Impact of supplementation with fortified balanced energy–protein during pregnancy on birth outcomes: a community-based randomized trial among pregnant females in southern Nepal

Background The World Health Organization recommends balanced energy–protein (BEP) dietary supplementation in undernourished populations to reduce risk of stillbirth and small-for-gestational age (SGA), but variation in the composition of interventions has hindered scientific consensus. Objectives To assess the effect of daily fortified BEP supplementation during pregnancy on SGA birth and secondary birth outcomes. Methods MINT (Maternal Infant Nutrition Trial) was a 2 × 2 factorial, household randomized, unblinded, efficacy trial to assess the effect of a daily fortified BEP supplement during pregnancy and/or lactation compared with no supplement on birth and infant growth outcomes in Sarlahi, Nepal. This analysis examines the effect of pregnancy supplementation on the primary outcome of SGA (<10th centile), among live-born infants with birth weight measured <72 h of delivery and secondary outcomes. A modified intention-to-treat analysis assessed the effect of pregnancy BEP supplementation on birth outcomes using log-binomial and linear regression models. Results A total of 1944 pregnant females were enrolled and randomly assigned to receive daily fortified BEP supplementation or not from November 2021 to August 2023. Of 1581 live births, 1209 infants had anthropometry <72 h of delivery. BEP supplementation did not reduce the incidence of SGA [relative risk: 0.99; 95% confidence interval (CI): 0.86, 1.13]. Maternal short stature, age, adherence, and other factors did not significantly modify this result. There was no difference between groups for low birth weight and short-for-gestational age (<10%). Mean difference in birth weight was 37.4 g (95% CI: −6.9, 81.8) and birth length was 0.20 cm (95% CI: −0.03, 0.43). Head circumference was higher in the supplement group (mean difference: 0.23 cm; 95% CI: 0.09, 0.38), and weight-for-gestational age was higher in the supplement group by 2.82 percentage points (95% CI: 0.53, 5.12) and 0.09 z -scores (95% CI: −0.00, 0.19). Differences in secondary outcomes were attenuated slightly after covariate adjustment. Conclusions In rural Nepal, fortified BEP dietary supplementation during pregnancy did not reduce the incidence of SGA births but resulted in small increases in infant head circumference and weight-for-gestational age centile. This trial was registered at clinicaltrials.gov as NCT03668977.