The impact of enhancing nutrition and antenatal infection treatment on birth outcomes in Amhara, Ethiopia: a pragmatic factorial, cluster-randomised clinical effectiveness study

Introduction We aimed to determine the impact of antenatal interventions to optimise maternal nutrition and infection management on birth outcomes in Ethiopia. Methods We conducted a pragmatic, open-label, 2×2 factorial randomised clinical effectiveness study among pregnant women enrolled <24 weeks gestation in 12 rural health centres in Amhara, Ethiopia. Eligible health centres were randomised to deliver an enhanced nutrition package (ENP) (iron-folic acid, iodised salt and targeted micronutrient fortified balanced energy protein (BEP) supplementation for undernourished women) or routine nutrition care (iron-folic acid only). Individual women were randomised to receive an enhanced infection management package (EIMP) (genitourinary tract infection screening-treatment and enhanced deworming) or routine infection care (syndromic management). The primary outcomes were birth weight and length; secondary outcomes were gestational age, preterm delivery, small-for-gestational-age, low birth weight, stillbirth, newborn weight-for-age and length-for-age z-scores, newborn head circumference, and maternal anemia. Analysis was intention to treat. Results From August 2020 to December 2021, 2392 women were randomised (604 ENP+EIMP, 600 ENP alone, 593 EIMP alone and 595 neither package) and followed until June 2022, with 2170 pregnancy outcomes analysed (565 ENP+EIMP, 549 ENP, 525 EIMP, 531 neither). In the ENP arm, 427 (36%) women were eligible for BEP and consumed on average 74 days. The prevalence of genitourinary tract infection was low (4.9%), while parasitic stool infections were common (31%). There was no difference in birth weight (ENP vs not-ENP: adjusted mean difference −4 g (−83 to 75); EIMP vs not-EIMP: 18 g (−35 to 70); ENP+EIMP vs neither: 14 g (−81 to 109)) or birth length (ENP: −0.3 cm (−1.1 to 0.5); EIMP: 0.2 cm (−0.1 to 0.5); ENP+EIMP: −0.1 cm (−1.2 to 1.1)) between study arms. In the ENP+EIMP group, the stillbirth rate was lower compared with the arm receiving neither package (7.1/1000 vs 24.7/1000 births; adjusted relative risk: 0.29 (0.09 to 0.94)). The packages did not significantly affect other secondary outcomes. Conclusions In this pragmatic study implemented within the Ethiopian health system, enhanced nutrition and infection packages did not affect birth weight or length. While stillbirth rates were lower in the group receiving both packages, these findings need to be supported by additional studies. Trial registration number ISRCTN15116516.