Aug 2026· JAMA pediatrics· 0 citations· 47 references
Medicine
TL;DR
Prenatal OP exposure was not associated with autism-related traits in childhood and results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders.
Abstract
Importance
Organophosphate pesticides (OPs) are established neurotoxicants; prenatal OP exposure is widespread in the US population, primarily through diet. Evidence linking prenatal OP exposure to autism spectrum disorder (ASD) and autism-related traits remains inconsistent.
Objective
To examine the association between prenatal OP exposure and autism-related traits in childhood and to assess potential differences in the association by child sex and maternal diet.
Design, Setting, and Participants
This pooled prospective cohort study used harmonized data from mother-child pairs from 20 study sites in the Environmental influences on Child Health Outcomes (ECHO) cohort. Participants were recruited from January 1997 through December 2019, and autism-related outcomes were assessed in children ages 2 to 19 years. Data analysis was performed from April 2024 and November 2025.
Exposure
Prenatal OP exposure using urinary concentrations of 3,5,6-trichloro-2-pyridinol (TCPy) and the sum of 6 dialkyl phosphate (ΣDAP) metabolites.
Main Outcomes and Measures
Parents reported autism-related traits in children using the Social Responsiveness Scale (SRS). Multivariable linear, quantile, and logistic regression models were used to estimate associations between biomarkers and SRS T scores overall and by child sex, adjusting for maternal sociodemographic and behavioral factors. We further adjusted for dietary factors in additional models and tested effect modification by maternal diet quality in exploratory analyses.
Results
Among 3339 mother-child pairs examined, mean (SD) maternal age was 31 (6) years, 1665 children (49.9%) were female, and the SRS was administered at a mean (SD) age of 6.4 (3.87) years. Crude or minimally adjusted models suggested inverse associations between prenatal TCPy or ΣDAP levels and SRS scores, but these associations attenuated and lost statistical significance after full adjustment (β per doubling of TCPy concentration [ng/mL] = -0.13; 95% CI, -0.57 to 0.31; β per doubling of ΣDAP [nmol/L] = -0.42; 95% CI, -1.03 to 0.19). Results were consistent across sex-stratified models, secondary analyses using quantile and logistic regressions, various sensitivity analyses, and after adjustments for dietary confounders. There was no evidence of effect modification by diet quality.
Conclusions and Relevance
In this large, prospective cohort study among the ECHO cohort, prenatal OP exposure was not associated with autism-related traits in childhood. Given the known adverse impacts of pesticides in other contexts, further research should consider interactions with other factors, genetic susceptibility, higher exposures, or combined chemical mixtures.
Exposure to persistent organic pollutants (POPs) during fetal development may increase the risk of autism spectrum disorder, but previous studies have relied on maternal pregnancy samples as proxies instead of directly measuring fetal exposures. Here, we used naturally shed deciduous teeth from autism cases and typically developing controls born between 1998 and 2014 from the California, USA, population-based case-control Childhood Autism Risk from Genetics and the Environment study. Using gas chromatography-tandem mass spectrometry, we quantified fetal second and third trimester and postnatal POPs in teeth dentine. In total, seven polychlorinated biphenyls, two organochlorine pesticides, and four brominated diphenyl ethers were quantified in deciduous teeth. We compared children clinically confirmed to have autism with typically developing children from the general population using logistic regression for exploratory single chemical analysis and Weighted Quantile Regression Analysis for mixture analysis. In the third trimester, the POPs mixture was positively associated with autism (median Odds Ratio (OR) = 1.54 (95% CI=[0.99, 2.83]). In sex-stratified interaction analysis, the OR for males (median=1.75) was significant (95% CI: [1.13, 3.2]), while the OR for females was small (1.16) and not significant (95% CI = [0.33, 3.5]). The POPs mixtures during the second trimester or postnatally were not significantly associated with autism risk. Therefore, direct fetal and early-life measures of POPs indicate the third trimester as a potential high-risk biological window for POPs exposures that increase autism risk, particularly in males.
L. Petrick, P. S. Dassanayake, C. Gennings et al.· Environmental Research· 0 citations
Prenatal TBEP exposure was associated with greater behavioral problems in early childhood, and Alter neonatal gut microbiota and related metabolic pathways may partly underlie this association.
Yuhan Zhou, Liyi Zhang, Qiang Li et al.· Environmental Research· 0 citations
Background: Metal exposures adversely impact prenatal neurodevelopment; however, their associations with child autism spectrum disorder (ASD) remain unclear. Methods: In the Environmental Influences on Child Health Outcomes Cohort, we analyzed prenatal blood (N = 479) and urinary (N = 482) metal concentrations in relation to Social Responsiveness Scale—Second Edition (SRS-2) total T-scores, SRS-2 subscale T-scores, and ASD diagnosis. Associations were examined using linear and logistic regression for individual metals and Bayesian Kernel Machine Regression for mixtures, adjusting for covariates. Results: Interquartile range increases in maternal blood lead and mercury were associated with higher SRS-2 total T-scores (lead: β = 0.11, 95% confidence interval [CI] = 0.03, 0.18; mercury: β = 0.19, 95% CI = 0.01, 0.37), and maternal blood cadmium was associated with higher odds of ASD diagnosis (OR = 2.42, 95% CI = 1.16, 5.03). Bayesian Kernel Machine Regression revealed joint effects of blood metal mixtures (arsenic, cadmium, mercury, and lead) on social awareness and cognition. Blood cadmium correlated with social awareness in females (raw score: β = 0.85, 95% CI = 0.09, 1.61) versus males (p-interaction = 0.02). Urinary barium correlated with social motivation in females (raw score: β = 0.273, 95% CI = 0.067, 0.478) versus males (p-interaction = 0.05). Conclusions: Future research should prioritize metal speciation, larger samples, and mechanistic studies to clarify sex-specific pathways.
Pi-I. D. Lin, Andrés Cárdenas, K. Lyall et al.· Environmental Epidemiology· 0 citations
Prenatal exposure to OPFRs and OPPs was associated with smaller left ventricular structural measures in early childhood, mainly reflected by lower left ventricular volume and mass, with OPFRs emerging as main contributors and stronger associations among girls.
Meng Wang, Xi Zhang, Hualin Wang et al.· Environmental Pollution· 0 citations
Evidence on the association between prenatal exposure to organophosphate ester (OPE) and small vulnerable newborn components is limited and inconsistent. This study included 3208 mother-child dyads from the Ma'anshan Birth Cohort. In the first, second, and third trimesters, urine samples were used to detect 6 OPE metabolites to reduce misclassification bias in exposure. Statistical models, including robust poisson regression and quantile g-computation model, were used to explore the associations of OPE exposure with small vulnerable newborns and their component variables and the co-exposure effects, respectively. Poisson regression analysis revealed that exposure to tris(2-chloroethyl) phosphate (TCEP) during the first trimester and diphenyl phosphate (DPHP) during the third trimester were associated with a decreased risk of small vulnerable newborns [risk ratio (RR) = 0.68, 95% confidence interval (CI): 0.49, 0.94 for TCEP; RR= 0.85, 95%CI: 0.75, 0.97 for DPHP), mirroring the results obtained from the mixture exposure analysis. This inverse relationship may inherently reflect an underlying phenomenon of prolonged gestational duration and increased birth weight. The study first explored the impact of prenatal exposure to OPEs on the entire small vulnerable newborns, suggesting that prenatal OPEs have sex- and trimester-specific effects on the risk of small vulnerable newborns. The analysis results of OPE for different small vulnerable newborn component variables also verified the complex relationship between OPE and adverse birth outcomes.
Ping Lv, Yi-fan Wang, Yongkang Liu et al.· Ecotoxicology and Environmen...· 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, M. Lu et al.· Environmental Science and Te...· 0 citations