Impact of Maternal Nutritional Supplementation During Pregnancy on Infant Antibody Response to Diphtheria-Tetanus-Pertussis Vaccine: A Randomized Trial in the Gambia

Abstract

Background A nutritionally deficient environment during fetal life may impair an infant's ability to mount an optimal immune response to vaccination. We examined the impact of supplementation during pregnancy with multiple micronutrients (MMN) and/or protein-energy (PE) on infant antibody responses to diphtheria-tetanus-pertussis (DTP) vaccination. Methods The Early Nutrition and Immune Development Trial (ISRCTN49285450) randomized 875 pregnant women from rural Gambia to receive one of four nutritional interventions (iron-folate (FeFol) as standard of care), MMN, PE and PE MMN) daily from enrolment (mean gestational age = 13·7±3·3 weeks) until delivery. Antibody responses to DTP administered to infants at 8, 12 and 16 weeks of age were measured in blood collected from a total of 670 and 563 infants at 12 and 24 weeks, respectively. The main outcome was the impact of maternal supplementation on log-transformed antibody titres in infants analysed using regression models with adjustment for confounders. Results At 12 weeks, adjusted mean (95% CI) anti-diphtheria titres were higher in infants born to mothers in the MMN (0·15 (0·13-0·18) IU/ml, p=0·002) and PE MMN (0·14 (0·12-0·16) IU/ml, p=0·028) groups, compared with the FeFol group (0·10 (0·09-0·12) IU/ml). This resulted in 72·2% (96/133) and 64·9% (87/134) of infants with protective anti-diphtheria titres (>0·1IU/ml) from the MMN and PE MMN groups, respectively, compared with 48·1% (64/133) from the FeFol group (p=0·001). Additionally, supplementation with PE MMN enhanced anti-tetanus titres (β=0·12, 95% CI 0·01-0·23, p=0·028) at 12 weeks; and anti-pertussis titres (β=0·26, 95% CI 0·02-0·50, p=0·035) at 24 weeks. Conclusions This study demonstrates that supplementation during pregnancy with MMN or a combination of MMN and PE enhances infant antibody responses to vaccination in rural Gambia. Overall, this research supports interventions that improve nutritional status in pregnancy and promote infant immune development, especially in settings with high rates of infection. Funding: Medical Research Council (UK). Declaration of Interest: No conflict of interest was declared. Ethical Approval: The ENID trial was approved by the joint Gambian Government/MRC Unit the Gambia ethics committee (SCC1126v2). Written informed consent was obtained from all participants. The trial observed Good Clinical Practice Standards and the current version of the Helsinki Declaration. The ENID trial was registered as ISRCTN49285450.