Prenatal exposure to replacement flame retardants and organophosphate esters and childhood adverse respiratory outcomes.

BACKGROUND: The association of prenatal exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with respiratory outcomes has not been previously investigated in humans, despite reports that these chemicals can cross the placenta and alter lung development as well as immune functions. METHODS: In a cohort of 342 pregnant women recruited between 2003 and 2006 in the greater Cincinnati, Ohio Metropolitan area, we measured indoor dust OPEs and RBFRs at 20 weeks of gestation and urinary OPEs at 16 and 26 weeks of gestation and at delivery. We performed generalized estimating equations and linear mixed models adjusting for covariates to determine the associations of prenatal OPEs and RBFRs exposures with adverse respiratory outcomes in childhood, reported every six months until age 5 years and with lung function at age 5 years. We used multiple informant modeling to examine time-specific associations between maternal urinary OPEs and the outcomes. RESULTS: Dust concentrations of triphenyl phosphate (TPHP) (RR: 1.40, 95% CI: 1.18-1.66), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (RR: 1.51, 95% CI: 1.23-1.85), and bis(2-ethylhexyl) tetrabromophthalate (RR: 1.57, 95% CI: 1.28-1.94) were associated with higher risk of wheezing during childhood. Dust TPHP concentrations were associated with higher risk of respiratory infections (RR: 1.43, 95% CI: 1.08-1.94), and dust tris-(2-chloroethyl) phosphate concentrations were associated with hay fever/allergies (RR: 1.11, 95% CI: 1.01-1.21). We also found that dust tris-(2-chloroethyl) phosphate loadings were associated with lower lung function. Urinary OPEs mainly at week 16 of gestation tended to be associated with adverse respiratory outcome, while bis(1-chloro-2-propyl) phosphate and diphenyl phosphate at delivery were associated with lower risk of hay fever/allergies. CONCLUSIONS: In-utero exposure to OPEs and RBFRs may be a risk factor for adverse respiratory outcomes in childhood, depending on the timing of exposure.

Maternal and newborn metabolomic changes associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations at delivery: an untargeted approach.

INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.

Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study.

BACKGROUND: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. OBJECTIVE: We aimed to examine the exposure pattern of urinary OPE metabolites in children. METHODS: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. RESULTS: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. SIGNIFICANCE: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. IMPACT STATEMENT: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood.

Exposure to dust organophosphate and replacement brominated flame retardants during infancy and risk of subsequent adverse respiratory outcomes.

BACKGROUND: Children are highly exposed to flame retardants in indoor environments, partly through inhalation. However, the associations of early life exposure to novel organophosphate (OPFRs) and replacement brominated flame retardants (RBFRs) with adverse respiratory outcomes during childhood are unclear. METHODS: We used a prospective birth cohort of 234 children recruited from the greater Cincinnati, Ohio metropolitan area between 2003 and 2006. OPFRs and RBFRs were analyzed in dust sampled from the homes' main activity room and the children's bedroom floor at child age 1 year. Caregivers reported subsequent respiratory symptoms every six months until child age 5 years and we measured forced expiratory volume in 1 s as well as peak expiratory flow (PEF) at child age 5 years. We performed generalized estimating equations and linear regression modeling adjusted for covariates to examine the exposure-outcome associations. RESULTS: Geometric means (GMs) (standard error [SE]) for dust concentrations were 10.27 (0.63) µg/g for total OPFRs (ΣOPFRs) and 0.48 (0.04) µg/g for total RBFRs (ΣRBFRs); GMs (SE) for dust loadings were 2.82 (0.26) µg/m2 for ΣOPFRs and 0.13 (0.01) µg/m2 for ΣRBFRs. Dust ∑OPFRs concentrations at age 1 year were associated with higher subsequent risks of wheezing (relative risk [RR]: 1.68, 95% confidence interval [CI]: 1.20-2.34), respiratory infections (RR: 4.01, 95% CI: 1.95-8.24), and hay fever/allergies (RR: 1.33, 95% CI: 1.10-1.60), whereas ∑OPFRs dust loadings at age 1 year were associated with higher risks of subsequent respiratory infections (RR: 1.87, 95% CI: 1.05-3.34) and hay fever/allergies (RR: 1.34, 95% CI: 1.19-1.51). PEF (mL/min) was lower with higher ∑OPFRs dust loadings (ß: -12.10, 95% CI: -21.10, -3.10) and with the RBFR bis(2-ethylhexyl) tetrabromophthalate (ß: -9.05, 95% CI: -17.67, -0.43). CONCLUSIONS: Exposure to OPFRs and RBFRs during infancy may be a risk factor for adverse respiratory outcomes during childhood.

STEP IN: Supporting Together Exercise and Play and Improving Nutrition; a Feasibility Study of Parent-Led Group Sessions and Fitness Trackers to Improve Family Healthy Lifestyle Behaviors in a Low-Income, Predominantly Black Population.

BACKGROUND: Pediatric obesity is prevalent and challenging to treat. Although family-centered behavioral management is the gold standard, many families face structural inequities to its access and efficacy. Identifying ways to manage pediatric obesity within primary care is needed. METHODS: This feasibility study included three sequential trials of peer-led group sessions occurring biweekly or monthly between 3/2016 and 2/2017. Parent-child dyads were recruited from a large academic primary care clinic via mailed invitations, prioritizing patients living in local zip codes of historical disinvestment. Eligible patients were 6 to 12 years with a body mass index ≥85th percentile, with parent and child interest in making healthy lifestyle changes, and English speaking. RESULTS: 27 dyads participated, 77% were non-Hispanic Black. Retention and attendance rates were highest in the initial four-session biweekly pilot (100%, 0 dropouts), high in the full six-session biweekly cohort (83%, 1 dropout), and moderate in the monthly cohort (62.7%, 4 dropouts). Families reported high satisfaction with the sessions (4.75/5). Qualitative comments suggested social connections had motivated behavior change in some families. CONCLUSION: Parent-led group sessions for pediatric weight management show promise in engaging families. A future large trial is needed to assess behavior change and anthropometric outcomes.

Early-life exposure to a mixture of organophosphate esters and child behavior.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003-2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = -5.74; 95% CI = -11.24, -0.24) and fewer overall behavioral problems at age 3 years (ß = -5.26; 95% CI = -10.33, -0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = -2.62; 95% CI = -5.13, -0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point.

Associations of gestational exposure to organophosphate esters with gestational age and neonatal anthropometric measures: The HOME study.

Organophosphate esters (OPEs) are developmental toxicants in experimental studies of animals, but limited evidence is available in humans. We included 340 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio, USA) for the analysis. We evaluated gestational exposure to OPEs with gestation age at birth and newborn anthropometric measures. We quantified four OPE urinary metabolites at 16 weeks and 26 weeks of gestation. We extracted gestational age at birth, newborn weight, length, and head circumference from the chart review. We calculated z-scores for these anthropometric measures and the ponderal index. We used multiple informant models to examine the associations between repeated OPE measurements and the outcomes. We used modified Poisson regression to estimate the association of gestational exposure to OPEs with preterm birth. We also explored effect modification by infant sex and the potential mediation effect by the highest maternal blood pressure and glucose levels. We found that bis(2-chloroethyl) phosphate (BCEP) at 16 weeks and diphenyl phosphate at 26 weeks of pregnancy were positively associated with gestational age and inversely associated with preterm birth. In female newborns, BCEP at 16 weeks was inversely related to birth weight and length z-scores. In male newborns, we observed negative associations of 26-week di-n-butyl phosphate with the ponderal index at birth. No mediation by the highest maternal blood pressure or glucose levels during pregnancy was identified. In this cohort, gestational exposure to some OPEs was associated with gestational age, preterm birth, and neonatal anthropometric measures. Certain associations tended to be window- and infant sex-specific.

Gestational exposure to organophosphate esters and infant anthropometric measures in the first 4 weeks after birth.

BACKGROUND: Few studies have examined whether gestational exposure to organophosphate esters (OPEs), widely used chemicals with potential endocrine-disrupting potency and developmental toxicity, is associated with impaired infant growth. METHODS: We analyzed data from 329 mother-infant pairs in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006, Cincinnati, Ohio, USA). We quantified concentrations of four OPE metabolites in maternal urine collected at 16 and 26 weeks of gestation, and at delivery. We calculated z-scores using 2006 World Health Organization (WHO) child growth standards for the 4-week anthropometric measures (weight, length, and head circumference), the ponderal index, and weekly growth rates. We used multiple informant models to examine window-specific associations between individual OPE metabolites and anthropometric outcomes. We further modeled OPEs as a mixture for window-specific associations with 4-week anthropometric outcomes using mean field variational Bayesian inference procedure for lagged kernel machine regression (MFVB-LKMR). We stratified the models by infant sex. RESULTS: Diphenyl phosphate (DPHP) in mothers at 16 weeks, and bis(2-chloroethyl) phosphate (BCEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) at delivery were positively associated with z-scores of weight, length, and head circumference in all infants at 4 weeks of age. After stratifying by infant sex, positive associations were only observed in males for DPHP at 16 weeks and BCEP at delivery and in females for BDCIPP at delivery. Negative associations not present in all infants were observed in males for di-n-butyl phosphate (DNBP) at 26 weeks of gestation with weight z-score and DPHP at delivery with head circumference z-score. Results were generally similar using MFVB-LKMR models with more conservative 95 % credible intervals. We did not identify consistent associations of gestational OPE metabolite concentrations with the ponderal index and weekly growth rates. CONCLUSION: In this cohort, exposure to OPEs during gestation was associated with altered infant anthropometry at 4 weeks after birth.

Childhood urinary organophosphate esters and cognitive abilities in a longitudinal cohort study.

The use of organophosphate esters (OPEs) as flame retardants, which has increased over the past two decades, raises concerns that OPEs may be harmful to humans, especially children. Animal studies and some human studies have reported that OPEs may adversely impact brain development, but few human studies evaluated OPE exposure during early childhood and neurodevelopmental outcomes. We aimed to fill this knowledge gap with the present study on urinary OPE metabolite concentrations at ages 1-5 years and cognitive abilities at 8 years. We used data of 223 children from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio. The point estimates for bis-2-chloroethyl-phosphate (BCEP) and bis(1,3-dichloro-2-propyl)-phosphate (BDCIPP) in association with IQ tended to be small and positive, while the point estimates for diphenyl-phosphate (DPHP) were small and negative, with 95% CIs including the null. However, we did find that socioeconomic status (SES) variables modified associations between OPEs and child IQ, with adverse OPE-IQ associations being stronger in socioeconomically disadvantaged children than in others. We identified an additional 1- to 2-point decrease in Full Scale IQ for every log-unit increase in BDCIPP, BCEP, and DPHP among those with lower maternal education, non-white race, lower income, or living in more deprived neighborhoods. We observed similar results for the Perceptual Reasoning, Verbal Comprehension, and Working Memory Index Scores. We suspect that there is residual confounding related to socioeconomic disadvantage, which was not captured with the available SES variables typically used in epidemiologic studies.

Maternal urinary organophosphate ester metabolite concentrations and glucose tolerance during pregnancy: The HOME Study.

BACKGROUND: Endocrine-disrupting chemicals may alter glucose homeostasis, especially during pregnancy. Biomonitoring studies suggest ubiquitous human exposure to organophosphate esters (OPEs), chemicals with endocrine-disrupting capabilities. Few studies have examined the association between maternal exposure to OPEs and blood glucose during pregnancy. METHODS: With data from 301 pregnant women in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA, we examined whether OPE concentrations were associated with changes in blood glucose. We quantified four OPE metabolites in maternal spot urine samples collected at 16- and 26-weeks pregnancy. We extracted results from the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) via medical chart review. Women with GCT ≥ 140 mg/dL or any abnormal values in OGTT (≥ 95 mg/dL fasting glucose, ≥ 180 mg/dL 1-h glucose, ≥ 155 mg/dL 2-h glucose, ≥ 140 mg/dL 3-h glucose) were defined as having elevated glucose levels. We used linear regression and Bayesian Kernel Machine Regression (BKMR) to estimate the associations of individual OPE metabolites and OPE mixtures with blood glucose levels during pregnancy. We used modified Poisson regression to estimate the associations of OPE metabolite concentrations with elevated glucose levels. We further examined effect measure modification by maternal characteristics (age, pre-pregnancy body mass index [BMI], and race/ethnicity). RESULTS: Diphenyl phosphate (DPHP) had the highest geometric mean concentration of the urinary OPE metabolites (1.83 µg/L at 16 weeks, 1.24 µg/L at 26 weeks). Thirty women (10.0%) had elevated glucose levels. Individual OPE metabolites or their mixtures were not significantly associated with continuous GCT results. We did not observe effect measure modification by maternal age, pre-pregnancy BMI categories, or race/ethnicity. Compared with women in the 1st tertile of average DPHP of 16- and 26 weeks of pregnancy, women in the 3rd tertile tended to have a reduced risk of elevated glucose levels (RR = 0.41, 95% CI = 0.16-1.06, p for trend = 0.06). CONCLUSION: In this cohort, maternal urinary OPE metabolite concentrations were weakly associated with blood glucose levels during pregnancy.

Maternal urinary OPE metabolite concentrations and blood pressure during pregnancy: The HOME study.

BACKGROUND: Few studies have examined the association between maternal exposure to organophosphate esters (OPEs) and systolic/diastolic blood pressure (SBP/DBP) during pregnancy. METHODS: We analyzed data from 346 women with a singleton live birth in the HOME Study, a prospective birth cohort in Cincinnati, Ohio, USA. We quantified four OPE metabolites in maternal spot urine samples collected at 16 and 26 weeks pregnancy, standardized by specific gravity. We calculated intraclass correlation coefficients (ICCs). We extracted the first two recorded BP measurements (<20 weeks), the two highest recorded BP measurements (≥20 weeks), and diagnoses of hypertensive disorders of pregnancy (HDP) via chart review. Women with two BP measurements ≥140/90 mmHg or HDP noted in the chart at ≥20 weeks pregnancy were defined as HDP cases. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations as continuous variables or in tertiles with maternal BP and HDP. RESULTS: ICCs of OPEs were 0.17-0.45. Diphenyl phosphate (DPHP) had the highest geometric mean concentration among OPE metabolites. Increasing the average bis(2-chloroethyl) phosphate (BCEP) concentrations were positively associated with two highest recorded DBP ≥20 weeks pregnancy. Compared with women in the 1st DPHP tertile, women in the 3rd tertile at 16 weeks pregnancy had 1.72 mmHg (95% CI: -0.01, 3.46) higher DBP <20 weeks pregnancy, and women in the 3rd tertile of the average DPHP concentrations had 2.25 mmHg (95% CI: 0.25, 4.25) higher DBP ≥20 weeks pregnancy. 33 women (9.5%) were identified with HDP. Di-n-butyl phosphate (DNBP) concentrations at 16 weeks were positively associated with HDP, with borderline significance (RR = 2.98, 95% CI 0.97-9.15). Other OPE metabolites were not significantly associated with HDP. CONCLUSION: Maternal urinary BCEP and DPHP concentrations were associated with increased BP during pregnancy. Maternal urinary DNBP concentrations were associated with HDP, with borderline significance.

Prenatal exposure to a mixture of organophosphate esters and intelligence among 8-year-old children of the HOME Study.

Many environmental chemicals are being identified as suspected neurotoxicants based on the findings of both experimental and epidemiological studies. Organophosphate esters (OPEs), which are among the chemicals that have replaced neurotoxic polybrominated diphenyl ethers (PBDEs) after 2004, have also become an important public health topic as evidence regarding their potential for early-life neurotoxicity is growing. In 233 mother child pairs from Cincinnati, OH, we measured concentrations of the OPE metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), bis-2-chloroethyl phosphate (BCEP), diphenyl phosphate (DPHP), and di-n-butyl phosphate (DNBP) in the urine of pregnant women at 16 and 26 weeks gestation and at delivery. At age 8 years, we assessed children's cognition using the Wechsler Intelligence Scale for Children-IV. In models adjusted for maternal race, income, body mass index, and IQ, maternal urinary BCEP was associated with a modest increase in child full-scale IQ (ß: 0.81 per a ln-unit BCEP increase; 95 % CI: 0.00, 1.61) while other OPEs were not associated with changes in full-scale IQ or any IQ subscales. Maternal serum PBDE concentrations did not confound the relationships between urinary OPE metabolites and child IQ. Using Bayesian kernel machine regression, we did not find that concentrations of a mixture of OPE metabolites during gestation was associated with any child cognition measures. The results of this study are not consistent with other published work, and a larger sample size would be beneficial to explore potential associations more fully. Therefore, additional studies are necessary to continue studying prenatal OPE exposure and child neurodevelopment and behavior.

Maternal Urinary Organophosphate Esters and Alterations in Maternal and Neonatal Thyroid Hormones.

Production of organophosphate esters (OPEs), which represent a major flame-retardant class present in consumer goods, has increased over the past 2 decades. Experimental studies suggest that OPEs may be associated with thyroid hormone disruption, but few human studies have examined this association. We quantified OPE metabolites in the urine of 298 pregnant women from Cincinnati, Ohio, in the Health Outcomes and Measures of the Environment Study (enrolled 2003-2006) at 3 time points (16 and 26 weeks' gestation, and at delivery), and thyroid hormones in 16-week maternal and newborn cord sera. Urinary bis(1,3-dichloro-2-propyl)-phosphate concentrations were generally associated with decreased triiodothyronine and thyroxine levels and increased thyroid-stimulating hormone levels in maternal and newborn thyroid hormones in quartile dose-response analyses and multiple informant models. There was weaker evidence for thyroid hormone alterations in association with diphenyl-phosphate and di-n-butyl-phosphate. Bis-2-chloroethyl-phosphate was not associated with alterations in thyroid hormones in any analyses. We did not observe any evidence of effect modification by infant sex. These results suggest that gestational exposure to some OPEs may influence maternal and neonatal thyroid function, although replication in other cohorts is needed.

Subclinical and Overt Newborn Opioid Exposure: Prevalence and First-Year Healthcare Utilization.

OBJECTIVES: To categorize newborn infants in Hamilton County, Ohio by late pregnancy fetal opioid exposure status and to assess their first-year healthcare utilization. STUDY DESIGN: We used a population-based cohort of 41 136 live births from 2014-2017 and analyzed healthcare encounters in the first year of life from electronic health records. We prospectively assessed for the presence of opioids in maternal urine collected at delivery and for a diagnosis of newborn neonatal abstinence syndrome (NAS). At birth, infants were classified as unexposed to opioids, exposed to opioids and diagnosed with NAS, or subclinically exposed to opioids (exposure that did not result in NAS). RESULTS: The prevalence of newborn opioid exposure was 37 per 1000 births. The duration of the hospital birth encounter was significantly longer for infants with subclinical exposure compared with unexposed infants (10% increase; 95% CI, 7%-13%). However, duration for infants with subclinical exposure was shorter compared to those with NAS. Neither subclinical exposure nor NAS was associated with total emergency department visits. Subclinical exposure was associated with increased odds of having at least 1 hospitalization in the first year. However, the total length of stay for hospitalizations was 82% that of the unexposed group (95% CI, 75%-89%). Infants with NAS had a 213% longer total length of stay compared with the unexposed group (95% CI, 191%-237%). CONCLUSIONS: Subclinical and overt opioid exposure among newborn infants was associated with increased first-year healthcare utilization. From 2014 to 2017, this cost the Hamilton County healthcare system an estimated $1 109 452 for longer birth encounters alone.

Organophosphate esters in a cohort of pregnant women: Variability and predictors of exposure.

Organophosphate esters (OPEs) are a group of chemicals used as flame retardants and plasticizers that replaced polybrominated diphenyl ethers in consumer products such as furniture and electronics. To characterize exposure to OPEs during fetal development, we measured urinary OPE metabolite concentrations in women twice during pregnancy (16 and 26 weeks' gestation) and at delivery (n = 357). We also previously quantified house dust OPE parent compound concentrations at 20 weeks' gestation (n = 317). Diphenyl phosphate (DPHP) had the highest geometric mean urinary concentrations (1.5-2.3 µg/g creatinine), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.75-0.99 µg/g creatinine), and bis(2-chloroethyl) phosphate (BCEP; 0.72-0.97 µg/g creatinine), while dibutyl phosphate (DNBP) had the lowest concentrations (0.25-0.28 µg/g creatinine). Urinary OPE metabolites were moderately correlated with each other at 26 weeks (rs: 0.23-0.38, p < 0.001) while the correlations at 16 weeks and delivery were slightly weaker. Intra-class correlations for urinary metabolites measured at three time points were poor (0.16-0.34), indicating high variability within individuals. Dust concentrations of OPE parent compounds were associated with BCEP, BDCIPP, and DPHP concentrations in urine at some but not all time points. In linear mixed models of urinary OPE metabolite concentrations, household size was inversely associated with BCEP concentrations, and being non-white was associated with lower BDCIPP and DPHP concentrations. Urine samples collected in the summer had the highest OPE metabolite concentrations. This study highlights the need to collect multiple urine samples during pregnancy to define exposure patterns and investigate potential periods of susceptibility.

Reduced gray matter volume and cortical thickness associated with traffic-related air pollution in a longitudinally studied pediatric cohort.

Early life exposure to air pollution poses a significant risk to brain development from direct exposure to toxicants or via indirect mechanisms involving the circulatory, pulmonary or gastrointestinal systems. In children, exposure to traffic related air pollution has been associated with adverse effects on cognitive, behavioral and psychomotor development. We aimed to determine whether childhood exposure to traffic related air pollution is associated with regional differences in brain volume and cortical thickness among children enrolled in a longitudinal cohort study of traffic related air pollution and child health. We used magnetic resonance imaging to obtain anatomical brain images from a nested subset of 12 year old participants characterized with either high or low levels of traffic related air pollution exposure during their first year of life. We employed voxel-based morphometry to examine group differences in regional brain volume, and with separate analyses, changes in cortical thickness. Smaller regional gray matter volumes were determined in the left pre- and post-central gyri, the cerebellum, and inferior parietal lobe of participants in the high traffic related air pollution exposure group relative to participants with low exposure. Reduced cortical thickness was observed in participants with high exposure relative to those with low exposure, primarily in sensorimotor regions of the brain including the pre- and post-central gyri and the paracentral lobule, but also within the frontal and limbic regions. These results suggest that significant childhood exposure to traffic related air pollution is associated with structural alterations in brain.

Concentrations and loadings of organophosphate and replacement brominated flame retardants in house dust from the home study during the PBDE phase-out.

Polybrominated diphenyl ethers, a class of flame retardants and endocrine disruptors, have been substituted in new products by organophosphate (OPFR) and replacement brominated flame retardants (RBFR). OPFRs and RBFRs readily migrate from consumer products into dust where humans are exposed via incidental ingestion and inhalation. We quantified concentrations and loadings of OPFRs and RBFRs in house dust samples (n = 317) collected from the homes of Cincinnati women between 2003 and 2006 and examined their associations with demographic and house characteristics. Tris-(1-chloro-2-propyl)-phosphate (TCIPP, geometric mean [GM]: 2140 ng g-1, range: 70.1-166,000 ng g-1), tris-(1,3-dichloro-2-propyl)-phosphate (TDCIPP, GM: 1840 ng g-1, range: 55.2-228,000 ng g-1), triphenyl phosphate (TPHP, GM: 1070 ng g-1, range: 34.1-62,100 ng g-1), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, GM: 59.5 ng g-1, range: 2.82-7800 ng g-1), and bis-(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP, GM: 121 ng g-1, range 2.17-13,600 ng g-1) were all detected in >90% of dust samples; tris-(2-chloroethyl)-phosphate (TCEP, GM: 669 ng g-1, range: 56.8-160,000 ng g-1) was detected in 80.1% of samples. Concentrations of EH-TBB and BEH-TEBP increased in house dust from 2003 to 2006. The number of people living in the home, race, education, floor type, and year of sample collection were associated with some OPFR and RBFR concentrations and loadings. This study suggests that OPFRs and RBFRs were ubiquitous in house dust during the PBDE phase-out and justifies more research on the consequences of exposure to these environmental chemicals.

Trimester specific PM2.5 exposure and fetal growth in Ohio, 2007-2010.

BACKGROUND: Exposure to particulate matter, particularly with aerodynamic diameter < 2.5 µm (PM2.5), may increase inflammation and oxidative stress in pregnant women and affect fetal growth. We examined trimester specific PM2.5 exposure levels and small for gestational age (SGA) using the statewide birth registry of Ohio from 2007 to 2010. METHODS: Exposure to PM2.5 in each trimester and for each gestational week was determined using data from 57 Environmental Protection Agency network monitoring stations across the state of Ohio. We restricted the data to 224,921 singleton live births, with a gestational age of 20-42 weeks, no genetic disorders or congenital abnormalities, and who had home addresses within a 10 km radius of any PM2.5 monitoring station. We estimated odds ratios of SGA using Generalized Linear Models (GLMs) and Distributed Lag Models (DLMs), and adjustment for maternal age, race, education, parity, body mass index, insurance type, tobacco use, prenatal care initiation, birth year, season of birth, and sex of the baby. RESULTS: Mean PM2.5 levels during the entire pregnancy were 13.03 µg/m3 with a standard deviation of 1.57 µg/m3. Covariates adjusted odds ratios and 95% confidence intervals of a 10 µg/m3 increase in PM2.5 levels with a 10 km buffer radius for SGA and trimesters modeled separately were 0.94 (0.88, 1.00) for the first trimester, 0.93 (0.86, 1.00) for the second trimester, 1.07 (1.00, 1.15) for the third trimester, and 0.92 (0.81, 1.06) for the entire pregnancy. When a 5 km buffer radius was used, adjusted odds ratios and 95% confidence intervals for SGA were 0.97 (0.89, 1.05) for the first trimester, 0.96 (0.88, 1.05) for the second trimester, 1.09 (1.02, 1.17) for the third trimester, and 0.99 (0.85, 1.14) for the overall pregnancy, indicating sensitivity to buffer choice. DLMs showed gestational weeks 30-35 to be a particular window of vulnerability. CONCLUSION: Increasing exposure to PM2.5 during the third trimester of pregnancy was associated with a small increase in risk of SGA in this population-based study. Selection of a buffer radius significantly impacted our results in the first trimester, but not in the third trimester.

Residential Greenspace Association with Childhood Behavioral Outcomes.

OBJECTIVE: To assess the relationship between greenspace exposure and childhood internalizing and externalizing behaviors. STUDY DESIGN: We analyzed data from the Cincinnati Childhood Allergy and Air Pollution Study, an ongoing prospective birth cohort. Greenspace exposure was estimated based on children's addresses using normalized difference vegetation index (NDVI) images. Neurobehavioral outcomes were assessed using the Behavioral Assessment System for Children, Second Edition. Regression models adjusted for neighborhood deprivation, maternal education, race, and sex assessed the risk for problematic internalizing and externalizing behaviors at residential greenspace buffers of 200, 400, and 800 m. RESULTS: There were 562 and 313 children in our age 7- and 12-year analyses, respectively. At age 7 years, a 0.1-unit increase in NDVI was associated with decreased conduct scores (ß = -1.10, 95% CI [-2.14, -0.06], 200 m). At age 12 years, a 0.1-unit increase in NDVI was associated with a decrease in anxiety scores (ß = -1.83, 95% CI [-3.44, -0.22], 800 m), decreased depression scores (ß = -1.36, 95% CI [-2.61, -0.12], 200 m), and decreased somatization scores (ß = -1.83, 95% CI [-3.22, -0.44], 200 m). CONCLUSIONS: This study provides evidence that increased exposure to residential greenspace is associated with reduced youth's problematic internal and external behaviors, measured by Behavioral Assessment System for Children, Second Edition, at ages 7 and 12 years. Improved understanding of this mechanism could allow for implementation of neighborhood-level approaches for reducing the risk for childhood behavioral problems.