Effects of Maternal Vitamin Supplements on Malaria in Children of HIV-Infected Women

Abstract

Source: Villamor E, Msamanga G, Saathoff E, et al. Effects of maternal vitamin supplements on malaria in children born to HIV-infected women. Am J Trop Med Hyg. 2007,76:1066–1071.Because the effects of maternal multivitamin supplementation on the risk of malaria in children are unknown,1,3,4 researchers from Boston, Mass; Munich, Germany; and Dar es Salaam, Tanzania, sought to learn the impact of providing multivitamins or vitamin A/β-carotene (VA/BC) supplements during pregnancy and lactation to HIV-infected women on their children’s risk of malaria in the first two years of life.A total of 1,078 HIV-infected pregnant women participated in this community-based, prospective, randomized, double-blind, placebo-controlled trial in Dar es Salaam. Antiretroviral therapy was unavailable at the time of the study. Women were randomized into one of four treatment arms: 1) multivitamins; 2) VA/ BC; 3) multivitamins and VA/BC; and 4) placebo. Multivitamins included B1, B2, B6, niacin, B12, C, E, and folic acid. The VA/BC supplements included 5,000 IU vitamin A plus 30 mg β-carotene. All women received daily folic acid and iron along with weekly chloroquine prophylaxis during pregnancy. Additionally, women in groups 2 and 3 received a supplemental dose of vitamin A at delivery. At six months of age and every six months thereafter, all children received an oral dose of vitamin A. Almost all women breastfed their infants. Blood films looking for Plasmodium parasitemia were obtained at three-month intervals and during acute febrile episodes. Malaria-related outcomes were defined as: 1) any parasitemia ( ≥1/μL); 2) high parasitemia (≥5,000/μL); 3) clinical malaria (parasitemia ≥5,000/μL with an axillary temperature >37.5°C); and 4) death from malaria.Most women were HIV-asymptomatic with a mean CD4 count of 416. Data were analyzed on 829 live-born, singleton children who had at least one assessment of malaria during their first two years of life. Of these children, 30% became HIV-infected during the first two years of life while 20% died. There were 405 cases of parasitemia, 109 cases of high parasitemia, and 28 cases of clinical malaria.Maternal supplementation with multivitamins alone resulted in a statistically significant reduction of 71% in the risk of clinical malaria (P=.02) whereas VA/BC alone was related to a nonstatistically significant reduction in clinical malaria by 63% (P=.06). Maternal vitamin supplements had no effect on parasitemia defined as ≥1/μL. Multivitamin supplementation resulted in a nonstatistically significant 30% reduction of high parasitemia. This reduction appeared to be larger when multivitamins were administered together with VA/BC (43% reduction, P=.04). The children’s HIV status did not significantly modify the effect of vitamins on the malaria outcomes considered. HIV transmission occurred more frequently among children whose mothers received VA/BC (33.5%) compared with those who did not receive VA/BC (25.6%; P=.01). The authors conclude that although maternal multivitamin supplements may be of benefit in preventing malaria in infants in East Africa, they cannot advocate daily supplementation with these supplements to HIV-infected lactating women as a strategy to prevent malaria in children.Dr. Dinerman has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.While this study suggests a modest protective effect for maternal vitamin supplementation on malaria in children, VA/BC may have increased the risk of mother-to-child transmission of HIV. HIV transmission occurred in 34% of children whose mothers received VA/BC, compared to a transmission rate of 26% in the absence of supplementation. Consequently, the authors conclude that daily supplementation with VA/BC in HIV-infected women to reduce the risk of childhood malaria cannot be recommended at this time. Rather, they hypothesize that direct supplementation of vitamin A to children older than six months of age might be a safer public health intervention (a hypothesis not investigated in this study).Prior research in the field of prophylactic supplementation showed mixed results. A study in Papua New Guinea demonstrated a protective effect of vitamin A.1 By comparison, animal studies showed that vitamins B2, B6, and E could worsen malaria.2 Another study demonstrated that iron, thiamine, riboflavin, and vitamin C had no effect on malaria.3 Additionally, a study in Tanzania showed that vitamins A, B, C, D, and E plus iron had no impact on malaria incidence.4 While vitamin supplementation is academically interesting, insecticide-treated nets (ITNs) and community education will continue to have the greatest impact on preventing malaria in children in Africa.