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Prenatal exposure to fine particulate matter (PM2.5) has been linked with increased neurodevelopmental disorders. However, the most detrimental component of PM2.5 and the most vulnerable exposure time windows remain undetermined, especially in areas with high PM2.5 levels. In a prospective cohort study involving 4494 mother-child dyads, we examined the associations of prenatal exposure to PM2.5 and its four main components with children's neurodevelopmental and behavioral problems (NBPs), separately in three pregnancy trimesters. Poisson regression and generalized additive models were used to depict the linear and nonlinear associations, respectively. Weighted quantile sum and Bayesian kernel machine regression models were applied to examine the effects of exposure to both mixed and individual components. Results showed that exposure to PM2.5 and its components throughout the three trimesters increased the risk of children's NBPs (Risk ratio for PM2.5: 1.16, 95 % confidence interval 1.14–1.18 per μg/m3 in the first trimester; 1.15, 1.12–1.17 in the second trimester; 1.06, 1.04–1.08 in the third trimester), with associations gradually diminishing as pregnancy progressed (P values for trends < 0.05). Among the four main components of PM2.5, exposure to SO42- posed the highest risks on children's NBPs, while organic matter contributed the largest proportion to the overall impacts of PM2.5 exposure. These results underscore the significance of mitigating PM2.5 exposure in pregnant women to reduce the risk of neurodevelopmental disorders in offspring. Our findings would inform risk assessment of PM2.5 exposure and facilitate the development of precision preventive strategies targeting specific components of PM2.5 in similar areas with high levels of exposure.

Background: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. Methods: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. Results: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. Conclusions: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Fetal sex hormone homeostasis disruption could lead to reproductive and developmental abnormalities. However, previous studies have reported inconsistent findings regarding the association of maternal per- and polyfluoroalkyl substances (PFAS) exposure with fetal sex hormone levels. A total of 277 mother-infant pairs from the Guangxi Zhuang Birth Cohort Study between 2015 and 2019 were selected. We quantified nine PFAS in maternal serum in early pregnancy, and detected three sex hormones, namely, estradiol (E2), progesterone (P4) and testosterone (TT), in cord blood. The generalized linear model (GLM) and Bayesian kernel machine regression (BKMR) model were used for single- and multiple-exposure analyses, respectively. In the GLM, there was no significant association between an individual PFAS and any hormone level or the E2/TT ratio, but a negative association between perfluorododecanoic acid (PFDoA) exposure and P4 levels in female infants was observed after stratification by sex. In the BKMR, a mixture of nine PFAS was positively associated with E2 levels and the E2/TT ratio, with the same main contributors, i.e., perfluoroundecanoic acid (PFUnA). And PFAS mixtures were not associated with P4 or TT levels. After stratification by infant sex, positive associations of PFAS mixtures with E2 levels and the E2/TT ratio were observed only in male infants, with the same main contributors, i.e., PFUnA. There was a positive association between PFAS mixtures and P4 levels in male infants, in which PFUnA was the main contributor; but a reverse association between PFAS mixtures and P4 levels in female infants, in which PFDoA was the main contributor. This study suggested that prenatal exposure to PFAS mixtures is associated with fetal sex hormones, and long-chain PFAS may play an important role in this association. Furthermore, sex differences in the association of maternal PFAS exposure with E2 and P4 levels need additional attention.

Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide, and it may be caused by environmental endocrine disruptors. Prenatal exposure to perfluoroalkyl substances (PFASs) in women has been linked to pregnancy disorders and adverse birth outcomes, but no data are available on the relationship between PFAS exposure during pregnancy and postpartum haemorrhage. This study aimed to explore the associations of maternal PFAS exposure with the postpartum haemorrhage risk and total blood loss. A total of 1496 mother-infant pairs in the Guangxi Zhuang birth cohort were included between June 2015 and May 2018. The concentration of PFASs in serum was detected using ultrahigh liquid chromatography-tandem mass spectrometry. Multiple binomial regression and linear regression models were used to analyse individual PFAS exposures. The mixture of PFASs was analysed using Bayesian Kernel Machine Regression (BKMR). In single substance exposure models, exposure to perfluorohexanesulfonic acid (PFHxS) increased the risk of postpartum haemorrhage (OR: 3.42, 95 % CI: 1.45, 8.07), while exposure to perfluorododecanoic acid (PFDoA) was inversely associated with the risk of postpartum haemorrhage (OR: 0.42, 95 % CI: 0.22, 0.80). The concentrations of perfluoroundecanoic acid (PFUnA) (β: 0.06, 95 % CI: 12.32, 108.82) and perfluorononanoic acid (PFNA) (β: 0.05, 95 % CI: 0.40, 88.95) exposure were positively correlated with the amount of postpartum haemorrhage; this result occurred only in the absence of covariate adjustment. In BKMR models, the risk of postpartum haemorrhage increased with increasing exposure to a PFAS mixture. In conclusion, our study suggested that maternal serum PFAS exposure during pregnancy was associated with the risk of postpartum haemorrhage.

Preterm birth (PTB), a serious adverse birth outcome, is the leading cause of perinatal mortality and morbidity. Bisphenols induce endocrine disruption that spreads across the placenta, which may affect fetal growth and development. However, the effects of bisphenols on PTB, particularly their combined effects, remain unknown. This study investigated the association between prenatal bisphenol exposure and PTB. Study participants were 2023 mother-infant pairs that were selected from the Guangxi Zhuang Birth Cohort. Maternal serum bisphenol levels were measured using ultrahigh performance liquid chromatography-tandem mass spectrometry, and pregnancy outcomes were obtained from medical records. Multivariate logistic regression, restricted cubic spline, principal component analysis (PCA), quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR) were used to examine the association between serum bisphenol levels and PTB. Ln-transformed BPA concentrations were associated with an increased risk of PTB only in female infants (OR = 1.30, 95% CI: 1.02, 1.64). Ln-transformed bisphenol F (BPF) concentrations were positively associated with the risk of PTB (OR = 1.73, 95% CI: 1.18, 2.55). Inverse U-shaped relationships were observed between bisphenol B (BPB), bisphenol S (BPS), and tetrabromobisphenol A (TBBPA) levels and the risk of PTB (P-overall < 0.05, P-non-linear < 0.05). After sex stratification, the association between BPA analogs and PTB was only observed in males. In Qgcomp analysis, bisphenol mixtures were related to an increased risk of PTB (OR = 1.52, 95% CI: 1.04, 2.21), with BPF (43.7%), BPS (29.6%) and BPA (26.8%) having the greatest positive contribution. Results indicate that prenatal exposure to bisphenol mixtures might increase the risk of PTB, which might be primarily driven by BPA, BPF and BPS. There may also be sex-specific and nonmonotonic dose-dependent effects.