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Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

BackgroundPhthalates are synthetic chemicals widely used in consumer products and have been identified to contribute to preterm birth. Existing studies have methodological limitations and potential effects of di-2-ethylhexyl phthalate (DEHP) replacements are poorly characterised. Attributable fractions and costs have not been quantified, limiting the ability to weigh trade-offs involved in ongoing use. We aimed to leverage a large, diverse US cohort to study associations of phthalate metabolites with birthweight and gestational age, and estimate attributable adverse birth outcomes and associated costs.MethodsIn this prospective analysis we used extant data in the US National Institutes of Health Environmental influences on Child Health Outcomes (ECHO) Program from 1998 to 2022 to study associations of 20 phthalate metabolites with gestational age at birth, birthweight, birth length, and birthweight for gestational age z-scores. We also estimated attributable adverse birth outcomes and associated costs. Mother-child dyads were included in the study if there were one or more urinary phthalate measurements during the index pregnancy; data on child's gestational age and birthweight; and singleton delivery.FindingsWe identified 5006 mother-child dyads from 13 cohorts in the ECHO Program. Phthalic acid, diisodecyl phthalate (DiDP), di-n-octyl phthalate (DnOP), and diisononyl phthalate (DiNP) were most strongly associated with gestational age, birth length, and birthweight, especially compared with DEHP or other metabolite groupings. Although DEHP was associated with preterm birth (odds ratio 1·45 [95% CI 1·05-2·01]), the risks per log10 increase were higher for phthalic acid (2·71 [1·91-3·83]), DiNP (2·25 [1·67-3·00]), DiDP (1·69 [1·25-2·28]), and DnOP (2·90 [1·96-4·23]). We estimated 56 595 (sensitivity analyses 24 003-120 116) phthalate-attributable preterm birth cases in 2018 with associated costs of US$3·84 billion (sensitivity analysis 1·63- 8·14 billion).InterpretationIn a large, diverse sample of US births, exposure to DEHP, DiDP, DiNP, and DnOP were associated with decreased gestational age and increased risk of preterm birth, suggesting substantial opportunities for prevention. This finding suggests the adverse consequences of substitution of DEHP with chemically similar phthalates and need to regulate chemicals with similar properties as a class.FundingNational Institutes of Health.

BackgroundSynthetic chemicals are increasingly being recognized for potential independent contributions to preterm birth (PTB) and low birth weight (LBW). Bisphenols, parabens, and triclosan are consumer product chemicals that act via similar mechanisms including estrogen, androgen, and thyroid disruption and oxidative stress. Multiple cohort studies have endeavored to examine effects on birth outcomes, and systematic reviews have been limited due to measurement of 1-2 spot samples during pregnancy and limited diversity of populations.ObjectiveTo study the effects of prenatal phenols and parabens on birth size and gestational age (GA) in 3,619 mother-infant pairs from 11 cohorts in the NIH Environmental influences on Child Health Outcomes program.ResultsWhile many associations were modest and statistically imprecise, a 1-unit increase in log10 pregnancy averaged concentration of benzophenone-3 and methylparaben were associated with decreases in birthweight, birthweight adjusted for gestational age and SGA. Increases in the odds of being SGA were 29% (95% CI: 5%, 58%) and 32% (95% CI: 3%, 70%), respectively. Bisphenol S in third trimester was also associated with SGA (OR 1.52, 95% CI 1.08, 2.13). Associations of benzophenone-3 and methylparaben with PTB and LBW were null. In addition, a 1-unit increase in log10 pregnancy averaged concentration of 2,4-dichlorophenol was associated with 43% lower (95% CI: -67%, -2%) odds of low birthweight; the direction of effect was the same for the highly correlated 2,5-dichlorophenol, but with a smaller magnitude (-29%, 95% CI: -53%, 8%).DiscussionIn a large and diverse sample generally representative of the United States, benzophenone-3 and methylparaben were associated with lower birthweight as well as birthweight adjusted for gestational age and higher odds of SGA, while 2,4-dichlorophenol. These associations with smaller size at birth are concerning in light of the known consequences of intrauterine growth restriction for multiple important health outcomes emerging later in life.

IntroductionMeta-analyses across diverse independent studies provide improved confidence in results. However, within the context of metabolomic epidemiology, meta-analysis investigations are complicated by differences in study design, data acquisition, and other factors that may impact reproducibility.ObjectiveThe objective of this study was to identify maternal blood metabolites during pregnancy (> 24 gestational weeks) related to offspring body mass index (BMI) at age two years through a meta-analysis framework.MethodsWe used adjusted linear regression summary statistics from three cohorts (total N = 1012 mother-child pairs) participating in the NIH Environmental influences on Child Health Outcomes (ECHO) Program. We applied a random-effects meta-analysis framework to regression results and adjusted by false discovery rate (FDR) using the Benjamini-Hochberg procedure.ResultsOnly 20 metabolites were detected in all three cohorts, with an additional 127 metabolites detected in two of three cohorts. Of these 147, 6 maternal metabolites were nominally associated (P  100), we failed to identify significant metabolite associations after FDR correction. Our investigation demonstrates difficulties in applying epidemiological meta-analysis to clinical metabolomics, emphasizes challenges to reproducibility, and highlights the need for standardized best practices in metabolomic epidemiology.

BackgroundWidespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results.ObjectivesWe conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex.MethodsWe included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex.ResultsThree OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age z-scores (β for detect vs. nondetect=0.04-0.07); other chemicals showed null associations.DiscussionIn the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182.

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BACKGROUND: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited. OBJECTIVES: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N = 1,433 Puerto Rico PROTECT study participants. METHODS: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes. RESULTS: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture oddsratio(OR) = 1:57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB [beta] = 0:78 (95% CI: 0.17, 1.38) and adjusted P-PB [beta] = 0:85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted [beta]= -0:57; 95% CI: -1:09, -0:05). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only. CONCLUSIONS: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008, Introduction Phenols and parabens are two classes of high production volume chemicals that are ubiquitous in consumer and personal care products (1,2) and have been associated with reproductive and developmental [...]

BACKGROUND: Organophosphate esters (OPEs), used ubiquitously as flame retardants and plasticizers in consumer products, are suspected of having developmental toxicity. OBJECTIVES: Our study aimed to estimate associations between prenatal exposure to OPEs and fetal growth, including both ultrasound (head circumference, abdominal circumference, femur length, and estimated fetal weight) and delivery [birth weight z-score, small-for-gestational age (SGA), and large-for-gestational age (LGA)] measures of growth. METHODS: In the LIFECODES Fetal Growth Study (2008-2018), an enriched case--cohort of 900 babies born at the small and large ends of the growth spectrum, we quantified OPE biomarkers in three urine samples per pregnant participant and abstracted ultrasound and delivery measures of fetal growth from medical records. We estimated associations between pregnancy-averaged log-transformed OPE biomarkers and repeated ultrasound measures of fetal growth using linear mixed-effects models, and delivery measures of fetal growth using linear (birth weight) and logistic (SGA and LGA) regression models. RESULTS: Most OPE biomarkers were positively associated with at least one ultrasound measure of fetal growth, but associations with delivery measures were largely null. For example, an interquartile range (IQR; 1.31 ng=mL) increase in bis(2-chloroethyl) phosphate concentration was associated with larger z-scores in head circumference [mean difference (difference): 0.09; 95% confidence interval (CI): 0.01, 0.17], abdominal circumference (difference: 0.10; 95% CI: 0.02, 0.18), femur length (difference: 0.11; 95% CI: 0.03, 0.19), and estimated fetal weight (difference: 0.13; 95% CI: 0.04, 0.22) but not birth weight (difference: 0.04; 95% CI: -0.08, 0.17). At delivery, an IQR (1.00 ng=mL) increase in diphenyl phosphate (DPHP) concentration was associated with an SGA birth (odds ratio: 1.46; 95% CI: 1.10, 1.94). CONCLUSIONS: In a large prospective cohort, gestational OPE exposures were associated with larger fetal size during pregnancy, but associations at delivery were null. DPHP concentrations were associated with heightened risk of an SGA birth. These findings suggest that OPE exposure may affect fetal development. https://doi.org/10.1289/EHP14647, Introduction Organophosphate esters (OPEs) are high-production chemicals in widespread global use. (1) They are organic esters of phosphoric acid--containing alkyl chains or aryl groups, which may be halo-genated or nonhalogenated. [...]

The Environmental Influences on Child Health Outcomes (ECHO)-Wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-Wide Cohort Data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in 5 main outcome areas: pre-, peri-, and postnatal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include factors at the level of place (e.g., air pollution, neighborhood socioeconomic status), family (e.g., parental mental health), and individuals (e.g., diet, genomics).

BackgroundPreterm birth is the leading cause of infant morbidity and mortality worldwide. Elevated levels of oxidative stress have been associated with an increased risk of delivering before term. However, most studies testing this hypothesis have been conducted in racially and demographically homogenous study populations, which do not reflect the diversity within the United States.ObjectiveWe leveraged 4 cohorts participating in the Environmental Influences on Child Health Outcomes Program to conduct the largest study to date examining biomarkers of oxidative stress and preterm birth (N=1916). Furthermore, we hypothesized that elevated oxidative stress would be associated with higher odds of preterm birth, particularly preterm birth of spontaneous origin.Study designThis study was a pooled analysis and meta-analysis of 4 birth cohorts spanning multiple geographic regions in the mainland United States and Puerto Rico (208 preterm births and 1708 full-term births). Of note, 8-iso-prostaglandin-F2α, 2,3-dinor-5,6-dihydro-8-iso-prostaglandin-F2α (F2-IsoP-M; the major 8-iso-prostaglandin-F2α metabolite), and prostaglandin-F2α were measured in urine samples obtained during the second and third trimesters of pregnancy. Logistic regression was used to calculate adjusted odds ratios and 95% confidence intervals for the associations between averaged biomarker concentrations for each participant and all preterm births, spontaneous preterm births, nonspontaneous preterm births (births of medically indicated or unknown origin), and categories of preterm birth (early, moderate, and late). Individual oxidative stress biomarkers were examined in separate models.ResultsApproximately 11% of our analytical sample was born before term. Relative to full-term births, an interquartile range increase in averaged concentrations of F2-IsoP-M was associated with higher odds of all preterm births (odds ratio, 1.29; 95% confidence interval, 1.11-1.51), with a stronger association observed for spontaneous preterm birth (odds ratio, 1.47; 95% confidence interval, 1.16-1.90). An interquartile range increase in averaged concentrations of 8-iso-prostaglandin-F2α was similarly associated with higher odds of all preterm births (odds ratio, 1.19; 95% confidence interval, 0.94-1.50). The results from our meta-analysis were similar to those from the pooled combined cohort analysis.ConclusionHere, oxidative stress, as measured by 8-iso-prostaglandin-F2α, F2-IsoP-M, and prostaglandin-F2α in urine, was associated with increased odds of preterm birth, particularly preterm birth of spontaneous origin and delivery before 34 completed weeks of gestation.

BackgroundPer- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress.ObjectivesWe estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships.MethodsWe included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS.ResultsWe observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of β=-0.15 [95% confidence interval (CI): -0.27, -0.03], β=-0.14 (95% CI: -0.28, -0.002), β=-0.22 (95% CI: -0.23, -0.10), β=-0.06 (95% CI: -0.18, 0.06), and β=-0.25 (95% CI: -0.37, -0.14), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: ORPFNA=0.56 (95% CI: 0.38, 0.83), ORPFDA=0.52 (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [-0.28; 95% highest posterior density (HPD): -0.44, -0.14] and decreased odds of large-for-gestational-age (OR=0.49; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress.DiscussionOur large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.

Assessing health outcomes associated with exposure to polychlorinated biphenyls (PCBs) is important given their persistent and ubiquitous nature. PCBs are classified as a Group 1 carcinogen, but the full range of potential noncancer health effects from exposure to PCBs has not been systematically summarized and evaluated. We used systematic review methods to identify and screen the literature using combined manual review and machine learning approaches. A protocol was developed that describes the literature search strategy and Populations, Exposures, Comparators, and Outcomes (PECO) criteria used to facilitate subsequent screening and categorization of literature into a systematic evidence map of PCB exposure and noncancer health endpoints across 15 organs/systems. A comprehensive literature search yielded 62,599 records. After electronic prioritization steps, 17,037 studies were manually screened at the title and abstract level. An additional 900 studies identified by experts or supplemental searches were also included. After full-text screening of 3889 references, 1586 studies met the PECO criteria. Relevant study details such as the endpoints assessed, exposure duration, and species were extracted into literature summary tables. This review compiles and organizes the human and mammalian studies from these tables into an evidence map for noncancer health endpoints and PCB mixture exposure to identify areas of robust research as well as areas of uncertainty that would benefit from future investigation. Summary data are available online as interactive visuals with downloadable metadata. Sufficient research is available to inform PCB hazard assessments for most organs/systems, but the amount of data to inform associations with specific endpoints differs. Furthermore, despite many years of research, sparse data exist for inhalation and dermal exposures, which are highly relevant human exposure routes. This evidence map provides a foundation for future systematic reviews and noncancer hazard assessments of PCB mixtures and for strategic planning of research to inform areas of greater uncertainty.

BackgroundNovel interventions tailored to blue collar workers are needed to reduce the disparities in smoking rates among occupational groups. ObjectiveThe main objective of this study was to evaluate the efficacy and usage of the Web-enhanced “Tobacco Tactics” intervention targeting operating engineers (heavy equipment operators) compared to the “1-800-QUIT-NOW” telephone line. MethodsOperating engineers (N=145) attending one of 25 safety training sessions from 2010 through 2012 were randomized to either the Tobacco Tactics website with nurse counseling by phone and access to nicotine replacement therapy (NRT) or to the 1-800-QUIT-NOW telephone line, which provided an equal number of phone calls and NRT. The primary outcome was self-reported 7-day abstinence at 30-day and 6-month follow-up. The outcomes were compared using chi-square tests, t tests, generalized mixed models, and logistic regression models. ResultsThe average age was 42 years and most were male (115/145, 79.3%) and white (125/145, 86.2%). Using an intent-to-treat analysis, the Tobacco Tactics website group showed significantly higher quit rates (18/67, 27%) than the 1-800-QUIT NOW group (6/78, 8%) at 30-day follow-up (P=.003), but this difference was no longer significant at 6-month follow-up. There were significantly more positive changes in harm reduction measures (quit attempts, number of cigarettes smoked per day, and nicotine dependence) at both 30-day and 6-month follow-up in the Tobacco Tactics group compared to the 1-800-QUIT-NOW group. Compared to participants in the 1-800-QUIT NOW group, significantly more of those in the Tobacco Tactics website group participated in the interventions, received phone calls and NRT, and found the intervention helpful. ConclusionsThe Web-enhanced Tobacco Tactics website with telephone support showed higher efficacy and reach than the 1-800-QUIT-NOW intervention. Longer counseling sessions may be needed to improve 6-month cessation rates. Trial RegistrationClinicaltrials.gov NCT01124110; http://clinicaltrials.gov/ct2/show/NCT01124110 (Archived by WebCite at http://www.webcitation.org/6TfKN5iNL).

BackgroundIn the United States, disparities in gestational age at birth by maternal race, ethnicity, and geography are theorized to be related, in part, to differences in individual- and neighborhood-level socioeconomic status (SES). Yet, few studies have examined their combined effects or whether associations vary by maternal race and ethnicity and United States Census region.MethodsWe assembled data from 34 cohorts in the Environmental influences on Child Health Outcomes (ECHO) program representing 10,304 participants who delivered a liveborn, singleton infant from 2000 through 2019. We investigated the combined associations of maternal education level, neighborhood deprivation index (NDI), and Index of Concentration at the Extremes for racial residential segregation (ICERace) on gestational weeks at birth using linear regression and on gestational age at birth categories (preterm, early term, post-late term relative to full term) using multinomial logistic regression.ResultsAfter adjustment for NDI and ICERace, gestational weeks at birth was significantly lower among those with a high school diploma or less (-0.31 weeks, 95% CI: -0.44, -0.18), and some college (-0.30 weeks, 95% CI: -0.42, -0.18) relative to a master's degree or higher. Those with a high school diploma or less also had an increased odds of preterm (aOR 1.59, 95% CI: 1.20, 2.10) and early term birth (aOR 1.26, 95% CI: 1.05, 1.51). In adjusted models, NDI quartile and ICERace quartile were not associated with gestational weeks at birth. However, higher NDI quartile (most deprived) associated with an increased odds of early term and late term birth, and lower ICERace quartile (least racially privileged) associated with a decreased odds of late or post-term birth. When stratifying by region, gestational weeks at birth was lower among those with a high school education or less and some college only among those living in the Northeast or Midwest. When stratifying by race and ethnicity, gestational weeks at birth was lower among those with a high school education or less only for the non-Hispanic White category.ConclusionIn this study, maternal education was consistently associated with shorter duration of pregnancy and increased odds of preterm birth, including in models adjusted for NDI and ICERace.

BackgroundMelamine, melamine derivatives, and aromatic amines are nitrogen-containing compounds with known toxicity and widespread commercial uses. Nevertheless, biomonitoring of these chemicals is lacking, particularly during pregnancy, a period of increased susceptibility to adverse health effects.ObjectivesWe aimed to measure melamine, melamine derivatives, and aromatic amine exposure in pregnant women across the United States (U.S.) and evaluate associations with participant and urine sample collection characteristics.MethodsWe measured 43 analytes, representing 45 chemicals (i.e., melamine, three melamine derivatives, and 41 aromatic amines), in urine from pregnant women in nine diverse ECHO cohorts during 2008-2020 (N = 171). To assess relations with participant and urine sample collection characteristics, we used generalized estimating equations to estimate prevalence ratios (PRs) for analytes dichotomized at the detection limit, % differences (%Δ) for continuous analytes, and 95% confidence intervals. Multivariable models included age, race/ethnicity, marital status, urinary cotinine, and year of sample collection.ResultsTwelve chemicals were detected in >60% of samples, with near ubiquitous detection of cyanuric acid, melamine, aniline, 4,4'-methylenedianiline, and a composite of o-toluidine and m-toluidine (99-100%). In multivariable adjusted models, most chemicals were associated with higher exposures among Hispanic and non-Hispanic Black participants. For example, concentrations of 3,4-dichloroaniline were higher among Hispanic (%Δ: +149, 95% CI: +17, +431) and non-Hispanic Black (%Δ: +136, 95% CI: +35, +311) women compared with non-Hispanic White women. We observed similar results for ammelide, o-/m-toluidine, 4,4'-methylenedianiline, and 4-chloroaniline. Most chemicals were positively associated with urinary cotinine, with strongest associations observed for o-/m-toluidine (%Δ: +23; 95% CI: +16, +31) and 3,4-dichloroaniline (%Δ: +25; 95% CI: +17, +33). Some chemicals exhibited annual trends (e.g., %Δ in melamine per year: -11; 95% CI: -19, -1) or time of day, seasonal, and geographic variability.DiscussionExposure to melamine, cyanuric acid, and some aromatic amines was ubiquitous in this first investigation of these analytes in pregnant women. Future research should expand biomonitoring, identify sources of exposure disparities by race/ethnicity, and evaluate potential adverse health effects.

BackgroundLower socioeconomic status (SES) and elevated psychosocial stress are known contributors to adverse pregnancy outcomes; however, biological mechanisms linking these factors to adverse pregnancy outcomes are not well-characterized. Oxidative stress may be an important, yet understudied mechanistic pathway. We used a pooled study design to examine biological, behavioral, and social factors as predictors of prenatal oxidative stress biomarkers.MethodsLeveraging four pregnancy cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program spanning multiple geographic regions across the United States (U.S.) (N = 2082), we measured biomarkers of oxidative stress in urine samples at up to three time points during pregnancy, including 8-isoprostane-prostaglandin F2α (8-isoPGF2α), its major metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane, and prostaglandin F2α (PGF2α). Maternal age, pre-pregnancy body mass index, marital/partnered status, parity, and smoking status were included as biological and behavioral factors while race/ethnicity, maternal education, and stressful life events were considered social factors. We examined associations between each individual biological, behavioral, and social factor with oxidative stress biomarkers using multivariable-adjusted linear mixed models.ResultsNumerous biological, behavioral, and social factors were associated with elevated levels of 8-isoPGF2α, its major metabolite, and PGF2α. Pregnant people who were current smokers relative to non-smokers or had less than a high school education relative to a college degree had 11.04% (95% confidence interval [CI] = -1.97%, 25.77%) and 9.13% (95% CI = -1.02%, 20.32%) higher levels of 8-isoPGF2α, respectively.ConclusionsOxidative stress biomarkers are elevated among pregnant people with higher socioeconomic disadvantage and may represent one pathway linking biological, behavioral, and social factors to adverse pregnancy and child health outcomes, which should be explored in future work.

Prenatal chemical exposures can influence maternal and child health; however, few industrial chemicals are routinely biomonitored. We assessed an extensive panel of contemporary and emerging chemicals in 171 pregnant women across the United States (U.S.) and Puerto Rico in the Environmental influences on Child Health Outcomes (ECHO) Program. We simultaneously measured urinary concentrations of 89 analytes (103 total chemicals representing 73 parent compounds) in nine chemical groups: bactericides, benzophenones, bisphenols, fungicides and herbicides, insecticides, organophosphate esters (OPEs), parabens, phthalates/alternative plasticizers, and polycyclic aromatic hydrocarbons (PAHs). We estimated associations of creatinine-adjusted concentrations with sociodemographic and specimen characteristics. Among our diverse prenatal population (60% non-Hispanic Black or Hispanic), we detected 73 of 89 analytes in ≥1 participant and 36 in >50% of participants. Five analytes not currently included in the U.S. biomonitoring were detected in ≥90% of samples: benzophenone-1, thiamethoxam, mono-2-(propyl-6-carboxy-hexyl) phthalate, monocarboxy isooctyl phthalate, and monohydroxy-iso-decyl phthalate. Many analyte concentrations were higher among women of Hispanic ethnicity compared to those of non-Hispanic White women. Concentrations of certain chemicals decreased with the calendar year, whereas concentrations of their replacements increased. Our largest study to date identified widespread exposures to prevalent and understudied chemicals in a diverse sample of pregnant women in the U.S.

The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate q-value  0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.

Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations.