Urinary polycyclic aromatic hydrocarbon (PAH) metabolite concentrations in three pregnancy cohorts from 7 U.S. study sites.

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.

A genome scale transcriptional regulatory model of the human placenta.

Gene regulation is essential to placental function and fetal development. We built a genome-scale transcriptional regulatory network (TRN) of the human placenta using digital genomic footprinting and transcriptomic data. We integrated 475 transcriptomes and 12 DNase hypersensitivity datasets from placental samples to globally and quantitatively map transcription factor (TF)-target gene interactions. In an independent dataset, the TRN model predicted target gene expression with an out-of-sample R2 greater than 0.25 for 73% of target genes. We performed siRNA knockdowns of four TFs and achieved concordance between the predicted gene targets in our TRN and differences in expression of knockdowns with an accuracy of >0.7 for three of the four TFs. Our final model contained 113,158 interactions across 391 TFs and 7712 target genes and is publicly available. We identified 29 TFs which were significantly enriched as regulators for genes previously associated with preterm birth, and eight of these TFs were decreased in preterm placentas.

Air Pollution Exposures and Child Executive Function: A U.S. Multi-Cohort Study.

BACKGROUND: Executive function, which develops rapidly in childhood, enables problem solving, focused attention, and planning. Animal models describe executive function decrements associated with ambient air pollution exposure, but epidemiologic studies are limited. METHODS: We examined associations between early childhood air pollution exposure and school-aged executive function in 1,235 children from three U.S. pregnancy cohorts in the ECHO-PATHWAYS Consortium. We derived point-based residential exposures to ambient particulate matter ≤2.5µm in aerodynamic diameter (PM2.5) and nitrogen dioxide (NO2), and ozone (O3) at ages 0-4 years from spatiotemporal models with a 2-week resolution. We assessed executive function across three domains -- cognitive flexibility, working memory, and inhibitory control -- using performance-based measures and calculated a composite score quantifying overall performance. We fitted linear regressions to assess air pollution - child executive function associations, adjusting for sociodemographic characteristics, maternal mental health, and health behaviors, and examined modification by child sex, maternal education, and neighborhood educational opportunity. RESULTS: In the overall sample, we found hypothesized inverse associations in crude but not adjusted models. Modified associations between NO2 exposure and working memory by neighborhood education opportunity were present (P interaction = 0.05), with inverse associations more pronounced in the "High" and "Very high" categories. Associations of interest did not differ by child sex or maternal education. CONCLUSIONS: This work contributes to the evolving science regarding early-life environmental exposures and child development. There remains a need for continued exploration in future research endeavors, to elucidate the complex interplay between natural environment and social determinants influencing child neurodevelopment.

Prenatal exposure to polycyclic aromatic hydrocarbons and executive functions at school age: Results from a combined cohort study.

BACKGROUND: Executive functions develop rapidly in childhood, enabling problem-solving, focused attention, and planning. Exposures to environmental toxicants in pregnancy may impair healthy executive function development in children. There is increasing concern regarding polycyclic aromatic hydrocarbons (PAHs) given their ability to transfer across the placenta and the fetal blood-brain barrier, yet evidence from epidemiological studies is limited. METHODS: We examined associations between prenatal PAH exposure and executive functions in 814 children of non-smoking mothers from two U.S. cohorts in the ECHO-PATHWAYS Consortium. Seven mono-hydroxylated PAH metabolites were measured in mid-pregnancy urine and analyzed individually and as mixtures. Three executive function domains were measured at age 8-9: cognitive flexibility, working memory, and inhibitory control. A composite score quantifying overall performance was further calculated. We fitted linear regressions adjusted for socio-demographics, maternal health behaviors, and psychological measures, and examined modification by child sex and stressful life events in pregnancy. Bayesian kernel machine regression was performed to estimate the interactive and overall effects of the PAH mixture. RESULTS: The results from primary analysis of linear regressions were generally null, and no modification by child sex or maternal stress was indicated. Mixture analyses suggested several pairwise interactions between individual PAH metabolites in varied directions on working memory, particularly interactions between 2/3/9-FLUO and other PAH metabolites, but no overall or individual effects were evident. CONCLUSION: We conducted a novel exploration of PAH-executive functions association in a large, combined sample from two cohorts. Although findings were predominantly null, the study carries important implications for future research and contributes to evolving science regarding developmental origins of diseases.

Associations Between Prenatal Vitamin D and Placental Gene Expression.

Background: Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. Objective: We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort. Methods: Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks' gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA). Results: The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy (N=774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (N=753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors including ARNT2, BHLHE40, FOSL2, JUND, and NFKB1. Conclusions: Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

Measurement bias in caregiver-report of early childhood behavior problems across demographic factors in an ECHO-wide diverse sample.

Background: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. Methods: Item-level data of CBCL/1.5-5 from a large sample of young children (N = 9087) were drawn from 26 cohorts in the Environmental influences on Child Health Outcomes program. Factor analyses and the alignment method were applied to examine measurement invariance (MI) and differential item functioning (DIF) across child (age, sex, bilingual status, and neurodevelopmental disorders), and caregiver (sex, education level, household income level, depression, and language version administered) characteristics. Child race was examined in sensitivity analyses. Results: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and Total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and Total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. Conclusions: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and Total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets.

Associations of prenatal ambient air pollution exposures with asthma in middle childhood.

We examined associations between prenatal fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) exposures and child respiratory outcomes through age 8-9 years in 1279 ECHO-PATHWAYS Consortium mother-child dyads. We averaged spatiotemporally modeled air pollutant exposures during four fetal lung development phases: pseudoglandular (5-16 weeks), canalicular (16-24 weeks), saccular (24-36 weeks), and alveolar (36+ weeks). We estimated adjusted relative risks (RR) for current asthma at age 8-9 and asthma with recent exacerbation or atopic disease, and odds ratios (OR) for wheezing trajectories using modified Poisson and multinomial logistic regression, respectively. Effect modification by child sex, maternal asthma, and prenatal environmental tobacco smoke was explored. Across all outcomes, 95% confidence intervals (CI) included the null for all estimates of associations between prenatal air pollution exposures and respiratory outcomes. Pseudoglandular PM2.5 exposure modestly increased risk of current asthma (RRadj = 1.15, 95% CI: 0.88-1.51); canalicular PM2.5 exposure modestly increased risk of asthma with recent exacerbation (RRadj = 1.26, 95% CI: 0.86-1.86) and persistent wheezing (ORadj = 1.28, 95% CI: 0.86-1.89). Similar findings were observed for O3, but not NO2, and associations were strengthened among mothers without asthma. While not statistically distinguishable from the null, trends in effect estimates suggest some adverse associations of early pregnancy air pollution exposures with child respiratory conditions, warranting confirmation in larger samples.

Individual and Neighborhood Level Predictors of Children's Exposure to Residential Greenspace.

Inequities in urban greenspace have been identified, though patterns by race and socioeconomic status vary across US settings. We estimated the magnitude of the relationship between a broad mixture of neighborhood-level factors and residential greenspace using weighted quantile sum (WQS) regression, and compared predictive models of greenspace using only neighborhood-level, only individual-level, or multi-level predictors. Greenspace measures included the Normalized Difference Vegetation Index (NDVI), tree canopy, and proximity of the nearest park, for residential locations in Shelby County, Tennessee of children in the CANDLE cohort. Neighborhood measures include socioeconomic and education resources, as well as racial composition and racial residential segregation. In this sample of 1012 mother-child dyads, neighborhood factors were associated with higher NDVI and tree canopy (0.021 unit higher NDVI [95% CI: 0.014, 0.028] per quintile increase in WQS index); homeownership rate, proximity of and enrollment at early childhood education centers, and racial composition, were highly weighted in the WQS index. In models constrained in the opposite direction (0.028 unit lower NDVI [95% CI: - 0.036, - 0.020]), high school graduation rate and teacher experience were highly weighted. In prediction models, adding individual-level predictors to the suite of neighborhood characteristics did not meaningfully improve prediction accuracy for greenspace measures. Our findings highlight disparities in greenspace for families by neighborhood socioeconomic and early education factors, and by race, suggesting several neighborhood indicators for consideration both as potential confounders in studies of greenspace and pediatric health as well as in the development of policies and programs to improve equity in greenspace access.

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8-9 years in a multi-site longitudinal study.

BACKGROUND AND AIM: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium. METHODS: We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8-9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression. RESULTS: The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant. CONCLUSIONS: In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8-9 years, though some adverse associations were observed among girls.

Sex-specific associations between placental corticotropin releasing hormone and problem behaviors in childhood.

Placental corticotropin-releasing hormone (pCRH) is a neuroactive peptide produced in high concentrations in mid-late pregnancy, during key periods of fetal brain development. Some evidence suggests that higher pCRH exposure during gestation is associated with adverse neurodevelopment, particularly in female offspring. In 858 mother-child dyads from the sociodemographically diverse CANDLE cohort (Memphis, TN), we examined: (1) the slope of pCRH rise in mid-late pregnancy and (2) estimated pCRH at delivery as a measure of cumulative prenatal exposure. When children were 4 years-old, mothers reported on problem behaviors using the Child Behavior Checklist (CBCL) and cognitive performance was assessed by trained psychologists using the Stanford-Binet Intelligence Scales. We fitted linear regression models examining pCRH in relation to behavioral and cognitive performance measures, adjusting for covariates. Using interaction models, we evaluated whether associations differed by fetal sex, breastfeeding, and postnatal neighborhood opportunity. In the full cohort, log-transformed pCRH measures were not associated with outcomes; however, we observed sex differences in some models (interaction p-values≤0.01). In male offspring, an interquartile (IQR) increase in pCRH slope (but not estimated pCRH at delivery), was positively associated with raw Total (ß=3.06, 95%CI: 0.40, 5.72), Internalizing (ß=0.89, 95%CI: 0.03, 1.76), and Externalizing (ß=1.25, 95%CI: 0.27, 2.22) Problem scores, whereas, in females, all associations were negative (Total Problems: ß=-1.99, 95%CI: -3.89, -0.09; Internalizing: ß=-0.82, 95%CI: -1.42, -0.23; Externalizing: ß=-0.56, 95%CI: -1.34, 0.22). No associations with cognitive performance were observed nor did we observe moderation by breastfeeding or postnatal neighborhood opportunity. Our results provide further evidence that prenatal pCRH exposure may impact subsequent child behavior in sex-specific ways, however in contrast to prior studies suggesting adverse impacts in females, steeper mid-gestation pCRH rise was associated with more problem behaviors in males, but fewer in females.

Subpopulations of children with multiple chronic health outcomes in relation to chemical exposures in the ECHO-PATHWAYS consortium.

A multimorbidity-focused approach may reflect common etiologic mechanisms and lead to better targeting of etiologic agents for broadly impactful public health interventions. Our aim was to identify clusters of chronic obesity-related, neurodevelopmental, and respiratory outcomes in children, and to examine associations between cluster membership and widely prevalent chemical exposures to demonstrate our epidemiologic approach. Early to middle childhood outcome data collected 2011-2022 for 1092 children were harmonized across the ECHO-PATHWAYS consortium of 3 prospective pregnancy cohorts in six U.S. cities. 15 outcomes included age 4-9 BMI, cognitive and behavioral assessment scores, speech problems, and learning disabilities, asthma, wheeze, and rhinitis. To form generalizable clusters across study sites, we performed k-means clustering on scaled residuals of each variable regressed on study site. Outcomes and demographic variables were summarized between resulting clusters. Logistic weighted quantile sum regressions with permutation test p-values associated odds of cluster membership with a mixture of 15 prenatal urinary phthalate metabolites in full-sample and sex-stratified models. Three clusters emerged, including a healthier Cluster 1 (n = 734) with low morbidity across outcomes; Cluster 2 (n = 192) with low IQ and higher levels of all outcomes, especially 0.4-1.8-standard deviation higher mean neurobehavioral outcomes; and Cluster 3 (n = 179) with the highest asthma (92 %), wheeze (53 %), and rhinitis (57 %) frequencies. We observed a significant positive, male-specific stratified association (odds ratio = 1.6; p = 0.01) between a phthalate mixture with high weights for MEP and MHPP and odds of membership in Cluster 3 versus Cluster 1. These results identified subpopulations of children with co-occurring elevated levels of BMI, neurodevelopmental, and respiratory outcomes that may reflect shared etiologic pathways. The observed association between phthalates and respiratory outcome cluster membership could inform policy efforts towards children with respiratory disease. Similar cluster-based epidemiology may identify environmental factors that impact multi-outcome prevalence and efficiently direct public policy efforts.

Associations of residential green space with internalizing and externalizing behavior in early childhood.

BACKGROUND: Green space exposures may promote child mental health and well-being across multiple domains and stages of development. The aim of this study was to investigate associations between residential green space exposures and child mental and behavioral health at age 4-6 years. METHODS: Children's internalizing and externalizing behaviors in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) cohort in Shelby County, Tennessee, were parent-reported on the Child Behavior Checklist (CBCL). We examined three exposures-residential surrounding greenness calculated as the Normalized Difference Vegetation Index (NDVI), tree cover, and park proximity-averaged across the residential history for the year prior to outcome assessment. Linear regression models were adjusted for individual, household, and neighborhood-level confounders across multiple domains. Effect modification by neighborhood socioeconomic conditions was explored using multiplicative interaction terms. RESULTS: Children were on average 4.2 years (range 3.8-6.0) at outcome assessment. Among CANDLE mothers, 65% self-identified as Black, 29% as White, and 6% as another or multiple races; 41% had at least a college degree. Higher residential surrounding greenness was associated with lower internalizing behavior scores (-0.66 per 0.1 unit higher NDVI; 95% CI: -1.26, -0.07) in fully-adjusted models. The association between tree cover and internalizing behavior was in the hypothesized direction but confidence intervals included the null (-0.29 per 10% higher tree cover; 95% CI: -0.62, 0.04). No associations were observed between park proximity and internalizing behavior. We did not find any associations with externalizing behaviors or the attention problems subscale. Estimates were larger in neighborhoods with lower socioeconomic opportunity, but interaction terms were not statistically significant. CONCLUSIONS: Our findings add to the accumulating evidence of the importance of residential green space for the prevention of internalizing problems among young children. This research suggests the prioritization of urban green spaces as a resource for child mental health.

Prenatal exposures to phthalates and life events stressors in relation to child behavior at age 4-6: A combined cohort analysis.

Prenatal exposures to chemical and psychosocial stressors can impact the developing brain, but few studies have examined their joint effects. We examined associations between prenatal phthalate exposures and child behavior, hypothesizing that prenatal stressful life events (PSLEs) may exacerbate risks. To do so, we harmonized data from three U.S. pregnancy cohorts comprising the ECHO-PATHWAYS consortium. Phthalate metabolites were measured in single mid-pregnancy urine samples. When children were ages 4-6 years, mothers completed the Child Behavior Checklist (CBCL), from which a Total Problems score was calculated. Mothers additionally provided recall on their exposure to 14 PSLEs during pregnancy. Primary models examined problem behaviors in relation to: (1) phthalate mixtures calculated through weighted quantile sums regression with permutation test-derived p-values; and (2) joint exposure to phthalate mixtures and PSLEs (counts) using interaction terms. We subsequently refitted models stratified by child sex. Secondarily, we fit linear and logistic regression models examining individual phthalate metabolites. In our main, fully adjusted models (n = 1536 mother-child dyads), we observed some evidence of weak main effects of phthalate mixtures on problem behaviors in the full cohort and stratified by child sex. Interaction models revealed unexpected relationships whereby greater gestational exposure to PSLEs predicted reduced associations between some phthalates (e.g., the metabolites of di-2-ethylhexyl phthalate, di-n-octyl phthalate, di-iso-nonyl phthalate) and problem behaviors, particularly in males. Few associations were observed in females. Additional research is needed to replicate results and examine potential mechanisms.

Placental transcriptomic signatures of prenatal and preconceptional maternal stress.

Prenatal exposure to maternal psychological stress is associated with increased risk for adverse birth and child health outcomes. Accumulating evidence suggests that preconceptional maternal stress may also be transmitted intergenerationally to negatively impact offspring. However, understanding of mechanisms linking these exposures to offspring outcomes, particularly those related to placenta, is limited. Using RNA sequencing, we identified placental transcriptomic signatures associated with maternal prenatal stressful life events (SLEs) and childhood traumatic events (CTEs) in 1 029 mother-child pairs in two birth cohorts from Washington state and Memphis, Tennessee. We evaluated individual gene-SLE/CTE associations and performed an ensemble of gene set enrichment analyses combing across 11 popular enrichment methods. Higher number of prenatal SLEs was significantly (FDR < 0.05) associated with increased expression of ADGRG6, a placental tissue-specific gene critical in placental remodeling, and decreased expression of RAB11FIP3, an endocytosis and endocytic recycling gene, and SMYD5, a histone methyltransferase. Prenatal SLEs and maternal CTEs were associated with gene sets related to several biological pathways, including upregulation of protein processing in the endoplasmic reticulum, protein secretion, and ubiquitin mediated proteolysis, and down regulation of ribosome, epithelial mesenchymal transition, DNA repair, MYC targets, and amino acid-related pathways. The directional associations in these pathways corroborate prior non-transcriptomic mechanistic studies of psychological stress and mental health disorders, and have previously been implicated in pregnancy complications and adverse birth outcomes. Accordingly, our findings suggest that maternal exposure to psychosocial stressors during pregnancy as well as the mother's childhood may disrupt placental function, which may ultimately contribute to adverse pregnancy, birth, and child health outcomes.

Ultra-processed and fast food consumption, exposure to phthalates during pregnancy, and socioeconomic disparities in phthalate exposures.

BACKGROUND: Consuming ultra-processed foods may increase exposure to phthalates, a group of endocrine disruptors prevalent in food contact materials. OBJECTIVES: Investigate associations between ultra-processed food intake and urinary phthalates during pregnancy, and evaluate whether ultra-processed foods mediate socioeconomic disparities in phthalate exposures. METHODS: In a socioeconomically diverse sample of 1031 pregnant women from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) Study in the urban South, the Block Food Frequency Questionnaire was administered and urinary phthalate metabolites were measured in the second trimester. Linear regressions modeled associations between phthalates and overall ultra-processed food consumption, individual ultra-processed foods, and exploratory factor analysis dietary patterns. Causal mediation analyses examined whether ultra-processed food intake mediates relationships between socioeconomic disparities and phthalate exposures. RESULTS: Ultra-processed foods constituted 9.8-59.0 % (mean = 38.6 %) of participants' diets. 10 % higher dietary proportion of ultra-processed foods was associated with 13.1 % (95 %CI: 3.4 %-22.9 %) higher molar sum concentrations of di(2-ethylhexyl) phthalate metabolites (ΣDEHP). 10 % higher consumption of minimally-processed foods was associated with lower ΣDEHP (10.8 %: 3.4 %-22.9 %). Ultra- and minimally-processed food consumption were not associated with non-DEHP metabolites. Standard deviation higher consumptions of hamburger/cheeseburger, French fries, soda, and cake were associated with 10.5 % (4.2 %-17.1 %), 9.2 % (2.6 %-16.2 %), 7.4 % (1.4 %-13.6 %), and 6.0 % (0.0 %-12.4 %), respectively, higher ΣDEHP. Exploratory factor analysis corroborated positive associations of processed food with ΣDEHP, and uncovered a healthy dietary pattern associated with lower urinary ΣDEHP, mono(2-ethyl-5-hydroxyhexyl) (MEHHP), mono(2-ethyl-5-carboxypentyl) (MECPP), mono(2-carboxymethylhexyl) (MCMHP), and mono-isononyl (MINP) phthalates. Significant indirect effects indicated that lower income and education levels were associated with 1.9 % (0.2 %-4.2 %) and 1.4 % (0.1 %-3.3 %) higher ΣDEHP, respectively, mediated via increased ultra-processed food consumption. CONCLUSIONS: Consumption of ultra-processed foods may increase exposure to phthalates. Policies to reduce dietary phthalate exposures from food packaging and processing are needed, as socioeconomic barriers can preclude dietary recommendations as a sole means to reduce phthalate exposures.

Life satisfaction for adolescents with developmental and behavioral disabilities during the COVID-19 pandemic.

BACKGROUND: This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. METHODS: Data were collected from a sample of 1084 adolescents aged 11-21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities. RESULTS: Adolescents with a history of depression, anxiety, autism, and attention-deficit/hyperactivity disorder were particularly susceptible to decreased life satisfaction in response to unique combinations of stressors experienced during the COVID-19 pandemic. These stressors included decreased social connectedness, decreased family engagement, stress related to medical care access, pandemic-related traumatic stress, and single-caregiver households. CONCLUSION: Findings from this study highlight the importance of interventions aimed specifically at increasing adolescent social connectedness, family engagement, and access to medical support for adolescents with MEBD disabilities, particularly in the face of stressors, such as a global pandemic. IMPACT: Through a machine learning process, we identified contextualized risks associated with life satisfaction among adolescents with neurodevelopmental disabilities during the COVID-19 pandemic. The COVID-19 pandemic resulted in large-scale social disruptions for children and families. Such disruptions were associated with worse mental health outcomes in the general pediatric population, but few studies have examined specific subgroups who may be at heightened risk. We endeavored to close that gap in knowledge. This study highlights the importance of social connectedness, family engagement, and access to medical support as contributing factors to life satisfaction during the COVID-19 pandemic for adolescents with neurodevelopmental disabilities.

Maternal stressful life events during pregnancy and childhood asthma and wheeze.

BACKGROUND: Studies have linked prenatal maternal psychosocial stress to childhood wheeze/asthma but have rarely investigated factors that may mitigate risks. OBJECTIVE: To investigate associations between prenatal stress and childhood wheeze/asthma, evaluating factors that may modify stress effects. METHODS: Participants included 2056 mother-child dyads from Environmental influences on Child Health Outcomes (ECHO)-PATHWAYS, a consortium of 3 prospective pregnancy cohorts (the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study, The Infant Development and Environment Study, and a subset of the Global Alliance to Prevent Prematurity and Stillbirth study) from 6 cities. Maternal stressful life events experienced during pregnancy (PSLEs) were reported using the Pregnancy Risk Assessment Monitoring System Stressful Life Events questionnaire. Parents reported child wheeze/asthma outcomes at age 4 to 6 years using standardized questionnaires. We defined outcomes as ever asthma, current wheeze, current asthma, and strict asthma. We used modified Poisson regression with robust standard errors (SEs) to estimate risk ratios (RRs) and 95% CI per 1-unit increase in PSLE, adjusting for confounders. We evaluated effect modification by child sex, maternal history of asthma, maternal childhood traumatic life events, neighborhood-level resources, and breastfeeding. RESULTS: Overall, we observed significantly elevated risk for current wheeze with increasing PSLE (RR, 1.09 [95% CI, 1.03-1.14]), but not for other outcomes. We observed significant effect modification by child sex for strict asthma (P interaction = .03), in which risks were elevated in boys (RR, 1.10 [95% CI, 1.02-1.19]) but not in girls. For all other outcomes, risks were significantly elevated in boys and not in girls, although there was no statistically significant evidence of effect modification. We observed no evidence of effect modification by other factors (P interactions > .05). CONCLUSION: Risk of adverse childhood respiratory outcomes is higher with increasing maternal PSLEs, particularly in boys.

Exclusionary School Discipline and School Achievement for Middle and High School Students, by Race and Ethnicity.

Importance: There are racial and ethnic inequities in exclusionary school discipline (ESD) (ie, a disciplinary action that removes students from their classroom or school environment, eg, referrals, suspensions, and/or expulsions) practices in the US. Exclusionary school discipline has been associated with negative education, health, and criminal justice outcomes. Objectives: To investigate whether experiencing an ESD event was associated with decreased grade point average (GPA) and whether minoritized students (eg, Black or Latine [description used in database]) are disproportionately affected compared with White students. Design, Setting, and Participants: In a cohort study using retrospective administrative longitudinal data of children in the 6th to 10th grades (August 18, 2014, to May 26, 2017) in a large, single urban school district in California, linear mixed models were applied to compare the timing of the first exclusionary event and the average change in GPA and evaluate the relative variation among minoritized students experiencing an exclusionary event. Data analysis was conducted from August 18, 2018, to August 21, 2023. Exposure: Year at which students experienced first ESD events over the study period. Main Outcomes and Measures: The primary outcome of interest was change in average grade point average (GPA); students' GPA averaged across courses was averaged across each year. Results: Of the 16 849 students (8756 [52.0%] male), 21.4% experienced at least 1 ESD event. The mean (SD) age was 14.3 (1.6) years, and 7.5% identified as Black, 25.6% Latine, and 10.0% White. Black and Latine students experienced exclusionary events at nearly 10 and 3 times more than White students (mean [SD]: Black, 6.69 [12.80] events; Latine, 2.01 [6.18] events; White, 0.71 [4.46] events; P < .001). When controlling for gender, maternal educational level, race and ethnicity, and school year, having experienced an ESD event in the first year was associated with an average decrease in GPA by 0.88 (95% CI, -0.91 to -0.84) points compared with no ESD events; experiencing ESD events also had significant differences in the second (-0.63 [95% CI, -0.67 to -0.59]) and third (-0.52 [95% CI, -0.57 to -0.47]) years. Black and Latine race and ethnicity was associated with the greatest decrease in GPA compared with White students (Black, -0.56 [95% CI, -0.61 to -0.51]; Latine, -0.51 [95% CI, -0.54 to -0.47]; P < .001). Conclusion and Relevance: This study observed racial and ethnic inequities in ESD prevalence and its association with educational attainment. The findings suggest that it may be beneficial for pediatricians and other health care professionals to screen for exclusion, as experiencing ESD events may affect health across the life course. In addition, it may be useful to categorize ESD events as an adverse childhood experience and abolish the practice from schools as a disciplinary measure.

Development and psychometric validation of the Pandemic-Related Traumatic Stress Scale for children and adults.

To assess the public health impact of the COVID-19 pandemic on mental health, investigators from the National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) research program developed the Pandemic-Related Traumatic Stress Scale (PTSS). Based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) acute stress disorder symptom criteria, the PTSS is designed for adolescent (13-21 years) and adult self-report and caregiver-report on 3-12-year-olds. To evaluate psychometric properties, we used PTSS data collected between April 2020 and August 2021 from non-pregnant adult caregivers (n = 11,483), pregnant/postpartum individuals (n = 1,656), adolescents (n = 1,795), and caregivers reporting on 3-12-year-olds (n = 2,896). We used Mokken scale analysis to examine unidimensionality and reliability, Pearson correlations to evaluate relationships with other relevant variables, and analyses of variance to identify regional, age, and sex differences. Mokken analysis resulted in a moderately strong, unidimensional scale that retained nine of the original 10 items. We detected small to moderate positive associations with depression, anxiety, and general stress, and negative associations with life satisfaction. Adult caregivers had the highest PTSS scores, followed by adolescents, pregnant/postpartum individuals, and children. Caregivers of younger children, females, and older youth had higher PTSS scores compared to caregivers of older children, males, and younger youth, respectively. (PsycInfo Database Record (c) 2023 APA, all rights reserved).