Elevated Levels of Environmental Enteric Dysfunction Biomarkers Among Rural Indonesian Infants: Associations with Water, Sanitation, Hygiene and Linear Growth.

Objective: To investigate the burden of environmental enteric dysfunction (EED) and its association with water, sanitation, and hygiene (WASH) and linear growth amongst infants in rural Central Java, Indonesia. Study design: A longitudinal study of 119 infants aged from 5-19 months was conducted in five villages of Wonosobo District, Central Java, Indonesia. Infant length and weight were measured at baseline and 5-month follow-up and stool samples were collected for the investigation of alpha-1-antitrypsin (AAT), neopterin (NEO), and myeloperoxidase (MPO) levels. Linear mixed-effects regression (LMER) models estimated the associations between WASH and height-for-age z-score (HAZ) on biomarker concentrations. Results: Biomarkers increased from baseline to follow-up where AAT, NEO, and MPO were elevated in 68.7%, 79.0%, and 71.4% of infants. Breastfed infants and infants with recent diarrhoea had higher biomarker levels than non-breastfed infants. After correction for multiple testing, few significant associations between EED biomarkers and WASH variables or HAZ were detected. EED biomarkers measured at baseline or follow-up were not significantly associated with growth faltering over the follow-up period. In cross-sectional analysis, compared to infants at risk of stunting (-2 < HAZ ≤ -1), infants with HAZ > -1 had lower AAT at baseline (β = -0.43, 95% CI = -0.82 to -0.05, padj < 0.05). Conclusions: Elevated EED biomarker levels were frequently observed and had mixed associations with WASH and HAZ, highlighting the complexity of EED and need to understand EED etiology through intervention studies.