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

Objective: B1a 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. Methods: Participants (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. Results: Unadjusted 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. Conclusions: In 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.