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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 (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.
Financial support: This study was supported by grants from the National Institute of Child Health and Human Development (NICHD R01 HD057941-01 and K24 HD 058795 [Christopher Duggan]).
Authors' addresses: Anne Marie Darling, Analee J. Etheredge, Nilupa S. Gunaratna, Ajibola Ibraheem Abioye, and Wafaie W. Fawzi, Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, MA, E-mails: firstname.lastname@example.org, email@example.com, firstname.lastname@example.org, email@example.com, and firstname.lastname@example.org. Ferdinand M. Mugusi, Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: email@example.com. Said Aboud, Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: firstname.lastname@example.org. Christopher Duggan, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, E-mail: email@example.com. Robert Mongi, Department of Parasitology/Medical Entomology, School of Public Health and Social Sciences, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania, E-mail: firstname.lastname@example.org. Donna Spiegelman, Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, E-mail: email@example.com. Drucilla Roberts, Department of Pathology, Massachusetts General Hospital, Boston, MA, E-mail: firstname.lastname@example.org. Davidson H. Hamer, Department of Global Health, Boston University School of Public Health, Boston, MA, E-mail: email@example.com. Kevin C. Kain, Department of Medicine, University of Toronto, Toronto, Canada, E-mail: firstname.lastname@example.org.