Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.

Randomized, double-blind, placebo-controlled 2x2 factorial trial in HIV-negative primigravida or secundigravida pregnant women enrolled in the first trimester at 8 antenatal clinics in Dar es Salaam, Tanzania. Enrollment ran from July 12, 2010 to September 17, 2013; 625 participants were assigned to each of the four groups.

Participants were randomized to oral, daily tablets started in the first trimester and continued until delivery: vitamin A 2,500 IU/day, zinc sulfate 25 mg/day, vitamin A 2,500 IU plus zinc sulfate 25 mg/day, or placebo. Tablets were identical in appearance; all women also received standard care iron 60 mg/day and folic acid 5 mg/day.

Zinc, but not vitamin A, reduced histopathology-detectable placental malaria; neither supplement improved PCR-detectable placental malaria or birth outcomes. In the unweighted analysis, zinc lowered histopathology-positive placental malaria from 71/690 to 44/671 (RR 0.64, 95% CI 0.44 to 0.91; P=0.01), with a similar marginal structural model estimate (RR 0.62, 95% CI 0.42 to 0.89). Vitamin A had no effect on histopathology-detectable placental malaria (RR 0.99, 95% CI 0.70 to 1.40; P=0.94) and was associated with more severe maternal anemia (17.4% vs 12.8%; RR 1.36, 95% CI 1.05 to 1.76; P=0.02). Birthweight, preterm birth, small-for-gestational-age outcomes, and PCR-detectable malaria were not significantly changed.

Outcome analyses used fewer participants than were randomized, with missing placental pathology and PCR data reducing the analyzable samples. The trial was conducted in a single urban Tanzanian setting among HIV-negative primigravida/secundigravida women, which limits generalizability. Follow-up was restricted to delivery, so longer-term maternal and infant outcomes were not assessed.