Polybrominated diphenyl ethers (PBDEs), used as chemical flame retardants, are developmental osteotoxicants in mechanistic studies, but the effects of in utero exposure on adolescent bone health are unknown. We examined associations of gestational serum PBDE concentrations and BMD Z-scores in adolescence. Among 184 mother-adolescent pairs enrolled in the Health Outcomes and Measures of the Environment Study (Cincinnati, OH: 2003-2006), we quantified five PBDEs in maternal serum and four organophosphate ester (OPE) metabolites in maternal urine collected at 16- or 26-weeks gestation. At age 12 years, we conducted dual energy x-ray absorptiometry scans and calculated bone mineral density (BMD) Z-scores for six skeletal sites. We estimated covariate-adjusted associations per log10 increase in maternal serum PBDE concentrations using linear regression and assessed effect measure modification (EMM) by adolescent's sex using interaction terms. We also examined PBDE and OPE mixtures using quantile-based g-computation. In adjusted models, BDE-153 concentrations were associated with lower femoral neck BMD (β: -0.42; 95 % CI: -0.79, -0.05). Results were similar but weaker for other individual PBDEs and their mixture. The associations of BDEs-28, -47, and -100 with hip and femoral neck BMD Z-score were modified by adolescent's sex. For example, log10 BDE-28 was associated with total hip BMD Z-score differences of -0.75 (95 % CI: -1.50, 0.01) for males and 0.21 (95 % CI: -0.31, 0.74) for females (EMM p = 0.04). Higher quartiles of the PBDE + OPE mixture showed weak, site-specific associations with BMD, though all CIs crossed the null. In utero PBDE exposure may negatively affect adolescent bone health.

Objectives. To examine trends in blood lead levels (BLLs) among US children aged 5 years or younger using national and state data. Methods. We analyzed 2011 to 2023 National Health and Nutrition Examination Survey (NHANES) data by year and available demographic characteristics. We report geometric means, the prevalence of BLLs of 3.5 micrograms per deciliter or above and 5.0 micrograms per deciliter or above, and linear trends. In addition, we summarize 2017 to 2023 surveillance data from 7 states. Results. National BLLs continue to decline. In 2021 to 2023, geometric mean BLLs and the prevalence of BLLs of 3.5 micrograms per deciliter or above were lower for all groups than in previous years. Small recent NHANES sample sizes and limited state-level subgroup data constrained detailed analyses. However, state-level data revealed disparities by geography, race, and ethnicity. Conclusions. National data indicate decreasing BLLs among children and elimination of racial disparities, but state and local BLL data unmask ongoing disparities. Public Health Implications. To better describe childhood lead exposures, NHANES should increase its sample size, oversample high-risk populations, and release timely data, and states should expand surveillance and risk factors and make data publicly available. Together, the data assessed here provide benchmarks to target prevention efforts and warn of emerging risks. (Am J Public Health. 2026;116(9): 1343-1351. https://doi.org/10.2105/AJPH.2026.308468).

BACKGROUND:Per- and polyfluoroalkyl substances (PFAS) are a ubiquitous class of persistent synthetic chemicals used in consumer and commercial products for decades. PFAS crosses the blood-placenta and blood-brain barriers to accumulate in the fetus, but the impact on neuroanatomy in early adolescence is unknown. OBJECTIVES:We estimated the association of gestational and early adolescent PFAS concentrations with brain morphometry in 155 participants of the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolled from 2003 to 2006. METHODS:We measured serum PFAS concentrations during gestation and at age 12. We acquired high resolution anatomical brain MRI to quantify global and regional volumes, cortical thickness and sulcal depth using morphometric methods at age 12. We used a general linear model framework with adjustment for adolescent biological sex, race, household income, maternal IQ, maternal pre-pregnancy BMI, primipara, and total intracranial volume. RESULTS:A doubling in age 12 perfluorooctanoic acid (PFOA) [f2 = 0.06, β = 10.79, (95% CI: 3.45, 18.13), p = 0.04] and perfluorononanoic acid (PFNA) [f2 = 0.04, β = 6.14, (95%CI: 1.09, 11.18), p = 0.018] concentrations were positively associated with total gray matter volume. A doubling in age 12 PFOA [f2 = 0.04, β = -8.49, (95%CI: -15.28, -1.69), p = 0.015] and perfluorooctanesulfonic acid (PFOS) [f2 = 0.03, β = -5.00, (95% CI: -9.81, -0.18), p = 0.042] concentrations were negatively associated with total white matter volume. A doubling in age 12 PFOA [(f2 = 0.03, β = 0.03, (95% CI: 0.00, 0.06), p = 0.034] and PFOS [(f2 = 0.03, β = 0.02, (95% CI: 0.00, 0.04), p = 0.035] concentrations were positively associated with whole brain average cortical thickness. A doubling in age 12 PFOA was positively associated with regional gray matter volumes up to 0.05 mm3 within cortical, subcortical and deep gray matter, and cortical thickness up to 0.1 mm predominately within the posterior cortex, respectively. No significant associations were observed for gestational PFAS concentrations and brain morphometry. CONCLUSION:Higher PFAS concentrations are concurrently associated with larger structural volumes and cortical thickness. The significance is uncertain but are consistent with delayed maturation processes delaying synaptic pruning.

Importance:Low-level lead exposure during early brain development is associated with lower cognitive abilities and externalizing behavioral problems in children. However, the association of lead exposure with depression and anxiety remains understudied, particularly in later childhood, when these symptoms often manifest. Objective:To examine associations between low-level, serial blood lead concentrations in children and symptoms of depression and anxiety and to investigate for periods of susceptibility. Design, Setting, and Participants:This cohort study used data from a prospective population of 218 caregiver-child dyads (218 children and 218 parents in the Health Outcomes and Measures of Environment [HOME] Study) recruited from 2003 to 2006 in Cincinnati, Ohio. Children and their families were followed up from the second trimester to age 12 years (2016-2019). Data were analyzed between June 2024 to November 2025. Exposure:Serial blood lead concentrations in children were measured at ages 1, 2, 3, 4, 5, 8, and 12 years. Main Outcomes and Measures:We measured self- and caregiver-reported child depressive and anxiety symptoms at age 12 years using the Behavioral Assessment System for Children-3 (BASC-3), Children's Depression Inventory-II (CDI-II), and Screen for Child Anxiety Related Disorders (SCARED). Results:Among 218 children (121 female [55.5%]; 78 Black [35.8%] and 140 White and other race or ethnicity [64.2%]; mean [SD] age, 12.4 [0.7] years), the median (IQR; range) mean within-child blood lead concentration was 9.6 (7.8 to 12.6; 4.8 to 32.4) μg/L. Each doubling in mean childhood blood lead concentrations was associated with increased risk of elevated child-reported depressive symptoms on the BASC-3 (relative risk [RR], 1.90; 95% CI, 1.00 to 3.66; P = .05) and increased risk of child- and caregiver-reported child depressive symptoms (RR, 1.76; 95% CI, 1.12 to 2.78; P = .02). By blood lead concentration, there were increasing adjusted mean differences in self-reported BASC-3 depression scores from age 1 year (1.82; 95% CI, -1.10 to 4.74; P = .22), a nonsignificant outcome, through age 8 years (3.22; 95% CI, 0.53 to 5.90; P = .02), a significant outcome. There were no associations between blood lead concentrations and self-reported depression measured with the Children's Depression Inventory-II or anxiety measured with the SCARED. Child sex and race did not modify these associations. Conclusions and Relevance:In this study, low-level childhood blood lead concentrations were associated with self-reported depressive symptoms in later childhood, with particularly large increases in risk for exposures occurring in late childhood and early adolescence. These findings suggest that lead exposure during childhood may be associated with mental health in later childhood, highlighting the need for continued efforts to prevent lead exposure.

Alterations to the gut microbiome have been linked to cardiometabolic disease, like type 2 diabetes and hypertension, in adults, but few studies have investigated these associations in adolescents. We examined the relation between the gut microbiome and cardiometabolic risk in adolescence and determined whether sex and race/ethnicity modified these associations. In 144 adolescents (age range: 11–14 years) from the Health Outcomes and Measures of the Environment (HOME) Study, we quantified gut microbiome alpha diversity using the Shannon index and species’ relative abundances (i.e., centered log-ratio normalized abundances) in stool DNA that underwent metagenomic sequencing. We assessed adolescent cardiometabolic risk using a cardiometabolic risk summary score, its individual components (i.e., visceral fat, leptin to adiponectin ratio, HOMA-IR, triglyceride to high-density lipoprotein cholesterol ratio, and systolic blood pressure), as well as total cholesterol and hemoglobin A1c. We used linear regression models to estimate covariate-adjusted cross-sectional associations of the Shannon diversity index and species’ relative abundances with cardiometabolic risk, and examine differences in these associations by sex and race/ethnicity. At the species level, the false discovery rate (FDR) correction, with q-value < 0.20, was considered statistically significant. Among all adolescents, a higher Shannon diversity index was associated with lower systolic blood pressure [β: -0.18 (95

Phthalates are ubiquitous endocrine disrupting chemicals previously linked with behavioral problems in children. We investigated associations of gestational phthalate exposure with problem behaviors and social skills in adolescents using the Health Outcomes and Measures of the Environment (HOME) Study. Parent offspring pairs (n = 216) were recruited between 2003 and 2006 in Cincinnati, Ohio. Maternal urine samples collected at 16- and 26-weeks' gestation were analyzed for nine phthalate metabolites. At the 12-year follow-up, adolescents and caregivers completed the Social Skills Improvement System (SSiS), which measures social skills (SSiS-SS) and problem behaviors (SSiS-PB). Multivariable linear regressions were performed for each phthalate metabolite controlling for potential confounders including maternal age, child race and ethnicity, maternal depression, marital status, income, child sex, cotinine, polybrominated diphenyl ether 47, and lead. Regressions were performed for the overall sample and stratified by sex. We evaluated mixture effects using quantile g-computation models. No individual phthalates were significantly associated with either the caregiver or adolescent reported SSiS-SS score. Mono-isobutyl phthalate (MiBP) was significantly associated with increased adolescent reported SSiS-PB score (β: 5.94, 95% CI: 0.75, 11.12, p = 0.03). In our sex-stratified analysis we found evidence for a detrimental association with phthalates and both SSiS-SS and SSiS-PB in male adolescents only. This was consistent in the linear and quantile g-computation models. We found evidence for sex specific associations between gestational phthalate exposures and social skills and problem behaviors in adolescents. This extends previous research on phthalates and child behavior into adolescence and suggests sex specific effects of phthalates.

Early life exposure to organophosphate esters (OPEs), a class of flame retardants and plasticizers, may be associated with adverse neurobehavioral outcomes. Due to OPEs’ relatively short biological half-life in humans, it is important to evaluate exposure-response associations using repeated measures during gestation and childhood. We examined the associations between OPE biomarkers and social skill/problem behavior using data from 236 caregiver-adolescent dyads in the Health Outcomes and Measures of the Environment (HOME) Study. We included urinary concentrations of four OPE biomarkers [bis-2-chloroethyl-phosphate (BCEP), bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP), di-n-butyl-phosphate (DNBP), diphenyl-phosphate (DPHP)] measured up to 9 times (3 in gestation and 6 in childhood) and calculated cumulative exposure measures during gestation, childhood, and the lifetime. Social and behavioral outcomes at age 12 years were assessed using the Social Skills Improvement System (SSiS) completed by adolescents and caregivers. We used quantile g-computation regression to evaluate joint associations between the OPE biomarker mixture and SSiS scores, while adjusting for covariates. Overall, we observed null associations between OPE biomarkers and adolescent social skill/problem behavior scores, but the effect measure modification by adolescent sex was statistically significant. Every quartile increase in childhood/lifetime OPE biomarker mixture was associated with improved caregiver-reported problem behavior among females (Ψchildhood -3.44 (95%CI: -6.05, -0.84); Ψlifetime -3.82 (95%CI: -6.43, -1.22)). Every quartile increase in lifetime OPE biomarker mixture was associated with impaired social skill scores in males (Ψlifetime -3.59 (95%CI: -6.79, -0.40). Further studies with a larger sample size will help provide additional insights into OPE exposures early in life and subsequent sex-specific associations with adolescent social skill/problem behavior scores.

Abstract Study Objectives Sleep during adolescence may influence biological aging, yet few studies have examined this association using objective sleep measures. We examined the associations between accelerometry-based sleep characteristics and epigenetic age (EA), epigenetic age acceleration (EAA), and the pace of biological aging. Methods For this preliminary analysis, we used data from the HOME Study (Cincinnati, OH). At age 12 years (2016-2019), we used accelerometers to assess total sleep time, sleep efficiency, number of awakenings, and sleep fragmentation. Using DNA methylation data at the same age, we estimated EA and EAA using skinbloodHorvath, Hannum, and Wu clocks, and the pace of biological aging using DunedinPACE. We used multivariable linear regression to estimate covariate-adjusted associations between sleep and epigenetic aging. We also evaluated sex modification by including product interaction terms and examined sex-stratified models. Results Among 138 adolescents (59% female; mean age 12.29 ± 0.64 years), general trends suggested that poorer sleep quality was associated with higher EA and EAA. However, all effect estimates were imprecise, and confidence intervals included the null. Notably, we found that sex modified these relationships: higher sleep fragmentation was associated with elevated EAA among males (Hannum β= 0.885, 95%CI: 0.132, 1.638; interaction p= 0.005), but not females (β= -0.325, 95%CI: -0.866, 0.217). These associations were consistent across first-generation clocks. Conclusions Overall, we did not find consistent evidence of associations between sleep characteristics and epigenetic aging in this preliminary analysis. However, sex-stratified analyses suggested that poorer sleep quality may be associated with greater epigenetic age acceleration among males.

BACKGROUND:Gestational exposure to environmental chemicals contributes to adverse neurodevelopmental outcomes in children. We aim to evaluate the joint associations between gestational chemical biomarkers and behavioral functioning in preschool-aged children. METHODS:We pooled data from 695 mother-child dyads (female, n = 353; male, n = 342) enrolled in the Health Outcomes and Measures of the Environment (HOME) & Maternal-Infant Research on Environmental Chemicals (MIREC) Studies. We assessed concentrations of 29 EDC biomarkers at gestation and assessed the child's behavior and executive functioning at 3 years using the Behavioral Assessment System for Children (BASC-2) and Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Higher scores on these instruments indicate adverse behavioral outcomes. We applied quantile g-computation to estimate joint associations, adjusting for covariates. FINDINGS:Every quartile increase in chemical biomarker mixture was associated with a 0.84-point higher behavior symptom index score (95% CI: -0.89, 2.57), 1.38-point higher externalizing behavior score (95% CI: -0.65, 3.41), and 1.34-point higher internalizing behavior score (95%CI: -0.97, 3.65); these associations were imprecise with confidence intervals including null. Although the interaction by child sex remained null (p = 0.69) for internalizing behavior scores, gestational chemical mixture was associated with higher internalizing behavior scores in males (Ψ: 3.59; 95%CI: 0.42, 6.75), but not in females. We found evidence of sex-specific trends for working memory scores (interaction p = 0.02), with an imprecise positive trend in males (Ψ: 3.04; 95%CI: -0.46, 6.55) and a negative trend in females. INTERPRETATION:Gestational exposure to a mixture of environmental chemicals showed suggestive but imprecise associations with internalizing problems and poorer working memory among preschool-age males, but not females. Associations were more pronounced in the HOME Study, which includes participants with higher concentrations for many chemical biomarkers, than in MIREC, raising the possibility that pooled estimates reflect cohort-specific exposure contexts. Sex-specific patterns, particularly for working memory, need further investigation, and our findings should be interpreted cautiously given the imprecision of subgroup estimates.

Exposure to extreme temperatures and fine particulate matter is hazardous to human health, especially among children. With growing evidence on the impact of these environmental hazards on child health-including increased risks of respiratory illnesses, heat-related illnesses, and developmental challenges-there is a substantial need to identify high-risk areas for potential adverse pediatric health outcomes. In this study, we developed pediatric vulnerability indices at the census tract scale across the contiguous United States (CONUS) using five dimensionality reduction methods, including unsupervised machine learning and deep learning approaches. We integrated these indices with data on extreme temperature (2012-2024), PM2.5, and black carbon exposures from 2010 to 2020, enabling spatial analysis of environmental hazards and pediatric vulnerability. Among the five methods tested, principal component analysis (PCA) was selected for its balanced representation of 12 vulnerability factors, which explained 23% of the variance in the data. We observed that co-exposure to extreme temperature and air pollutant exposures were highest in the West, Southwest, and certain parts of the South and Northeast. Approximately 36% of the CONUS showed statistically significant hotspots of co-exposures to higher temperatures and air pollutants, concentrated in the West, Northwest, and Southwest. High-risk areas for pediatric vulnerability and co-exposure to environmental hazards were identified in both urban and rural communities, including indigenous lands and agricultural regions. These findings can aid policymakers and public health officials as a preliminary resource in developing heat action plans and allocating cooling centers to protect children living in the most affected communities.

Background Organophosphate esters (OPEs) can be used as flame retardants and plasticizers in consumer products. Early life exposure may disrupt brain development by modifying brain structure and neurochemistry. Objectives To evaluate the associations between gestational and childhood OPE metabolite urinary concentrations and their mixtures with neurobehavioral outcomes, explore the potential mediation of brain structure and neurochemistry, and identify potential windows of susceptibility. Methods We employed quantile-based g-computation models to investigate the mixture associations of OPE metabolite concentrations with three distinct categories of outcomes within the HOME Study at age 12 years: 1) magnetic resonance imaging (MRI)-based morphometric measurements; 2) magnetic resonance spectroscopy (MRS)-derived neurochemical concentrations; and 3) neurobehavioral outcomes across four non-overlapping exposure windows: 1) gestational, 2) birth, 3) ages 1-3 years, and 4) ages 5-8 years. We identified outcomes associated with OPE metabolite concentrations. We conducted analyses to evaluate the potential mediation of changes in brain structure and neurochemistry. Results Urinary concentrations of the mixture of OPE metabolites were primarily associated with morphometric measurements compared to neurobehavioral outcomes and were seen across all windows investigated before adjusting for multiple comparisons. The OPE metabolite mixture in the 5-8 year window was associated with reduced cortical volume of the pars triangularis, which mediated 27% of the increase in dominant hand drops on the grooved pegboard test before adjusting for multiple comparisons. Discussion Cortical volume of the pars triangularis may mediate the adverse relationship between OPE metabolite mixture concentrations and adolescent visual motor function during the 5-8-year window.

BACKGROUND:Gestational polybrominated diphenyl ethers (PBDE) exposure is linked with adverse neurobehavioral outcomes in children, but scientists do not fully understand how these flame retardants damage the developing brain. OBJECTIVE:We estimated the association of gestational PBDE serum concentrations and intrinsic functional connectivity in 143 adolescents from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort enrolling from 2003 to 2006. METHODS:We measured maternal serum concentrations of five PBDE congeners and created a summary variable (∑5BDE) during pregnancy. At age 12 years, we acquired high resolution anatomical and resting state functional magnetic resonance neuroimaging to examine the relationship between gestational concentrations and intrinsic functional connectivity, adjusting for covariates. We assessed behaviors, mental health symptoms, and executive function using self- and caregiver-reports. We examined whether functional connectivity patterns mediated the observed associations between gestational PBDE concentrations and neurobehavioral outcomes. RESULTS:Higher gestational BDE-153 serum concentrations were associated with higher local correlation in the left inferior lateral occipital cortex. Higher gestational PBDE serum concentrations (BDE-28, -47, -99, -100, and the ∑5BDE) were associated with reduced global correlation in the primary visual cortex. Seed-to-voxel connectivity patterns showed significant mediation for associations between ∑5BDE and neurobehavioral outcomes. DISCUSSION:Higher gestational PBDE serum concentrations were associated with diminished connectivity in the primary visual cortex. Connectivity patterns also mediated the relationship between gestational ∑5BDE concentrations and neurobehavioral outcomes at age 12. These findings suggest that gestational PBDE exposure alters how the brain processes visual information across global networks.

Context:Per- and polyfluoroalkyl substances (PFAS) may affect adolescent bone mineral density (BMD), but few studies have examined periods of susceptibility. Objective:To assess associations of repeated serum PFAS concentrations with early adolescent BMD. Methods:Among 218 children in a prospective pregnancy and birth cohort, we quantified serum concentrations of perfluorohexane sulfonic acid (PFHxS), perfluoroctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) at delivery (cord) and ages 3, 8, and 12 years. We measured BMD at 6 skeletal sites using dual-energy X-ray absorptiometry at age 12 years. We estimated covariate-adjusted differences and 95% confidence intervals (CIs) in BMD Z-scores per interquartile range (IQR) increase in each PFAS at each time point using multiple informant linear regression models. Results:Higher PFOA concentrations were associated with lower 1/3 distal radius BMD at every time point: delivery (β: -0.39; 95% CI: -0.69, -0.10), 3 years (β: -0.36; 95% CI: -0.86, 0.14), 8 years (β: -0.54; 95% CI: -0.91, -0.16), and 12 years (β: -0.40; 95% CI: -0.75, -0.04). Higher 3-year PFHxS and PFOS concentrations were significantly associated with higher whole body, total hip, and femoral neck BMD Z-scores, while higher 12-year PFNA concentrations were associated with lower BMD Z-scores. Associations of 12-year PFAS with lower 1/3 distal radius BMD were stronger among females than males. Conclusion:Serum PFOA concentrations from delivery to age 12 years were associated with lower 1/3 distal radius BMD in early adolescence, while associations of other PFAS with BMD varied by exposure assessment time point, skeletal site, and sex.

Fetal development is a vulnerable period for exposure to per- and polyfluoroalkyl substances (PFAS). However, certified analytical standards do not exist for many PFAS, limiting our ability to quantify overall exposure burden to PFAS as a chemical class. PFAS-focused nontargeted analysis (NTA) enables detection of PFAS for which chemical standards may not exist. The overall objectives of this study were to provide a more comprehensive picture of PFAS exposure in cord blood, develop cumulative exposure burden scores for the PFAS detected, and evaluate differences in the infant's PFAS burden score with respect to mother's parity. We measured PFAS using targeted and NTA methods in cord blood samples collected between 2003 and 2006 in the HOME Study (Cincinnati, Ohio). Using NTA, we putatively identified 42 PFAS in cord blood, 4 of which were also detected in targeted analysis. We summarized an infant's overall prenatal exposure burden to PFAS using item response theory methods. We constructed two scores, one based on PFAS concentrations from targeted analysis ("PFAS exposure burden scores"), and one based on relative abundance from NTA ("PFAS-omics scores"). As expected, infants with multiparous mothers had significantly lower PFAS exposure burden scores than those with nulliparous mothers, but these disparities were not present when comparing their PFAS-omics scores. Our results show that infants are exposed to a wide range of PFAS, including perfluorinated chemicals, polyfluorinated chemicals, and fluorotelomers, before birth. Further, PFAS-focused NTA can help estimate total exposure to PFAS. Lastly, reported disparities in PFAS exposure burden across parity may depend on the panel of assessed PFAS and their half-lives.

Phthalates and bisphenols may contribute to childhood allergies through oxidative stress (OS). We examined OS as a potential pathway using two approaches: maternal OS biomarkers to evaluate mediation, and an OS genetic pathway function score reflecting child-level susceptibility to evaluate gene-environment interactions. In an Australian population-based birth cohort (n = 797), nine phthalate metabolites, three bisphenols, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured from spot urine samples at 36 weeks' gestation, with allergic and lung function outcomes assessed up to age four. Associations were estimated with generalised linear models for single exposures, and mixtures were analysed using weighted quantile sum regression (mediation) and quantile g-computation (interaction). The phthalate mixture (mainly driven by dimethyl and diethyl phthalates) was associated with a 14.6% increase in 8-OHdG (95% confidence interval [CI]: 9.4, 18.8). 8-OHdG mediated the association between the phthalate mixture and ventilation inhomogeneity (LCI2.5), with a mediated effect of 0.051 SD (95% CI: 0.002, 0.100). There were additive interactions between diethyl and dibutyl phthalates and genetic susceptibility for asthma and wheeze. The phthalate mixture was associated with higher LCI2.5 (β = 0.89 SD; 95% CI: 0.33, 1.45) and increased risks of asthma (risk ratio [RR] = 2.47; 95% CI: 1.31, 4.65) and wheeze (RR = 1.89; 95% CI: 1.21, 2.94), only in children genetically susceptible (p for interaction ≤0.002). No associations were observed for bisphenols or for other outcomes. This study suggests that OS may be a pathway through which maternal phthalate exposure impairs respiratory health in early childhood.

Exposure to plastic additives, such as phthalates and bisphenols, has been associated with a higher risk of allergic conditions, but the evidence is inconsistent for children younger than five. To examine the association between pre- and postnatal urinary phthalates and bisphenols, and allergic conditions, and potential effect modification by sex, in pre-school children, through a pooled analysis. We pooled data from the Barwon Infant Study (Australia), the Canadian Healthy Infant Longitudinal Development Study (Canada), the Health Outcomes and Measures of the Environment (United States) and the Environmental Influences on Child Health Outcomes–wide cohorts (United States). Urinary phthalates and bisphenols were measured during pregnancy and early childhood. We estimated daily intakes from urinary concentrations, except for mono-(3-carboxypropyl) phthalate (MCPP). Outcomes, including asthma, wheeze, eczema, and rhinitis, were assessed up to five years of age through questionnaires and clinical assessments. We used generalised estimating equations for single compounds and quantile G-computation for the chemical mixtures. 5306 children were included. A two-fold increase in prenatal dibutyl phthalates (DBP; risk ratio [RR] = 1.08; 95

The microbiome of adolescents is poorly understood, as are factors influencing its composition. We aimed to describe the healthy adolescent microbiome and identify early-life and concurrent predictors of its composition. We performed metagenomic sequencing of 247 fecal specimens from 167 adolescents aged 11–14 years participating in the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort (Cincinnati, OH). We described common features of the adolescent gut microbiome and applied self-organizing maps (SOMs)—a machine-learning approach—to identify distinct microbial profiles (n = 4). Using prospectively collected data on sociodemographic characteristics, lifestyle, diet, and sexual maturation, we identified early-life and concurrent factors associated with microbial diversity and phylum relative abundance with linear regression models and composition with Kruskal–Wallis and Fisher’s exact tests. We found that household income and other sociodemographic factors were consistent predictors of the microbiome, with higher income associated with lower diversity and differential relative abundances of Firmicutes (increased) and Actinobacteria (decreased). Sexual maturation, distinct from chronological age, was related to higher diversity in females and differences in phylum relative abundances and compositional profiles in both males and females. Our study suggests that adolescence is a unique window for gut microbial composition and that it may be shaped by both early-life and concurrent exposures, highlighting its potential in future epidemiologic research.

Background:Toxicological studies suggest neonicotinoids increase oxidative stress and inflammation, but few epidemiological studies have explored these effects.Methods:National Health and Nutrition Examination Survey (NHANES) 2015-2016 data were used to estimate associations between neonicotinoid exposure and inflammatory markers, including the C-reactive protein-to-lymphocyte count ratio (CLR), monocyte-to-high-density lipoprotein ratio (MHR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) using linear and multinomial logistic regression models. Sex was evaluated as a potential modifier.Results:Detection of any parent neonicotinoid (beta = -0.62, 95% confidence interval [CI] = -0.98, -0.26) and imidacloprid (beta = -0.48, 95% CI = -0.87, -0.10) was associated with decreased CLR. Clothianidin was linked to reduced MLR (beta = -0.04, 95% CI = -0.07, -0.02), but increased lymphocyte-to-monocyte ratio (beta = 0.52, 95% CI = 0.27, 0.77). Higher dNLR (beta = 0.85; 95% CI = 0.26, 1.43) was noted with detection of any neonicotinoid metabolite. Moderately high PLR was observed with detection of any neonicotinoid metabolite (relative risk ratio [RRR] = 1.63, 95% CI = 1.27, 2.09) or 5-hydroxy-imidacloprid (RRR = 2.19, 95% CI = 1.40, 3.41). Sex-modified analyses showed positive associations in males and inverse associations in females for MHR (Pint = 0.099, clothianidin), PLR (Pint = 0.026, clothianidin), and SII (Pint = 0.056, any parent neonicotinoid; Pint = 0.002, clothianidin), while the opposite pattern was noted with CLR (Pint = 0.073, any parent neonicotinoid) and NLR (Pint = 0.084, clothianidin).Conclusion:Neonicotinoids may be associated with inflammatory changes, with potential sexual dimorphism. Further studies are required to explore these findings.

BACKGROUND:This study aims to evaluate the mediating role of placental transcriptomic and metabolomic changes in the association between gestational exposure to fine particulate matter and spontaneous preterm birth (sPTB). METHODS:This study includes 72 participants from the CellulaR Injury and Preterm Birth Study. Daily exposure to PM2.5 and black carbon during the first 20 weeks of pregnancy was estimated using fused 1-km resolution model outputs linked to maternal delivery addresses. High exposure was defined as days with PM2.5 >9 μg/m3 or black carbon >1 μg/m3, calculated monthly across gestation. Early sPTB (<32 weeks) and covariates were extracted from electronic health records. Associations between high-exposure days and expression of 432 sPTB-related genes were evaluated using gene-wise negative binomial models, and associations with 866 placental metabolites were assessed using multiple linear regression. Both analyses adjusted for covariates, using q < 0.2 for statistical significance. High-dimensional mediation analysis was conducted on genes/metabolites with at least one significant hit (q < 0.05). RESULTS:Black carbon exposure during gestational months 3-5 was associated with increased odds of sPTB. We identified 63 genes linked to black carbon and 50 to PM2.5, mainly related to cellular stress, immune response, and developmental pathways. For black carbon, 23 genes showed consistent associations across multiple exposure windows (9 genes consistently negatively associated, 13 positively associated). An increase in expression of genes MPO, ELANE, and GNRH2 mediated the association between black carbon exposure and increased sPTB. CONCLUSION:Gestational exposure to black carbon is associated with increased odds of sPTB, and this association was mediated by altered placental gene expression.

BACKGROUND:Some epidemiological studies suggest that phthalates adversely affect children's neurodevelopment, but results are inconsistent and often only consider individual chemicals. OBJECTIVES:We examined associations between gestational phthalate metabolites and intelligence at ages 3-4 and investigated effect modification by child sex. METHODS:We analyzed data from 511 mother-child pairs enrolled in the Maternal-Infant Research on Environmental Chemicals study. We measured specific gravity-standardized urinary concentrations of 20 phthalate metabolites (from nine parent compounds) in trimesters 1 and 2 and computed the average. We used linear regression models (log2-transformed), adjusting for covariates, to examine single-chemical associations with Full-Scale (FSIQ), Performance (PIQ), and Verbal IQ (VIQ) measured by the Weschler Preschool and Primary Scale of Intelligence-III. We estimated mixture effects using weighted quantile sum (WQS) regression. RESULTS:Detection frequencies of the metabolites ranged from 42 to 99%. In single-chemical analyses, the sum of di-isodecyl phthalate metabolites (ΣDiDPm) was associated with decreased FSIQ (-0.5, 95%CI: -2.1, -0.0) and PIQ (-0.6, 95%CI: -1.2, -0.0). Monomethyl phthalate (MMP) was associated with increased FSIQ (1.7, 95%CI: 0.4, 3.1), PIQ (1.7, 95%CI: 0.2, 3.1) and VIQ; (1.6, 95%CI: 0.3, 2.8). Monobenzyl phthalate (MBzP) was positively associated with PIQ (0.9, 95%CI: 0.0, 1.9). Associations between ΣDiDPm and VIQ and MMP and PIQ differed by child sex (negative for boys and positive for girls, respectively). WQS analyses were not statistically significant. CONCLUSIONS:Findings from this pan-Canadian cohort provide some evidence that gestational ΣDiDPm is adversely associated with child cognition, with sex-specific vulnerabilities. The positive associations with MMP and MBzP warrant further research.