title: Vitamin A and Zinc Supplementation Among Pregnant Women to Prevent Placental Malaria: A Randomized, Double-Blind, Placebo-Controlled Trial in Tanzania.
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.
authors.affiliation: Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Darling
authors.affiliation: Department of Internal Medicine, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Ferdinand M
authors.initials: FM
authors.lastname: Mugusi
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Analee J
authors.initials: AJ
authors.lastname: Etheredge
authors.affiliation: Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Nilupa S
authors.initials: NS
authors.lastname: Gunaratna
authors.affiliation: Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Ajibola Ibraheem
authors.initials: AI
authors.lastname: Abioye
authors.affiliation: Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Said
authors.initials: S
authors.lastname: Aboud
authors.affiliation: Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
authors.affiliation: Department of Parasitology/Medical Entomology, School of Public Health and Social Sciences, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
authors.forename: Robert
authors.initials: R
authors.lastname: Mongi
authors.affiliation: Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Donna
authors.initials: D
authors.lastname: Spiegelman
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Drucilla
authors.initials: D
authors.lastname: Roberts
authors.affiliation: Department of Global Health, Boston University School of Public Health, Boston, Massachusetts.|Center for Global Health and Development, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Davidson H
authors.initials: DH
authors.lastname: Hamer
authors.affiliation: Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Canada.|Sandra A. Rotman Laboratories, Sandra Rotman Centre for Global Health, University Health Network-Toronto General Hospital, University of Toronto, Toronto, Canada.|Depatment of Medicine, University of Toronto, Toronto, Canada.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
authors.affiliation: Department of Global Health and Population, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts.|Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts.
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
mesh_terms: D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D010920:Placenta / Q000469:parasitology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000517:prevention & control*; D011256:Pregnancy Outcome; D012680:Sensitivity and Specificity; D013636:Tanzania / Q000453:epidemiology; D014801:Vitamin A / Q000008:administration & dosage*; D015032:Zinc / Q000008:administration & dosage*
chemical_list: D014801:Vitamin A; D015032:Zinc