Associations of Prenatal Per- and Polyfluoroalkyl Substance Exposure with Neonatal Birth Weight z-Scores: The Potential Mediating Role of Maternal Glucose Homeostasis.
Aug 2026· Environmental Pollution· pp.
129003
· 0 citations· 61 references
Medicine
TL;DR
It is suggested that prenatal PFAS exposure is associated with reduced BW-z, particularly among female infants, and that altered fasting glucose may represent one possible, but not primary, pathway linking selected PFAS to fetal growth.
Abstract
Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with impaired fetal growth, yet evidence regarding mixture effects and the potential mediating role of maternal glucose homeostasis remains limited. We examined these associations in 642 mother-infant pairs from a prospective birth cohort in Ma'anshan, China. Multivariable linear regression (MLR) was used to assess associations of individual PFAS with neonatal birth weight z-scores (BW-z) and maternal glucose homeostasis. Weighted quantile sum regression (WQS) and Bayesian kernel machine regression (BKMR) were applied to characterize cumulative mixture effects. Sex-stratified analyses were conducted to evaluate potential effect modification. PFNA, PFDA, PFOS, L-PFHxS, 6:2 Cl-PFESA, and 8:2 Cl-PFESA were negatively associated with BW-z, with stronger negative associations observed in female infants. Mixture analyses further supported an overall negative association between PFAS mixture exposure and BW-z. Several PFAS were positively associated with 1-h and 2-h glucose levels, whereas PFNA, PFDoA, and 8:2 Cl-PFESA were negatively associated with fasting plasma glucose (FPG); in turn, higher FPG was associated with increased BW-z. Mediation analyses suggested statistically significant indirect effects through FPG in the associations of 8:2 Cl-PFESA and PFNA with BW-z, although the mediation proportions were modest at 11.5% and 9.5%, respectively. These findings suggest that prenatal PFAS exposure is associated with reduced BW-z, particularly among female infants, and that altered fasting glucose may represent one possible, but not primary, pathway linking selected PFAS to fetal growth.
Early-pregnancy PFAS exposure was associated with impaired fetal growth and altered amino acid and lipid metabolism may underlie these associations, and metabolomics data suggested several exploratory candidate intermediate metabolite features that may be involved in the associations.
Zhen-Hua Li, Cheng-Yang Hu, Xia-Juan Lu et al.· Environment International· 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
BACKGROUND
Prenatal exposure to parabens (PBs) has been associated with infantile eczema; however, the mediating role of inflammatory cytokines and the potential modifying effect of breastfeeding remain unclear.
METHODS
This prospective study included 336 mother-infant dyads. Maternal serum concentrations of five parabens, namely methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), butylparaben (BuP), and hexylparaben (HeP), and eight inflammatory cytokines were measured during pregnancy. Infantile eczema and feeding patterns during the first six months were recorded. Weighted quantile sum (WQS) regression assessed mixture effects; single-chemical associations were examined using covariate-adjusted logistic and linear regression. Mediation and moderated mediation analyses were performed to evaluate the role of interleukin-17A (IL-17A) and the modifying effect of breastfeeding. Network toxicology was employed to identify shared molecular targets and pathways.
RESULTS
The PBs mixture was significantly associated with increased eczema risk (WQS OR = 1.97, 95% CI: 1.24-3.12). In single-chemical models, PrP (OR = 1.08, 95% CI: 1.02-1.15) and HeP (OR = 1.38, 95% CI: 1.02-1.87) were positively associated with eczema. Maternal PrP was positively associated with serum IL-17A (β = 0.034, 95% CI: 0.006-0.063). Elevated IL-17A was strongly associated with eczema (OR = 3.46, 95% CI: 1.45-8.26). IL-17A accounted for approximately 14.9% of the association between PrP and eczema (indirect effect β = 0.003, 95% CI: 0.001-0.010). Moderated mediation revealed that breastfeeding significantly modified the pathway from IL-17A to eczema (interaction P = 0.018). The indirect effect was significant only in formula-fed infants (β = 0.069, P = 0.040) and absent in breastfed infants (P = 0.680). Network toxicology identified 11 common targets of PrP and eczema enriched in IL-17, Toll-like receptor, and NF-κB signaling pathways.
CONCLUSIONS
Maternal IL-17A may partially mediate the association between prenatal PrP exposure and infantile eczema, and breastfeeding may modify the association between IL-17A and eczema. These findings support the importance of further evaluating prenatal paraben exposure during pregnancy and promoting breastfeeding to mitigate early-life allergic disease risk.
M. Chang, Xian-Jia Li, Ye Li et al.· Environmental Pollution· 0 citations
BACKGROUND
Prenatal exposure to metal mixtures may influence newborn birth size, but the underlying metabolic mechanisms remain unclear. This study aimed to evaluate the associations of 19 individual maternal metals and metal mixtures during pregnancy with birth size indicators, specifically birth weight z score (BWZ) and birth length z score (BLZ), and to identify potential metabolic pathways and mediating metabolites based on cord blood metabolomics.
METHODS
A total of 1059 mother-infant pairs were included in the full cohort. We applied ExWAS, ENET/DSA, WQS, qgcomp, and BKMR to assess both single-metal and joint exposure effects. Exploratory MWAS, pathway enrichment, and mediation analyses were conducted using cord blood metabolomics data.
RESULTS
In single-metal analyses, Zn, Se, and Mn showed positive associations with BWZ and BLZ, whereas Cu was positively associated with BWZ only; As, Pb, and Cd generally showed inverse associations. In mixture analyses, the negative-direction WQS index was associated with lower BLZ (β = -0.039, P = 0.042). Exploratory metabolomics analyses highlighted lipid-related metabolites, organic acid derivatives, and nucleotide-related metabolites, with enrichment in caffeine metabolism and steroid hormone biosynthesis pathways. Mediation analyses suggested potential indirect effect signals, including As-BWZ via 10-hydroxystearic acid (19.6%), Cu-BWZ via 2-ethyl-2-hydroxybutyric acid (30.8%), and Se-BLZ via 2-ethyl-2-hydroxybutyric acid (21.1%).
CONCLUSION
In this industrial city cohort, our findings provide evidence linking prenatal metal exposure to newborn birth size and suggest that cord blood metabolic profiles may offer exploratory mechanistic clues for understanding metal-related fetal growth patterns.
Hai-Yang Weng, Zhen-Hua Li, Chun-Yong Wang et al.· Ecotoxicology and Environmen...· 0 citations
Limited evidence is available for the association between prenatal per- and polyfluoroalkyl substances (PFAS) exposure and childhood bone mineral density (BMD). Among 755 mother-child pairs in the Shanghai Birth Cohort, ten PFAS were measured in first-trimester maternal plasma using high-performance liquid chromatography/tandem mass spectrometry, and childhood lumbar spine BMD was assessed using dual-energy X-ray absorptiometry. Multivariable linear regression, Bayesian kernel machine regression (BKMR) and quantile g-computation (qgcomp) were applied. In the overall analyses, PFHpA was suggestively associated with higher total BMD (β = 0.13; 95% CI: 0.00, 0.27). Sex-stratified analyses indicated possible differences by sex. Among girls, PFDA and PFDoA showed inverse associations with total BMD (β = -0.29; 95% CI: -0.57, 0.00 and β = -0.27; 95% CI: -0.50, -0.04, respectively). Among boys, PFHpA showed a positive association with total BMD (β = 0.20; 95% CI: 0.04, 0.37). BKMR analyses suggested that mixture effects tended to be inverse among girls and positive among boys at higher quantiles. In qgcomp models, the positive association was most evident for L3 BMD among boys (β = 0.23; 95% CI: 0.00, 0.45). Our findings provide preliminary evidence that prenatal PFAS exposure may be associated with childhood BMD, with possible sex-specific patterns.
Lingyan Lou, Qian Chen, Jian Xu et al.· Journal of Hazardous Materia...· 0 citations
Prenatal exposure to environmental chemicals has been implicated in impaired fetal and early childhood growth. However, most previous studies have focused on single exposure domains, limiting understanding of the combined effects of co-occurring chemical mixtures. We investigated the joint effects of a prenatal multi-domain chemical mixture comprising endocrine-disrupting chemicals (EDCs), heavy metals, and ambient air pollutants on infant growth from birth to 36 months using data from the Korean Children's Environmental Health Study (Ko-CHENS), a nationwide prospective birth cohort of 5,056 mother-child pairs. We applied weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to estimate mixture effects and identify key contributing exposures, WQS and BKMR were fitted separately at each of five assessment ages, and a latent class mixed model (LCMM) was used to characterize prenatal exposure trajectory subgroups, whose association with repeated growth measures was then evaluated in a linear mixed model. Ten mixture-outcome tests (two outcomes x five ages) were pre-specified as primary and were corrected for multiplicity using the Benjamini-Hochberg false discovery rate (FDR) procedure. WQS regression identified a significant inverse association between the prenatal chemical mixture and infant length-for-age z-scores at birth and 6 months, with late-pregnancy BPF and BPS consistently emerging as the top-weighted contributors; both associations remained below a 5% FDR threshold. Overall mixture effects estimated by BKMR were null at every assessment age, although BKMR suggested nonlinear and exposure-specific dose-response relationships involving bisphenol analogues and ambient air pollutants across multiple assessment time points. No significant associations were observed between LCMM-derived exposure trajectory class and longitudinal growth outcomes through 36 months. Domain-specific patterns were observed across both analyses: bisphenol analogues showed more consistent associations with length outcomes, whereas ambient air pollutants were more frequently identified as key contributors in weight-related models. These exploratory findings suggest that prenatal exposure to bisphenol analogues and ambient air pollutants may be associated with early childhood growth and warrants further investigation. They support the use of mixture-based approaches in environmental health research but should not be interpreted as evidence of causal effects.
Sungryul Shim, Taemi Kim, Sungchul Seo et al.· Environmental Pollution· 0 citations
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