Effect of maternal and neonatal vitamin A supplementation and other postnatal factors on anemia in Zimbabwean infants: a prospective, randomized study.

BACKGROUND: Anemia is prevalent in infants in developing countries. Its etiology is multifactorial and includes vitamin A deficiency. OBJECTIVE: Our primary aim was to measure the effect of maternal or neonatal vitamin A supplementation (or both) on hemoglobin and anemia in Zimbabwean infants. Our secondary aim was to identify the underlying causes of postnatal anemia. DESIGN: A randomized, placebo-controlled trial was conducted in 14 110 mothers and their infants; 2854 infants were randomly selected for the anemia substudy, of whom 1592 were successfully observed for 8-14 mo and formed the study sample. Infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A; mothers received vitamin A and infants received placebo; mothers received placebo and infants received vitamin A; and mothers and infants received placebo. The vitamin A doses were 400,000 and 50,000 IU in the mothers and infants, respectively. RESULTS: Vitamin A supplementation had no effect on hemoglobin or anemia (hemoglobin <105 g/L) in unadjusted or adjusted analyses. Infant HIV infection independently increased anemia risk >6-fold. Additional predictors of anemia in HIV-negative and -positive infants were male sex and lower total body iron at birth. In addition, in HIV-positive infants, the risk of anemia increased with early infection, low maternal CD4+ lymphocyte count at recruitment, and frequent morbidity. Six-month plasma ferritin concentrations <12 microg/L were a risk factor in HIV-negative but not in HIV-positive infants. Maternal HIV infection alone did not cause anemia. CONCLUSION: Prevention of infantile anemia should include efforts to increase the birth endowment of iron and prevent HIV infection.

Neonatal erythropoiesis and subsequent anemia in HIV-positive and HIV-negative Zimbabwean babies during the first year of life: a longitudinal study.

BACKGROUND: Anemia is common in HIV infection and independently associated with disease progression and mortality. The pathophysiology of HIV-related anemia is not well understood especially in infancy. METHODS: We conducted a longitudinal cohort study nested within the Zimbabwe Vitamin A for Mothers and Babies Project. We measured hemoglobin, erythropoietin (EPO), serum transferrin receptor (TfR) and serum ferritin at 6 weeks, 3 and 6 months of age and hemoglobin at 9 and 12 months in 3 groups of randomly selected infants: 136 born to HIV-negative mothers, and 99 born to HIV-positive mothers and who were infected themselves by 6 weeks of age, and 324 born to HIV-positive mothers but who did not become infected in the 6 months following birth. RESULTS: At one year of age, HIV-positive infants were 5.26 (adjusted odds ratio, P < 0.001) times more likely to be anemic compared to HIV-negative infants. Among, HIV-negative infants, EPO was or tended to be inversely associated with hemoglobin and was significantly positively associated with TfR throughout the first 6 months of life; TfR was significantly inversely associated with ferritin at 6 months; and EPO explained more of the variability in TfR than did ferritin. Among infected infants, the inverse association of EPO to hemoglobin was attenuated during early infancy, but significant at 6 months. Similar to HIV-negative infants, EPO was significantly positively associated with TfR throughout the first 6 months of life. However, the inverse association between TfR and ferritin observed among HIV-negative infants at 6 months was not observed among infected infants. Between birth and 6 months, mean serum ferritin concentration declined sharply (by approximately 90%) in all three groups of babies, but was significantly higher among HIV-positive compared to HIV-negative babies at all time points. CONCLUSION: HIV strongly increases anemia risk and confounds interpretation of hematologic indicators in infants. Among HIV-infected infants, the EPO response to anemia is attenuated near the time of infection in the first weeks of life, but normalizes by 6 months.

Total body iron in HIV-positive and HIV-negative Zimbabwean newborns strongly predicts anemia throughout infancy and is predicted by maternal hemoglobin concentration.

One method of preventing postnatal iron deficiency is to ensure that the infant is born with a full endowment of iron. We calculated total body iron at birth (TBI) as the sum of hemoglobin iron (HbI) and body storage iron (BSI) in 2021 Zimbabwean newborns, and related TBI to subsequent anemia from 3 to 12 mo of age and to maternal and fetal characteristics. We estimated the mean +/- SD TBI to be 210 +/- 41 mg. There was an inverse dose-response association between TBI quartile and risk of anemia at all postnatal ages. The odds of anemia were >3 times higher in the lowest vs. highest TBI quartile (P < 0.001) at 6, 9 and 12 mo. Preterm birth and parity were not independently associated with TBI after controlling for birthweight. The predicted change in TBI per kilogram increase in birthweight was 68 mg (P < 0.001). After adjusting for birthweight, TBI increased by 25 mg with each 10-y decrement in maternal age (P = 0.033). Maternal hemoglobin was a strong linear predictor of TBI (P < 0.001). Maternal and infant HIV infection, especially among girls, was associated with apparently greater estimated TBI. We speculate that this is actually an artifact, explained by an inflammatory response, and that there was a sex difference in the response. We conclude that we can make satisfactory estimates of TBI and that the assumptions required for this approach are sufficiently robust to lead to an acceptable estimate of the prenatally acquired iron endowment. Babies born with low birthweight or to mothers with low hemoglobin are born with less TBI, which confers a substantially greater risk of anemia from 3 to 12 mo of age.