Fetal exposure to perfluoroalkyl substances (PFAS) in drinking water and congenital malformations: A nation-wide register-based study on PFAS in drinking water

Abstract

Background: Teratogenic properties of perfluoroalkyl substances (PFAS) have been assessed in a few studies, however, epidemiological evidence for an association is inconclusive. Objectives: We conducted a Swedish nation-wide register-based cohort study to assess the associations of estimated fetal exposure to the sum of drinking water perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) with major congenital malformations. Methods: We included all births in Sweden during 2012-2018 of mothers residing ≥four years prior to partus in localities served by municipal drinking water where PFAS concentrations have been measured in drinking water. We estimated the fetal PFAS4 exposure by using a one-compartment toxicokinetic model - including maternal residential history, municipal PFAS water concentration and year-specific PFAS maternal background concentrations as input data - and accounting thereafter PFAS-specific transplacental transfer factors to estimate the fetal PFAS4 exposure. By register linkage we obtained birth outcomes and covariates. Odd ratios (OR) and 95 % confidence intervals (CI) of the associations between estimated PFAS in foetuses and major congenital malformations were estimated by logistic regressions and, complementary, by quantile g-computation regression for mixture effects. Results: Analyses of 256,659 newborns of which 5,357 were diagnosed with major congenital malformations, revealed associations between fetal PFAS4 exposure and malformations on the nervous system OR, 2.84 (95 % CI: 1.38-5.84, p-trend: 0.008) and chromosomal anomalies OR, 1.50 (95 % CI: 1.07-2.10, p-trend: 0.009) comparing extreme quartiles. For the individual PFAS and in the quantile g-computation model, there were indications of an association between PFAS and urinary defects, OR 1.96 (95 % CI: 1.59-2.43, p-trend mixed effect: <0.001), primarily driven by PFOA and PFHxS. Discussion: Modelled fetal sum of PFAS4 was associated with malformations of the nervous system and chromosomal anomalies, while the mixture assessment revealed associations with defects on urinary system. As the underlying toxicological mechanisms remains unclear, further investigation is warranted.