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

Abstract

Vitamin 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 ( = 1,404), which represents 56% of total participants and 62% of all pregnancies lasting 28 weeks or longer ( = 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.

Vitamin and Mineral Supplementation During Pregnancy on Maternal, Birth, Child Health and Development Outcomes in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis

“…Nine studies assessed vitamin A supplementation compared to placebo or no treatment [53,60,63,79,86,92,94,110,111]. Of these, one study was excluded from meta-analysis because it reported no poolable outcomes, but was narratively synthesized [53] (see Supplementary Materials, Table S3).…”

“…Of these, one study was excluded from meta-analysis because it reported no poolable outcomes, but was narratively synthesized [53] (see Supplementary Materials, Table S3). Thus, eight studies were included in the meta-analyses [60,63,79,86,92,94,110,111]. Four of these studies were conducted in the sub-Saharan Africa-of which, two were in Ghana [79,86], one in Malawi [92] and one in Tanzania [94].…”

Prenatal nutrition, stimulation, and exposure to punishment are associated with early child motor, cognitive, language, and socioemotional development in Dar es Salaam, Tanzania

“…Notably, we recently determined the prevalence of moderate vitamin A deficiency (defined as serum retinol <0.07 μmol/L) in Dar es Salam to be low (8%) in a separate pregnancy cohort (Masanja et al, ). In the parent trial, we found no effect of prenatal vitamin A on placental malaria, small‐for‐gestational age birth, or prematurity (Darling et al, ). As a result, the low level of deficiency in this population may have led to no effect of supplementation on maternal and child health, cognitive/language, and socioemotional outcomes.…”

“…Additionally, all women were given a daily dose of 60 mg of iron and 5 mg of folic acid in accordance with Tanzanian standard of care. The mean compliance rate across all women in the parent trial was 84.5% (median 97.6%; Darling et al, 2017).…”

Vitamin A Supplementation for Prevention and Treatment of Malaria during Pregnancy and Childhood: A Systematic Review and Meta-analysis

“…One article was added from the references of the included articles. Of these 58, 15 articles or 11 distinct studies/trials [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] were finally selected for inclusion in this systematic review. The flow diagram of the literature search along with the reasons for 43 excluded studies is shown in Fig.…”