Gestational exposure to poly/perfluoroalkyl substances and risk of congenital structural malformations: A nested case-control study

Abstract

Congenital structural malformations (CSM) have become a significant public health and social issue, affecting the health status of children and the level of population quality. Emerging research increasingly suggests that environmental pollutants may contribute to the development of CSM. However, current epidemiologic evidence on the effects of per- and polyfluoroalkyl substances (PFAS) on CSM is limited and restrictive. A nested case-control study examined how maternal exposure to PFAS during pregnancy affects the risk of CSM. Logistic regression and Bayesian kernel machine regression (BKMR) were used to assess the effects of single PFAS and PFAS mixture exposure on CSM. Perfluorodecanoic acid (PDA) showed a strong positive association with CSM in the logistic regression model (Adjusted OR: 4.79, 95 % CI: 1.55 ∼ 18.52). The BKMR analysis indicated an increased risk of CSM as PFAS mixture levels rose above the 55th percentile. Individual PFAS were ranked by posterior inclusion probabilities (PIPs), with PDA (PIP = 1.00), perfluorooctanoic acid (PFOA) (PIP = 1.00), potassium 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (9Cl_PF3ONS) (PIP = 0.88), and perfluorononanoic acid (PFNA) (PIP = 0.82) contributing most to the mixture’s effect on CSM. No significant interactions were observed between PFAS mixtures when other exposures were held constant at the 50th percentile. In conclusion, we found that prenatal exposure to PDA and PFAS mixtures was significantly linked to a heightened risk of CSM, with PDA, PFOA, 9Cl_PF3ONS, and PFNA being significant contributors to the mixture effect. In addition, our study did not identify any previous interactions of PFAS.