The impact of cotrimoxazole on healthy birth and growth in rural Zimbabwe. (360G-Wellcome-108065_Z_15_Z)

The goal of this proposal is to evaluate the impact of cotrimoxazole, integrated with a package of nutrition interventions early in the lifecourse, on healthy birth and growth in rural Zimbabwe. Stunting is highly prevalent, begins in utero and causes increased mortality and reduced long-term productivity. Current nutrition-specific interventions have only a marginal impact. New approaches targeting mechanistic pathways early in the life-cycle are needed. We will use cotrimoxazole to test the hy pothesis that inflammation is a common mechanism underlying preterm birth, intrauterine growth restriction and postnatal stunting. We hypothesize that inflammation is driven predominantly by clinical and subclinical infections, abnormal micobiota composition and environmental enteric dysfunction, all of which will be impacted by cotrimoxazole. The specific questions are: 1) Does antenatal cotrimoxazole improve fetal growth and reduce prematurity? 2) Does postnatal cotrimoxazole improve li near growth? 3) Through what mechanistic pathways does cotrimoxazole operate? We will conduct a randomised clinical trial of cotrimoxazole, integrated with a package of evidence-based nutrition interventions, in two phases. First, women will receive a lipid-based nutrient supplement (LiNS) and nutrition education during pregnancy and will be randomised to daily cotrimoxazole or placebo, with a primary outcome of birth weight. Second, breastfeeding women will continue to receive LiNS and nut rition education; their infants will be randomised to daily cotrimoxazole or placebo, with a primary outcome of height-for-age Z-score at 6 months. Finally, we will investigate the impact of cotrimoxazole on underlying biological pathways to better understand its mechanism of action.