Maternal vitamin A supplementation increases natural antibody concentrations of preadolescent offspring in rural Nepal

Abstract

ObjectiveB1a lymphocytes—which constitutively produce most natural antibodies (NAb)—arise from an early wave of progenitors unique to fetal life. Vitamin A regulates early lymphopoiesis. In animals, deficiency during this critical period compromises B1 cell populations. The aim of this study was to investigate the effect of maternal supplementation with vitamin A or β-carotene from preconception through lactation on NAb concentrations of offspring. MethodsParticipants (N = 290) were born to participants of a cluster-randomized, placebo-controlled trial of weekly maternal vitamin A or β-carotene supplementation (7000 μg retinol equivalents) conducted in Sarlahi, Nepal (1994–1997) and assessed at ages 9 to 13 y (2006–2008). Serum retinol was measured by reversed-phase high-performance liquid chromatography at mid-pregnancy and 3 mo of age. Enzyme-linked immunosorbent assay (ELISA) was used to measure children's plasma NAb concentrations at 9 to 13 y. ResultsUnadjusted geometric mean concentrations were 20.08 U/mL (95% confidence interval [CI], 17.82–22.64) in the vitamin A group compared with 17.64 U/mL (95% CI, 15.70–19.81) and 15.96 U/mL (95% CI, 13.43–18.96) in the β-carotene and placebo groups (P = 0.07), respectively. After adjustment, maternal vitamin A supplementation was associated with a 0.39 SD increase in NAb concentrations (P = 0.02). The effect was mediated by infant serum retinol in our statistical models. Although girls had 1.4-fold higher NAb concentrations (P < 0.001), sex did not modify the vitamin A effect. ConclusionsIn an undernourished population, maternal vitamin A supplementation enhanced NAb concentrations of preadolescent children. We posit that this was due to a greater allotment of B1a precursors during fetal life and a sustained higher count of NAb-secreting B1a cells.