Per-and polyfluoroalkyl substances exposure during pregnancy and adverse pregnancy and birth outcomes: A systematic review and meta-analysis

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with adverse pregnancy and birth outcomes; however, the findings have been inconsistent. We aimed to conduct a systematic review and meta-analysis to provide an overview of these associations. Methods: The online databases PubMed, EMBASE and Web of Science were searched comprehensively for eligible studies from inception to February 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using random- or fixed-effects models, and dose-response meta-analyses were also conducted when possible. Findings: A total of 29 studies (32,905 participants) were included. The pooled results demonstrated that perfluomoctane sulfonate (PFOS) exposure during pregnancy was linearly associated with increased preterm birth risk (pooled OR per 1-ng/ml increase: 1.01, 95% CIs: 1.00-1.02, P = 0.009) and perfluomnonanoate (PFNA) and perfluorooctanoate (PFOA) exposure showed inverted U-shaped associations with preterm birth risk (P values for the nonlinear trend: 0.025 and 0.030). Positive associations were also observed for exposure to perfluorodecanoate (PFDA) and miscarriage (pooled OR per 1-ng/ml increase: 1.87, 95% CIs: 1.15-3.03) and PFOS and preeclampsia (pooled OR per 1-log increase: 1.27, 95% CIs: 1.06-1.51), whereas exposure to perfluomundecanoate (PFUnDA) was inversely associated with preeclampsia risk (pooled OR per 1-log increase: 0.81, 95% CIs: 0.71-0.93). Based on individual evidence, detrimental effects were observed between PFDA exposure and small for gestational age and between PFOA and PFOS and intrauterine growth restriction. No significant associations were found between pregnancy PFAS exposure and other adverse pregnancy outcomes (i. e., gestational diabetes mellitus, pregnancy-induced hypertension, low birth weight, and large and small for gestational age). Interpretation: Our findings indicated that PFOS, PFOA and PFNA exposure during pregnancy might be associated with increased preterm birth risk and that PFAS exposure might be associated with the risk of miscarriage and preeclampsia. Due to the limited evidence obtained for most associations, additional studies are required to confirm these findings.

Automated summary

The study findings suggest that exposure to PFOS, PFOA, and PFNA during pregnancy may be associated with an increased risk of preterm birth, while PFAS exposure may be linked to the risk of miscarriage and preeclampsia. More research is needed to confirm these findings due to limited evidence for most associations.