Affective Symptoms in Pregnancy are Associated with the Vaginal Microbiome.

Composition of the vaginal microbiome in pregnancy is associated with adverse maternal, obstetric, and child health outcomes. Identifying the sources of individual differences in the vaginal microbiome is therefore of considerable clinical and public health interest. The current study tested the hypothesis that vaginal microbiome composition during pregnancy is associated with an individual's experience of affective symptoms and stress exposure. Data were based on a prospective longitudinal study of a diverse and medically healthy community sample of 275 mother-infant pairs. Affective symptoms and stress exposure and select measures of associated biomarkers (diurnal salivary cortisol, serum measures of sex hormones) were collected at each trimester; self-report, clinical, and medical records were used to collect detailed data on socio-demographic factors and health behavior, including diet and sleep. Vaginal microbiome samples were collected in the third trimester (34-40 weeks) and characterized by 16S rRNA sequencing. Identified taxa were clustered into three community state types (CST1-3) based on dissimilarity of vaginal microbiota composition. Results indicate that depressive symptoms during pregnancy were reliably associated with individual taxa and CST3 in the third trimester. Prediction of functional potential from 16S taxonomy revealed a differential abundance of metabolic pathways in CST1-3 and individual taxa, including biosynthetic pathways for the neuroactive metabolites, serotonin and dopamine. With the exception of bioavailable testosterone, no significant associations were found between symptoms- and stress-related biomarkers and CSTs. Our results provide further evidence of how prenatal psychological distress during pregnancy alters the maternal-fetal microbiome ecosystem that may be important for understanding maternal and child health outcomes. Importance: Prenatal affective symptoms and stress are associated with maternal, obstetric, and child health outcomes, but the mechanisms underlying these links and their application to intervention remain unclear. The findings from this investigation extend prior microbiome-oriented research by demonstrating that the maternal vaginal microbiome composition has a biologically plausible mechanistic link with affective symptoms that also suggest additional clinical applications for assessment and intervention.

Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGß), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGß: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGß. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGß only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGß only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGß differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

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.

Prenatal maternal immune activation predicts observed fearfulness in infancy.

Fear reactivity is an early emerging temperament trait that predicts longer term behavioral and health outcomes. The current analysis tests the hypothesis, an extension of prior research on maternal immune activation (MIA), that the prenatal maternal immune system is a reliable predictor of observed fear reactivity in infancy. The analysis is based on a prospective longitudinal cohort study that collected data from the first trimester and conducted observational assessments of temperament at approximately 12 months of age (n = 281 infants). MIA was assessed from immune biomarkers measured in maternal blood at each trimester; infant temperament was assessed using the Laboratory Temperament Assessment Battery assessment at 12 months; covariates included family and sociodemographic factors. Patterns of inflammatory markers across gestation reliably predicted observed temperament: elevated prenatal MIA was associated with high fear reactivity to novel stimuli. The findings provide novel evidence of prenatal origins of fear reactivity and suggest developmental mechanisms that may underlie early emerging individual differences in child temperament. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Birth outcomes in relation to neighborhood food access and individual food insecurity during pregnancy in the Environmental Influences on Child Health Outcomes (ECHO)-wide cohort study.

BACKGROUND: Limited access to healthy foods, resulting from residence in neighborhoods with low-food access or from household food insecurity, is a public health concern. Contributions of these measures during pregnancy to birth outcomes remain understudied. OBJECTIVES: We examined associations between neighborhood food access and individual food insecurity during pregnancy with birth outcomes. METHODS: We used data from 53 cohorts participating in the nationwide Environmental Influences on Child Health Outcomes-Wide Cohort Study. Participant inclusion required a geocoded residential address or response to a food insecurity question during pregnancy and information on birth outcomes. Exposures include low-income-low-food-access (LILA, where the nearest supermarket is >0.5 miles for urban or >10 miles for rural areas) or low-income-low-vehicle-access (LILV, where few households have a vehicle and >0.5 miles from the nearest supermarket) neighborhoods and individual food insecurity. Mixed-effects models estimated associations with birth outcomes, adjusting for socioeconomic and pregnancy characteristics. RESULTS: Among 22,206 pregnant participants (mean age 30.4 y) with neighborhood food access data, 24.1% resided in LILA neighborhoods and 13.6% in LILV neighborhoods. Of 1630 pregnant participants with individual-level food insecurity data (mean age 29.7 y), 8.0% experienced food insecurity. Residence in LILA (compared with non-LILA) neighborhoods was associated with lower birth weight [ß -44.3 g; 95% confidence interval (CI): -62.9, -25.6], lower birth weight-for-gestational-age z-score (-0.09 SD units; -0.12, -0.05), higher odds of small-for-gestational-age [odds ratio (OR) 1.15; 95% CI: 1.00, 1.33], and lower odds of large-for-gestational-age (0.85; 95% CI: 0.77, 0.94). Similar findings were observed for residence in LILV neighborhoods. No associations of individual food insecurity with birth outcomes were observed. CONCLUSIONS: Residence in LILA or LILV neighborhoods during pregnancy is associated with adverse birth outcomes. These findings highlight the need for future studies examining whether investing in neighborhood resources to improve food access during pregnancy would promote equitable birth outcomes.

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.

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.

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.

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.

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.

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.

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.

Molecular pathways in placental-fetal development and disruption.

The first trimester of pregnancy ranks high in priority when minimizing harmful exposures, given the wide-ranging types of organogenesis occurring between 4- and 12-weeks' gestation. One way to quantify potential harm to the fetus in the first trimester is to measure a corollary effect on the placenta. Placental biomarkers are widely present in maternal circulation, cord blood, and placental tissue biopsied at birth or at the time of pregnancy termination. Here we evaluate ten diverse pathways involving molecules expressed in the first trimester human placenta based on their relevance to normal fetal development and to the hypothesis of placental-fetal endocrine disruption (perturbation in development that results in abnormal endocrine function in the offspring), namely: human chorionic gonadotropin (hCG), thyroid hormone regulation, peroxisome proliferator activated receptor protein gamma (PPARγ), leptin, transforming growth factor beta, epiregulin, growth differentiation factor 15, small nucleolar RNAs, serotonin, and vitamin D. Some of these are well-established as biomarkers of placental-fetal endocrine disruption, while others are not well studied and were selected based on discovery analyses of the placental transcriptome. A literature search on these biomarkers summarizes evidence of placenta-specific production and regulation of each biomarker, and their role in fetal reproductive tract, brain, and other specific domains of fetal development. In this review, we extend the theory of fetal programming to placental-fetal programming.

Prenatal Exposure to Nonpersistent Environmental Chemicals and Postpartum Depression.

Importance: Postpartum depression (PPD) affects up to 20% of childbearing individuals, and a significant limitation in reducing its morbidity is the difficulty in modifying established risk factors. Exposure to synthetic environmental chemicals found in plastics and personal care products, such as phenols, phthalates, and parabens, are potentially modifiable and plausibly linked to PPD and have yet to be explored. Objective: To evaluate associations of prenatal exposure to phenols, phthalates, parabens, and triclocarban with PPD symptoms. Design, Setting, and Participants: This was a prospective cohort study from 5 US sites, conducted from 2006 to 2020, and included pooled data from 5 US birth cohorts from the National Institutes of Health Environmental Influences on Child Health Outcomes (ECHO) consortium. Participants were pregnant individuals with data on urinary chemical concentrations (phenols, phthalate metabolites, parabens, or triclocarban) from at least 1 time point in pregnancy and self-reported postnatal depression screening assessment collected between 2 weeks and 12 months after delivery. Data were analyzed from February to May 2022. Exposures: Phenols (bisphenols and triclosan), phthalate metabolites, parabens, and triclocarban measured in prenatal urine samples. Main Outcomes and Measures: Depression symptom scores were assessed using the Edinburgh Postnatal Depression Scale (EPDS) or the Center for Epidemiologic Studies Depression Scale (CES-D), harmonized to the Patient-Reported Measurement Information System (PROMIS) Depression scale. Measures of dichotomous PPD were created using both sensitive (EPDS scores ≥10 and CES-D scores ≥16) and specific (EPDS scores ≥13 and CES-D scores ≥20) definitions. Results: Among the 2174 pregnant individuals eligible for analysis, nearly all (>99%) had detectable levels of several phthalate metabolites and parabens. PPD was assessed a mean (SD) of 3 (2.5) months after delivery, with 349 individuals (16.1%) and 170 individuals (7.8%) screening positive for PPD using the sensitive and specific definitions, respectively. Linear regression results of continuous PROMIS depression T scores showed no statistically significant associations with any chemical exposures. Models examining LMW and HMW phthalates and di (2-ethylhexyl) phthalate had estimates in the positive direction whereas all others were negative. A 1-unit increase in log-transformed LMW phthalates was associated with a 0.26-unit increase in the PROMIS depression T score (95% CI, -0.01 to 0.53; P = .06). This corresponded to an odds ratio (OR) of 1.08 (95% CI, 0.98-1.19) when modeling PPD as a dichotomous outcome and using the sensitive PPD definition. HMW phthalates were associated with increased odds of PPD (OR, 1.11; 95% CI, 1.00-1.23 and OR, 1.10; 95% CI, 0.96-1.27) for the sensitive and specific PPD definitions, respectively. Sensitivity analyses produced stronger results. Conclusions and Relevance: Phthalates, ubiquitous chemicals in the environment, may be associated with PPD and could serve as important modifiable targets for preventive interventions. Future studies are needed to confirm these observations.

Association between maternal occupational exposure to cleaning chemicals during pregnancy and childhood wheeze and asthma.

Background: Asthma is a leading cause of childhood morbidity in the U.S. and a significant public health concern. The prenatal period is a critical window during which environmental influences, including maternal occupational exposures, can shape child respiratory health. Cleaning chemicals are commonly encountered in occupational settings, yet few studies have examined the potential link between prenatal occupational exposures to cleaning chemicals and risk of childhood wheeze and asthma. Methods: We evaluated the potential influence of maternal occupational exposure to cleaning chemicals during pregnancy on pediatric asthma and wheeze at child age 4-6 years in 453 mother-child pairs from two longitudinal pregnancy cohorts, TIDES and GAPPS, part of the ECHO prenatal and early childhood pathways to health (ECHO-PATHWAYS) consortium. Maternal occupational exposure to cleaning chemicals was defined based on reported occupation and frequency of occupational use of chemicals during pregnancy. Child current wheeze and asthma outcomes were defined by parental responses to a widely-used, standardized respiratory outcomes questionnaire administered at child age 4-6 years. Multivariable Poisson regression with robust standard errors was used to estimate relative risk (RR) of asthma in models adjusted for confounding. Effect modification by child sex was assessed using product interaction terms. Results: Overall, 116 mothers (25.6%) reported occupational exposure to cleaning chemicals during pregnancy, 11.7% of children had current wheeze, and 10.2% had current asthma. We did not identify associations between prenatal exposure to cleaning chemicals and current wheeze [RRadjusted 1.03, 95% confidence interval (CI): 0.56, 1.90] or current asthma (RRadjusted 0.89, CI: 0.46, 1.74) in the overall sample. Analyses of effect modification suggested an adverse association among females for current wheeze (RR 1.82, CI: 0.76, 4.37), compared to males (RR 0.68, CI: 0.29, 1.58), though the interaction p-value was >0.05. Conclusion: We did not observe evidence of associations between maternal prenatal occupational exposure to cleaning chemicals and childhood wheeze or asthma in the multi-site ECHO-PATHWAYS consortium. We leveraged longitudinal U.S. pregnancy cohorts with rich data characterization to expand on limited and mixed literature. Ongoing research is needed to more precisely characterize maternal occupational chemical exposures and impacts on child health in larger studies.

Beauty Beware: Associations between Perceptions of Harm and Safer Hair-Product-Purchasing Behaviors in a Cross-Sectional Study of Adults Affiliated with a University in the Northeast.

(1) Background: Widespread personal care product (PCP) use can expose individuals to endocrine-disrupting chemicals (EDCs) associated with adverse health outcomes. This study investigated the association between harm perceptions and hair-product-purchasing behaviors in adults enrolled in a cross-sectional study. (2) Methods: Respondents rated their agreement with five PCP-related harm statements using a five-point Likert scale. Multivariable-adjusted logistic regression models were used to examine the associations between harm perceptions with hair-product-purchasing behaviors and hair product use (i.e., number of products used). (3) Results: Among 567 respondents (non-Hispanic White, 54.9%; non-Hispanic Black, 9.5%; Hispanic/Latinx, 10.1%; Asian American/Pacific Islander, 20.1%; and multiracial/other, 5.5%), stronger harm perceptions around PCP use were associated with potentially "safer" hair-product-purchasing behaviors. Respondents who strongly agreed that consumers should be concerned about the health effects of PCPs had more than fourfold increased odds of always/usually using healthy product apps (OR 4.10, 95% CI: 2.04-8.26); reading ingredient labels (OR 4.53, 95% CI: 2.99-6.87); and looking for natural, non-toxic, or eco-friendly product labels (OR 4.53, 95% CI: 2.99-6.88) when buying hair products. (4) Conclusions: Promoting environmental health literacy and raising awareness of potential PCP use-related harms might encourage healthier hair product use behaviors.

Racial and Ethnic Disparities in Phthalate Exposure and Preterm Birth: A Pooled Study of Sixteen U.S. Cohorts.

BACKGROUND: Phthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth. OBJECTIVES: We 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Phthalate 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.