Individual and combined effects of maternal per- and polyfluoroalkyl substances exposure on preterm birth: a nested case-control study in China

Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic chemicals with ubiquitous human exposure. Maternal PFAS exposure has been linked with adverse birth outcomes, but their associations with preterm birth (PTB) remained ambiguous. To assess the associations of individual and mixed PFAS exposure with preterm birth (PTB) and its subtypes (spontaneous and iatrogenic), a nested case-control study involving 177 PTB cases and 531 controls was conducted in Shanghai, China. Serum concentration of seven PFAS were measured in early pregnancy via ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). PTB, gestational weeks and birth weight were obtained from electronic medical record system. Conditional logistic regression and restricted cubic spline regression (RCS) were used for individual assessment. Weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) were conducted for PFAS mixture. Subtype analysis and sex stratified analysis were further examined. Both individually and in mixtures, significant associations were observed between elevated PFAS concentrations and increased PTB risk, along with reduced gestational weeks and lower birth weight. The WQS, QGC, and BKMR identified perfluorooctanoic acid (PFOA), per-fluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) as the major contributors, with PFOA being particularly significant. Moreover, higher risks of PFAS-associated PTB were observed in the iatrogenic PTB subgroup and pregnant women with male infants. Maternal exposure to PFAS, whether individually or in mixtures, was significantly associated with increased risk of PTB. These associations might be subtype-specific and sex-specific. Further research is needed to validate our results and elucidate the underlying mechanisms.