Associations between maternal exposure to per- and polyfluoroalkyl substances and functional constipation in children at 3 and 4 years: the Japan Environment and Children’s Study

Abstract

Background: Research over the past decade has indicated that exposure to per- and polyfluoroalkyl substances (PFAS) disrupts the intestinal barrier, potentially contributing to the development of gastrointestinal disorders. More recently, constipation has been hypothesized as one such outcome. However, epidemiological studies examining this association remain limited.

Methods: We analyzed data from 17,686 mothers and their children from the Japan Environment and Children’s Study, a Japanese birth cohort study. We used maternal plasma samples collected during pregnancy to determine PFAS concentrations. Of the 28 PFAS compounds analyzed, we included seven compounds that were quantified in more than 80% of the samples. We assessed functional constipation in children at ages 3 and 4 using caregiver-completed questionnaires based on the Rome III criteria. Logistic regression models were used to examine associations between maternal PFAS concentrations and childhood functional constipation, applying a Bonferroni-corrected significance threshold of P < 0.0035 to account for multiple comparisons.

Results: Functional constipation was observed in 11.3% of children at age 3 and 9.8% at age 4. After adjusting for potential confounders, we observed no significant associations between any of the seven maternal PFAS concentrations and functional constipation in children at 3 years of age. However, at 4 years, perfluorooctanoic acid (PFOA) concentrations were significantly associated with functional constipation, with an adjusted odds ratio of 1.13 (95% confidence interval: 1.05–1.21, P = 0.00057) per doubling of concentration. The remaining six PFAS compounds showed no significant associations at 4 years.

Conclusions: The single positive association between maternal PFOA concentration and functional constipation at 4 years of age is unlikely to reflect a true causal relationship, given limited biological plausibility. Our results do not provide evidence of an association between prenatal PFAS exposure and functional constipation in children, although further investigation is warranted.