Background/Objectives: Inflammation may play a critical role in the pathogenesis of gestational diabetes mellitus (GDM). However, evidence linking early-pregnancy cytokines to subsequent GDM risk remains inconsistent, with most prior research focusing only on CRP, IL6, and TNFα. In this study, we expand on prior work by evaluating a broader range of immune markers and assessing sociodemographic factors as potential moderators. Methods: Data from a prospective U.S. pregnancy cohort (n = 308) were analyzed. Twenty cytokines were quantified in maternal first-trimester plasma using the MILLIPLEX High-Sensitivity Human Cytokine Magnetic Bead Panel. One-hour oral glucose (50 g) tolerance test (OGTT) values assessed at an average gestational age of 27.7 weeks (SD = 2.9) and GDM diagnosis were abstracted from medical records. Multivariable linear and logistic regression models were used to examine associations between cytokines and 1 h 50 g OGTT levels or GDM diagnosis, adjusting for key sociodemographic factors. Interactions terms were included to evaluate whether sociodemographic factors moderated cytokine–GDM relationships. Results: Sixteen women (5.1%) were diagnosed with GDM. Higher first-trimester high-sensitivity-IL6 levels were significantly associated with increased 1 h 50 g OGTT values (b = 3.76; 95% CI: 0.21, 7.32; p = 0.04) and greater odds of GDM (OR = 2.36; 95% CI: 1.17, 4.77; p = 0.02). These associations were more pronounced among Non-Hispanic White women compared to Non-Hispanic Black women (p for interaction = 0.03) and potentially those with normal weight or underweight during early pregnancy compared to overweight or obese women (p for interaction = 0.08). Conclusions: Elevated inflammatory markers, particularly high-sensitivity IL6, in early pregnancy are linked to impaired glucose metabolism and increased GDM risk later in pregnancy. These relationships appeared stronger in Non-Hispanic White women and women with normal weight or underweight during early pregnancy, underscoring the potential to develop serology-based early identification and prevention strategies.

Importance:Gestational environmental chemical exposures are widespread. Some chemicals are known to adversely affect birth outcomes, but many remain understudied. Objective:To evaluate associations of gestational exposure to a priori identified chemicals in 10 classes with birth outcomes in a large, diverse US cohort. Design, Setting, and Participants:In the prospective Environmental influences on Child Health Outcomes Cohort study, 5318 mother-child pairs were enrolled from January 1, 2000, to December 31, 2021, with data on gestational urinary chemical concentrations, gestational age at birth, and birth weight. Statistical analysis was performed from January 2024 to February 2026. Exposures:In single, midgestation (median, 25 weeks [IQR, 21-30 weeks]) urine samples, concentrations of 113 analytes (chemicals or their metabolites) from 10 chemical classes were simultaneously measured: fungicides and herbicides (n = 11), insecticides (n = 20), halogenated phenols (n = 5), organophosphate esters (n = 10), benzophenones (n = 6), bisphenols (n = 14), parabens (n = 6), antimicrobials (n = 2), phthalates or alternative plasticizers (n = 32), and polycyclic aromatic hydrocarbons (PAHs) (n = 7). Main Outcomes and Measures:Linear mixed-effects regression models with a random effect for site were used to estimate covariate-adjusted differences in gestational age at birth (days) and birth weight-for-gestational age (BW-GA) z scores per IQR increase in urinary analyte concentrations. In secondary analyses, odds ratios (ORs) for preterm birth and small for gestational age (SGA) were estimated. Results:In the sample of 5318 mother-child pairs, most infants (2667 female [50%]; median gestational age at birth, 39.0 weeks [IQR, 38.0-40.0 weeks]) were born to college-educated (67% [3218 of 4785]), parous (56% [2815 of 5007]) mothers (median age at delivery, 30.7 years [IQR, 26.1-34.3 years]). A total of 43 of 113 analytes (38%) were detected in 50% or more of samples. Multiple phthalates or alternative plasticizers were associated with younger gestational age at birth or lower BW-GA z scores; for example, summed diisononyl phthalate metabolites were associated with a 0.6-day (95% CI, -1.0 to -0.1 days) younger gestational age (preterm birth OR, 1.16 [95% CI, 1.01-1.34]), and summed phthalate or alternative plasticizers were associated with a 0.06 (95% CI, -0.11 to -0.02) lower BW-GA z score (SGA OR, 1.09 [95% CI, 0.93-1.27]). Two halogenated phenols, benzophenone 8, bisphenol F, and several PAHs were associated with lower BW-GA z scores; for example, 1- and 9-hydroxphenanthrene were associated with a 0.04 (95% CI, -0.08 to -0.01) lower BW-GA z score (SGA OR, 1.13 [95% CI, 1.01-1.27]). Conclusions and Relevance:This large cohort study of diverse US pregnancies found widespread exposure to 10 classes of environmental chemicals, many of which were associated with differences in gestational age at birth or lower BW-GA z scores. These findings indicate that reducing gestational exposure to chemicals, particularly phthalates or alternative plasticizers and PAHs, could promote healthy deliveries and better child outcomes.

INTRODUCTION:Human chorionic gonadotropin (hCG) is a heterodimeric hormone regulated in part by the maternal neuroendocrine-placenta axis. Serum levels of the beta subunit (hCGβ) are higher in Black vs. White pregnancies. The underlying causes of the difference remain unclear. The objective of the study was to measure associations of maternal demographic and anthropometric characteristics, and self-reported measures of stress and discrimination with hCG and its subunits in a racially diverse sample. METHODS:Serum samples were provided by longitudinal birth cohorts in Rochester, NY and in Pittsburgh, PA. Research participants were enrolled in early pregnancy from 2015 to 2019. Serum hCG levels in the first and second trimesters, measured by immunofluorometric assays (IFMA) as intact hCG, its hyperglycosylated form (h-hCG) and free alpha and beta subunits (hCGα and hCGβ), were normalized for gestational day of blood draw as the multiple of the median (MoM). Minimally adjusted generalized linear models were fit to explore associations of exposures, including maternal demographic characteristics, pregnancy characteristics, perceived stress, depression, stressful life events, experiences of discrimination and everyday discrimination, with serum levels of hCGs. RESULTS:Research subjects (n = 451) identified as Black (24%) and White (59%). hCGα was lower (-0.35 log MoM; 95% CI -0.45, -0.24) in Black vs. White participants and intact hCG and hCGβ were higher (0.19 log MoM; 95% CI 0.02, 0.36). Body mass index, weight, gravidity and smoking were negatively associated with hCGα. Maternal age, education, income, and partnered (vs. single) status were positively associated with hCGα. Number of stressful life events and experiences of discrimination were negatively associated with hCGα. Everyday discrimination was positively associated with hCGβ. CONCLUSION:An hCG-subunit specific pattern of association was described with maternal social and psychosocial experience in early pregnancy. More work is needed to understand these differences and their applicability to interventions to reduce stress and its long-term impacts on maternal and child health.

Maternal depressive symptoms during pregnancy have consequences for offspring brain development, likely mediated via biological signals. However, gestational biological correlates of maternal depression may differ depending on childhood maltreatment (CM) history. We investigated the association of maternal depressive symptoms in pregnancy and CM history with newborn global white matter microstructure. In a sample of N = 90 mother-infant dyads from two cohorts, maternal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. CM was assessed with the Childhood Trauma Questionnaire or the Adverse Childhood Experiences scale. Diffusion-weighted imaging was performed in the infants within 90 days of birth. Fiber profiles of fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were determined, and a global mean for each metric was computed. In adjusted models, there was a significant interaction effect of maternal depression and CM on newborn global FA (β = -0.523, p = .029) and RD (β = 0.590, p = .014) but not AD (β = 0.367, p = .120). In infants of women with CM history, maternal depressive symptoms were correlated negatively with FA and positively with RD. In contrast, infants of women without CM exhibited the reverse pattern of associations between depressive symptoms and diffusion metrics. These findings suggest that the impact of prenatal exposures, such as maternal depressive symptoms, on offspring brain development may be conditional on the presence or absence of maltreatment history. These findings highlight the importance of assessing trauma history and monitoring psychosocial well-being during pregnancy.

BACKGROUND: Environmental exposures to toxicants, such as per- and polyfluoroalkyl substances (PFAS), during gestation can disrupt immune development, causing long-term impacts on a child's ability to generate a well-regulated, protective immune response. T-cells coordinate with all immune cell types to orchestrate both cellular and antibody-mediated responses. While there is compelling evidence that PFAS alters immunity in humans, the specific effects of early life PFAS exposure on infant T-cell development are unreported. Because of their central role in immunity, altered T-cell development in infants would have implications on immune responses broadly and long-term. OBJECTIVES: We seek to model longitudinal changes in the frequency of functionally distinct CD4+ T-cell subpopulations from birth through 12 months and their association with in utero PFAS exposure. METHODS: Maternal-infant dyads were recruited as part of the UPSIDE-ECHO cohort during the first trimester between 2015 and 2019 in Rochester, New York; dyads were followed through the infant's first birthday. Maternal PFAS concentrations (PFOS, PFOA, PFNA, PFHXS and PFDA) were quantified in serum during the second trimester using high-performance liquid chromatography and tandem mass spectrometry. Infant lymphocyte frequencies were assessed at birth, 6- and 12-months using mass cytometry and high-dimensional clustering methods. Linear mixed-effects models were employed to analyze the relationship between maternal PFAS concentrations and CD4+ T-cell subpopulations (n = 200). All models included a PFAS and age interaction and were adjusted for parity, infant sex, and prepregnancy body mass index. RESULTS: In utero PFAS exposure correlated with multiple CD4+ T-cell subpopulations in infants. The greatest effect sizes were seen in T follicular helper (Tfh) and T-helper 2 (Th2) cells at 12 months. A log(2)-unit increase in PFOS was associated with lower Tfh [0.17% (95% CI: -0.30, -0.40)] and greater Th2 [0.27% (95% CI: 0.18, 0.35)] cell percentages at 12 months. Similar trends were observed for PFOA, PFNA, PFHXS, and PFDA. DISCUSSION: Maternal PFAS exposures correlate with cell-specific changes in the infant T-cell compartment, including key CD4+ T-cell subpopulations that play central roles in coordinating well-regulated protective immunity. Future studies into the role of PFAS-associated T-cell distribution and the risk of adverse immune-related health outcomes in children are warranted.

Zearalenone (ZEN) is a mycotoxin that widely contaminates human food supplies. In animal models, exposure to ZEN has extensive impacts on reproduction and pregnancy including contributing to early parturition. Here, we translate that research to humans by examining gestational exposure to ZEN in relation to the timing of birth and placental corticotropin releasing hormone (pCRH), a hormone that regulates the timing of parturition. Utilizing data from a pregnancy cohort (UPSIDE; Rochester, NY; n = 299), we investigated exposure to ZEN and its metabolites in relation to: 1) gestational age at birth; and 2) pCRH across pregnancy. Adjusted linear regression models were fitted to examine gestational age at birth and pCRH in relation to three maternal urinary mycoestrogen measures in each trimester: (1) ZEN; (2) its metabolite, α-zearalenol (aZOL); and (3) the sum of ZEN and its five metabolites (∑mycoestrogens). For models examining pCRH, we additionally fitted linear mixed effects models to account for repeated measures. All models were refitted stratified by fetal sex. Mycoestrogens were detected in over 90% of samples in each trimester. Sex-stratified analyses showed distinct sex differences in trimester 2 in relation to exposure, with higher gestational age at birth in males (β:2.35 days, 95%CI:0.14, 4.56) and lower gestational age at birth in females (β:-1.70 days, 95%CI:-3.35, -0.07). In linear mixed effects models examining pCRH, ZEN was positively associated with pCRH concentrations: ZEN (%Δ:5.17, 95%CI:1.09, 9.36). Mycoestrogen exposure may be associated with sex-specific changes in gestational age at birth and higher pCRH, a risk factor for preterm birth.

OBJECTIVE:Exposure to per- and polyfluoroalkyl substances (PFAS) may increase the risk of gestational diabetes mellitus (GDM), with adverse consequences for pregnant women and their offspring. However, epidemiologic studies have shown inconsistent results. We addressed this question in a large, pooled sample of U.S. women. RESEARCH DESIGN AND METHODS:Participants (n = 5,229) from 16 cohorts had singleton pregnancies. PFAS were quantified in a single plasma or serum sample during pregnancy (1999-2021); six PFAS detected in ≥60% of participants were analyzed. The primary outcome was GDM diagnosis based on self-report or medical record documentation. The secondary outcome, among 1,213 participants, was fasting glucose. We estimated associations between each PFAS and GDM using generalized estimating equations models with Poisson distribution and robust variance, and estimated associations between each PFAS and fasting glucose using generalized estimating equations models for linear regression. Effect modification by prepregnancy BMI or race and ethnicity was evaluated via interaction terms and stratification. We quantified the combined effect of the PFAS mixture using quantile-based g-computation. RESULTS:Associations between individual PFAS and GDM were null or weakly inverse; the association with the six-PFAS mixture was negative (prevalence ratio [95% CI] per quartile increase: 0.75 [0.58, 0.96]). Certain PFAS were more strongly negatively associated with GDM among participants with BMI <25 kg/m2. Associations between PFAS and fasting glucose were largely null, although both positive and negative associations were observed in specific race and ethnicity strata. CONCLUSIONS:In a large, pooled sample of U.S. pregnant women, greater concentrations of PFAS were not associated with higher prevalence of GDM.

Mycotoxins are fungal-derived metabolites found in the global food supply, particularly in cereal grains and processed foods. Zearalenone (ZEN), one of the more common mycotoxins, widely contaminates human food supplies at concentrations above established maximum contamination levels. However, the effects of ZEN exposure on human health have only begun to be explored, with most studies on this topic focusing on its endocrine-disrupting effects in the reproductive system. ZEN is readily absorbed following oral administration, making the gastrointestinal (GI) tract and its microbiota primary targets for toxicity. The gut microbiome plays a critical role in nutrient processing and immune function and can be heavily influenced by dietary and chemical exposures. Given widespread human dietary exposure to ZEN, we conducted a comprehensive literature review of ZEN and its metabolites in relation to the mammalian gut microbiome. We identified 19 studies, all conducted in animal models, and each reported alterations in gut microbiome composition in ZEN-treated groups compared with control animals. Several papers reported modified metabolism in ZEN-treated groups, particularly related to short-chain fatty acids. In light of this small but compelling literature and the expected increase in mycotoxin contamination due to the industrialization of the food supply and warmer weather conditions, we identified several priority areas for future study. These include better understanding the mechanisms by which ZEN and its metabolites affect the microbiome and ultimate translation to human health.

BACKGROUND:Zearalenone (ZEN) is a grain-contaminating mycotoxin and potent estrogen receptor agonist linked to reproductive and perinatal disruption in animal models, with emerging epidemiologic evidence in humans. Despite widespread U.S. exposure, dietary sources remain unclear. OBJECTIVE:This pilot study assessed prenatal mycoestrogen exposure and related dietary sources in a U.S. pregnant cohort. METHODS:Pregnant women (n = 33) recruited in New Brunswick, NJ provided urine samples and completed time-matched 24-h dietary recalls at three points across pregnancy (Visit 1: 18-20 weeks; Visit 2: 24-26 weeks and Visit 3: 28-32 weeks gestation). Urinary mycoestrogens were quantified using LC/MSMS and corrected for specific gravity. RESULTS:At least one ZEN metabolite was detected in every sample (Visit, median: 1: 0.058 ng/mg; 2: 0.042 ng/mg; 3: 0.055 ng/mg), and intraclass correlation coefficients among detected metabolites ranged from 0.62 to 0.95. Across visits, Hispanic participants (39%) had 52-109% higher mycoestrogen concentrations compared to non-Hispanic participants (p < 0.05). Consumption of corn and other grain products within the past 24 h was strongly correlated with urinary concentrations of ZEN and its metabolites (r: 0.30-0.92; p < 0.05), with weaker positive correlations observed for oils and popcorn. SIGNIFICANCE:Given robust toxicologic evidence and emerging epidemiologic findings suggesting adverse maternal and child health impacts, identifying key exposure pathways is critical. IMPACT:This pilot study identifies corn and cereal-based foods as key contributors to ZEN prenatal exposure and highlights higher concentrations among Hispanic participants. By clarifying exposure pathways, these findings support improved food-safety monitoring and targeted strategies to reduce endocrine-disrupting chemical exposures during pregnancy.

Importance Assessment of cardiovascular health (CVH) during pregnancy may unmask latent metabolic vulnerability and indicate long-term disease risk. However, the prognostic value of the American Heart Association’s Life’s Essential 8 (LE8) framework during pregnancy remains uncertain. Objective To evaluate CVH during pregnancy using a modified LE8 (mLE8) score in association with time to incident cardiometabolic disease. Design, Setting, and Participants This cohort study used electronic medical record (EMR) surveillance for 7 years post partum (August 2018 to March 2026) and included singleton pregnancies in individuals aged 18 to 44 years without preexisting diabetes or cardiovascular disease (CVD) from a large academic medical system in South Carolina. Data were analyzed from December 2024 to April 2026. Exposures A 7-component mLE8 score assessed during pregnancy, incorporating hypertensive disorders of pregnancy (HDP), 50 g glucose tolerance test results, early pregnancy body mass index, smoking status, sleep adequacy, diet quality, and physical activity. Scores ranged from 0 to 100, with higher scores indicating more favorable CVH. Main Outcomes and Measures Postdelivery incident cardiometabolic conditions captured through EMRs and classified as chronic hypertensive conditions, chronic metabolic conditions (eg, dyslipidemia, impaired glucose regulation), and CVD (eg, cardiac arrest, cardiomyopathy). Adjusted accelerated time-to-failure models estimated mLE8 associations with incident conditions. Time to incident diagnosis was measured in days from delivery. Results Among 1225 pregnancies (mean [SD] age, 25.0 [5.3] years), 499 incident cardiometabolic events occurred over a median (IQR) follow-up of 6.2 (2.8) years. Each 10-point higher mLE8 score was associated with a longer time to incident diagnosis of chronic hypertensive conditions (time ratio [TR], 1.26; 95% CI, 1.11-1.42) and chronic metabolic conditions (TR, 1.20; 95% CI, 1.11-1.29). Healthier HDP (1.06 [1.03-1.10]), glucose (1.15 [1.10-1.21]), body mass index (1.07 [1.04-1.11]), and sleep (1.05 [1.00-1.09]) scores were associated with longer time to diagnosis of chronic metabolic conditions. Associations were generally similar after excluding individuals with gestational diabetes or HDP. Conclusions and Relevance In this cohort study of 1225 pregnancies, better CVH during pregnancy was associated with a longer time to incident postdelivery diagnosis of cardiometabolic conditions. Pregnancy-based CVH assessment may help identify individuals with elevated and emerging cardiometabolic risk who could benefit from early, targeted intervention and enhanced longitudinal surveillance.

BACKGROUND: Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during the pregnancy. Objective: We investigated whether OPE urinary concentrations during pregnancy were associated with child's autism-related outcomes. METHODS: We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [>median], moderate [≤median], nondetect), or as detect/nondetect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS: Compared with nondetectable concentrations, high exposure to bis-(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis-(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs nondetect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs nondetect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis-(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION: Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with a higher risk of autism diagnosis and related traits in childhood.

BACKGROUND:Increased placental oxidative stress is frequently documented in pregnant women with adverse maternal outcomes such as preeclampsia. However, environmental determinants of placental oxidative stress remain poorly understood. OBJECTIVES:To determine whether exposure to air pollution and polycyclic aromatic hydrocarbons (PAHs) are associated with placental levels of malondialdehyde (MDA), a biomarker of oxidative stress; to assess whether placental MDA reflects short-term (lag days 0-7) or longer-term (trimester-specific) exposure; and to evaluate whether these associations differ by fetal sex. METHODS:Participants were drawn from the UPSIDE ECHO BABIES cohort (n = 222). Placental MDA concentrations were quantified using an HPLC method. The ambient PM2.5 and NO2 exposures were estimated using high-resolution random forest models. PAH exposure was assessed using trimester-specific maternal blood concentration of PAH-hemoglobin adducts. Associations between exposure and placental MDA were evaluated using multivariable linear regression and distributed lag non-linear models (DLNMs), adjusting for maternal and demographic covariates. RESULTS:A 1-IQR increase in the second trimester, specifically month 5 p.m.2.5, was associated with a 24.8% (95% CI: 3.3-50.7), and 13.7% (95% CI: 0.1-29.16) increase in MDA concentration, respectively. Similarly, the second-trimester hemoglobin adduct of benzo [a]pyrene showed a positive, non-significant association with MDA. Although week-specific DLNM estimates were not statistically significant, the analysis showed that exposure to PM2.5 during gestational weeks 16-20 was positively associated with MDA concentration. When stratified by placenta sex, female placentas had increased MDA in the second trimester associated with PM2.5, and male placentas had increased MDA in the second trimester associated with PAH-hemoglobin adducts. No significant associations were observed for either pollutant when estimated one lag week before birth. No significant associations were observed for NO2 exposure. CONCLUSIONS:Second-trimester PM2.5 exposure was linked to elevated placental MDA concentration at delivery, indicating that placental MDA may reflect longer-term air pollution exposure. These findings emphasize the importance of investigating specific gestational windows through which air pollution induces oxidative injury to the placenta.

Although the devastation of war is well recognized, no study has combined conflict intensity, humanitarian access, environment and infrastructure to assess their collective impact on health vulnerability. Here, using spatial and suitability models, we evaluated multidimensional vulnerabilities in Ukraine during the Russian invasion, including mental health, environmental stressors and infrastructure disruptions. We developed a multi-source database (news sources, UNICEF and Ukrainian ministries) on conflict-related health impacts, integrating data from a national survey (4,675 Ukrainian households) on sleep, mental health and casualties. Data were cleaned, geolocated across 461 cities (hromadas) and analysed using inverse distance weighting interpolation. We applied logistic and spatial regression to assess how conflict exposure and living conditions influence mental health, sleep loss and cold-related injury, creating a composite vulnerability index via weighted principal component analysis. Areas facing intense conflict, inadequate housing, power outages, food shortages, and limited healthcare and aid access showed heightened vulnerability. Cold, damp conditions, damaged housing and scarce resources sharply worsened household living conditions in eastern and northern Ukraine. Mental health burdens varied, with cold, damp, crowded housing, food insecurity and power outages as key drivers. Post-traumatic stress disorder, depression and insomnia were highest in regions with harsh winters, poor infrastructure and limited aid. War’s effects go beyond violence, with interacting conflict, environmental stressors and infrastructure damage shaping health and well-being outcomes. A multi-source dataset including a survey on 2,364 Ukrainian citizens pinpoints the spatial and temporal features associated with stronger interactions between conflict-related and baseline stressors and health-related outcomes, in a Ukraine-wide analysis involving 461 cities.

BACKGROUND:The rising global prevalence of pediatric mental health problems requires the identification of preventable factors underlying their development. This study assessed whether maternal adverse childhood experiences (ACEs) and pregnancy stress were intergenerationally associated with offspring mental health. METHODS:This study used data from 34 sites in the nationwide Environmental Influences on Child Health Outcomes Cohort. Eligible parent-child dyads (child age: 1.5-18 years) provided data on at least one measure of maternal stress and at least one measure of child mental health. Study aims were evaluated using regression analyses, including interaction tests to determine potential effect modifiers. RESULTS:Participants were organized into three subsamples with data on (1) maternal ACEs (N = 2,906), (2) perceived prenatal stress (N = 4,441), and (3) both stress exposures (N = 834). After adjusting for confounders, maternal ACEs and prenatal stress were significantly associated with child mental health problems (B = 2.53 [95% confidence interval [CI]: 2.09, 2.96], p < 0.0001 and B = 2.36 [95% CI: 2.03, 2.68], p < 0.0001, respectively). Among participants with data on both stress exposures, maternal ACEs (B = 1.72, 95% CI: [0.96, 2.48], p < 0.0001) and prenatal stress (B = 2.05, 95% CI: [1.29, 2.80], p < 0.0001) were independently associated with child mental health problems. Neither maternal ACEs nor child sex modified the association between prenatal stress and child mental health problems. CONCLUSIONS:Maternal exposure to ACEs and pregnancy stress were associated with the development of child mental health problems. These findings highlight the need for policies and interventions that mitigate exposure to adversity and protect pregnant individuals and their children from the intergenerational transmission of mental health problems.

Oxidative stress (OS), an imbalance between reactive oxygen species and antioxidants, has been linked to impaired placental function and suboptimal fetal growth, yet trimester-specific associations remain poorly understood. We examined 561 mother-infant pairs from The Infant Development and Environmental Study, measuring maternal urinary biomarkers of DNA oxidation (8-hydroxydeoxyguanosine (8-OHdG)), lipid peroxidation (malondialdehyde (MDA) and F2-isoprostanes), and protein oxidation (dityrosine (diY)) at first and second trimesters. Using generalized linear models, we examined prospective associations between OS and ultrasound-derived growth velocities. Early pregnancy OS biomarkers were persistently associated with reduced second and third trimester growth velocities. First trimester lipid peroxidation markers (8-PGF2α, 15-PGF2α, and 8,15-PGF2α) were associated with slower estimated fetal weight (EFW) growth velocity in both second trimester (-0.81, -0.93, and -1.72 g/week per log-unit increase, respectively) and third trimester (-4.25, -5.60, and -6.74 g/week). Similarly, first trimester 8-OHdG and diY were associated with both second trimester (-1.31 and -1.17 g/week, respectively) and third trimester EFW velocity (-8.01 and -6.75 g/week, respectively). Second trimester 8-OHdG and MDA were associated with slower third trimester EFW velocity (-8.57 and -9.25 g/week, respectively). These results provide novel insights into trimester-specific associations between OS and fetal growth.

BACKGROUND:Direct measurement of in utero phthalate exposure in placental and fetal tissues is generally not possible. Maternal urinary levels serve as proxies and may introduce measurement error, biasing health effect estimates. OBJECTIVE:We adjusted for measurement error when using maternal urinary phthalates as proxies for placental-fetal exposure and to evaluate the impact of this correction on the association between prenatal phthalate exposure and anogenital distance (AGD). METHOD:We biopsied and analyzed 68 placentas from the TIDES study (San Francisco site: n = 204, 2010-2012). Phthalate metabolite concentrations were measured in three placental tissue types: chorion smooth (CS), chorion frondosum (CF), and basal plate (BP). Phthalate concentrations were standardized to remove pre-processing variation. Regression calibration (RC) and multiple imputation for measurement error (MIME) were used for correction. Associations between phthalates and AGD were estimated by generalized linear models. Bias was quantified by calculating the percent change in the beta coefficient from the gold standard (placental phthalate) to the proxy (urinary phthalate), after correction for measurement error. RESULTS:Phthalate metabolites were detected in over 70% of placental tissues. Monoethylhexyl (MEHP) phthalate was the most abundant metabolite in CF and in CS. Phthalate concentrations were lowest in BP and varied across placental tissues. Weak associations were found between urinary and placental phthalates. MIME outperformed RC, reducing bias in the average phthalate effect on AGD in the male by 30% for AGD-penis and 69% for AGD-scrotum, and in the female by 32% for AGD-clitoris and 45% for AGD-fourchette. SIGNIFICANCE:Placental phthalate concentrations varied by tissue type and showed poor correlation with maternal urinary levels. MIME outperformed RC in adjusting for measurement error in this setting. Findings suggest maternal and placental exposures are distinct constructs, highlighting the need for direct placental measurement in phthalate toxicity studies. Further research can improve phthalate exposure assessment and knowledge of maternal-placental-fetal transfer. IMPACT:This study highlights a key gap in environmental health research, where maternal urinary phthalates are often used as proxies for placental and fetal exposure. Using two correction methods, we found that maternal urinary and placental phthalates represent distinct exposure constructs and are not interchangeable.

Recognizing that social and environmental exposures may co-occur and impact perinatal outcomes, we examined associations between neighborhood stress and social vulnerability, and placental metals concentrations. Pregnant participants (n = 242) in the UPSIDE study (Rochester, NY) completed the City Stress Inventory which has two subscales: neighborhood disorder (e.g., vacant buildings) and violence (personal experiences of violence). Neighborhood disorder was considered as quartiles (Q) and violence was considered binary (any/none). Participant addresses were linked to the CDC’s Social Vulnerability Index (SVI) and its four sub-themes (socioeconomic status, household composition and disability, minority status and language, housing type and transportation). SVI assigns each census tract a U.S.-wide percentile ranking (0–1) with higher values indicating greater vulnerability). We categorized SVI measures as low, medium [M], and high. At delivery, placenta were collected and lead, arsenic, cadmium, chromium, and manganese were analyzed by ICP-MS. We fitted adjusted linear regression models associating neighborhood stress and SVI measures with each log-transformed metal. Results are reported as percentage difference (

Background:Men with prostate cancer (PCa) may be especially vulnerable to per- and polyfluoroalkyl substances (PFAS) exposure due to their endocrine-disrupting and cardiometabolic impacts and cardiotoxicity and immune suppression of treatments. Objective:A pilot study was launched to measure serum and tap water PFAS concentrations in PCa survivors. Methods:Men with PCa were recruited from Rutgers Cancer Institute between February 2025 and March 2026, with ongoing enrollment and follow-up. Eligible men were aged ≥40 years on active surveillance or within 3-12 months of initial definitive treatment. Participants provided blood and residential tap water samples, which were analyzed using mass spectrometry (serum) and modified EPA method 537 (water). Geometric means were used to summarize PFAS concentrations by race and assess serum-tap water correlations. Results:Of 235 eligible patients, 124 (60%) enrolled. Median age was 64 years; 63% were non-Hispanic White, 43% had a Gleason score ≤6. Roughly half of participants provided serum and/or tap water samples. In serum, six PFAS analytes had >80% detection; of these analytes, median concentrations ranged from 0.13 ng/mL (IQR: 0.07-0.20) for PFHpS to 2.55 ng/mL (IQR:1.54-3.82) for nPFOS. Among 74 tap water samples, 9 PFAS analytes had >60% detection; of these, median concentrations of PFNA (0.56 ng/L; IQR: 0.33-0.75), PFOA (3.75 ng/L; IQR: 1.21-5.27), and PFOS (2.29 ng/L; IQR: 0.46-2.89), were below New Jersey Maximum Contaminant Levels. Non-White participants had significantly higher levels of multiple PFAS analytes in both serum and tap water. Serum-tap water correlations were modest (r=0.22-0.41). Significance:The pilot study has demonstrated both the feasibility and importance of studying PFAS exposure pathways as well as potential impacts of PFAS exposure in diverse populations. Impact Statement:This study provides some of the first estimates of PFAS exposure among prostate cancer patients in serum and tap water, showing moderate correlations between tap water and serum concentrations of specific PFAS analytes. These findings can support larger studies to identify environmental exposure sources and evaluate the role of PFAS in prostate cancer progression and outcomes.