Effects of water, sanitation, handwashing, and nutritional interventions on environmental enteric dysfunction in young children: a cluster-randomized controlled trial in rural Bangladesh

BACKGROUND:We hypothesized that drinking water, sanitation, handwashing (WSH) and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting. METHODS:Within a subsample of a cluster-randomized controlled trial in rural Bangladesh, we enrolled pregnant women in four arms: control, combined WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and combined nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1β) at median ages 3, 14, and 28 months. Analysis was intention-to-treat. RESULTS:We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L, CI -0.37, -0.05) and N+WSH (-0.20 log nmol/L, CI -0.34, -0.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH (0.23 log ng/ml, CI 0.06, 0.39) and nutrition (0.27 log ng/ml, CI 0.07, 0.47) arms and lactulose was higher in the WSH arm (0.30 log mmol/L, CI 0.07, 0.53). CONCLUSIONS:Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of better understanding the pathophysiology of EED and targeting interventions early in childhood during the critical period when they are likely to have the largest benefit to intestinal health.(ClinicalTrials.gov NCT01590095).