P104 Per- and poly-fluoroalkyl substances (PFAS) exposure in early life is associated with intestinal inflammation

Abstract Background Early life environmental exposures are linked with intestinal inflammation and inflammatory bowel disease (IBD) later in life. Per- and poly-fluoroalkyl substances (PFAS) are a large class of fluorinated organic chemicals used widely in consumer products that may be risk factors for IBD; however, the association between exposure to PFAS in early life and intestinal inflammation has not yet been studied. Dried blood spots (DBS) are archived neonatal capillary blood samples collected and stored as part of the New York State neonatal screening program and a cost-effective early life environmental exposure screening resource. Methods We measured 135 PFAS in DBS collected at birth from offsprings of women with and without IBD [n=37 (44%) and 47 (56%), respectively] enrolled in the MEChanisms Of disease traNsmission In Utero through the Microbiome (MECONIUM) cohort between January 2015 and November 2020, using untargeted metabolomics with liquid chromatography high-resolution mass spectrometry. In a subsample (n = 46), we also measured offspring fecal calprotectin (FC) at one year. We fitted exposome-wide regression models to estimate the association between each PFAS signal in the DBS and continuous FC at one year of age. For the significant associations (nominal p-value <0.05), we further explored potential effect modification by stratifying by maternal IBD status. All models were adjusted for relevant confounders. Results The mean (SE) of FC at age one year was 213.9 (23.8) ug/gm. The PFAS chemicals perfluoroundecanoic acid (PFUnDA) and N-ethyl-perfluorooctane sulfonamido acetic acid (N-Et-FOSAA) were significantly associated with increased scaled and log-transformed FC per decile increase in exposures [estimate (95% CI) = 0.52 (0.13,0.91) and 0.34 (0.05,0.63), Figure A]. Associations tended to be stronger in offspring of women with IBD relative to offspring of women without IBD (Figure B). estimate (95% CI) for the associations between PFUnDA and FC were 0.86 (0.34,1.39) and 0.12 (-0.47,0.71), respectively, and between N-Et-FOSAA and FC, these were 0.54 (-0.01,1.08) and 0.31(-0.07,0.68), respectively. Conclusion DBS can be used to measure early life exposure to toxins, and prenatal PFAS exposure is associated with elevated FC, with a slightly stronger effect in the offspring of women with IBD. Larger prospective studies are needed to validate these associations and understand potential underlying mechanisms through which early life PFAS exposures may contribute to IBD etiology.