Effect on birthweight of an antenatal multiple micronutrient supplementation programme compared with iron-folic acid supplementation: a cluster-randomised, controlled trial in 85 698 Ethiopian women.

Abstract

Prenatal multiple micronutrient supplementation (MMS) including iron, folic acid, and other essential micronutrients, has shown potential to improve birth outcomes in controlled studies. We did an effectiveness study in Ethiopia to determine the effect on mean birthweight of MMS provided as part of routine antenatal care, relative to iron-folic acid supplementation (IFA). A pragmatic, two-arm, facility-based, cluster-randomised controlled trial was conducted across 42 districts in five regions of Ethiopia to determine the effect on birthweight of MMS relative to IFA. Districts were randomly assigned to either retain IFA as part of routine antenatal care or switch to MMS. Randomisation was stratified by region and done using a random number generator within statistical software. All live singleton births at participating health facilities were eligible for inclusion and birthweights were recorded. Additionally, data were collected on maternal receipt and utilisation of MMS or IFA. The primary outcome was birthweight, analysed in the intention-to-treat population. This completed trial is registered at ClinicalTrials.gov, NCT05708183. Between Jan 1, 2023, and Dec 31, 2024, birthweights were recorded for 47 325 babies in the 21 IFA districts and 36 473 babies in the 21 MMS districts. Mean age of mothers was 26·2 years (SD 5·3) and median gestational age of babies at birth was 38 weeks (IQR 38-39). The effect of MMS on birthweight was a mean increase of 38 g (95% CI 20-55) in the MMS arm relative to the IFA arm after adjustment for time, geographical region stratification factor, gestational age, sex of baby, and parity. Among women who reported taking at least 90 tablets of their assigned supplement, the increase in mean birthweight in the MMS arm relative to the IFA arm was 58 g (38-79). Stillbirth risk was 7·5 per 1000 births in the IFA arm and 6·9 per 1000 births in the MMS arm. The findings of this trial are consistent with those from efficacy trials in other settings, indicating that the transition from IFA to MMS as part of routine antenatal care in Ethiopia could lead to a small but clear improvement in birthweight, although adherence to supplements and programme sustainability require careful attention. Children's Investment Fund Foundation.