Association Between Biomarkers of Environmental Enteric Dysfunction and Linear Growth and Neurodevelopment in Guatemalan Infants

Growing evidence implicates environmental enteric dysfunction (EED) as a driver of poor growth and neurodevelopment (ND) in early childhood. To investigate these findings, a cross-sectional study examining associations between biomarkers reflecting various domains of EED and growth and ND in Guatemalan infants was conducted. A subset of 114 cohort infants was randomly selected from a 2017-2019 population-based cohort study of 499 infants in rural southwest Guatemala. Growth and neurodevelopmental performance were assessed at a household visit at ∼13 months of age using the Mullen Scales of Early Learning (MSEL). Serum samples collected at the visit were analyzed for concentrations of biomarkers, assessing inflammation (α-1 acid glycoprotein), intestinal repair (glucagon-like peptide-2), and intestinal barrier disruption (anti-flagellin immunoglobulin A [anti-FliC IgA]). Multivariable regression analyses, adjusting for relevant confounders, were conducted to define the associations between these EED biomarkers and length-for-age z-scores (LAZ) and neurodevelopmental performance. Analyses both including and excluding infants who exhibited acute infectious disease symptoms at the time of the visit were planned. However, no significant associations were found between these biomarkers and LAZ or MSEL scores in the analysis of all children. Removing infants with acute infectious symptoms revealed an association between anti-FliC IgA and MSEL. Specifically, an increase of 10 ng/L in anti-FliC IgA concentration was associated with a decrease in the MSEL Early Learning Composite (ELC) raw score of 3.2 points, equating to approximately a nine-point decrease in the ELC standard score. Having higher levels of anti-FliC IgA may represent a significant risk to long-term health and development.