Environmental exposure to per- and perfluoroalkyl substances in early pregnancy and newborn anogenital distance: A prospective cohort study

Abstract

Per- and polyfluoroalkyl substances (PFAS) are persistent, ubiquitous pollutants, and the current epidemiological evidence regarding the impact of in utero exposure to PFAS on anogenital distance (AGD) is limited and inconclusive. The primary aim of this study was to investigate the potential associations between maternal exposure to PFAS during pregnancy and AGD in newborns. A total of 2273 mother-child pairs were recruited for this study, and both PFAS levels and AGD were measured. Multiple linear regression models were utilized to explore the relationships between individual PFAS and AGD. Additionally, quantile-based g-computation (QGC) was employed to assess the joint effects of mixtures of PFAS on AGD. Our findings showed that maternal exposure to PFOS (β = 0.518, 95% CI: 0.093, 0.942), PFNA (β = 0.487, 95% CI: 0.037, 0.937), PFDA (β = 0.443, 95% CI: 0.048, 0.838), PFUA (β = 0.434, 95% CI: 0.031, 0.838), and PFBS (β = 0.444, 95% CI: 0.124, 0.763) during early pregnancy had a significant positive association with AGD in boys. Similarly, in girls, maternal exposure to PFOS (β = 0.423, 95% CI: 0.006, 0.841), PFNA (β = 0.641, 95% CI: 0.207, 1.074), PFDA (β = 0.670, 95% CI: 0.306, 1.033), PFUA (β = 0.895, 95% CI: 0.509, 1.281), and PFBS (β = 0.474, 95% CI: 0.178, 0.770) had a positive association with AGD, while PFOA (β = -1.254, 95% CI: -1.786, -0.723) had a negative association. QGC models further confirmed that PFAS mixtures were positively associated with AGD. Moreover, PFBS was the primary contributor to the joint effects of PFAS mixtures on AGD. In summary, our study has provided further corroboration for the possibility that PFAS exposure can have an impact on AGD in both boys and girls. The use of AGD as a promising biomarker for endocrine disruption highlights the significance of our findings, which may have valuable clinical implications for reproductive diseases.

Keywords: Anogenital distance (AGD); In utero exposure; Joint effects; Per- and polyfluoroalkyl substances (PFAS); Quantile-based g-computation (QGC).