Observational Studies

Observational studies of the relationship between micronutrient status and pregnancy outcomes in HIV-positive populations have been predominantly focused on the role of vitamin A. In studies in sub-Saharan Africa, low maternal vitamin A status was associated with an increased risk of adverse pregnancy outcomes. In studies in Malawi, Semba and colleagues demonstrated that low maternal plasma vitamin A levels were associated with an increased risk of low birth weight (<2,500 grams), infant mortality, and MTCT of HIV [31, 32]. Low plasma concentrations of vitamin A were also associated with a greater risk of MTCT of HIV in an observational study in Rwanda [33].

Findings regarding vitamin A status and adverse pregnancy outcomes in the United States have been divergent. In a study conducted by Burns et al., maternal plasma vitamin A concentrations were associated with a significant decrease in the risk of low birth weight, and a nonsignificant reduction in the rate of MTCT of HIV [34]. Greenberg and colleagues also identified an increased risk of vertical HIV transmission in the presence of low vitamin A status among HIV-infected pregnant women in two urban areas in the United States [35]. However, in a study by Burger et al., maternal plasma concentrations of vitamin A and beta-carotene were not associated with the risk of MTCT of HIV [36].

The association between other micronutrients and pregnancy outcomes in HIV-infected women were examined in other observational studies in resource-limited settings. In a cross-sectional study ofpregnant women in Zimbabwe, HIV infection was associated with reduced concentrations of serum retinol, beta-carotene, folate, ferritin, and hemoglobin [37, 38]. The observed reductions in hemoglobin were particularly profound among HIV-positive women with low serum retinol and nondepleted iron stores (12.9 g/l lower hemoglobin level; 95% CI: 8.9, 16.8); the decrease was less pronounced in women with other combinations of serum ferritin and retinol (7-8 g/l lower hemoglobin levels; P for interaction = 0.038). In an observational study in Haiti, lower serum zinc concentrations were associated with an increased risk of vertical HIV transmission, although this finding was not statistically significant [39].

In an observational study of HIV-infected pregnant women in Tanzania, lower baseline plasma selenium concentrations were associated with a significant increase in risk of mortality over a median follow-up period of 5.7 years [40]. Low maternal selenium status was also associated with a greater risk of fetal death, child mortality, and HIV transmission via the intrapartum route. Although low maternal selenium concentrations were associated with a reduced risk of small size for gestational age, no significant relationships were noted between maternal selenium status and infant low birth weight or preterm birth [41]. Comment

The aforementioned observational studies have a few limitations, which warrant caution while interpreting the results. HIV infection may lead to decreased nutrient absorption and increased excretion, resulting in lower serum concentrations of the micronutrient and an apparent deficiency. Reductions in concentrations of micronutrients such as vitamin A, zinc, and selenium may also be attributable to the acute phase response to infection, rather than being a marker of actual micronutrient status. The observed associations between micronutrient deficiencies and adverse pregnancy outcomes may therefore be due to reverse causation. Further, although the observational studies mentioned above adjusted for some confounders in multivariate analyses, most did not adjust for important potential confounders such as micronutrient supplement use, intake of other dietary nutrients, and presence of lower genital infections. Therefore, residual confounding of the relationship between micronutrient status and pregnancy outcomes by these covariates may lead to biased results.

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