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

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

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

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

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.

Role of Air Pollution in the Development of Asthma Among Children with a History of Bronchiolitis in Infancy.

BACKGROUND: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. METHODS: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. RESULTS: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m 3 PM 2.5 , 8.5 (6.4-9.9) ppb NO 2 , and 26.6 (25.6-27.7) ppb O 3 . RRs (CI) for current wheeze per 2-ppb higher O 3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO 2 was inversely associated with wheeze and asthma whereas associations with PM 2.5 were null. We observed interactions between NO 2 and PM 2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. CONCLUSION: Our results are consistent with the hypothesis that exposure to modest postnatal O 3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis.

Urinary oxidative stress biomarkers are associated with preterm birth: an Environmental Influences on Child Health Outcomes program study.

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

Trends in Degree Conferrals, Degree-Associated Debt, and Employment Outcomes Among Undergraduate Public Health Degree Graduates, 2001‒2020.

Objectives. To characterize the trends in degree conferrals, degree-associated debt, and employment outcomes among undergraduate public health degree (UGPHD) graduates. Methods. We reported administrative data on degree conferrals from 2001 to 2020 from the National Center for Education Statistics (NCES). For alumni graduating from 2015 to 2019, we also reported degree-associated debt and earnings 1 year after graduation compiled by NCES. Finally, we utilized a data set on 1-year postgraduation employment outcomes for graduates from 2015 to 2020 from the Association of Schools and Programs of Public Health. Results. As of 2020, more than 18 000 UGPHDs were awarded each year, more than 140 000 in total over the past 20 years. UGPHD graduates are highly diverse, with more than 80% being women and 55% being individuals from communities of color. We find alumni worked mostly in for-profit organizations (34%), health care (28%), nonprofits (11%), academic organizations (10%), government (10%), and other (6%). Degree-associated debt was $24 000, and the median first-year earnings were $34 000. Conclusions. While growth in UGPHD conferrals has slowed, it remains among the fastest-growing degree in the nation. However, the limited pathways into government remains a significant challenge. (Am J Public Health. 2023;113(1):115-123. https://doi.org/10.2105/AJPH.2022.307113).

Prenatal bisphenol A and S exposure and atopic disease phenotypes at age 6.

BACKGROUND: Atopic disease may be influenced by prenatal and early life exposure to endocrine disrupting chemicals, including bisphenols, but results from epidemiological studies have been mixed. This study aimed to extend the epidemiological literature, hypothesizing that children with higher prenatal bisphenol exposure are more likely to have childhood atopic disease. METHODS: Urinary bisphenol A (BPA) and S (BPS) concentrations were measured in each trimester from 501 pregnant women in a multi-center, prospective pregnancy cohort. Ever asthma, current asthma, wheeze, and food allergy) were assessed at age six via standardized ISAAC questionnaire. We constructed generalized estimating equations to examine BPA and BPS exposure jointly at each trimester for each atopy phenotype. BPA was modeled as a log-transformed continuous variable, whereas BPS was modeled as detected versus not detected. We also modeled pregnancy-averaged BPA values and a categorical indicator for number of detectable BPS values over pregnancy (0-3) in logistic regression models. RESULTS: First trimester BPA was associated with inverse odds of food allergy among the entire study sample (OR = 0.78, 95% CI = 0.64-0.95, p = 0.01) and females only (OR = 0.69, 95% CI = 0.52-0.90, p = 0.006). The inverse relationship persisted in pregnancy-averaged models of BPA among females (OR = 0.56, 95% CI = 0.35-0.90, p = 0.006). Second trimester BPA was associated with greater odds of food allergy in the entire sample (OR = 1.27, 95% CI = 1.02-1.58, p = 0.03) and among males only (OR = 1.48, 95% CI = 1.02-2.14, p = 0.04). Odds of current asthma increased among males in the pregnancy-averaged BPS models (OR = 1.65, 95% CI = 1.01-2.69, p = 0.045). CONCLUSION: We saw opposite effects of BPA on food allergy that were trimester- and sex-specific. These divergent associations warrant further investigation. There is some evidence to suggest that prenatal BPS is associated with asthma among males, but further research is required in cohorts with a greater proportion of prenatal urine samples with detectable BPS to validate these results.

Prenatal exposure to polycyclic aromatic hydrocarbons is not associated with behavior problems in preschool and early school-aged children: A prospective multi-cohort study.

BACKGROUND: Epidemiological study findings are inconsistent regarding associations between prenatal polycyclic aromatic hydrocarbon (PAH) exposures and childhood behavior. This study examined associations of prenatal PAH exposure with behavior at age 4-6 years in a large, diverse, multi-region prospective cohort. Secondary aims included examination of PAH mixtures and effect modification by child sex, breastfeeding, and child neighborhood opportunity. METHODS: The ECHO PATHWAYS Consortium pooled 1118 mother-child dyads from three prospective pregnancy cohorts in six U.S. cities. Seven PAH metabolites were measured in prenatal urine. Child behavior was assessed at age 4-6 using the Total Problems score from the Child Behavior Checklist (CBCL). Neighborhood opportunity was assessed using the socioeconomic and educational scales of the Child Opportunity Index. Multivariable linear regression was used to estimate associations per 2-fold increase in each PAH metabolite, adjusted for demographic, prenatal, and maternal factors and using interaction terms for effect modifiers. Associations with PAH mixtures were estimated using Weighted Quantile Sum Regression (WQSR). RESULTS: The sample was racially and sociodemographically diverse (38% Black, 49% White, 7% Other; household-adjusted income range $2651-$221,102). In fully adjusted models, each 2-fold increase in 2-hydroxynaphthalene was associated with a lower Total Problems score, contrary to hypotheses (b = -0.80, 95% CI = -1.51, -0.08). Associations were notable in boys (b = -1.10, 95% CI = -2.11, -0.08) and among children breastfed 6+ months (b = -1.31, 95% CI = -2.25, -0.37), although there was no statistically significant evidence for interaction by child sex, breastfeeding, or neighborhood child opportunity. Associations were null for other PAH metabolites; there was no evidence of associations with PAH mixtures from WQSR. CONCLUSION: In this large, well-characterized, prospective study of mother-child pairs, prenatal PAH exposure was not associated with child behavior problems. Future studies characterizing the magnitude of prenatal PAH exposure and studies in older childhood are needed.

Intergenerational transmission of stress: Multi-domain stressors from maternal childhood and pregnancy predict children's mental health in a racially and socioeconomically diverse, multi-site cohort.

PURPOSE: Despite growing recognition that unfortunately common maternal stress exposures in childhood and pregnancy may have intergenerational impacts on children's psychiatric health, studies rarely take a life course approach. With child psychopathology on the rise, the identification of modifiable risk factors is needed to promote maternal and child well-being. In this study, we examined associations of maternal exposure to childhood traumatic events (CTE) and pregnancy stressful life events (PSLE) with child mental health problems in a large, sociodemographically diverse sample. METHODS: Participants were mother-child dyads in the ECHO-PATHWAYS consortium's harmonized data across three U.S. pregnancy cohorts. Women completed questionnaires regarding their own exposure to CTE and PSLE, and their 4-6-year-old child's mental health problems using the Child Behavior Checklist (CBCL). Regression analyses estimated associations between stressors and child total behavior problems, adjusting for confounders. RESULTS: Among 1948 dyads (child age M = 5.13 (SD = 1.02) years; 38% Black, 44% White; 8.5% Hispanic), maternal history of CTE and PSLE were independently associated with children's psychopathology: higher CTE and PSLE counts were related to higher total problems ([ßCTE = 0.11, 95% CI [.06, .16]; ßSLE = 0.21, 95% CI [.14, 0.27]) and greater odds of clinical levels of problems (ORCTE = 1.41; 95% CI [1.12, 1.78]; ORPSLE = 1.36; 95% CI [1.23, 1.51]). Tests of interaction showed PSLEs were more strongly associated with child problems for each additional CTE experienced. CONCLUSION: Findings confirm that maternal exposure to CTE and PSLE are independently associated with child mental health, and history of CTE exacerbates the risk associated with PSLE, highlighting intergenerational risk pathways for early psychopathology. Given the prevalence of these exposures, prevention and intervention programs that reduce childhood trauma and stress during pregnancy will likely positively impact women's and their children's health.

Combining Urinary Biomarker Data From Studies With Different Measures of Urinary Dilution.

BACKGROUND: Guidance is lacking for how to combine urinary biomarker data across studies that use different measures of urinary dilution, that is, creatinine or specific gravity. METHODS: Among 741 pregnant participants from four sites of The Infant Development and Environment Study (TIDES) cohort, we assessed the relation of maternal urinary di-2-ethylhexyl phthalate (DEHP) concentrations with preterm birth. We compared scenarios in which all sites measured either urinary creatinine or specific gravity, or where measure of dilution differed by site. In addition to a scenario with no dilution adjustment, we applied and compared three dilution-adjustment approaches: a standard regression-based approach for creatinine, a standard approach for specific gravity (Boeniger method), and a more recently developed approach that has been applied to both (covariate-adjusted standardization method). For each scenario and dilution-adjustment method, we estimated the association between a doubling in the molar sum of DEHP (∑DEHP) and odds of preterm birth using logistic regression. RESULTS: All dilution-adjustment approaches yielded comparable associations (odds ratio [OR]) that were larger in magnitude than when we did not perform dilution adjustment. A doubling of ∑DEHP was associated with 9% greater odds of preterm birth (OR = 1.09, 95% confidence interval [CI] = 0.91, 1.30) when applying no dilution-adjustment method, whereas dilution-adjusted point estimates were higher, and similar across all scenarios and methods: 1.13-1.20 (regression-based), 1.15-1.18 (Boeniger), and 1.14-1.21 (covariate-adjusted standardization). CONCLUSIONS: In our applied example, we demonstrate that it is possible and straightforward to combine urinary biomarker data across studies when measures of dilution differ.

The association between duration of breastfeeding and childhood asthma outcomes.

BACKGROUND: Postnatal exposures, including breastfeeding, may influence asthma development. OBJECTIVE: To investigate the association between breastfeeding duration and child asthma. METHODS: We studied 2021 mother-child dyads in the ECHO PATHWAYS consortium of prospective pregnancy cohorts (GAPPS, CANDLE, TIDES). Women reported the duration of any and exclusive breastfeeding and child asthma outcomes during follow-up at child age 4 to 6 years. Outcomes included current wheeze (previous 12 months), ever asthma, current asthma (having ≥2 of current wheeze, ever asthma, medication use in past 12-24 months), and strict current asthma (ever asthma with either or both current wheeze and medication use in past 12-24 months). We used multivariable logistic regression to assess associations (odds ratios and 95% confidence intervals) between breastfeeding and asthma outcomes adjusting for potential confounders. We assessed effect modification by mode of delivery, infant sex, and maternal asthma. RESULTS: Among women, 33%, 13%, 9%, and 45% reported 0 to less than 2, 2 to 4, 5 to 6, and more than 6 months of any breastfeeding, respectively. The duration of any breastfeeding had a protective linear trend with ever asthma but no other outcomes. There was a duration-dependent protective association of exclusive breastfeeding and child asthma outcomes (eg, current asthma adjusted odds ratio [95% confidence interval], 0.64 [0.41-1.02], 0.61 [0.38-0.98], and 0.52 (0.31-0.87) for 2to 4 months, 5 to 6 months, and more than 6 months, respectively, compared with <2 months). For exclusive breastfeeding, protective associations were stronger in dyads with children born by vaginal vs cesarean delivery although interactions did not reach statistical significance (Pinteractions 0.12-0.40). CONCLUSION: Longer duration of exclusive breastfeeding had a protective association with child asthma.

Urinary glyphosate concentration in pregnant women in relation to length of gestation.

Human exposure to glyphosate-based herbicides (GBH) is increasing rapidly worldwide. Most existing studies on health effects of glyphosate have focused on occupational settings and cancer outcomes and few have examined this common exposure in relation to the health of pregnant women and newborns in the general population. We investigated associations between prenatal glyphosate exposure and length of gestation in The Infant Development and the Environment Study (TIDES), a multi-center US pregnancy cohort. Glyphosate and its primary degradation product [aminomethylphosphonic acid (AMPA)] were measured in urine samples collected during the second trimester from 163 pregnant women: 69 preterm births (<37 weeks) and 94 term births, the latter randomly selected as a subset of TIDES term births. We examined the relationship between exposure and length of gestation using multivariable logistic regression models (dichotomous outcome; term versus preterm) and with weighted time-to-event Cox proportional hazards models (gestational age in days). We conducted these analyses in the overall sample and secondarily, restricted to women with spontaneous deliveries (n = 90). Glyphosate and AMPA were detected in most urine samples (>94 %). A shortened gestational length was associated with maternal glyphosate (hazard ratio (HR): 1.31, 95 % confidence interval (CI) 1.00-1.71) and AMPA (HR: 1.32, 95%CI: 1.00-1.73) only among spontaneous deliveries using adjusted Cox proportional hazards models. In binary analysis, glyphosate and AMPA were not associated with preterm birth risk (<37 weeks). Our results indicate widespread exposure to glyphosate in the general population which may impact reproductive health by shortening length of gestation. Given the increasing exposure to GBHs and the public health burden of preterm delivery, larger confirmatory studies are needed, especially in vulnerable populations such as pregnant women and newborns.

Association of prenatal exposure to ambient air pollution with adverse birth outcomes and effect modification by socioeconomic factors.

BACKGROUND: Maternal exposure to air pollution has been associated with birth outcomes; however, few studies examined biologically critical exposure windows shorter than trimesters or potential effect modifiers. OBJECTIVES: To examine associations of prenatal fine particulate matter (PM2.5), by trimester and in biologically critical windows, with birth outcomes and assess potential effect modifiers. METHODS: This study used two pregnancy cohorts (CANDLE and TIDES; N = 2099) in the ECHO PATHWAYS Consortium. PM2.5 was estimated at the maternal residence using a fine-scale spatiotemporal model, averaged over pregnancy, trimesters, and critical windows (0-2 weeks, 10-12 weeks, and last month of pregnancy). Outcomes were preterm birth (PTB, <37 completed weeks of gestation), small-for-gestational-age (SGA), and continuous birthweight. We fit multivariable adjusted linear regression models for birthweight and Poisson regression models (relative risk, RR) for PTB and SGA. Effect modification by socioeconomic factors (maternal education, household income, neighborhood deprivation) and infant sex were examined using interaction terms. RESULTS: Overall, 9% of births were PTB, 10.4% were SGA, and mean term birthweight was 3268 g (SD = 558.6). There was no association of PM2.5 concentration with PTB or SGA. Lower birthweight was associated with higher PM2.5 averaged over pregnancy (ß -114.2, 95%CI -183.2, -45.3), during second (ß -52.9, 95%CI -94.7, -11.2) and third (ß -45.5, 95%CI -85.9, -5.0) trimesters, and the month prior to delivery (ß -30.5, 95%CI -57.6, -3.3). Associations of PM2.5 with likelihood of SGA and lower birthweight were stronger among male infants (p-interaction ≤0.05) and in those with lower household income (p-interaction = 0.09). CONCLUSIONS: Findings from this multi city U.S. birth cohort study support previous reports of inverse associations of birthweight with higher PM2.5 exposure during pregnancy. Findings also suggest possible modification of this association by infant sex and household income.

Women's knowledge and hypothetical acceptance of expedited partner therapy for chlamydia.

Background Expedited partner therapy (EPT) for chlamydia can be an important public health tool to treat the sex partners of newly diagnosed individuals, especially when those sex partners are women of reproductive ages. Untreated and repeat chlamydia infections increase a woman's risk for subfertility. This study aimed to determine the knowledge of EPT, and the factors associated with EPT knowledge, among reproductive-aged women. Methods Women aged 18-40 years were recruited for a community sample from a large state fair; 871 women completed a questionnaire for this study. Women reported on their knowledge of sexually transmitted infections, and about their knowledge and attitudes toward EPT. Using a hypothetical example, women were asked if they would accept EPT. Results This community sample of reproductive-aged women found overwhelming hypothetical support for chlamydia testing, partner notification, and partner treatment. However, only 12% of women reported having heard of EPT prior to the survey; once EPT was described, there were high levels of support for EPT and the belief that EPT could reduce chlamydia rates. Half of the women strongly agreed that EPT could reduce chlamydia rates, and 48% supported the state law allowing for EPT. Working in the healthcare field was the only independent determinant of prior EPT knowledge, increasing the odds of hearing about EPT by more than 2.5-fold. Conclusions Despite overwhelming support of the tenets of EPT, our results indicate that prior knowledge of EPT is low among women, meaning that education about EPT is needed for those outside of the healthcare field.

Associations between prenatal phthalate exposure and sex-typed play behavior in preschool age boys and girls.

Phthalates, a class of chemicals found widely in consumer products including plastic toys, food contaminants and food packaging, personal care products, cosmetics, air fresheners, and some medications, have been shown to be anti-androgenic in numerous laboratory and epidemiological studies. In a prior cohort enrolled in 2000-2002, we observed associations between prenatal urinary concentrations of di-ethyl hexyl phthalate (DEHP) and dibutyl phthalate (DBP) metabolites and less male-typed play behavior in preschool age boys. The aim of this study was to examine phthalate exposure in pregnancy in relation to play behavior at age 4 years in a larger cohort of pregnant women enrolled in The Infant Development and the Environment Study (TIDES) between 2010 and 2012 at four study sites (Minneapolis, MN; Rochester, NY; San Francisco, CA; Seattle, WA). Maternal urinary metabolites of DEHP, DiBP, DnBP, BBzP, and DEP were measured during the first (n=498) and third trimester (n=468) and mothers completed the Preschool Activities Inventory (PSAI), a validated maternal questionnaire designed to assess child toy preference and sex-typed play behavior when children were 4-5 years of age. After adjusting for child age, maternal education, race, urine dilution, parental attitudes about opposite sex-typed play behavior, and presence of a same sex older sibling, we observed associations between first trimester (mean 10.7±2.1 weeks gestation) (log10) SpG-adjusted MnBP, MiBP, and MBzP and lower masculine scores in boys (ß-coefficient [95% confidence intervals]: MnBP -2.18, [-4.16, -0.20]), MiBP -2.1[-4.3,0.1], and MBzP -2.42 [-4.12, -0.71]). In girls, first trimester maternal urinary MBzP was associated with lower masculine scores (-2.12 [-3.98,-0.25]), while third trimester (mean 32.8±3.0 weeks gestation) maternal urinary MiBP was associated with higher masculine scores (2.69 [0.68,4.70]). Third trimester maternal urinary phthalate levels were not associated with play behavior in boys. These findings in boys are largely consistent with previous studies that report that prenatal phthalate exposure is associated with less masculine play behavior. No associations in girls have been previously reported.

Pregnancy intention and phthalate metabolites among pregnant women in The Infant Development and Environment Study cohort.

BACKGROUND: Preconception life style and health play a pivotal role in positively impacting the health of a pregnancy, and this includes the reduction of exposure to endocrine-disrupting chemicals such as phthalates. We have previously demonstrated that women planning a pregnancy with assisted reproductive technology (ART) have lower phthalate metabolite concentrations than their non-ART-using counterparts. OBJECTIVE: To determine whether women who intended to become pregnant had lower phthalate metabolite concentrations than those who had an unintended pregnancy, or whether change in phthalate exposure across pregnancy differed between these two groups. METHODS: A total of 721 women enrolled in The Infant Development and Environment Study (TIDES), a multicentre US prospective pregnancy cohort; 513 (71%) indicated their pregnancy was planned. Urine samples from first- and third-trimester visits were analysed for 10 specific-gravity-adjusted, natural-log-transformed phthalate metabolites. Simple and multivariable linear regression, adjusting for centre, race, age, income, marital status, and parity, were employed to determine whether phthalate metabolite concentrations differed by pregnancy intention. RESULTS: In bivariate analyses, the geometric mean concentrations of all first-trimester and most third-trimester phthalates were higher in women with unplanned pregnancies. However, after covariate adjustment, only first-trimester monoisobutyl phthalate (MiBP) remained associated with pregnancy intention, and the association changed direction such that unplanned pregnancies had lower MiBP concentrations (ß -0.18, 95% CI -0.35, -0.02). CONCLUSIONS: We did not find evidence of a difference in phthalate exposure between pregnancy planners and non-planners.

Phthalates and Phthalate Alternatives Have Diverse Associations with Oxidative Stress and Inflammation in Pregnant Women.

Exposure to environmental chemicals such as phthalates has been linked to numerous adverse pregnancy outcomes, potentially through an oxidative stress mediated mechanism. Most research examined urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) as the oxidative stress biomarker. However, 8-iso-PGF2α also originates from enzymatic sources linked to inflammation. Therefore, associations between phthalates and 8-iso-PGF2α could have been misinterpreted. To clarify this, the 8-iso-PGF2α/prostaglandin F2α ratio approach was used to quantitatively distinguish between inflammation or oxidative stress derived 8-iso-PGF2α and estimate their associations with phthalate metabolites in a cohort of 758 pregnant women from The Infant Development and Environment Study (TIDES). Most urinary phthalate metabolites were associated with a significant increase in 8-iso-PGF2α. For example, a 22.4% higher 8-iso-PGF2α concentration (95% confidence interval = 14.4, 30.9) was observed with an interquartile range increase in mono- n-butyl phthalate. For most metabolites, associations were observed solely with oxidative stress derived 8-iso-PGF2α. In contrast, monocarboxy-isononyl phthalate and monoisononyl phthalate (MNP) were associated with both sources of 8-iso-PGF2α. Metabolites of the phthalate alternative 1,2-cyclohexane dicarboxylic acid, diisononyl ester (DINCH), were only associated with inflammation-derived 8-iso-PGF2α, which is interesting because DINCH metabolites and MNP have structural similarities.In conclusion, phthalates metabolites are not exclusively associated with oxidative stress derived 8-iso-PGF2α. Depending on the metabolite structure, some are also associated with inflammation derived sources, which provides interesting insights in the toxicology of phthalates.

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

Association between prenatal psychological stress and oxidative stress during pregnancy.

BACKGROUND: Prenatal psychological stress during pregnancy has been associated with adverse reproductive outcomes. A growing animal literature supports an association between psychological stress and oxidative stress. We assessed this relationship in pregnant women, hypothesising that psychological stress is associated with higher concentrations of oxidative stress biomarkers during pregnancy. METHODS: Psychosocial status and stressful life events (SLE) were self-reported. 8-iso-prostaglandin F2α (8-iso-PGF2α ) was measured as a biomarker of oxidative stress in urine samples at median 32 weeks' gestation. We examined SLEs individually (ever vs never) and in summary (any vs none) and psychosocial status as measured by individual subscales and in summary (poor vs good). Linear models estimated associations between these parameters and urinary 8-iso-PGF2α concentrations after adjusting for covariates. RESULTS: The geometric mean of 8-iso-PGF2α was significantly higher among pregnant women who were non-White, smokers, had less than a college education, higher pre-pregnancy BMI and were unmarried. Having ever had a death in the family (n = 39) during pregnancy was associated with a 22.9% increase in 8-iso-PGF2α in unadjusted models (95% confidence interval [CI] 1.50, 48.8). Poor psychosocial status was associated with a 13.1% (95% CI 2.43, 25.0) greater mean 8-iso-PGF2α in unadjusted analyses. Associations were attenuated, but remained suggestive, after covariate adjustment. CONCLUSIONS: These data suggest that 8-iso-PGF2α is elevated in pregnant women with who are at a sociodemographic disadvantage and who have higher psychological stress in pregnancy. Previous studies have observed that 8-iso-PGF2α levels are associated with adverse birth outcomes, oxidative stress could be a mediator in these relationships.

Prenatal Stress as a Modifier of Associations between Phthalate Exposure and Reproductive Development: results from a Multicentre Pregnancy Cohort Study.

BACKGROUND: Prenatal phthalate exposure is associated with altered male reproductive tract development, and in particular, shorter anogenital distance (AGD). AGD, a sexually dimorphic index of prenatal androgen exposure, may also be altered by prenatal stress. How these exposures interact to impact AGD is unknown. Here, we examine the extent to which associations between prenatal phthalate exposure and infant AGD are modified by prenatal exposure to stressful life events (SLEs). METHODS: Phthalate metabolites [including those of diethylhexyl phthalate (DEHP) and their molar sum (ΣDEHP)] were measured in first trimester urine from 738 pregnant women participating in The Infant Development and the Environment Study (TIDES). Women completed questionnaires on SLEs, and permitted infant AGD measurements at birth. Subjects were classified as 'lower' and 'higher' stress (0 first trimester SLEs vs. 1+).We estimated relationships between phthalate concentrations and AGD (by infant sex and stress group) using adjusted multiple regression interaction models. RESULTS: In the lower stress group, first trimester ΣDEHP was inversely associated with two measures of male AGD: anoscrotal distance (AGD-AS; ß = -1.78; 95% CI -2.97, -0.59) and anopenile distance (AGD-AP; ß = -1.61; 95% CI -3.01, -0.22). By contrast, associations in the higher stress group were mostly positive and non-significant in male infants. No associations were observed in girls. CONCLUSIONS: Associations between prenatal phthalate exposure and altered genital development were only apparent in sons of mothers who reported no SLEs during pregnancy. Prenatal stress and phthalates may interact to shape fetal development in ways that have not been previously explored.