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.
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Electronic address: Apalme17@jhu.edu.
Amanda C
AC
Palmer
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Kerry J
KJ
Schulze
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; Nepal Nutrition Intervention Project-Sarlahi, Nepal and the National Society for the Prevention of Blindness, Kathmandu, Nepal.
Subarna K
SK
Khatry
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Luigi M
LM
De Luca
Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Keith P
KP
West
D000328:Adult; D000906:Antibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000502:physiology; D002648:Child; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D038041:Lymphopoiesis / Q000187:drug effects*; D008297:Male; D044342:Malnutrition / Q000188:drug therapy / Q000276:immunology; D009390:Nepal; D011247:Pregnancy; D011248:Pregnancy Complications; D011295:Prenatal Care; D039401:Prenatal Nutritional Physiological Phenomena; D012424:Rural Population; D014801:Vitamin A / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D014802:Vitamin A Deficiency / Q000188:drug therapy* / Q000276:immunology; D014815:Vitamins / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D055815:Young Adult; D019207:beta Carotene / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use
D000906:Antibodies; D014815:Vitamins; D019207:beta Carotene; D014801:Vitamin A
B1a lymphocytes; Developmental origins of health and disease; Immune development; Lymphopoiesis; Programming