Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Maternal steroids during pregnancy and their associations with exposure to lifetime stressful life events, prenatal stress appraisal and psychological functioning.

BACKGROUND: During pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied. AIM: To assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22-40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334). METHODS: Serum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects. RESULTS: High prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [ß (95%CI): androgens: -0.13 (-0.25;-0.01); estrogens: -0.16 (-0.31;-0.01)], particularly among women carrying males [androgens: -0.22 (-0.39;-0.05); estrogens: -0.28 (-0.50;-0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite-5alpha-androstan-3alpha,17alpha-diol disulfate-negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males. CONCLUSIONS: Increased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.

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.

Ambient temperature, heat stress and fetal growth: A review of placenta-mediated mechanisms.

Pregnancy is increasingly considered a period of vulnerability for extreme heat exposure. Multiple lines of evidence support that heat stress is associated with placental insufficiency, poor fetal growth and decreased birth weight. In this narrative review, we first summarize evidence linking ambient temperature or experimentally-induced heat stress with fetal and placental growth outcomes in humans, ruminants and murine species. We then synthesize the literature on putative underlying biological pathways with a focus on the placenta. Reviewed mechanisms include: reduced uterine-placental blood flow, impaired supply of metabolic substrates to the fetus, activation of the maternal stress-response system, and disruption of other endocrine and immune system endpoints. Taken together, this body of evidence supports that exposure to extreme ambient heat likely has adverse consequences for placental development and function. However, research investigating placenta-mediated pathophysiological mechanisms in humans remains extremely limited.

A short form of the Crisis in Family Systems (CRISYS) in a racially diverse sample of pregnant women.

Assessing stressful life events in large-scale epidemiologic studies is challenged by the need to measure potential stressful events in a reasonably comprehensible manner balanced with burden on participants and research staff. The aim of this paper was to create a short form of the Crisis in Family Systems-Revised (CRISYS-R) plus 17 acculturation items, a measure that captures contemporary life stressors across 11 domains. Latent class analysis (LCA) was used to segment the sample of 884 women from the PRogramming of Intergenerational Stress Mechanisms (PRISM) study experiencing different patterns of exposure to stressful events and identify items from each domain that best discriminate between individuals with different patterns of stressful-event exposures (high vs. low stress exposure). The results from the LCA, in conjunction with the expert opinions provided by the original developers of the CRISYS, yielded a 24-item item short form (CRISYS-SF) with at least one question from each of the original domains. Scores on the 24-item CRISYS-SF had high correlations with scores on the 80-item CRISYS. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-021-02335-w.

Maternal urinary bisphenols and phthalates in relation to estimated fetal weight across mid to late pregnancy.

BACKGROUND: Bisphenols and phthalates are high production volume chemicals used as additives in a variety of plastic consumer products leading to near ubiquitous human exposure. These chemicals have established endocrine disrupting properties and have been linked to a range of adverse reproductive and developmental outcomes. Here, we investigated exposure in relation to fetal growth. METHODS: Participants included 855 mother-fetal pairs enrolled in the population-based New York University Children's Health and Environment Study (NYU CHES). Bisphenols and phthalates were measured in maternal urine collected repeatedly during pregnancy. Analyses included 15 phthalate metabolites and 2 bisphenols that were detected in 50 % of participants or more. Fetal biometry data were extracted from electronic ultrasonography records and estimated fetal weight (EFW) was predicted for all fetuses at 20, 30, and 36 weeks gestation. We used quantile regression adjusted for covariates to model exposure-outcome relations across percentiles of fetal weight at each gestational timepoint. We examined sex differences using stratified models. RESULTS: Few statistically significant associations were observed across chemicals, gestational time periods, percentiles, and sexes. However, within gestational timepoints, we found that among females, the molar sums of the phthalates DiNP and DnOP were generally associated with decreases in EFW among smaller babies and increases in EFW among larger babies. Among males, the opposite trend was observed. However, confidence intervals were generally wide at the tails of the distribution. CONCLUSION: In this sample, exposure to bisphenols and phthalates was associated with small sex-specific shifts in fetal growth; however, few associations were observed at the median of fetal weight and confidence intervals in the tails were wide. Findings were strongest for DiNP and DnOP, which are increasingly used as replacements for DEHP, supporting the need for future research on these contaminants.

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm.

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Impact of sedentary behavior and emotional support on prenatal psychological distress and birth outcomes during the COVID-19 pandemic.

Abstract. BACKGROUND: Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics. METHODS: Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report. RESULTS: After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed. CONCLUSIONS: There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

Prenatal exposure to polybrominated diphenyl ethers and birth outcomes.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) were used as flame retardants and from their end-use products they can be released to accumulate within indoor environments. This may result in exposures to pregnant women with potential adverse effects on the developing fetus. While studies have shown associations between prenatal PBDE exposure and poor birth outcomes, research has mainly focused on birth weight and gestational age and may miss important indicators of newborn size. METHODS: The sample included a cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners (BDE-47, BDE-99, BDE-100, and BDE-153) were measured in cord serum at birth and dichotomized into low (<80th percentile) and high (>80th percentile) categories. Weight, length, head circumference, and gestational age were measured at birth and the ponderal index (birth weight/length x 100), size for gestational age, and population-based z-scores were calculated (n = 305). Separate regression analyses were conducted to estimate associations between PBDEs or PBDE sum (ng/g lipid) and birth outcomes. Quantile g-computation was performed to estimate the effect of total PBDE mixture. We also assessed effect modification by sex and ethnicity. RESULTS: Adjusting for relevant covariates, the high exposure category of BDE-153 was associated with lower birth weight z-score (-0.25, 95% CI: -0.5, 0.0) and longer gestation (0.43 weeks, 95% CI: 0.07, 0.79). The high exposure category of BDE-99 was associated with lower birth length z-score (-0.55, 95% CI: -0.98, -0.12). There was a negative association between the overall PBDE mixture and birth length z-score (-0.10, 95% CI: -0.21, 0.00) per 1 quintile increase in PBDEs. There was no effect modification by sex or ethnicity. CONCLUSIONS: These results suggest that prenatal exposures to BDE-153, BDE-99, and total PBDE mixture are associated with birth outcomes in a cohort of Dominican and African American newborns.

Characteristics of Individuals in the United States Who Used Opioids During Pregnancy.

Background: Opioid use has disproportionally impacted pregnant people and their fetuses. Previous studies describing opioid use among pregnant people are limited by geographic location, type of medical coverage, and small sample size. We described characteristics of a large, diverse group of pregnant people who were enrolled in the Environmental Influences on Child Health Outcomes (ECHO) Program, and determined which characteristics were associated with opioid use during pregnancy. Materials and Methods: Cross-sectional data obtained from 21,905 pregnancies of individuals across the United States enrolled in the ECHO between 1990 and 2021 were analyzed. Medical records, laboratory testing, and self-report were used to determine opioid-exposed pregnancies. Multiple imputation methods using fully conditional specification with a discriminant function accounted for missing characteristics data. Results: Opioid use was present in 2.8% (n = 591) of pregnancies. The majority of people who used opioids in pregnancy were non-Hispanic White (67%) and had at least some college education (69%). Those who used opioids reported high rates of alcohol use (32%) and tobacco use (39%) during the pregnancy; although data were incomplete, only 5% reported heroin use and 86% of opioid use originated from a prescription. After adjustment, non-Hispanic White race, pregnancy during the years 2010-2012, higher parity, tobacco use, and use of illegal drugs during pregnancy were each significantly associated with opioid use during pregnancy. In addition, maternal depression was associated with increased odds of opioid use during pregnancy by more than two-fold (adjusted odds ratio 2.42, 95% confidence interval: 1.95-3.01). Conclusions: In this large study of pregnancies from across the United States, we found several factors that were associated with opioid use among pregnant people. Further studies examining screening for depression and polysubstance use may be useful for targeted interventions to prevent detrimental opioid use during pregnancy, while further elucidation of the reasons for use of prescription opioids during pregnancy should be further explored.

Validation of a neighborhood sentiment and safety index derived from existing data repositories.

BACKGROUND: The communities we live in are central to our health. Neighborhood disadvantage is associated with worse physical and mental health and even early mortality, while resident sense of safety and positive neighborhood sentiment has been repeatedly linked to better physical and mental health outcomes. Therefore, understanding where negative neighborhood sentiment and safety are salient concerns can help inform public health interventions and as a result, improve health outcomes. To date, fear of crime and neighborhood sentiment data or indices have largely been based on the administration of time consuming and costly standardized surveys. OBJECTIVE: The current study aims to develop a Neighborhood Sentiment and Safety Index (NSSI) at the census tract level, building on publicly available data repositories, including the US Census and ACS surveys, Data Axle, and ESRI repositories. METHODS: The NSSI was created using Principal Component Analysis. Mineigen and minimum loading values were 1 and 0.3, respectively. Throughout the step-wise PCA process, variables were excluded if their loading value was below 0.3 or if variables loaded into multiple components. RESULTS: The novel index was validated against standardized survey items from a longitudinal cohort study in the Northeastern United States characterizing experiences of (1) Neighborhood Characteristics with a Pearson correlation of -0.34 (p < 0.001) and, (2) Neighborhood Behavior Impact with a Pearson correlation of -0.33 (p < 0.001). It also accurately predicted the Share Care Community Well Being Index (Spearman correlation = 0.46) and the neighborhood deprivation index (NDI) (Spearman correlation = -0.75). SIGNIFICANCE: Our NSSI can serve as a predictor of neighborhood experience where data is either unavailable or too resource consuming to practically implement in planned studies. IMPACT STATEMENT: To date, fear of crime and neighborhood sentiment data or indices have largely been based on the administration of time consuming and costly standardized surveys. The current study aims to develop a Neighborhood Sentiment and Safety Index (NSSI) at the census tract level, building on publicly available data repositories, including the US Census and ACS surveys, Data Axle, and ESRI repositories. The NSSI was validated against four separate measures and can serve as a predictor of neighborhood experience where data is either unavailable or too resource consuming to practically implement in planned studies.

Ambient PM2.5 exposure and salivary cortisol output during pregnancy in a multi-ethnic urban sample.

OBJECTIVES: Evidence from murine research supports that fine particulate matter (PM2.5) may stimulate the hypothalamic-pituitary-adrenal axis, leading to elevated circulating glucocorticoid levels. Epidemiologic research examining parallel associations document similar associations. We examined these associations among a diverse sample of pregnant individuals exposed to lower levels of ambient PM2.5. MATERIALS AND METHODS: Participants included pregnant individuals enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pre-birth cohort. Daily residential PM2.5 exposure was estimated using a satellite-based spatial-temporal hybrid model. Maternal 3rd trimester salivary cortisol levels were used to calculate several features of the diurnal cortisol rhythm. We used multivariable linear regression to examine PM2.5 during the pre-conception period and during each trimester in relation to cortisol awakening rise (CAR), slope, and area under the curve relative to ground (AUCG). RESULTS AND DISCUSSION: The average PM2.5 exposure level across pregnancy was 8.13 µg/m3. PM2.5 in each exposure period was positively associated with AUCG, a measure of total cortisol output across the day. We also observed an inverse association between PM2.5 in the 3rd trimester and diurnal slope, indicating a steeper decline in cortisol throughout the day with increasing exposure. We did not detect strong associations between PM2.5 and slope for the other exposure periods or between PM2.5 and CAR for any exposure period. CONCLUSIONS: In this sample, PM2.5 exposure across the preconception and pregnancy periods was associated with increased cortisol output, even at levels below the U.S. National Ambient Air Quality Annual Standard for PM2.5 of 12.0 µg/m3.

Prenatal exposure to polybrominated diphenyl ethers and inattention/hyperactivity symptoms in mid to late adolescents.

Introduction: Prenatal exposure to polybrominated diphenyl ethers (PBDEs) has been associated with increased symptoms of attention deficit/hyperactivity disorder (ADHD) in early to middle childhood, as well as early adolescence. However, data are limited for the long-lasting impact of exposure on outcomes assessed across the entire adolescent period and the sex-specificity of such associations. Methods: We investigated the association between continuous natural-log-transformed cord plasma PBDE concentrations and ADHD rating scale 4th edition (ADHD-RS-IV) score from mid adolescence (approximately 11 years old) to late adolescence (approximately 17 years old). The study sample includes a subset (n = 219) of the African American and Dominican children enrolled in the Columbia Center for Children's Environmental Health Mothers and Newborns birth cohort. We used generalized estimating equations to account for the repeated measure of ADHD-RS scores. We examined interactions between exposure to PBDE and sex using cross-product terms and sex-stratified models. In addition, we used linear regression using an age-stratified sample as a sensitivity analysis. Results and Discussion: Associations between prenatal exposure and parents' reports of ADHD symptoms varied by sex (p-interaction <0.20), with positive relationships observed among girls but not boys from sex-stratified models. Our finding suggests prenatal exposure to PBDE may affect ADHD symptoms assessed during middle to late adolescence and the sex-specificity of such impact. Our results can be confirmed by future studies with larger and more diverse samples.

Prenatal exposure to polybrominated diphenyl ethers and BMI Z-scores from 5 to 14 years.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are flame-retardant compounds widely used in household products until phase out in 2004. PBDEs are endocrine disruptors and are suggested to influence signaling related to weight control. Prenatal exposures to PBDEs may alter childhood adiposity, yet few studies have examined these associations in human populations. METHODS: Data were collected from a birth cohort of Dominican and African American mother-child pairs from New York City recruited from 1998 to 2006. PBDE congeners BDE-47, - 99, - 100, and - 153 were measured in cord plasma (ng/µL) and dichotomized into low (< 80th percentile) and high (>80th percentile) exposure categories. Height and weight were collected at ages 5, 7, 9, 11, and an ancillary visit from 8 to 14 years (n = 289). Mixed-effects models with random intercepts for participant were used to assess associations between concentrations of individual PBDE congeners or the PBDE sum and child BMI z-scores (BMIz). To assess associations between PBDEs and the change in BMIz over time, models including interactions between PBDE categories and child age and (child age)2 were fit. Quantile g-computation was used to investigate associations between BMIz and the total PBDE mixture. Models were adjusted for baseline maternal covariates: ethnicity, age, education, parity, partnership status, and receipt of public assistance, and child covariates: child sex and cord cholesterol and triglycerides. RESULTS: The prevalence of children with obesity at age 5 was 24.2% and increased to 30% at age 11. Neither cord levels of individual PBDEs nor the total PBDE mixture were associated with overall BMIz in childhood. The changes in BMIz across childhood were not different between children with low or high PBDEs. Results were similar when adjusting for postnatal PBDE exposures. CONCLUSIONS: Prenatal PBDE exposures were not associated with child growth trajectories in a cohort of Dominican and African American children.

Associations between combined exposure to environmental hazards and social stressors at the neighborhood level and individual perinatal outcomes in the ECHO-wide cohort.

Limited studies examine how prenatal environmental and social exposures jointly impact perinatal health. Here we investigated relationships between a neighborhood-level combined exposure (CE) index assessed during pregnancy and perinatal outcomes, including birthweight, gestational age, and preterm birth. Across all participants, higher CE index scores were associated with small decreases in birthweight and gestational age. We also observed effect modification by race; infants born to Black pregnant people had a greater risk of preterm birth for higher CE values compared to White infants. Overall, our results suggest that neighborhood social and environmental exposures have a small but measurable joint effect on neonatal indicators of health.

Associations between antenatal maternal asthma status and placental DNA methylation.

INTRODUCTION: Maternal asthma in pregnancy is associated with adverse perinatal and child health outcomes; however, mechanisms are poorly understood. METHODS: The PRogramming of Intergenerational Stress Mechanisms (PRISM) prospective pregnancy cohort characterized asthma history during pregnancy via questionnaires and quantified placental DNAm using the Illumina Infinium HumanMethylation450 BeadChip. We performed epigenome-wide association analyses (n = 223) to estimate associations between maternal active or inactive asthma, as compared to never asthma, and placental differentially methylated positions (DMPs) and differentially variable positions (DVPs). Models adjusted for maternal pre-pregnancy body mass index, smoking status, parity, age and education level and child sex. P-values were FDR-adjusted. RESULTS: One hundred and fifty-nine (71.3%) pregnant women reported no history of asthma (never asthma), 15 (6.7%) reported inactive, and 49 (22%) reported active antenatal asthma. Women predominantly self-identified as Black/Hispanic Black [88 (39.5%)] and Hispanic/non-Black [42 (18.8%)]. We identified 10 probes at FDR<0.05 and 4 probes at FDR<0.10 characterized by higher variability in maternal active asthma compared to never asthma mapping to GPX3, LHPP, PECAM1, ATAD3C, and ARHGEF4 and 2 probes characterized by lower variation mapping to CHMP4A and C5orf24. Amongst women with inactive asthma, we identified 52 probes, 41 at FDR<0.05 and an additional 11 at FDR <0.10, with higher variability compared to never asthma; BMP4, LHPP, PHYHIPL, and ZSCAN23 were associated with multiple DVPs. No associations were observed with DMPs. DISCUSSION: We observed alterations in placental DNAm in women with antenatal asthma, as compared to women without a history of asthma. Further research is needed to understand the impact on fetal development.

The association between prenatal F2-isoprostanes and child wheeze/asthma and modification by maternal race.

BACKGROUND: Childhood wheeze, asthma, and allergic rhinitis are common and likely have prenatal origins. Oxidative stress is associated with respiratory disease, but the association of oxidative stress during the prenatal period with development of respiratory and atopic disease in childhood, particularly beyond the infancy period, is unknown. This study aims to investigate associations between prenatal oxidative stress, measured by maternal urinary F2-isoprostanes, and child respiratory outcomes, including effect modification by maternal race. METHODS: We prospectively studied Black (n = 717) and White (n = 363) mother-child dyads. We measured F2-isoprostanes in 2nd-trimester urine (ng/mg-creatinine). At approximately age 4, we obtained parent report of provider-diagnosed asthma (ever), current wheeze, current asthma (diagnosis, symptoms and/or medication), and current allergic rhinitis (current defined as previous 12 months). We used multivariable logistic regression to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) per interquartile range (IQR) increase in F2-isoprostane concentration, controlling for confounders. We examined modification by maternal race using interaction terms. RESULTS: The prevalence of provider-diagnosed asthma and current wheeze, asthma and allergic rhinitis was 14%, 19%, 15%, and 24%, respectively. Median (IQR) F2-isoprostane levels were 2.1 (1.6, 2.9) ng/mg-creatinine. Associations between prenatal F2-isoprostanes and provider-diagnosed asthma, current wheeze, and current asthma were modified by maternal race. Results were strongest for current wheeze (aOR [95%CI]: 1.55 [1.16, 2.06] for White; 0.98 [0.78, 1.22] for Black; p-interaction = 0.01). We observed no association between F2-isoprostanes and allergic rhinitis. CONCLUSION: Prenatal urinary F2-isoprostanes may be a marker associated with childhood wheeze/asthma in certain populations. Research is needed to understand underlying mechanisms and racial differences.

Maternal steroids during pregnancy and their associations with ambient air pollution and temperature during preconception and early gestational periods.

Hormones play critical roles in facilitating pregnancy progression and the onset of parturition. Several classes of environmental contaminants, including fine particulate matter (PM2.5) and ambient temperature, have been shown to alter hormone biosynthesis or activity. However, epidemiologic research has not considered PM2.5 in relation to a broader range of steroid hormones, particularly in pregnant women. Using metabolomics data collected within 20-40 weeks of gestation in an ethnically diverse pregnancy cohort study, we identified 42 steroid hormones that we grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids) based on their biosynthesis type. We found that exposure to PM2.5 during the pre-conception and early prenatal periods was associated with higher maternal androgen concentrations in late pregnancy. We also detected a positive association between early pregnancy PM2.5 exposure and maternal pregnenolone levels and a marginal positive association between early pregnancy PM2.5 exposure and progestin levels. When considering each hormone metabolite individually, we found positive associations between early pregnancy PM2.5 exposure and five steroids, two of which survived multiple comparison testing: 11beta-hydroxyandrosterone glucuronide (a pregnenolone steroid) and adrosteroneglucuronide (a progestin steroid). None of the steroid classes were statistically significant associated with ambient temperature. In sex-stratified analyses, we did not detect any sex differences in our associations. This is the first study showing that exposure to fine particulate matter during the pre-conception and early prenatal periods can lead to altered steroid adaptation during the state of pregnancy, which has been shown to have potential consequences on maternal and child health.

Correction: Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts.

[This corrects the article DOI: 10.1371/journal.pone.0245064.].