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

Maternal undernutrition is a direct risk factor for infant growth faltering. We evaluated the effect of postnatal Balanced Energy Protein (BEP) supplementation in lactating women and Azithromycin (AZ) in infants on infant growth outcomes. 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 less than 23 cm and live infants between 0-6 days of life were randomly assigned to one of three 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 months of age. In intervention arm 1, mothers additionally received two 75-gram sachets of BEP per day, while in intervention arm 2 along with the standard-of-care and BEP, the infant also received one dose of Azithromycin (at 20 mg per kilogram) at 42 days of life. The primary outcome was infant length velocity at 6 months. The total sample size was 957 (319 in each arm). From August 1, 2018 to May 19, 2020, 319 lactating mother-newborn dyads were randomized in each arm, and the last follow-up was completed on November 20, 2020. The mean difference in length velocity (cm per month) between BEP alone and control was 0.01 (95% 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) non-fatal events (injectable treatment and/or hospitalizations) were recorded. Postnatal maternal BEP supplementation and infant AZ administration could modestly improve infant growth outcomes at 6 months, suggesting potential benefits in simultaneously addressing maternal and infant undernutrition. This trial is registered on ClinicalTrials.gov NCT03564652 on June 21, 2018.