Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.
What this study found
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;…
- Study & population
- 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.
- Intervention
- 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.
- Key limitation
- Outcome analyses used fewer participants than were randomized, with missing placental pathology and PCR data reducing the analyzable samples.
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Open PDFOriginal abstract
AbstractVitamin A and zinc are important for immune function and may improve host defense against malaria and reduce the risk of adverse pregnancy outcomes. Our objective was to determine whether daily oral supplementation with either or both nutrients starting in the first trimester reduces the risk of placental malaria and adverse pregnancy outcomes. We undertook a randomized, double-blind placebo-controlled trial with a factorial design among 2,500 human immunodeficiency virus-negative primigravid or secundigravid pregnant women in their first trimester of pregnancy in Dar es Salaam, Tanzania. We randomly allocated equal numbers of participants to 2,500 IU of vitamin A, 25 mg of zinc, both 2,500 IU of vitamin A and 25 mg of zinc, or a placebo until delivery. A total of 625 participants were allocated to each treatment group. Our primary outcome, placental malaria infection (past or current), was assessed in all randomized participants for whom placental samples were obtained at delivery (N = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer (N = 2,266). Birth outcomes were obtained for 2,434 of the 2,500 randomized participants. Secondary outcomes included small for gestational age (SGA) births and prematurity. All analyses were intent to treat. Those who received zinc had a lower risk of histopathology-positive placental malaria compared with those who did not receive zinc (risk ratio = 0.64, 95% confidence interval = 0.44, 0.91), but neither nutrient had an effect on polymerase chain reaction-positive malaria, SGA, or prematurity. No safety concerns were identified. We recommend additional studies in other geographic locations to confirm these findings.