Effect of fortified balanced energy-protein supplementation during pregnancy and lactation on infant neurodevelopment: a community-based randomized controlled trial in rural Nepal

Introduction: Infant neurodevelopment is associated with maternal nutritional status, yet few studies have evaluated the effects of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation. Methods: The Maternal Infant Nutrition Trial (NCT03668977) was a 2x2 factorial, household randomized, unblinded, efficacy trial conducted in Sarlahi District, Nepal. Pregnant women were randomized to daily fortified BEP supplementation or no supplementation, and those with a live birth were re-randomized after delivery to supplementation or not until 6-months postpartum. The first 100 infants in each of the four intervention groups were enrolled in a neurodevelopment substudy. At 6-months, these infants underwent a cognitive, motor, language, and socioemotional assessment using the Bayley Scales of Infant and Toddler Development, fourth edition. Results: Baseline characteristics were similar across the four trial groups. A significant interaction (p< 0.05) between pregnancy and lactation supplementation groups was observed in the language domain only. Infants born to mothers who received BEP supplementation during pregnancy did not differ in standard scores for cognitive (mean difference (MD): 2.0, 95% confidence interval (CI): -0.29, 4.29), motor (MD: 0.98, 95% CI: -1.41, 3.36), or socioemotional (MD: -2.35, 95% CI: -5.27, 0.57) domains compared to the pregnancy control group. Similarly, for these three domains, there were no significant differences among infants whose mothers received BEP in lactation period vs. not. Infants born to mothers supplemented in both pregnancy and lactation had significantly higher mean language standard scores of 2.12 (95% CI: 0.16, 4.08; p-interaction = 0.015), driven by the expressive communication subtest, compared to those with no BEP supplementation in either period. Conclusion: BEP supplementation during pregnancy and/or lactation was not associated with improvements in cognitive, motor, or socioemotional domains at 6 months; however, infants of women supplemented in pregnancy and lactation had significant improvements in the language domain. Evaluation at later ages is warranted.