Association between biomarkers of environmental enteric dysfunction and growth and neurodevelopment in Guatemalan infants

BACKGROUNDThere 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 -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. RESULTSNo 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. CONCLUSIONSIn 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. AUTHOR SUMMARYThere is growing evidence that a key driver of stunting and poor neurodevelopment in low-resource settings is environmental enteric dysfunction. Environmental enteric dysfunction is a subclinical condition of the small intestine that may include chronic mucosal inflammation and/or increased intestinal permeability; it is common in children experiencing repeated infections with fecal-oral pathogens. In this preliminary study, we examined the link between biomarkers of environmental enteric dysfunction and neurodevelopment in 114 infants. After excluding children with acute infectious symptoms (which could transiently modify biomarker levels), we found a strong link between one marker of EED and poor neurodevelopment, independent of child growth. Further research is warranted to explore the associations between EED and ND to guide future interventions to reduce these risks.