplements to reduce adverse pregnancy outcomes among HIV-infected women in Tanzania. Am J Clin Nutr. 2010 Feb;91(2):391-7.
Pregnant women who are infected with the human immunodeficiency virus (HIV), compared with those who are not, are at greater risk of adverse pregnancy outcomes.(1) In turn, low birth weight is associated with higher infant mortality rates, stunting, and impaired mental development.(2) Women infected with HIV often suffer from malnutrition and micronutrient deficiencies. Therefore, multivitamins given to HIV-infected pregnant women could improve fetal growth and survival rates.(3) A placebo-controlled trial in Tanzania showed that HIV-infected pregnant women who took multivitamins gave birth to fewer low-weight and preterm infants.(4)
To determine whether multiple doses compared with single doses of the Recommended Dietary Allowance (RDA) of multivitamins can decrease the risk of adverse outcomes of pregnancy among HIV-infected women in Africa
Double blind randomized controlled trial
Antenatal clinics in Dar es Salaam, Tanzania
Pregnant women who are HIV-infected, between 12 and 27 weeks of gestation at enrollment, living in Dar es Salaam, and available for follow-up
Between November 2002 and June 2004, 1129 women were enrolled and randomly assigned to receive either single or multiple RDA multivitamins until six weeks after delivery. Multiple supplements included 3x higher doses of Vitamin E, 7x higher doses of Vitamin C, and >10x higher doses of B-vitamins than the RDA. Vitamin A and zinc were not included. Women in both arms received daily iron (60 mg), folic acid (0.25 mg), and malaria prophylaxis with sulfadoxine-pyrimethamine, and a single dose of nevirapine (NVP) 200 mg at onset of labor; infants received NVP syrup within 72 hours of birth. Compliance was determined by pill counting. Women and infants were followed every month.
Outcomes of interest included low birth weight (<2500 g) and preterm delivery (<37 weeks), severe low birth weight (<2000 g) and severe preterm delivery (<34 weeks), small size for gestational age, head circumference, fetal death, and infant death during the first six weeks of life; maternal hemoglobin, CD4 cell counts, and viral load were also measured. The mean age of the women was 26.5 years; at enrollment, the mean gestational age was 21.8 weeks; mean time from randomization to six weeks post-partum was 5.1 months; compliance with the regimen was 85%-87% and did not differ between arms. Among those receiving multiple RDA vitamins, 20 women were lost to follow-up and the vital status of an additional 32 infants was unknown. Among women receiving single RDA of vitamins, 13 were lost to follow-up, and the status of an additional 23 infants was unknown. There were no significant differences in any outcome variable between either arm. The risk of fetal death was 6% in both groups; the mean birth weight was also similar (3045 g vs. 3052 g). There were no differences between the two groups in maternal CD4 cell counts, mean hemoglobin concentrations, or viral load through the six-week post-partum follow-up period.
This study found that multivitamin (B complex, C, and E) supplements at a single dose of the RDA are as efficacious as multiple doses of the RDA in reducing the risk of adverse pregnancy outcomes among HIV-infected women. The long-term benefits of single compared with multiple doses in delaying progression of HIV disease still are not clear.
This was a high quality study given the double-blind randomized trial design; however, the study may have been slightly underpowered to detect a difference, based on the number of women enrolled. Follow-up and compliance were good.
Comments and Policy Implications
At least a single dose of the RDA of multivitamins should be provided to all HIV-infected pregnant women; data do not support taking doses higher than the RDA. Multivitamins may also improve birth outcomes among HIV-negative pregnant women, as demonstrated in numerous studies.(5, 6) There is some concern, however, that supplements in uninfected women could increase the risk of perinatal mortality due to birth asphyxia and large head-size during labor, but this is mostly an issue when there is limited obstetric and antenatal care.(7) Therefore, the benefit of providing multivitamins to all pregnant women, particularly in settings where HIV testing coverage is low, needs to be balanced against possible adverse outcomes of giving birth to larger infants when prenatal and obstetric care are unavailable. In non-pregnant HIV-infected persons, multivitamins have also been shown to reduce morbidity and mortality.(8)
- Habib NA, Daltveit AK, Bergsjo P, Shao J, Oneko O, Lie RT. Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry-based study. BJOG 2008;115:616-24.
- Lawn JE, Cousens S, Zupan J. 4 million neonatal deaths: When? Where? Why? Lancet 2005;365:891-900.
- Black RE, Allen LH, Bhutta ZA, et al. Maternal and child undernutrition: global and regional exposures and health consequences. Lancet 2008;371:243-60.
- Fawzi WW, Msamanga GI, Spiegelman D, et al. Randomised 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.
- Friis H, Gomo E, Nyazema N, et al. Effect of multimicronutrient supplementation on gestational length and birth size: a randomized, placebo-controlled, double-blind effectiveness trial in Zimbabwe. Am J Clin Nutr 2004;80:178-84.
- Shankar AH, Jahari AB, Sebayang SK, et al. Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial. Lancet 2008;371:215-27.
- Christian P, Osrin D, Manandhar DS, Khatry SK, de L Costello AM, West KP Jr. Antenatal micronutrient supplements in Nepal. Lancet 2005;366:711-2.
- Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004;351:23-32.