Effect of Small‐Quantity Lipid‐Based Nutrient Supplementation on Children's Cortisol Concentration

This study investigated the role of early-life nutrition supplementation in regulating the development of hypothalamic-pituitary-adrenal (HPA) axis activity, as evidenced by hair cortisol concentration (HCC), in the iLiNS-DYAD randomized controlled trial in Ghana. Pregnant women were randomized to one of three conditions: (1) iron and folic acid (IFA) during pregnancy and placebo 0-6 mo postpartum; (2) multiple micronutrients (MMN) during pregnancy and 0-6 mo postpartum; or (3) small-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and 0-6 mo postpartum and for their children from 6 to 18 mo. At 9-11 y of age, usable hair samples were obtained from 680 children from which cortisol was assayed. ANCOVA models assessed differences between groups and potential effect modifiers, including maternal education, household asset index, pre-pregnancy BMI, child sex, child BMI, and pubertal stage. HCC did not differ between SQ-LNS and control groups in adjusted and unadjusted models (p > 0.10), but maternal education was a significant effect modifier (P-interaction = 0.043). Children exposed to SQ-LNS had lower HCC than control children among those whose mothers had 0-5 years schooling (Median (interquartile range): 6.3 (4.8, 9.9) vs. 7.8 (5.3, 9.9); p = 0.031) but not among those whose mothers had > 5 years of schooling (p = 0.949). No other interactions were significant. Although these findings should be viewed with caution, they suggest that early-life SQ-LNS may buffer physiological stress in children of less educated mothers, highlighting its potential to compensate for socioeconomic disadvantage with regard to HPA axis regulation. Trial Registration: Clinical Trial Registry number and website: clinicaltrials.gov as NCT00970866 https://clinicaltrials.gov/ct2/show/record/NCT00970866.