Yuyan Wang

ObjectivePhthalates are recognized endocrine disruptors and emerging neurotoxicants. Di-2-ethylhexyl phthalate (DEHP), one of the most widely produced phthalates, has been linked to adverse neurodevelopmental and neuropsychiatric outcomes with onset in childhood and adolescence. We hypothesized that maternal oxidative stress may play a mechanistic role in DEHP’s neurotoxicity.Materials and MethodsParticipants were drawn from the New York University Children’s Health and Environment Study (NYU CHES). Prenatal DEHP exposure and maternal lipid peroxidation were assessed using repeated creatinine-adjusted maternal urinary measurements across pregnancy. Neonatal BDNF was measured in cord serum (N=337), and internalizing and externalizing problems were assessed in early childhood using the CBCL 1½–5 (N=824). DEHP metabolites were averaged across pregnancy, and cumulative lipid peroxidation biomarkers were estimated using area under the curve (AUC) values from linear mixed-effects spline models. Partial least squares path modeling (PLS-PM) evaluated direct and indirect associations using latent constructs for DEHP exposure, lipid peroxidation, CBCL, and socioeconomic status; other covariates were modeled as single variables. Sex differences were assessed using bootstrapping and sex-stratified models, adjusting for maternal age, parity, pre-pregnancy BMI, cotinine exposure, and socioeconomic status.ResultsPrenatal DEHP exposure was positively associated with maternal lipid peroxidation in all models. Sex-stratified analyses showed that prenatal DEHP exposure was positively associated with childhood CBCL total problems in male children only, but not with neonatal BDNF in either sex. Maternal lipid peroxidation was not associated with neonatal BDNF or CBCL outcomes in either sex.ConclusionPrenatal DEHP exposure is associated with maternal oxidative stress and total behavioral problems in male children only, but oxidative stress does not mediate these relationships. Alternative upstream mechanisms may underlie both maternal oxidative stress and neurobehavioral outcomes. Given the sex-specific findings, future studies should investigate endocrine, metabolic, and epigenetic pathways to clarify DEHP neurotoxicity.

Objectives: To assess the effects of World Trade Center (WTC) exposures, obesity, and smoking on post-bronchodilator (post-BD) lung function in WTC Survivors. Methods: Data included 5,243 participants enrolled in WTC Environmental Health Center (WTC EHC) program between 2005 and 2022. WTC-related exposures included dust-cloud exposure and occupational/residential roles. Lung function included post-BD spirometry (FEV ₁ , FVC) and impulse oscillometry (R ₅ , R ₂₀ , AX). Multivariable linear and quantile regressions assessed associations with WTC exposures, BMI, and smoking, adjusting for demographics. Results: Dust-cloud exposure and Worker status were associated with elevated AX, R ₅ , and R ₂₀ , indicating small airway dysfunction. Spirometry showed minimal impact from dust exposure, though Workers had lower FEV₁ and FVC than Residents. Obesity and smoking were consistently linked to poorer lung function, with effect sizes surpassing WTC exposure. No significant interactions were found between BMI and WTC exposures. Conclusions: WTC exposures are associated with small airway dysfunction, especially in Workers. Obesity and smoking independently worsen lung function, underscoring the importance of both environmental and physiological risk factors in disaster-exposed populations. Post-BD oscillometry adds critical sensitivity in detecting injury to small airways.

Prenatal organophosphate (OP) pesticide exposure may be associated with reduced fetal growth, although studies are limited and have mixed results. We investigated associations between prenatal OP pesticide exposure and fetal size and modification by fetal sex. Maternal urinary concentrations of dialkyl phosphate (DAP) metabolites were measured at 3 time points. Fetal biometrics were obtained from ultrasounds in the second (n = 773) and third (n = 535) trimesters. Associations between pregnancy-averaged ΣDAP and fetal biometry z scores were determined through multiple linear regression. Modification by sex was investigated through stratification and interaction. In the second trimester, one ln-unit increase in ΣDAP was associated with lower estimated fetal weight (–0.15 SD; 95% CI, –0.29 to –0.01), head circumference (–0.11 SD; CI, –0.22 to 0.01), biparietal diameter (–0.14 SD; CI, –0.27 to –0.01), and abdominal circumference (–0.12 SD; CI, –0.26 to 0.01) in females. In the third trimester, one ln-unit increase in ΣDAP was associated with lower head circumference (–0.14 SD; CI, –0.28 to 0.00) and biparietal diameter (–0.12 SD; CI, –0.26 to 0.03) in males. Our results suggest that prenatal OP pesticide exposure is negatively associated with fetal growth in a sex-specific manner, with associations present for females in mid-gestation and males in late gestation. This article is part of a Special Collection on Environmental Epidemiology.

The destruction of the World Trade Center (WTC) on September 11, 2001 (9/11) released large amounts of toxic dusts and fumes into the air that exposed many community members who lived and/or worked in the local area. Many community members, defined as WTC survivors by the federal government, developed lower respiratory symptoms (LRS). We previously reported the persistence of these symptoms in patients with normal spirometry despite treatment with inhaled corticosteroids and/or long-acting bronchodilators. This report expands upon our study of this group with the goal to identify molecular markers associated with exposure and heterogeneity in WTC survivors with LRS using a selected plasma biomarker approach. Samples from WTC survivors with LRS (n = 73, WTCS) and samples from healthy control participants of the NYU Bellevue Asthma Registry (NYUBAR, n = 55) were compared. WTCS provided information regarding WTC dust exposure intensity. Hierarchical clustering of the linear biomarker data identified two clusters within WTCS and two clusters within NYUBAR controls. Comparison of the WTCS clusters showed that one cluster had significantly increased levels of circulating matrix metalloproteinases (MMP1, 2, 3, 8, 12, 13), soluble inflammatory receptors (receptor for advanced glycation end-products-RAGE, Interleukin-1 receptor antagonist (IL-1RA), suppression of tumorigenicity (ST)2, triggering receptor expressed on myeloid cells (TREM)1, IL-6Ra, tumor necrosis factor (TNF)RI, TNFRII), and chemokines (IL-8, CC chemokine ligand- CCL17). Furthermore, this WTCS cluster was associated with WTC exposure variables, ash at work, and the participant category workers; but not with the exposure variable WTC dust cloud at 9/11. A comparison of WTC exposure categorial variables identified that chemokines (CCL17, CCL11), circulating receptors (RAGE, TREM1), MMPs (MMP3, MMP12), and vascular markers (Angiogenin, vascular cell adhesion molecule-VCAM1) significantly increased in the more exposed groups. Circulating biomarkers of remodeling and inflammation identified clusters within WTCS and were associated with WTC exposure.