Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to low birth weight but higher childhood weight and obesity. However, little is known regarding the associations between PFAS exposure and dynamic body mass index (BMI) trajectories, particularly from birth through preadolescence. To evaluate the associations of cord serum PFAS concentrations with BMI trajectories from birth to age 10 years and longitudinal BMI in different periods. Based on 887 mother-child pairs in the longitudinal prospective birth cohort, we measured 12 PFAS congeners in cord serum and calculated BMI with anthropometric indicators at 9 follow-up time points from birth to age 10 years. The BMI trajectories were identified using group-based trajectory model (GBTM). To estimate the associations of cord serum PFAS levels with BMI trajectories and longitudinal changes in BMI, logistic regression models, linear mixed models, Bayesian kernel machine regression, and quantile-based g-computation models (QGC) were used. The median concentrations of 10 PFAS congeners included in statistical analysis ranged from 0.047 to 3.623 μg/L. Two BMI trajectory classes were identified by GBTM, characterized by high group and low group. In logistic regression models, five PFAS congeners (PFBA, PFHpA, PFHxS, PFHpS, and PFDoDA) were associated with the higher probability of being in high BMI trajectory group (odds ratio, OR: 1.21 to 1.74, p < 0.05). Meanwhile, higher PFAS mixture were related to elevated odds for the high group in both BKMR models and QGC models, with PFHpA and PFHpS being the two most important drivers jointly. In the sex-stratified analysis, the positive associations remained significant exclusively among males. In the longitudinal analysis, PFUnDA and PFDoDA were associated with increased BMI from birth to age 10 years. Furthermore, PFBS and PFHpA were negatively related to BMI throughout infancy and toddlerhood (from birth to age 3 years), whereas PFDoDA confirmed a positive association with mid-childhood (from age 6 to 10 years) BMI. Prenatal PFAS exposure was positively associated with BMI trajectories from birth to preadolescence and longitudinal BMI in various periods. Future research could use better trajectory modeling strategies to shape more complete growth trajectories and explore the relationship between BMI trajectories and adulthood health.

Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) influences neurodevelopment. Thyroid homeostasis disruption is thought to be a possible underlying mechanism. However, current epidemiological evidence remains inconclusive. This study aimed to explore the effects of prenatal PFAS exposure on the intelligence quotient (IQ) of school-aged children and assess the potential mediating role of fetal thyroid function. The study included 327 7-year-old children from the Sheyang Mini Birth Cohort Study (SMBCS). Cord serum samples were analyzed for 12 PFAS concentrations and 5 thyroid hormone (TH) levels. IQ was assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models (GLM) and Bayesian Kernel Machine Regression (BKMR) were used to evaluate the individual and combined effects of prenatal PFAS exposure on IQ. Additionally, the impact on fetal thyroid function was examined using a GLM, and a mediation analysis was conducted to explore the potential mediating roles of this function. The molar sum concentration of perfluorinated carboxylic acids (ΣPFCA) in cord serum was significantly negatively associated with the performance IQ (PIQ) of 7-year-old children (β = -6.21, 95 % confidence interval [CI]: -12.21, -0.21), with more pronounced associations observed among girls (β = -9.57, 95 % CI: -18.33, -0.81) than in boys. Negative, albeit non-significant, cumulative effects were noted when considering PFAS mixture exposure. Prenatal exposure to perfluorooctanoic acid, perfluorononanoic acid, and perfluorooctanesulfonic acid was positively associated with the total thyroxine/triiodothyronine ratio. However, no evidence supported the mediating role of thyroid function in the link between PFAS exposure and IQ. Increased prenatal exposure to PFASs negatively affected the IQ of school-aged children, whereas fetal thyroid function did not serve as a mediator in this relationship.

Neonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. This study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. The study included 860 mother-child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of p-NNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. Higher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI (β = -0.15, 95 %CI: -0.26, -0.03), ∑DIN (β = -0.22, 95 %CI: -0.40, -0.03), ∑IMI (β = -0.20, 95 %CI: -0.35, -0.06) and ∑NNIs (β = -0.23, 95 %CI: -0.42, -0.04). ∑IMI and ∑DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between ∑DIN and TT3 (β = -0.013, 95 %CI: -0.025, -0.002), ∑IMI and T (β = -0.035, 95 %CI: -0.065, -0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal ∑DIN and ∑IMI exposure with head circumference. Our findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.

Gestational exposure to manganese (Mn), an essential trace element, is associated with fetal and childhood physical growth. However, it is unclear which period of growth is more significantly affected by prenatal Mn exposure. The current study was conducted to assess the associations of umbilical cord-blood Mn levels with birth outcomes and childhood continuous physical development. The umbilical cord-blood Mn concentrations of 1179 mother–infant pairs in the Sheyang mini birth cohort were measured by graphite furnace atomic absorption spectrometry (GFAAS). The association of cord-blood Mn concentrations with birth outcomes, and the BMI z-score at 1, 2, 3, 6, 7 and 8 years old, were estimated separately using generalized linear models. The relationship between prenatal Mn exposure and BMI z-score trajectory was assessed with generalized estimating equation models. The median of cord-blood Mn concentration was 29.25 μg/L. Significantly positive associations were observed between Mn exposure and ponderal index (β, regression coefficient = 0.065, 95% CI, confidence interval: 0.021, 0.109; p = 0.004). Mn exposure was negatively associated with the BMI z-score of children aged 1, 2, and 3 years (β = −0.383 to −0.249, p < 0.05), while no significant relationships were found between Mn exposure and the BMI z-score of children at the age of 6, 7, and 8 years. Prenatal Mn exposure was related to the childhood BMI z-score trajectory (β = −0.218, 95% CI: −0.416, −0.021; p = 0.030). These results indicated that prenatal Mn exposure was positively related to the ponderal index (PI), and negatively related to physical growth in childhood, which seemed most significant at an early stage.

Per- and polyfluoroalkyl substances (PFAS) have been suspected as potential environmental obesogens, with several mechanisms being proposed, including the role of metabolomics. However, current epidemiological studies have yielded inconclusive findings. We aimed to estimate the associations of prenatal exposure to PFAS with offspring adiposity measures, and to explore the potential metabolic pathways underlying these associations. A total of 464 mother-child pairs from the Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. Cord serum concentrations of 12 PFAS and urine metabolite profiles at age 10 were obtained from the SMBCS database. Adiposity-related anthropometric measurements and body composition estimates of children aged 10 were used to assess offspring obesity. Multiple linear regression models and quantile g-computation were conducted to estimate the associations of prenatal exposure to individual and multiple PFAS with obesity at 10 years old. Metabolomics analysis was performed to characterize the biological pathways associated with PFAS exposure or obesity, subsequently identifying the overlapping metabolic pathways underlying the PFAS-obesity relationship. Prenatal exposure to several PFAS was significantly associated with elevated obesity-related markers in 10-year-old children. After stratification by sex, the effects were more pronounced in girls. Quantile g-computation results indicated that exposure to higher levels of PFAS mixtures during pregnancy was associated with increased odds of obesity in girls, with PFNA emerging as the predominant driving compound. Untargeted metabolomics results showed that several amino acid metabolic pathways were characterized as the overlapping pathways underlying the above associations. Taken together, our findings suggested the potential obesogenic effects of prenatal exposure to PFAS and offered insight into the possible metabolic mechanisms underlying PFAS-related offspring obesity.