Prenatal zinc and Vitamin A reduce the benefit of iron on maternal hematologic and micronutrient status at delivery in Tanzania

Background: Zinc and Vitamin A supplementation have both been shown to affect iron status, hemoglobin (Hb) concentration, and anemia in animal and human studies. However, evidence on their combined use in pregnancy, in the context of iron-folic acid (IFA) supplementation, remains limited. Objective: This study determined the effects of prenatal zinc, Vitamin A, and iron supplementation on maternal hematologic and micronutrient status at delivery in Tanzania. Methods: We analyzed 2 large randomized controlled trials, using generalized estimating equations, and examined the effect of daily zinc (25 mg) and Vitamin A (2500 IU) supplementation starting in the first trimester of pregnancy compared with placebo (n = 2500), and separately evaluated the safety and efficacy of daily iron (60 mg) supplementation among iron-replete pregnant women (n = 1500). Blood samples from baseline and delivery were tested for Hb, serum ferritin, soluble transferrin receptor, plasma zinc, and zinc protoporphyrin. Results: Zinc and Vitamin A supplementation were associated with lower Hb concentrations at delivery of −0.26 g/dL (95% CI: −0.50, −0.02 g/dL) and −0.25 g/dL (95% CI: −0.49, −0.01 g/dL), respectively. Vitamin A increased mean ferritin concentrations at delivery (14.3 μg/L, 95% CI: 1.84, 29.11 μg/L), but was associated with increased risk of severe anemia (RR: 1.41; 95% CI: 1.06, 1.88). Among women who were iron replete at baseline, iron supplementation reduced the risk of iron depletion at delivery by 47% (RR: 0.53; 95% CI: 0.43, 0.65). There was no effect of zinc or iron supplements on plasma zinc concentrations. Conclusions: Our findings support existing WHO guidelines on prenatal iron, Vitamin A, and zinc supplementation among pregnant women. In this setting, scaling uptake of prenatal iron supplements is warranted, but prenatal zinc and Vitamin A supplementation did not benefit maternal hematologic status at delivery. In settings where Vitamin A deficiency is endemic, the efficacy and safety of the WHO recommended prenatal Vitamin A supplementation require further evaluation.