Prenatal exposure to aromatic amines and associations with infant cognition in the ECHO.CA.IL cohorts

Aromatic amines (AAs) are carcinogenic compounds widely used in consumer products. However, few studies have assessed exposure to AAs during pregnancy, and no human studies have examined associations between AAs and infant cognition, despite in vitro evidence of neurotoxicity.

We conducted an analysis of prenatal AA exposure and infant cognitive outcomes using a subset of the Illinois Kids Development Study and Chemicals in Our Bodies, two prospective birth cohorts that together make up ECHO.CA.IL (N = 250).

AAs, including aniline, o/m-toluidine, 4-chloroaniline, o-anisidine, 4,4'methylenedianiline, and cotinine, were measured in 2^nd trimester urine samples and detected in >50% of participants. Infant cognition was assessed using a visual recognition memory (VRM) task administered using an infrared eye tracker at 7.5 months. We used linear regression to examine associations between individual natural log transformed AAs and their molar sum with VRM outcomes. We examined effect modification and interaction by child sex.

A natural log unit increase in ΣAAs and the individual analyte 4,4'methylenedianiline was associated with an increase in time to reach familiarization, suggesting poorer attention (β = 7.1, 95% confidence interval [CI] = -0.97, 15.16; β = 3.95, 95% CI = -0.27, 8.17, respectively). Cotinine was associated with worsening novelty preference (β=-0.01, 95% CI = -0.02, 0), indicating poorer working memory. Aniline was associated with an increase in time to reach familiarization only among females (p-value for interaction=0.06).

This is the first epidemiologic study to evaluate prenatal exposure to aromatic amines in relation to infant cognition. We leverage biomarkers of aromatic amines exposure during pregnancy and a sensitive, eye-tracking-based visual recognition memory task at 7.5 months to capture early cognitive domains rarely assessed in environmental epidemiology. By examining individual compounds, their molar sum, and sex-specific effects within a prospective cohort, this study extends concerns about aromatic amines beyond carcinogenicity to early neurodevelopment, highlighting a previously unrecognized pathway of potential harm during a critical developmental window.