Effect of maternal postnatal balanced energy protein supplementation and infant azithromycin on infant growth outcomes: an open-label randomized controlled trial

Background: Maternal undernutrition is a direct risk factor for infant growth faltering. Objectives: We evaluated the effect of postnatal balanced energy protein (BEP) supplementation in lactating women and azithromycin (AZ) in infants on infant growth outcomes. Methods: A randomized controlled superiority trial of lactating mother–newborn dyads was conducted in Karachi, Pakistan. Mothers intending to breastfeed their newborns with mid-upper arm circumference of <23 cm and live infants between 0 and 6 d of life were randomly assigned to 1 of 3 arms in a 1:1:1 ratio. Lactating mothers in the control arm received standard-of-care counseling on exclusive breastfeeding, nutrition, infant immunization, and health promotion plus iron-folate supplementation until the infant was 6 mo old. In intervention arm 1, mothers additionally received two 75-g sachets of BEP per day. In intervention arm 2, along with the standard-of-care and BEP to the mother, the infant also received 1 dose of azithromycin (20 mg/kg) at the age of 42 d. The primary outcome was infant length velocity at 6 mo. The total sample size was 957 (319 in each arm). Results: From 1 August, 2018 to 19 May, 2020, 319 lactating mother–newborn dyads were randomly assigned in each arm, and the last follow-up was completed on 20 November, 2020. The mean difference in length velocity (cm/mo) between BEP alone and control was 0.01 (95% confidence interval [CI]: −0.03, 0.06), BEP plus AZ and control was 0.08 (95% CI: 0.03, 0.13), and between BEP + AZ and BEP alone was 0.06 (95% CI: 0.01, 0.11). There were 1.46% (14/957) infant deaths in the trial, and 17.9% (171/957) nonfatal events (injectable treatment and/or hospitalizations) were recorded. Conclusions: Postnatal maternal BEP supplementation and infant AZ administration could modestly improve infant growth outcomes at 6 mo, suggesting potential benefits in simultaneously addressing maternal and infant undernutrition. This trial was registered at clinicaltrials.gov as NCT03564652.