BACKGROUND. There is growing evidence that environmental enteric dysfunction (EED) is a driver of poor growth and neurodevelopment (ND) in early childhood. To further investigate this, we measured the associations between biomarkers reflecting various domains of EED and growth and ND in Guatemalan infants. METHODS. A subset of 114 cohort infants were randomly selected for inclusion from a 2017-2019 population-based cohort study of 499 young infants in rural southwest Guatemala. Growth and neurodevelopmental performance using the Mullen Scales of Early Learning (MSEL) were assessed at a household visit around 12 months of age. Serum samples collected at the visit were analyzed for concentrations of α-1 acid glycoprotein (AGP), glucagon-like peptide-2 (GLP-2), and anti-flagellin IgA (Anti-FliC IgA), Multivariable regression analyses adjusted for relevant confounders were conducted to define associations between these EED biomarkers and length-for-age z-score (LAZ) and neurodevelopmental performance. We planned a priori to conduct analyses with and without excluding infants who had acute infectious disease symptoms (fever, cough, vomiting, diarrhea) at the 12-month visit. RESULTS. No significant association between biomarkers representing different domains of EED and LAZ or MSEL scores at 12-14 months of age was found. However, removing children with acute infectious symptoms uncovered an association between Anti-FliC IgA and MSEL. Specifically, an increase in 10ng/L in Anti-FliC IgA concentration was associated in a decrease in the MSEL Early Learning Composite (ELC) raw score of 3.2 points, which equates to approximately a 9-point decrease in the ELC standard score. CONCLUSIONS. In this study, having increased levels of Anti-FliC IgA was associated with lower ND in the first year of life and may represent an important risk to long-term health and development.

The authors have declared no competing interest.

This secondary analysis did not receive any funding.

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The institutional review board of the University of North Carolina at Chapel Hill gave ethical approval for this work.

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