Mixture effects of prenatal exposure to polybrominated diphenyl ethers on urinary oxidative stress biomarkers in the Chemicals in Our Bodies Cohort.

Polybrominated diphenyl ethers (PBDEs) exposure is associated with preterm birth. Laboratory studies suggest that PBDEs lead to elevated oxidative stress, a known contributor to preterm birth in epidemiologic studies. We hypothesized that elevated levels of PBDEs would be associated with increased oxidative stress during human pregnancy. Participants in this analysis were enrolled in the Chemicals in Our Bodies cohort and resided in the San Francisco Bay Area (N=201). Four PBDEs (BDE-47, -99, -100, -153) were measured in second trimester serum. Urinary oxidative stress biomarkers were measured at two timepoints (second and third trimester) and included 8-isoprostane-prostaglandin-F2α [8-iso-PGF2α], 2,3-dinor-5,6-dihydro-8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and prostaglandin-F2α [PGF2α]. Associations between individual PBDEs and oxidative stress biomarkers (averaged and trimester specific) were examined using linear regression. Quantile g-computation and Bayesian kernel machine regression (BKMR) were used to assess cumulative effects of PBDEs. Quantile g-computation showed that higher concentrations of PBDEs were associated with increasing 8-iso-PGF2α, 2,3-dinor-8-iso-PGF2α, and PGF2α. Associations were greatest in magnitude for second trimester levels of 2,3-dinor-8-iso-PGF2α (mean change per quartile increase=0.25, 95% confidence interval=0.09, 0.41). Associations were similar using BKMR and linear regression. Our findings suggest that oxidative stress may be a plausible biological pathway by which PBDE exposure might lead to preterm birth.

Water Fluoridation and Birth Outcomes in California.

BACKGROUND: There is a lack of research on the relationship between water fluoridation and pregnancy outcomes. OBJECTIVES: We assessed whether hypothetical interventions to reduce fluoride levels would improve birth outcomes in California. METHODS: We linked California birth records from 2000 to 2018 to annual average fluoride levels by community water system. Fluoride levels were collected from consumer confidence reports using publicly available data and public record requests. We estimated the effects of a hypothetical intervention reducing water fluoride levels to 0.7 ppm (the current level recommended by the US Department of Health and Human Services) and 0.5 ppm (below the current recommendation) on birth weight, birth-weight-for-gestational age z-scores, gestational age, preterm birth, small-for-gestational age, large-for-gestational age, and macrosomia using linear regression with natural cubic splines and G-computation. Inference was calculated using a clustered bootstrap with Wald-type confidence intervals. We evaluated race/ethnicity, health insurance type, fetal sex, and arsenic levels as potential effect modifiers. RESULTS: Fluoride levels ranged from 0 to 2.5 ppm, with a median of 0.51 ppm. There was a small negative association on birth weight with the hypothetical intervention to reduce fluoride levels to 0.7 ppm [-2.2g; 95% confidence interval (CI): -4.4, 0.0] and to 0.5 ppm (-5.8g; 95% CI: -10.0, -1.6). There were small negative associations with birth-weight-for-gestational-age z-scores for both hypothetical interventions (0.7 ppm: -0.004; 95% CI: -0.007, 0.000 and 0.5 ppm: -0.006; 95% CI: -0.013, 0.000). We also observed small negative associations for risk of large-for-gestational age for both the hypothetical interventions to 0.7 ppm [risk difference (RD)=-0.001; 95% CI: -0.002, 0.000 and 0.5 ppm (-0.001; 95% CI: -0.003, 0.000)]. We did not observe any associations with preterm birth or with being small for gestational age for either hypothetical intervention. We did not observe any associations with risk of preterm birth or small-for-gestational age for either hypothetical intervention. CONCLUSION: We estimated that a reduction in water fluoride levels would modestly decrease birth weight and birth-weight-for-gestational-age z-scores in California. https://doi.org/10.1289/EHP13732.

Ambient Environment and the Epidemiology of Preterm Birth.

Preterm birth (PTB) is associated with substantial mortality and morbidity. We describe environmental factors that may influence PTB risks. We focus on exposures associated with an individual's ambient environment, such as air pollutants, water contaminants, extreme heat, and proximities to point sources (oil/gas development or waste sites) and greenspace. These exposures may further vary by other PTB risk factors such as social constructs and stress. Future examinations of risks associated with ambient environment exposures would benefit from consideration toward multiple exposures - the exposome - and factors that modify risk including variations associated with the structural genome, epigenome, social stressors, and diet.

Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

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.

Pregnancy exposure to PM2.5 from wildland fire smoke and preterm birth in California.

BACKGROUND: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown. METHODS: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age < 37 weeks). We assigned smoke exposure to geocoded residence at birth for all live singleton births in California conceived 2007-2018, using weekly average concentrations of particulate matter ≤ 2.5 µm (PM2.5) attributable to wildland fires from United States Environmental Protection Agency's Community Multiscale Air Quality Model. Logistic regression yielded odds ratio (OR) for preterm birth in relation to increases in average exposure across the whole pregnancy, each trimester, and each week of pregnancy. Models adjusted for season, age, education, race/ethnicity, medical insurance, and smoking of the birthing parent. RESULTS: For the 5,155,026 births, higher wildland fire PM2.5 exposure averaged across pregnancy, or any trimester, was associated with higher odds of preterm birth. The OR for an increase of 1 µg/m3 of average wildland fire PM2.5 during pregnancy was 1.013 (95 % CI:1.008,1.017). Wildland fire PM2.5 during most weeks of pregnancy was associated with higher odds. Strongest estimates were observed in weeks in the second and third trimesters. A 10 µg/m3 increase in average wildland fire PM2·5 in gestational week 23 was associated with OR = 1.034; 95 % CI: 1.019, 1.049 for preterm birth. CONCLUSIONS: Preterm birth is sensitive to wildland fire PM2.5; therefore, we must reduce exposure during pregnancy.

Prenatal phthalate exposure and adverse birth outcomes in the USA: a prospective analysis of births and estimates of attributable burden and costs.

BACKGROUND: Phthalates 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. METHODS: In 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. FINDINGS: We 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). INTERPRETATION: In 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. FUNDING: National Institutes of Health.

Measuring long-term exposure to wildfire PM2.5 in California: Time-varying inequities in environmental burden.

Wildfires have become more frequent and intense due to climate change and outdoor wildfire fine particulate matter (PM2.5) concentrations differ from relatively smoothly varying total PM2.5. Thus, we introduced a conceptual model for computing long-term wildfire PM2.5 and assessed disproportionate exposures among marginalized communities. We used monitoring data and statistical techniques to characterize annual wildfire PM2.5 exposure based on intermittent and extreme daily wildfire PM2.5 concentrations in California census tracts (2006 to 2020). Metrics included: 1) weeks with wildfire PM2.5 < 5 µg/m3; 2) days with non-zero wildfire PM2.5; 3) mean wildfire PM2.5 during peak exposure week; 4) smoke waves (≥2 consecutive days with <15 µg/m3 wildfire PM2.5); and 5) mean annual wildfire PM2.5 concentration. We classified tracts by their racial/ethnic composition and CalEnviroScreen (CES) score, an environmental and social vulnerability composite measure. We examined associations of CES and racial/ethnic composition with the wildfire PM2.5 metrics using mixed-effects models. Averaged 2006 to 2020, we detected little difference in exposure by CES score or racial/ethnic composition, except for non-Hispanic American Indian and Alaska Native populations, where a 1-SD increase was associated with higher exposure for 4/5 metrics. CES or racial/ethnic × year interaction term models revealed exposure disparities in some years. Compared to their California-wide representation, the exposed populations of non-Hispanic American Indian and Alaska Native (1.68×, 95% CI: 1.01 to 2.81), white (1.13×, 95% CI: 0.99 to 1.32), and multiracial (1.06×, 95% CI: 0.97 to 1.23) people were over-represented from 2006 to 2020. In conclusion, during our study period in California, we detected disproportionate long-term wildfire PM2.5 exposure for several racial/ethnic groups.

Prenatal Phenol and Paraben Exposures and Adverse Birth Outcomes: A Prospective Analysis of U.S. Births.

BACKGROUND: Synthetic 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. OBJECTIVE: To 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. RESULTS: While 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%). DISCUSSION: In 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.

Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program.

BACKGROUND: Widespread 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. OBJECTIVES: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. METHODS: We 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. RESULTS: Three 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 (ß for detect vs. nondetect=0.04-0.07); other chemicals showed null associations. DISCUSSION: In 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.

Association of maternal education, neighborhood deprivation, and racial segregation with gestational age at birth by maternal race/ethnicity and United States Census region in the ECHO cohorts.

Background: In 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. Methods: We 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. Results: After 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. Conclusion: In 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.

Prenatal sleep health and risk of offspring ADHD symptomatology and associated phenotypes: a prospective analysis of timing and sex differences in the ECHO cohort.

Background: Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. Methods: Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. Findings: Pregnant participants were 32.30 ± 5.50 years and children were 46% female. 44 percent of pregnant participants identified as Hispanic or Latine; 49% identified as White. Second-trimester sleep duration was associated with offspring ADHD symptoms (b = -0.35 [95% CI = -0.57, -0.13], p = 0.026), such that shorter duration was associated with greater symptomatology. Poorer sleep quality in the second trimester was also associated with increased ADHD symptomatology (b = 0.66 [95% CI = 0.18, 1.14], p = 0.037). Greater sleep disturbances in the first trimester were associated with offspring ADHD (b = 1.03 [95% CI = 0.32, 1.03], p = 0.037) and in the second trimester with sleep problems (b = 1.53 [95% CI = 0.42, 2.92], p = 0.026). We did not document substantial offspring sex moderation. Interpretation: Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. Funding: NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts.

Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways. Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids. Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation. Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase. Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

PFAS concentrations in early and mid-pregnancy and risk of gestational diabetes mellitus in a nested case-control study within the ethnically and racially diverse PETALS cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals and are commonly found in everyday items. PFAS have been linked to disrupting glucose homeostasis, however, whether they are associated with gestational diabetes mellitus (GDM) risk remains inconclusive. We examined prospective associations of PFAS concentrations measured twice in pregnancy with GDM risk. METHODS: In the PETALS pregnancy cohort, a nested case-control study which included 41 GDM cases and 87 controls was conducted. PFAS analytes were measured in blood serum collected in both early and mid-pregnancy (mean [SD]: 13.9 [2.2] and 20.2 [2.2] gestational weeks, respectively), with cumulative exposure calculated by the area-under-the-curve (AUC) to integrate both the PFAS concentration and the timing of the exposure. Individual adjusted weighted unconditional logistic regression models examined seven PFAS in association with GDM risk. P-values were corrected using the false-discovery-rate (FDR). Mixture models were analyzed with Bayesian kernel machine regression (BKMR). RESULTS: PFDA, PFNA and PFOA were individually associated with higher GDM risk per interquartile range (IQR) in early pregnancy (OR [95% CI]: 1.23 [1.09, 1.38]), 1.40 [1.24, 1.58]), and 1.15 [1.04, 1.27], respectively), mid-pregnancy (1.28 [1.15, 1.43], 1.16 [1.05, 1.28], and 1.20 [1.09, 1.33], respectively), and with cumulative exposure (1.23 [1.09, 1.38], 1.21 [1.07, 1.37], and 1.19 [1.09, 1.31], respectively). PFOS in mid-pregnancy and with cumulative exposure was associated with increased GDM risk (1.41 [1.17, 1.71] and 1.33 [1.06, 1.58], respectively). PFUnDA in early pregnancy was associated with lower GDM risk (0.79 [0.64, 0.98]), whereas mid-pregnancy levels were associated with higher risk (1.49 [1.18, 1.89]). PFHxS was associated with decreased GDM risk in early and mid-pregnancy (0.48 [0.38, 0.60] and 0.48 [0.37, 0.63], respectively) and with cumulative exposure (0.49 [0.38,0.63]). PFPeA was not associated with GDM. Similar conclusions were observed in BKMR models; however, overall associations in these models were not statistically significant. CONCLUSIONS: Higher risk of GDM was consistently observed in association with PFDA, PFNA, and PFOA exposure in both early and mid-pregnancy. Results should be corroborated in larger population-based cohorts and individuals of reproductive age should potentially avoid known sources of PFAS.

Neighborhood Opportunity and Vulnerability and Incident Asthma Among Children.

Background: The extent to which physical and social attributes of neighborhoods play a role in childhood asthma remains understudied. Objective: To examine associations of neighborhood-level opportunity and social vulnerability measures with childhood asthma incidence. Design, Setting, and Participants: This cohort study used data from children in 46 cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program between January 1, 1995, and August 31, 2022. Participant inclusion required at least 1 geocoded residential address from birth and parent or caregiver report of a physician's diagnosis of asthma. Participants were followed up to the date of asthma diagnosis, date of last visit or loss to follow-up, or age 20 years. Exposures: Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) at birth, infancy, or early childhood, grouped into very low (<20th percentile), low (20th to <40th percentile), moderate (40th to <60th percentile), high (60th to <80th percentile), or very high (≥80th percentile) COI or SVI. Main Outcomes and Measures: The main outcome was parent or caregiver report of a physician's diagnosis of childhood asthma (yes or no). Poisson regression models estimated asthma incidence rate ratios (IRRs) associated with COI and SVI scores at each life stage. Results: The study included 10 516 children (median age at follow-up, 9.1 years [IQR, 7.0-11.6 years]; 52.2% male), of whom 20.6% lived in neighborhoods with very high COI and very low SVI. The overall asthma incidence rate was 23.3 cases per 1000 child-years (median age at asthma diagnosis, 6.6 years [IQR, 4.1-9.9 years]). High and very high (vs very low) COI at birth, infancy, or early childhood were associated with lower subsequent asthma incidence independent of sociodemographic characteristics, parental asthma history, and parity. For example, compared with very low COI, the adjusted IRR for asthma was 0.87 (95% CI, 0.75-1.00) for high COI at birth and 0.83 (95% CI, 0.71-0.98) for very high COI at birth. These associations appeared to be attributable to the health and environmental and the social and economic domains of the COI. The SVI during early life was not significantly associated with asthma incidence. For example, compared with a very high SVI, the adjusted IRR for asthma was 0.88 (95% CI, 0.75-1.02) for low SVI at birth and 0.89 (95% CI, 0.76-1.03) for very low SVI at birth. Conclusions: In this cohort study, high and very high neighborhood opportunity during early life compared with very low neighborhood opportunity were associated with lower childhood asthma incidence. These findings suggest the need for future studies examining whether investing in health and environmental or social and economic resources in early life would promote health equity in pediatric asthma.

Developing a National-Scale Exposure Index for Combined Environmental Hazards and Social Stressors and Applications to the Environmental Influences on Child Health Outcomes (ECHO) Cohort.

Tools for assessing multiple exposures across several domains (e.g., physical, chemical, and social) are of growing importance in social and environmental epidemiology because of their value in uncovering disparities and their impact on health outcomes. Here we describe work done within the Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study to build a combined exposure index. Our index considered both environmental hazards and social stressors simultaneously with national coverage for a 10-year period. Our goal was to build this index and demonstrate its utility for assessing differences in exposure for pregnancies enrolled in the ECHO-wide Cohort Study. Our unitless combined exposure index, which collapses census-tract level data into a single relative measure of exposure ranging from 0-1 (where higher values indicate higher exposure to hazards), includes indicators for major air pollutants and air toxics, features of the built environment, traffic exposures, and social determinants of health (e.g., lower educational attainment) drawn from existing data sources. We observed temporal and geographic variations in index values, with exposures being highest among participants living in the West and Northeast regions. Pregnant people who identified as Black or Hispanic (of any race) were at higher risk of living in a "high" exposure census tract (defined as an index value above 0.5) relative to those who identified as White or non-Hispanic. Index values were also higher for pregnant people with lower educational attainment. Several recommendations follow from our work, including that environmental and social stressor datasets with higher spatial and temporal resolutions are needed to ensure index-based tools fully capture the total environmental context.

Associations between area-level arsenic exposure and adverse birth outcomes: An Echo-wide cohort analysis.

BACKGROUND: Drinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood. OBJECTIVES: This study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). METHODS: Data for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes. RESULTS: Compared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA. CONCLUSIONS: Our study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

Retrospective analysis of wildfire smoke exposure and birth weight outcomes in the San Francisco Bay Area of California.

Despite the occurrence of wildfires quadrupling over the past four decades, the health effects associated with wildfire smoke exposures during pregnancy remains unknown. Particulate matter less than 2.5 µms (PM2.5) is among the major pollutants emitted in wildfire smoke. Previous studies found PM2.5 associated with lower birthweight, however, the relationship between wildfire-specific PM2.5 and birthweight is uncertain. Our study of 7923 singleton births in San Francisco between January 1, 2017 and March 12, 2020 examines associations between wildfire smoke exposure during pregnancy and birthweight. We linked daily estimates of wildfire-specific PM2.5 to maternal residence at the ZIP code level. We used linear and log-binomial regression to examine the relationship between wildfire smoke exposure by trimester and birthweight and adjusted for gestational age, maternal age, race/ethnicity, and educational attainment. We stratified by infant sex to examine potential effect modification. Exposure to wildfire-specific PM2.5 during the second trimester of pregnancy was positively associated with increased risk of large for gestational age (OR = 1.13; 95% CI: 1.03, 1.24), as was the number of days of wildfire-specific PM2.5 above 5 µg m-3 in the second trimester (OR = 1.03; 95% CI: 1.01, 1.06). We found consistent results with wildfire smoke exposure in the second trimester and increased continuous birthweight-for-gestational age z-score. Differences by infant sex were not consistent. Counter to our hypothesis, results suggest that wildfire smoke exposures are associated with increased risk for higher birthweight. We observed strongest associations during the second trimester. These investigations should be expanded to other populations exposed to wildfire smoke and aim to identify vulnerable communities. Additional research is needed to clarify the biological mechanisms in this relationship between wildfire smoke exposure and adverse birth outcomes.