Per- and Polyfluoroalkyl Substances in Early Life Are Associated With Childhood Intestinal Inflammation: Analyses of...

Early life exposures shape intestinal and immune development and later risk of inflammatory bowel disease. Per- and polyfluoroalkyl substances, or forever chemicals, are associated with intestinal inflammation and inflammatory bowel disease. However, the impact of early life per- and polyfluoroalkyl substances exposure on later intestinal inflammation is not known.

We conducted untargeted per- and polyfluoroalkyl substances analyses in early life samples from mother-offspring dyads across 3 cohorts. These included dried blood spots from offspring (n = 84) and cord blood (n = 93) from 2 prospective birth cohorts of mothers with and without inflammatory bowel disease in New York, New York, and maternal serum during pregnancy (n = 14) from a birth cohort in Mexico City, Mexico. Fecal calprotectin, a biomarker of intestinal inflammation, was measured longitudinally in offspring stool. Covariate-adjusted weighted quantile sum regression models were used to estimate associations between per- and polyfluoroalkyl substances and fecal calprotectin.

Per- and polyfluoroalkyl substances metabolites were detected across all sample types. Higher levels of per- and polyfluoroalkyl substances mixtures were associated with higher fecal calprotectin between 1 and 6 years of age in both dried blood spot and cord blood analyses (covariate-adjusted β estimates for change in log-transformed fecal calprotectin at age 6 years per decile increase in the per- and polyfluoroalkyl substances mixture was 0.44 [95% confidence interval, 0.18-0.70] and 0.69 [95% confidence interval, 0.53-0.85], respectively) Similarly, higher levels of per- and polyfluoroalkyl substances mixtures in maternal serum were associated with higher fecal calprotectin in late childhood (β, 0.19; 95% confidence interval, 0.05-0.33). Compared with mother-offspring dyads without maternal inflammatory bowel disease, those with maternal inflammatory bowel disease were more likely to have higher perfluoro-1-octane sulfonamide acetic acid and 3-perfluorohexyl-2-hydroxypropyl acrylate levels in dried blood spots and cord blood, respectively; these per- and polyfluoroalkyl substances metabolites were also the top contributors to offspring fecal calprotectin.

Per- and polyfluoroalkyl substances chemicals are detectable in early life samples, indicating exposure during this period of vulnerability, and are associated with higher fecal calprotectin in childhood across 3 birth cohorts.