Aug 2026· Environmental Research· Vol 307, pp.
125429
· 0 citations· 42 references
Medicine
TL;DR
The findings add to a limited evidence base on prenatal PFAS exposure and parent-reported sleep-related behaviors in early childhood and warrant confirmation in future studies that incorporate harmonized trimester-specific exposure assessment, objective sleep measures, and mixture-based analytic approaches.
Abstract
Per- and polyfluoroalkyl substances (PFAS) are persistent endocrine-disrupting chemicals that readily cross the placenta and may interfere with hormonal systems essential for neurodevelopment and circadian regulation. We examined associations between prenatal exposure to individual PFAS and early childhood sleep quality. The analytic sample included 2,836 mother-child pairs from 14 study sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort. We assessed Child Behavior Checklist (CBCL) Sleep Problems T-scores from ages 1-5 years. Maternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) were measured during pregnancy. Linear mixed-effects models with random intercepts estimated associations between log2-transformed PFAS concentrations and CBCL scores, with covariate adjustment. The mean maternal age was 29.6 years, and the sample was racially and socioeconomically diverse (43% non-Hispanic White, 24% Black, and 23% Hispanic; 27% holding advanced degrees; and 36% reporting annual incomes <$30,000). In adjusted analyses, higher prenatal PFOA concentrations were associated with higher CBCL sleep problem scores in early childhood (β=0.13; 95% CI: 0.05, 0.21). Associations for PFOS, PFNA, and PFHxS were small and not statistically significant. Higher prenatal PFOA concentrations were associated with modestly higher CBCL Sleep Problems T-scores during early childhood, while associations for PFOS, PFNA, and PFHxS were small and imprecise. Although the magnitude of the observed PFOA association was modest, the findings add to a limited evidence base on prenatal PFAS exposure and parent-reported sleep-related behaviors in early childhood and warrant confirmation in future studies that incorporate harmonized trimester-specific exposure assessment, objective sleep measures, and mixture-based analytic approaches.
OBJECTIVE
To examine the association between prenatal exposure to a mixture of EDCs and attention-deficit/hyperactivity disorder (ADHD) symptoms in children.
METHODS
Participating were mother-child pairs from the Environmental influences on Child Health Outcomes (ECHO) Cohort (n = 3,962, 18 Sites, 2001-2021). Maternal spot urine samples collected during pregnancy were sent to the Wadsworth Center Human Health Exposure Analysis Resource laboratory and analyzed using a single assay workflow. From those samples, 24 urinary metabolites of EDCs with detection frequency > 70%, were grouped as molar sum of high- and low-molecular-weight phthalates, polycyclic aromatic hydrocarbons, bisphenol S, organophosphate esters, and organophosphate and pyrethroid pesticides. Child ADHD symptoms were assessed using raw scores from the Child Behavior Checklist for preschool-aged (CBCL/1½-5) and school-aged (CBCL/6-18) Attention-Deficit/Hyperactivity Problems subscale. Scores ≥ the 85th and 95th percentiles were respectively classified as borderline and clinical thresholds. Quantile g-computation estimated the expected change in ADHD outcome associated with a one-quartile increase in all prenatal EDC mixture concentrations, using negative binomial models for raw scores and binomial models for percentile thresholds.
RESULTS
Prenatal exposure to the EDC mixture was not associated with child ADHD symptoms in preschool-aged or school-aged children in adjusted models for either continuous raw scores or percentile thresholds.
CONCLUSION
Overall our findings on prenatal EDC mixture exposure and ADHD symptoms were not robust to full adjustment. Future research that can delineate factors such as windows of vulnerability and trajectories of ADHD-related symptoms may help clarify mixed findings in the literature.
Teresa Herrera, Sara Hyman, Roger Newman et al.· Environment International· 0 citations
Early-life exposure to PAE mixtures is associated with sex-specific alterations in reproductive hormone levels during minipuberty, highlighting minipuberty as a sensitive window for endocrine disruption and underscore the importance of considering chemical mixtures in environmental health research.
V. Trevisani, L. Lucaccioni, Federico Starace et al.· Frontiers in Endocrinology· 0 citations
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be associated with child neurodevelopment, but evidence based on fetal-proximal exposure biomarkers, mixture effects, and domain-specific outcomes remains limited.
In the Shanghai Birth Cohort (
n
= 1,668 mother-child pairs), we quantified 32 PFAS compounds in umbilical cord blood and assessed neurodevelopment at 24 months using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Associations were evaluated using adjusted single-pollutant regression models as the primary analyses. Developmental risk defined as BSID-III composite score < 90 was evaluated as a complementary outcome, and weighted quantile sum (WQS) regression was used to evaluate PFAS mixture associations.
Nineteen PFAS compounds had detection rates greater than 65% and were included in association analyses. In adjusted single-pollutant models, several long-chain PFAS were inversely associated with cognitive and language scores. PFNA was associated with lower cognitive (β = −5.39, 95% CI: −7.22, − 3.57) and language scores (β = −3.62, 95% CI: −4.94, − 2.31), as well as higher odds of cognitive developmental risk defined as BSID-III score < 90 (OR = 1.95, 95% CI: 1.40, 2.71). PFUdA, PFTrDA, and PFDoA showed similar inverse associations. The emerging substitute 8:2 Cl-PFESA was also inversely associated with cognitive (β = −1.86, 95% CI: −2.52, − 1.19) and language scores (β = −1.21, 95% CI: −1.68, − 0.73). PFHxA was positively associated with cognitive (β = 1.53), language (β = 0.83), and motor scores (β = 1.15), and PFOA was positively associated with cognitive scores (β = 3.37). In negative-direction WQS regression, the PFAS mixture index was inversely associated with cognitive (β = −4.66, 95% CI: −6.51, − 2.80) and language scores (β = −3.14, 95% CI: −4.65, − 1.63), whereas associations with motor, social-emotional, and adaptive behavior scores were less consistent. No consistent associations were observed for social-emotional or adaptive behavior domains after FDR correction.
Higher cord blood concentrations of selected long-chain PFAS and 8:2 Cl-PFESA were associated with lower cognitive and language performance at 24 months. WQS regression also suggested inverse mixture associations with cognitive and language scores, but these mixture findings should be interpreted cautiously because WQS is directionally constrained and single-pollutant results were not uniformly in the same direction. These findings support continued evaluation of legacy and emerging PFAS in relation to early neurodevelopment.
Yiming Li, Bin Wu, Shiyang Li et al.· Environmental Health· 0 citations
BackgroundExposure to per- and polyfluoroalkyl substances (PFAS) is linked to reduced fetal growth, yet little is known about potentially modifiable factors that may mitigate these harmful effects.AimIn this study, we assessed whether prenatal dietary factors, including folate, vitamin D, and dietary inflammation, may modify the inverse associations between prenatal PFAS exposure and birthweight for gestational age z-scores (BWZ).MethodsParticipants were a subset of the prospective Atlanta African American Maternal-Child Cohort (N = 268, delivery dates between 2014 and 2018), which includes serum and dietary intake data. Serum collected at 8-14 weeks' gestation was analyzed for four PFAS (perfluorohexane sulfonic acid, perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid) and total and free 25-hydroxyvitamin D (25(OH)D). A semi-quantitative food frequency questionnaire administered during early pregnancy was used to ascertain dietary folate equivalents (DFE) and dietary inflammatory index (DII) over the last three months. We used linear regression stratified by dichotomized dietary measures (DFE, total and free 25(OH)D, and DII) to assess effect modification of the association between individual PFAS and BWZ. Mixture effects were estimated using quantile-based g-computation and Bayesian kernel machine regression.SummaryA natural log increase in PFOS and PFOA was more strongly associated with lower BWZ only among participants with pro-inflammatory diets (DII ≥75th percentile) or low 25(OH)D (total 25(OH)D < 75th percentile). Similar patterns were observed in PFAS mixture analyses (e.g. ΨDII≥75thpercentile = -0.47, 95% CI = -0.77, -0.18, and ΨDII<75thpercentile = -0.08, 95% CI = -0.24, 0.07). Overall, maternal dietary factors may influence susceptibility to PFAS-related fetal growth effects.
Yun-Jie Huang, Dong-Hai Liang, Anne L. Dunlop et al.· Nutrition and Health· 0 citations
Bile acids (BAs) are crucial signaling molecules in neurodevelopment, and per- and polyfluoroalkyl substances (PFAS) exposure has been linked to adverse neurodevelopmental outcomes. However, the role of specific BAs in modifying the association between PFAS and longitudinal neurodevelopmental trajectories remains unknown. We quantified 32 PFAS in maternal serum and 17 BAs in serum from 3-year-old children in the Maoming Birth Cohort. Neurodevelopment was repeatedly evaluated using age-standardized instruments. PFAS effects were evaluated by logistic regression and grouped weighted quantile sum (GWQS). Random forest analysis identified six primary conjugated BAs associated with low neurodevelopmental trajectories, and their interactions with PFAS were assessed. Group-based trajectory modeling identified two neurodevelopmental trajectories: persistently high (n = 242) and low (n = 36). Higher prenatal levels of legacy PFAS were associated with low neurodevelopmental trajectories. GWQS regression revealed mixture effects for legacy PFAS [odds ratio (OR) = 2.18, 95% confidence interval (CI): 1.01-4.73]. Primary conjugated BAs [e.g., taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA)] modified the observed associations. The odds of perfluorooctane sulfonate-associated low neurodevelopmental trajectories were greater for children with lower TCDCA levels (OR = 2.70; 95%CI: 1.02-7.17; Pfor interaction = 0.0063) than for those with higher levels. Children with higher TCA levels exhibited lower odds of low neurodevelopmental trajectories than those with lower levels (Pfor interaction = 0.0088). Our findings provide longitudinal evidence on PFAS-related lower neurodevelopment and identify primary conjugated BAs as significant effect modifiers. The mechanisms underlying this effect modification require further investigation.
Qiong Zhang, Yan-Xi Li, Hua-Lian Chen et al.· Journal of Environmental Exp...· 0 citations
Although neurotoxic, prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) and their effects on preschoolers' autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) cotrajectories and underlying metabolic mechanisms remain unclear, we aimed to elucidate these links. Maternal urinary OPEs/PAEs were measured in 3040 dyads from the Ma'anshan Birth Cohort across three trimesters. Child ADHD/ASD symptom scale scores were assessed at ages 3, 5, and 6, and cotrajectories were identified using group-based multitrajectory modeling. Single-pollutant models revealed that bis(2-ethylhexyl) phosphate (BEHP) across pregnancy was positively associated with high-score trajectories (HST) (OR = 1.20, 95% CI: 1.06, 1.37), whereas bis(2-butoxyethyl) phosphate (BBOEP) exhibited U-shaped associations. Second-trimester diphenyl phosphate (DPHP) (OR = 1.13, 95% CI: 1.01, 1.26), BEHP (OR = 1.14, 95% CI: 1.04, 1.24), and monobutyl phthalate (OR = 1.15, 95% CI: 1.00, 1.32) were positively associated with HST. First-trimester DPHP exhibited a positive correlation with moderate-score trajectories and HST in girls, while bis(1-chloro-2-propyl) phosphate across pregnancy was inversely associated with HST in boys (psex-int < 0.05). No mixed effects were detected. BBOEP across pregnancy was negatively associated with ADHD symptoms, whereas BEHP was positively associated. BEHP, monomethyl phthalate, and mono-(2-ethyl-5-oxohexyl) phthalate were positively associated with ASD symptoms, whereas dibutyl phosphate and monoethyl phthalate were negatively associated (p < 0.05). Cord blood metabolomics identified pyrimidine, biotin, lysine, cysteine, and methionine metabolism as key mediators of OPE-induced cotrajectories, and purine metabolism mediated PAEs' effects (p < 0.05). This study highlights OPE/PAE neurotoxicity and reveals novel cord metabolomic insights.
Xing Wang, J. Tong, Meng-Juan Lu et al.· Environmental Science and Te...· 0 citations
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