A methodologic framework for modeling and assessing biomarkers of environmental enteropathy as predictors of growth in infants: an example from a Peruvian birth cohort

Background: Environmental enteropathy (EE) impairs the gut's absorptive capacity and immune function and causes decelerations in statural growth that manifest gradually over time.Objective: To illustrate an approach for assessing emerging biomarkers of EE, we separately assessed the associations between 3 such markers and subsequent nutritional status.Design: Stool samples were routinely collected between January 2010 and November 2014 from a cohort of 303 Peruvian infants and analyzed for concentrations of the biomarkers α-1-antitrypsin (AAT), myeloperoxidase, and neopterin. For each marker, a mixed-effects linear regression model was fitted for length-for-age z scores (LAZs) obtained from anthropometric assessments that incorporated covariate predictors, polynomial terms for age, and product interaction terms to test associations over varying lag lengths. The biomarkers' contribution to the models was assessed with the use of the likelihood ratio test and partial R2 statistics.Results: Test statistics for the combined inclusion of the 4-model terms that involved the biomarker were highly statistically significant for AAT (28.71; P < 0.0001) and myeloperoxidase (62.79; P