Determinants of low birth weight among HIV-infected pregnant women in Tanzania.

BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little is known about its causes among HIV-infected populations in sub-Saharan Africa. OBJECTIVE: We assessed sociodemographic, nutritional, immunologic, parasitic, and infant risk factors for birth weight, LBW, and small-for-gestational-age (SGA) status in a cohort of 822 HIV-positive women enrolled in a clinical trial of vitamin supplementation and pregnancy outcomes in Dar es Salaam, Tanzania. DESIGN: Women were enrolled at prenatal care clinics during their second trimester, at which time blood, stool, urine, and genital specimens were collected, and anthropometric measurements and sociodemographic data were recorded. Birth weight was measured at hospital delivery. RESULTS: The mean (+/-SD) birth weight was 3015 +/- 508 g, 11.1% of newborns weighed <2500 g (LBW), and 11.5% were SGA. In multivariate analyses, maternal weight at enrollment and a low CD8 cell count were inversely associated with LBW. Advanced-stage HIV disease, previous history of preterm birth, Plasmodium falciparum malaria, and any helmintic infection were associated with higher risk of LBW. The intestinal parasites Entamoeba histolytica and Strongyloides stercoralis were predictors of LBW despite their low prevalence in the cohort. In a multivariate-adjusted linear regression model, BMI, midupper arm circumference, a CD4 cell count <200 x 10(6) cells/L (200 cells/mm(3)), primiparity, maternal literacy, and infant HIV infection at birth were significantly associated with birth weight in addition to risk factors included in the LBW model. Determinants of SGA included maternal weight, low serum vitamin E concentration, candidiasis, malaria, and infant HIV infection at birth. CONCLUSION: Prevention of HIV disease progression and vertical transmission, improved nutritional status, and better management of malaria and intestinal parasitic infections are likely to reduce the incidence of LBW in Tanzania.

Nutritional factors and infectious disease contribute to anemia among pregnant women with human immunodeficiency virus in Tanzania.

The objective of this cross-sectional study was to identify risk factors for anemia among human immunodeficiency virus (HIV)-positive pregnant women in Dar es Salaam, Tanzania. Baseline data from 1064 women enrolled in a clinical trial on the effect of vitamin supplementation in HIV infection were examined to identify potential determinants of anemia. The mean hemoglobin (Hb) level was 94 g/L, and the prevalence of severe anemia (Hb < 85 g/L) was 28%; 83% of the women had Hb < 110 g/L. Iron deficiency and infectious disease appeared to be the predominant causes of anemia. Significant independent associations with severe anemia were observed for women with body mass index (BMI) < 19 kg/m(2) compared with women with BMI > 24 kg/m(2) [odds ratio (OR) 3.13, 95% confidence interval (CI): 1. 37-7.14); malaria parasite densities > 1000/mm(3) (OR 2.70, CI: 1. 58-4.61) compared with women with no parasites; eating soil during early pregnancy (OR 2.47, CI: 1.66-3.69); CD4+ cell count < 200/microL compared with CD4+ count > 500/microL (OR 2.70, CI: 1. 42-5.12); and serum retinol levels < 70 micromol/L (OR 2.45, CI: 1. 44-4.17) compared with women with retinol levels > 1.05 micromol/L. The most significant risk factors associated with severe anemia in this population are preventable. Public health recommendations include increasing the effectiveness of iron supplementation and malaria management during pregnancy, and providing health education messages that increase awareness of the potentially adverse nutritional consequences of eating soil during pregnancy.

Rationale and design of the Tanzania Vitamin and HIV Infection Trial.

We present the rationale and design of a randomized, double-blind, placebo-controlled trial of vitamin supplements among HIV-positive pregnant women in Dar es Salaam, Tanzania. Higher levels of intake of vitamins A, B, C, and E may decrease the risk of vertical transmission and progression of HIV infection by enhancing maternal and infant immune function; by reducing viral load in the blood, breast milk, or lower genital tract secretions; and/or by strengthening the placental barrier to infection. Eligible pregnant women were randomized to receive vitamin A, multivitamins excluding A, vitamin A and multivitamins, or placebo. The main endpoints include vertical transmission of HIV infection, as assessed by examination of infection in infants using polymerase chain reaction (PCR), and progression of HIV disease as measured by the WHO clinical staging system. Over a period of 2 years, 13,876 women were tested for HIV infection, with appropriate pre- and posttest counseling, to enroll 1085 consenting HIV-positive women. The trial assesses women and their children once a month for a minimum of 18 months after delivery or up to the end of this 5-year study. We examine recruitment strategies and means of enhancing cohort retention in long-term follow-up. We assess compliance with the use of supplements by direct questioning, by counting pills, and biochemically by using serum beta-carotene and urine riboflavin levels. Briefly, we discuss ethical issues related to the conduct of AIDS prevention trials in this setting. In sub-Saharan Africa, most HIV-infected persons lack access to the relevant antiretroviral and prophylactic drugs, and the region urgently needs low-cost treatments and preventive strategies. The Tanzania trial should provide valuable data to address the effect of vitamin supplements in the transmission and progression of HIV infection.

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.

PIP: Poor micronutrient status has been associated, in HIV-positive women, with faster progression of HIV disease and adverse birth outcomes. This randomized, double-blind, placebo-controlled study assessed the effects of vitamin A and multivitamins on birth outcomes in 1075 HIV-positive pregnant women at 12-27 weeks' gestation from Dar es Salaam, Tanzania. There were no differences in baseline plasma vitamin concentrations between groups. 267 women received a placebo, 269 were given vitamin A, 269 were administered a multivitamin excluding vitamin A, and 270 received a multivitamin including vitamin A. There were 30 fetal deaths in the group of women who received multivitamins (with and without vitamin A) compared with 49 among those not given multivitamins (relative risk (RR), 0.61; 95% confidence interval (CI), 0.39-0.94). Multivitamin supplementation decreased the risk of low birth weight (2500 g) by 44% (RR, 0.56; 95% CI, 0.38-0.82), of preterm birth (prior to 34 weeks gestation) by 39% (RR, 0.61; 95% CI, 0.38-0.96), and of small size for gestational age at birth by 43% (RR, 0.57; 95% CI, 0.39-0.82). Vitamin A had no significant effect on these variables. Multivitamins, but not vitamin A, were associated with significant increases in CD4, CD8, and CD3 counts. The clinical relevance of multivitamin supplementation for vertical transmission of HIV and the progression of disease remain unknown. However, these results indicate such supplementation is a low-cost means of substantially decreasing adverse pregnancy outcomes and increasing T cell counts in HIV-infected women. The observed beneficial effects of multivitamins on birth outcomes may have been mediated through improved maternal immune status.