Publications by authors named "Ann M Vuong"

45 Publications

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

Am J Epidemiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Production of organophosphate esters (OPEs), which represent a major flame retardant class present in consumer goods, has risen over the past two 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 in the Health Outcomes and Measures of the Environment Study from Cincinnati, Ohio (enrolled 2003-2006) at three time points (16 and 26 weeks' gestation, 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 and increased thyroid stimulating hormone 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.
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http://dx.doi.org/10.1093/aje/kwab086DOI Listing
March 2021

Hypertension, BMI, and cardiovascular and cerebrovascular diseases.

Open Med (Wars) 2021 21;16(1):149-155. Epub 2021 Jan 21.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 232-1163 Xinmin Street, Changchun, 130021, Jilin, China.

Hypertension is associated with body mass index (BMI) and cardiovascular and cerebrovascular diseases (CCDs). Whether hypertension modifies the relationship between BMI and CCDs is still unclear. We examined the association between BMI and CCDs and tested whether effect measure modification was present by hypertension. We identified a population-based sample of 3,942 participants in Shuncheng, Fushun, Liaoning, China. Hypertension was defined as any past use of antihypertensive medication or having a measured systolic/diastolic blood pressure ≥130/80 mm Hg. BMI was calculated from measured body weight and body height. Data on diagnosed CCDs were self-reported and validated in the medical records. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between BMI and CCDs. Higher BMI was associated with increased odds of having CCDs (OR = 1.19, 95% CI: 1.07-1.31). This association was significantly modified by hypertension ( for interaction <0.001), with positive associations observed among hypertensive individuals (OR = 1.28, 95% CI: 1.14-1.42). Age, sex, and diabetic status did not modify the relationship between BMI and CCDs (all for interaction >0.10). Although higher BMI was associated with increased odds of CCDs, the relationship was mainly limited to hypertensive patients.
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http://dx.doi.org/10.1515/med-2021-0014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862997PMC
January 2021

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and neurobehavior in US children through 8 years of age: The HOME study.

Environ Res 2021 04 2;195:110825. Epub 2021 Feb 2.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Background: Studies of prenatal per- and polyfluoroalkyl substances (PFAS) and attention deficit hyperactivity disorder (ADHD)-related behaviors in children are inconsistent.

Objectives: To examine associations between maternal serum PFAS concentrations and child behavior in 241 mother-child dyads within the Health Outcomes and Measures of the Environment (HOME) Study.

Methods: We quantified perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) in maternal serum collected during pregnancy or at delivery. We evaluated a total of 17 outcomes of child behavior using the Behavioral Assessment System for Children-2 (BASC-2) at 5 and 8 years (n = 240) and ADHD diagnostic symptoms and criteria with the Diagnostic Interview Schedule for Children-Young Child (DISC-YC) at 5 years (n = 190). We used linear mixed models and logistic regression with generalized estimating equations to assess associations between PFAS and continuous or dichotomous "at risk" BASC-2 scores; negative binomial regression to calculate incident rate ratios for counts of ADHD symptoms; and Poisson regression with robust standard errors to calculate relative risks of meeting ADHD diagnostic criteria.

Results: Each ln-unit increase in PFOS, PFHxS, and PFNA was associated with higher BASC-2 scores and increased odds of "at-risk" scores for externalizing behaviors, including hyperactivity (PFOS: odds ratio [OR] 2.7, 95% confidence interval [CI] 1.2, 5.9; PFHxS: OR 2.5, 95% CI 1.5, 4.3; PFNA: OR 3.2, 95% CI 1.3, 8.0). PFHxS was also associated with internalizing problems (OR 2.0, 95% CI 1.1, 3.4) and somatization (OR 2.2, 95% CI 1.2, 4.0). PFOS and PFNA were significantly associated with 50-80% more DISC-YC symptoms and diagnostic criteria related to hyperactive-impulsive type ADHD. Prenatal PFNA was associated with increased risk of any-type ADHD.

Conclusions: Prenatal PFOS and PFNA were consistently associated with measures related to hyperactive-impulsive type ADHD across two validated assessment instruments. PFHxS was associated with increased problems with both externalizing and internalizing behaviors. No associations were noted between PFOA and child neurobehavior.
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http://dx.doi.org/10.1016/j.envres.2021.110825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987860PMC
April 2021

Proximity to traffic and exposure to polycyclic aromatic hydrocarbons in relation to Attention Deficit Hyperactivity Disorder and conduct disorder in U.S. children.

Int J Hyg Environ Health 2021 Mar 9;232:113686. Epub 2021 Jan 9.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Currently at Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: Traffic related air pollution (TRAP) and its component polycyclic aromatic hydrocarbons (PAHs) may be neurotoxic in children. There is limited research on postnatal exposure to TRAP and PAHs and child neurodevelopment.

Methods: We linked data from the U.S. NHANES 2001-2004 with the National Highway Planning Network 2005 to examine the proximity to major roads (highway or urban/rural principal arterials), urinary PAH metabolites, and diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) and Conduct Disorder (CD) based on Diagnostic Interview Schedule for Children (C-DISC) in 1253 children aged 8-15 years. We calculated odds ratios (ORs) and 95% Confidence Intervals (CIs) for ADHD and CD by traffic proximity and PAH exposures using logistic regression adjusted for confounders.

Results: Higher ADHD prevalence was observed among children living <500 m (9.86%) compared to those ≥500 m (3.84%) from a major road. Prevalence of children with CD was comparable (<500 m: 2.51% and ≥500 m: 2.43%). We found little difference in urinary PAH metabolite levels between children living near major roads and those who did not. Children living <500 m from a major road had a non-significant OR of 2.06 (95% CI 0.85-5.03) for ADHD diagnosis. Children living on ≥2 major roads within 500 m of a highway had a non-significant OR of 2.27 (95% CI 0.71-7.26) for ADHD diagnosis. There was no association between proximity to major roads and CD diagnosis.

Conclusion: We found living close to a major road was not associated with increased PAH levels. We did not find statistically significant relation between proximity to a major road or urinary PAH metabolite levels and ADHD or CD diagnosis in this cross-sectional analysis. Prospective studies are needed for the investigation of postnatal TRAP exposure and ADHD and CD diagnosis.
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http://dx.doi.org/10.1016/j.ijheh.2020.113686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854500PMC
March 2021

Flame retardants and neurodevelopment: An updated review of epidemiological literature.

Curr Epidemiol Rep 2020 Dec 10;7(4):220-236. Epub 2020 Nov 10.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Purpose Of Review: Flame retardant (FR) compounds can adversely impact neurodevelopment. This updated literature review summarizes epidemiological studies of FRs and neurotoxicity published since 2015, covering historical (polybrominated biphenyls [PBBs], polychlorinated biphenyls [PCBs]), contemporary (polybrominated diphenyl ethers [PBDEs], hexabromocyclododecane [HBCD], and tetrabromobisphenol A [TBBPA]), and current-use organophosphate FRs (OPFRs) and brominated FRs (2-ethylhexyl 2,3,4,5-tetrabromobezoate [EH-TBB] TBB), bis(2-ethylhexyl) tetrabromophthalate [BEH-TEBP]), focusing on prenatal and postnatal periods of exposure.

Recent Findings: Continuing studies on PCBs still reveal adverse associations on child cognition and behavior. Recent studies indicate PBDEs are neurotoxic, particularly for gestational exposures with decreased cognition and increased externalizing behaviors. Findings were suggestive for PBDEs and other behavioral domains and neuroimaging. OPFR studies provide suggestive evidence of reduced cognition and more behavioral problems.

Summary: Despite a lack of studies of PBBs, TBBPA, EH-TBB, and BEH-TEBP, and only two studies of HBCD, recent literature of PCBs, PBDEs, and OPFRs are suggestive of developmental neurotoxicity, calling for more studies of OPFRs.
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http://dx.doi.org/10.1007/s40471-020-00256-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781237PMC
December 2020

Effects of β-carotene intake on the risk of fracture: a Bayesian meta-analysis.

BMC Musculoskelet Disord 2020 Oct 31;21(1):711. Epub 2020 Oct 31.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun, 130021, Jilin, China.

Background: Epidemiological studies examining the association between β-carotene intake and risk of fracture have reported inconsistent findings. We conducted a meta-analysis to investigate the association between β-carotene intake and risk of fracture.

Methods: We systematically searched PubMed, EMBASE and Cochrane library databases for relevant articles that were published until December 2019. We also identified studies from reference lists of articles identified from the clinical databases. The frequentist and Bayesian random-effects model was used to synthesize data.

Results: Nine studies with a total of 190,545 men and women, with an average age of 59.8 years, were included in this meta-analysis. For β-carotene intake (1.76-14.30 mg/day), the pooled risk ratio (RR) of any fracture was 0.67 (95% Credible Interval (CrI): 0.51-0.82; heterogeneity: P = 0.66, I = 0.00%) and 0.63 (95%CrI: 0.44-0. 82) for hip fracture. By study design, the pooled RRs were 0.55 (95% CrI: 0.14-0.96) for case-control studies and 0.82 (95% CrI: 0.58-0.99) for cohort studies. By geographic region, the pooled RRs were 0.58 (95% CrI: 0.28-0.89), 0.86 (95% CrI: 0.35-0.1.37), and 0.91(95% CrI: 0.75-1.00) for studies conducted in China, the United States, and Europe, respectively. By sex, the pooled RRs were 0.88 (95% CrI: 0.73-0.99) for males and 0.76 (95% CrI, 0.44-1.07) for females. There was a 95% probability that β-carotene intake reduces risk of hip fracture and any type of fracture by more than 20%.

Conclusions: The present meta-analysis suggests that β-carotene intake was inversely associated with fracture risk, which was consistently observed for case-control and cohort studies. Randomized controlled trials are warranted to confirm this relationship.
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http://dx.doi.org/10.1186/s12891-020-03733-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603770PMC
October 2020

Ornithine and breast cancer: a matched case-control study.

Sci Rep 2020 09 23;10(1):15502. Epub 2020 Sep 23.

Department of Breast Surgery, The First Affiliated Hospital of Jinzhou Medical University, 5-2 Renmin Street, Jinzhou, 121001, Liaoning, China.

In vivo and vitro evidence indicates that ornithine and its related metabolic products play a role in tumor development. Whether ornithine is associated with breast cancer in humans is still unclear. We examined the association between circulating ornithine levels and breast cancer in females. This 1:1 age-matched case-control study identified 735 female breast cancer cases and 735 female controls without breast cancer. All cases had a pathological test to ascertain a breast cancer diagnosis. The controls were ascertained using pathologic testing, clinical examinations, and/or other tests. Fasting blood samples were used to measure ornithine levels. The average age for cases and controls were 49.6 years (standard deviation [SD] 8.7 years) and 48.9 years (SD 8.7 years), respectively. Each SD increase in ornithine levels was associated with a 12% reduction of breast cancer risk (adjusted odds ratio [OR] 0.88; 95% confidence interval [CI] 0.79-0.97). The association between ornithine and breast cancer did not differ by pathological stages of diagnosis or tumor grades (all P for trend > 0.1). We observed no effect measure modification by molecular subtypes (P for interaction = 0.889). In conclusion, higher ornithine levels were associated with lower breast cancer risk in females.
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http://dx.doi.org/10.1038/s41598-020-72699-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511971PMC
September 2020

Maternal cadmium exposure and neurobehavior in children: The HOME study.

Environ Res 2020 07 25;186:109583. Epub 2020 Apr 25.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Background: It is unclear whether cadmium (Cd) exposure during fetal brain development is associated with child neurobehavior.

Objective: To examine the potential associations between Cd exposure during pregnancy and neurobehavior among children.

Methods: We used data from 276 children in the Health Outcomes and Measures of the Environment (HOME) Study, a well-established prospective pregnancy and birth cohort. We measured maternal urinary Cd concentrations at 26 weeks of gestation. For cognitive function, we assessed Mental Development Index (MDI) and Full-Scale Intelligence Quotient (FSIQ) using the Bayley Scales of Infant Development-II, the Wechsler Preschool and Primary Scales of Intelligence-III, or the Wechsler Intelligence Scales for Children-IV at ages 1, 2, 3, 5, and 8 years. We assessed child behaviors using the Behavior Assessment System for Children-2 at ages 2, 3, 4, 5, and 8 years, yielding four composite measures: Externalizing Problems, Internalizing Problems, Behavioral Symptoms Index, and Adaptive Skills. We used linear mixed models with covariate adjustment to estimate the associations between maternal urinary Cd concentrations and child neurobehavior.

Results: We categorized study participants into three groups based on maternal urinary Cd concentrations (Group 1: < limit of detection (LOD), Group 2: 0.06-0.22 μg/g creatinine, Group 3: >0.22 μg/g creatinine). In linear mixed models adjusting for maternal and child characteristics, maternal urinary Cd levels were not significantly associated with cognitive function at ages 1, 2, 3, 5, and 8 years or with behavioral composite measures at 2, 3, 4, 5, and 8 years.

Conclusions: No significant associations were observed between maternal urinary Cd and cognitive or behavioral measures in children at 1-8 years of age in this study.
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http://dx.doi.org/10.1016/j.envres.2020.109583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7368093PMC
July 2020

Chemical mixtures and neurobehavior: a review of epidemiologic findings and future directions.

Rev Environ Health 2020 Sep;35(3):245-256

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA, USA.

Background Epidemiological studies have historically focused on single toxicants, or toxic chemicals, and neurodevelopment, even though the interactions of chemicals and nutrients may result in additive, synergistic, antagonistic, or potentiating effects on neurological endpoints. Investigating the impact of environmentally-relevant chemical mixtures, including heavy metals and endocrine disrupting chemicals (EDCs), is more reflective of human exposures and may result in more refined environmental policies to protect the public. Objective In this review, we provide a summary of epidemiological studies that have analyzed chemical mixtures of heavy metals and EDCs and neurobehavior utilizing multi-chemical models, including frequentist and Bayesian methods. Content Studies investigating chemicals and neurobehavior have the opportunity to not only examine the impact of chemical mixtures, but they can also identify chemicals from a mixture that may play a key role in neurotoxicity, investigate interactive effects, estimate non-linear dose response, and identify potential windows of susceptibility. The examination of neurobehavioral domains is particularly challenging given that traits emerge and change over time and subclinical nuances of neurobehavior are often unrecognized. To date, only a handful of epidemiological studies examining neurodevelopment have utilized multi-pollutant models in the investigation of heavy metals and EDCs. However, these studies were successful in identifying contaminants of importance from the exposure mixtures. Summary and Outlook Investigators are encouraged to broaden their focus to include more environmentally relevant mixtures of chemicals using advanced statistical approaches, particularly to aid in identifying potential mechanisms underlying associations.
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http://dx.doi.org/10.1515/reveh-2020-0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781354PMC
September 2020

Prenatal exposure to a mixture of persistent organic pollutants (POPs) and child reading skills at school age.

Int J Hyg Environ Health 2020 07 7;228:113527. Epub 2020 Jun 7.

Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address:

Background: Prenatal exposure to persistent organic pollutants (POPs) may affect child neurobehavior; however, exposures to mixtures of POPs have rarely been examined.

Methods: We estimated associations of prenatal serum concentrations of 17 POPs, namely 5 polybrominated diphenyl ethers (PBDEs), 6 polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and 4 per- and polyfluoroalkyl substances (PFAS), with Wide Range Achievement Test-4 reading composite scores at age 8 years in 161 children from a pregnancy and birth cohort (Health Outcomes and Measures of the Environment [HOME] Study, 2003-present) in Cincinnati, OH. We applied 6 statistical methods: least absolute shrinkage and selection operator (LASSO), elastic net (ENET), Sparse Principal Component Analysis (SPCA), Weighted Quantile Sum (WQS) regression, Bayesian Kernel Machine Regression (BKMR), and Bayesian Additive Regression Trees (BART), to estimate covariate-adjusted associations with individual and their mixtures in multi-pollutant models.

Results: Both LASSO and ENET models indicated inverse associations with reading scores for BDE-153 and BDE-28, and positive associations for CB-118, CB-180, perfluoroctanoate (PFOA), and perfluorononanoate (PFNA). The SPCA identified inverse associations for BDE-153 and BDE-100 and positive associations for perfluorooctane sulfonate (PFOS), PFOA, and PFNA, as parts of different principal component scores. The WQS regression showed the highest weights for BDE-100 (0.35) and BDE-28 (0.16) in the inverse association model and for PFNA (0.29) and CB-180 (0.21) in the positive association model. The BKMR model identified BDE-100 and BDE-153 for inverse associations and CB-118, CB-153, CB-180, PFOA, and PFNA for positive associations. The BART method found dose-response functions similar to the BKMR model. No interactions between POPs were identified.

Conclusions: Despite some inconsistency among biomarkers, these analyses revealed inverse associations between prenatal PBDE concentrations and children's reading scores. Positive associations of PCB congeners and PFAS with reading skills were also found.
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http://dx.doi.org/10.1016/j.ijheh.2020.113527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328128PMC
July 2020

Polybrominated diphenyl ether (PBDE) and poly- and perfluoroalkyl substance (PFAS) exposures during pregnancy and maternal depression.

Environ Int 2020 06 5;139:105694. Epub 2020 Apr 5.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, 423 Guardian Drive, Blockley Hall 231, Philadelphia, PA 19104, USA.

Background: Experimental studies in rodents suggest that polybrominated diphenyl ethers (PBDEs) and poly- and perfluoroalkyl substances (PFAS) may contribute to depressive symptoms. Few studies have examined the impact of these chemicals on depression in adults.

Objective: To examine the associations between serum PBDE and PFAS concentrations during pregnancy and repeated measures of depressive symptoms in women assessed from pregnancy to 8 years postpartum.

Methods: This study was based on 377 women from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (USA). PBDEs (BDE-28, -47, -99, -100, -153, and ∑PBDEs) and PFAS (perfluorooctanoate [PFOA], perfluorooctane sulfonate [PFOS], perfluorohexane sulfonate [PFHxS], perfluorononanoate [PFNA]) were quantified in maternal serum at 16 ± 3 weeks gestation. Depressive symptoms were measured using the Beck Depression Inventory-II (BDI-II) at ~20 weeks gestation and up to seven times during postpartum visits (4 weeks, 1, 2, 3, 4, 5, and 8 years). We used linear mixed models to estimate covariate-adjusted associations between chemical concentrations and repeated measures of BDI-II. Multinomial logistic regression models were used to estimate the relative risk ratios of having a medium or high depression trajectory.

Results: We found that a 10-fold increase in BDE-28 at 16 ± 3 weeks gestation was associated with significantly increased BDI-II scores (β = 2.5 points, 95% confidence interval [CI] 0.8, 4.2) from pregnancy to 8 years postpartum. Significant positive associations were also observed with BDE-47, -100, -153, and ∑PBDEs. A 10-fold increase in ∑PBDEs was associated with a 4.6-fold increased risk (95% CI 1.8, 11.8) of a high trajectory for BDI-II compared to a low trajectory. We observed no significant associations between PFAS and BDI-II scores.

Conclusion: PBDEs during pregnancy were associated with more depressive symptoms among women in this cohort.
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http://dx.doi.org/10.1016/j.envint.2020.105694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275897PMC
June 2020

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

Environ Res 2020 05 13;184:109255. Epub 2020 Feb 13.

Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

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 (r: 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.
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http://dx.doi.org/10.1016/j.envres.2020.109255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103481PMC
May 2020

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

Chemosphere 2020 Jan 3;239:124701. Epub 2019 Sep 3.

Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

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, range: 70.1-166,000 ng g), tris-(1,3-dichloro-2-propyl)-phosphate (TDCIPP, GM: 1840 ng g, range: 55.2-228,000 ng g), triphenyl phosphate (TPHP, GM: 1070 ng g, range: 34.1-62,100 ng g), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB, GM: 59.5 ng g, range: 2.82-7800 ng g), and bis-(2-ethylhexyl)-tetrabromophthalate (BEH-TEBP, GM: 121 ng g, range 2.17-13,600 ng g) were all detected in >90% of dust samples; tris-(2-chloroethyl)-phosphate (TCEP, GM: 669 ng g, range: 56.8-160,000 ng g) 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.
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http://dx.doi.org/10.1016/j.chemosphere.2019.124701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854320PMC
January 2020

Prenatal and childhood exposure to poly- and perfluoroalkyl substances (PFAS) and cognitive development in children at age 8 years.

Environ Res 2019 05 16;172:242-248. Epub 2019 Feb 16.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA.

Background: Toxicological studies indicate that poly- and perfluoroalkyl substances (PFAS) may be neurotoxic, but human studies have yet to provide compelling evidence for PFAS' impact on cognitive abilities.

Objective: To test whether prenatal and childhood PFAS are associated with cognitive abilities at 8 years and whether sex modifies these associations.

Methods: We included 221 mother-child pairs from the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort in Cincinnati, OH (USA). We quantified PFAS in maternal serum at 16 ± 3 weeks gestation and in child serum at 3 and 8 years. We used the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) at age 8 years, assessing Full Scale IQ (FSIQ), verbal comprehension, perceptual reasoning, working memory, and processing speed. We used multiple informant models to estimate covariate-adjusted differences in WISC-IV scores by repeated ln-transformed PFAS.

Results: Prenatal and childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were not associated with WISC-IV measures. We observed an increase of 4.1-points (95% CI 0.3, 8.0) and 5.7-points (95% CI 1.2, 10.2) in working memory with 1-ln unit increase in prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA), respectively. In addition, PFNA at 3 years was associated with better FSIQ and perceptual reasoning. Child sex modified the relationship between prenatal PFOA and FSIQ; the association was positive in females only. Sex also modified the association between concurrent PFOS and FSIQ, with males having higher scores.

Conclusion: We did not observe adverse associations between prenatal and childhood PFAS and cognitive function at age 8 years.
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http://dx.doi.org/10.1016/j.envres.2019.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511326PMC
May 2019

Exposure to polybrominated diphenyl ethers (PBDEs) during childhood and adiposity measures at age 8 years.

Environ Int 2019 02 4;123:148-155. Epub 2018 Dec 4.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA.

Background: Animal studies suggest polybrominated diphenyl ethers (PBDEs) may be obesogens. However, epidemiologic studies investigating childhood exposure to PBDEs and adiposity are limited, with several reporting an inverse association.

Objectives: To investigate associations between repeated childhood PBDE concentrations and adiposity measures at age 8 years.

Methods: We examined 206 children from the Health Outcomes and Measures of the Environment Study, a birth cohort in Cincinnati, OH (2003-2006). Serum PBDEs were measured at ages 1, 2, 3, 5, and 8 years. We used multiple imputation to estimate missing PBDE concentrations. At 8 years, we measured weight, height, waist circumference, and body fat percentage. We used multiple informant models to estimate age-specific associations between PBDEs and adiposity measures.

Results: We observed significant inverse associations between BDE-153 with all adiposity measures that became increasingly stronger with later childhood measurements. A 10-fold increase in BDE-153 at ages 1 and 8 years was associated with 2% (95% CI -3.9, -0.1) and 7% (95% CI -9.1, -4.7) lower body fat, respectively. No statistically significant associations were found with BDE-28, -47, -99, or -100. Child sex modified some associations; inverse associations between BDE-153 and body fat were stronger among boys, while positive and null associations were noted among girls.

Conclusions: Childhood BDE-153 concentrations were inversely associated with adiposity measures and these associations became stronger as BDE-153 measurements were more proximal to adiposity measures. Inverse associations could be attributed to reverse causality arising from greater storage of PBDEs in adipose tissue of children with higher adiposity.
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http://dx.doi.org/10.1016/j.envint.2018.11.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400314PMC
February 2019

Childhood polybrominated diphenyl ether (PBDE) serum concentration and reading ability at ages 5 and 8 years: The HOME Study.

Environ Int 2019 01 28;122:330-339. Epub 2018 Nov 28.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Background: Polybrominated diphenyl ethers (PBDEs) exist extensively in the environment and human beings. PBDE concentrations are higher in children than adults. A previous study found that prenatal PBDE exposure was associated with decreased reading skills in children; however, evidence is limited on the potential impact of childhood exposure to PBDEs. The study examined the association between childhood PBDE exposures and reading ability in children at ages 5 and 8 years.

Methods: The study included 230 children from an ongoing prospective pregnancy and birth cohort study, the Health Outcomes and Measures of Environment (HOME) Study, conducted in Cincinnati, Ohio. Children's serum concentrations of eleven PBDE congeners were measured at 1, 2, 3, 5, and 8 years. The Woodcock-Johnson Tests of Achievement - III and the Wide Range Achievement Test - 4 were administered to assess children's reading skills at ages 5 and 8 years, respectively. We used multiple informant models to examine the associations between repeated measures of PBDEs and reading scores at ages 5 and 8 years. We also estimated the βs and 95% CIs of the association of PBDE measure at each age by including interaction terms between PBDE concentrations and child age in the models.

Results: All childhood BDE-153 concentrations were inversely associated with reading scores at 5 and 8 years, but associations were not statistically significant after covariate adjustment. For example, a 10-fold increase in BDE-153 concentrations at ages 3 and 5 years was associated with a -5.0 (95% confidence interval (CI): -11.0, 1.0) and -5.5 (95% CI: -12.5, 1.4) point change in Basic Reading score at age 5 years, respectively. Similarly, the estimates for Brief Reading score at age 5 years were -4.5 (95% CI: -10.5, 1.5) and -5.2 (95% CI: -12.2, 1.7) point changes, respectively. Serum concentration of BDE-47, -99, -100, and SumPBDEs (sum of BDE-47, 99, 100, and 153) at every age were inversely associated with reading scores at ages 5 and 8 years in unadjusted analyses. While the adjusted estimates were much attenuated and became non-significant, the direction of most of the associations was not altered.

Conclusion: Our study has shown a suggestive but non-significant trend of inverse associations between childhood PBDE serum concentrations, particularly BDE-153, and children's reading skills. Future studies with a larger sample size are needed to examine these associations.
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http://dx.doi.org/10.1016/j.envint.2018.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324196PMC
January 2019

Prenatal and childhood exposure to perfluoroalkyl substances (PFAS) and measures of attention, impulse control, and visual spatial abilities.

Environ Int 2018 10 20;119:413-420. Epub 2018 Jul 20.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA. Electronic address:

Background: Despite evidence from toxicological studies describing the potential neurotoxicity of perfluoroalkyl substances (PFAS), their role in neurodevelopment remains uncertain amid inconsistent findings from epidemiological studies.

Methods: Using data from 218 mother-child dyads from the Health Outcomes and Measures of the Environment Study, we examined prenatal and childhood (3 and 8 years) serum concentrations of four PFAS and inattention, impulsivity, and visual spatial abilities. At 8 years, we used the Conners' Continuous Performance Test-II to assess attention and impulse control and the Virtual Morris Water Maze (VMWM) to measure visual spatial abilities.

Results: In multiple informant models, there was no evidence to indicate that prenatal or childhood PFAS are associated with attention. However, there was an inverse association between prenatal ln-perfluorooctanoate (PFOA) and errors of commission (β = -2.0, 95% Confidence Interval [CI] -3.8, -0.3). Ln-perfluorononanoate (PFNA) at 3 years was associated with longer (poorer) VMWM completion times of 3.6 seconds (CI 1.6, 5.6). However, higher concurrent concentrations of ln-perfluorohexane sulfonate (PFHxS) (β = -2.4 s, 95% CI -4.4, -0.3) were associated with shorter (better) times. Higher prenatal PFHxS was positively associated with percentage of traveling distance in the correct quadrant (β = 4.2%, 95% CI 0.8, 7.7), indicating better performance.

Conclusion: Findings were mixed for prenatal and childhood PFAS concentrations and visual spatial abilities. There is not enough evidence to support that PFAS are associated with visual spatial abilities as assessed by the VMWM or CPT-II measures of inattention or impulsivity in children at age 8 years.
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http://dx.doi.org/10.1016/j.envint.2018.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442289PMC
October 2018

Childhood perfluoroalkyl substance exposure and executive function in children at 8 years.

Environ Int 2018 10 4;119:212-219. Epub 2018 Jul 4.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA. Electronic address:

Background: Toxicological studies highlight the potential neurotoxicity of perfluoroalkyl substances (PFAS) during fetal development. However, few epidemiological studies have examined the impact of childhood PFAS on neurodevelopment.

Methods: We employed data from 208 children in the Health Outcomes and Measures of the Environment Study, a birth cohort (Cincinnati, OH), to examine associations of six serum PFAS concentrations measured at 3 and 8 years with executive function assessed at 8 years using the validated parent-completed Behavior Rating Inventory of Executive Function survey. We used multiple informant models to identify susceptible windows of neurotoxicity to PFAS and executive function. We investigated trajectories of PFAS concentrations and whether sex modified these associations.

Results: Each ln-increase in perfluorononanoate (PFNA) at 8 years was associated with a 3.4-point increase (95% CI 0.4, 6.3) in metacognition score, indicating poorer function. Children with PFNA above the median at 8 years had poorer global executive functioning compared to children with concentrations consistently below median levels (β = 6.5, 95% CI 0.2, 12.9). Higher concurrent PFNA was associated with poorer behavior regulation among males, while associations among females were null (p = 0.018). Children with higher concurrent perfluorooctanoate (PFOA) had increased odds of being at risk of having clinical impairments in metacognition (OR = 3.18, 95% CI 1.17, 8.60). There were no associations between perfluorooctane sulfonate and perfluorohexane sulfonate and executive function.

Conclusions: PFNA and PFOA at 8 years, but not 3 years, may be related to poorer executive function at 8 years. Results need to be confirmed in cohort studies with larger sample sizes.
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http://dx.doi.org/10.1016/j.envint.2018.06.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442288PMC
October 2018

Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years.

Environ Int 2018 08 19;117:339-347. Epub 2018 May 19.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati 45267, OH, USA. Electronic address:

Background: Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood.

Methods: We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years.

Results: Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T (FT) in males. Prenatal ∑PBDEs were not associated with TT, FT, or total T.

Conclusions: These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males.
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http://dx.doi.org/10.1016/j.envint.2018.05.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997562PMC
August 2018

Exposure to polybrominated diphenyl ethers (PBDEs) and child behavior: Current findings and future directions.

Horm Behav 2018 05 7;101:94-104. Epub 2017 Dec 7.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA.

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood. As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs' potential role in behavioral development. We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD). While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior (e.g., hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children. Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures.
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http://dx.doi.org/10.1016/j.yhbeh.2017.11.008DOI Listing
May 2018

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study.

Int J Hyg Environ Health 2018 01 16;221(1):87-94. Epub 2017 Oct 16.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH, 45267, USA. Electronic address:

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β=4.6, 95% CI 0.5, 8.7) and BDE-153 (β=4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.
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http://dx.doi.org/10.1016/j.ijheh.2017.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726937PMC
January 2018

Prenatal and postnatal polybrominated diphenyl ether (PBDE) exposure and measures of inattention and impulsivity in children.

Neurotoxicol Teratol 2017 Nov 11;64:20-28. Epub 2017 Sep 11.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, P.O. Box 670056, Cincinnati, OH 45267, USA. Electronic address:

Exposure to polybrominated diphenyl ethers (PBDEs) during fetal development may be associated with deficits in attention and impulse control. However, studies examining postnatal PBDE exposures and inattention and impulsivity have been inconsistent. Using data from 214 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort with enrollment from 2003 to 2006 in the Greater Cincinnati Area, we investigated the relationship of both prenatal and postnatal PBDE exposures with attention and impulse control. Serum PBDEs were measured at 16±3weeks of gestation and during childhood at 1, 2, 3, 5, and 8years. We assessed children's attention and impulse control using the Conners' Continuous Performance Test-Second Edition (CPT-II) at 8years. We used multiple informant models to estimate associations of repeated PBDE measures with inattention and impulsivity. There was a pattern of associations between PBDEs and poorer performance on CPT-II measures of attention. For BDE-153, adverse associations extended to exposures at preschool and kindergarten ages; ten-fold increases in exposure were associated with higher omission errors (BDE-153 at 3years: β=4.0 [95% CI: -2.4, 10.5]; at 5years: β=4.6 [95% CI: -2.8, 12.0]; at 8years: β=4.1 [95% CI: -3.4, 11.5]). Longer hit reaction times, indicated by the exponential part of the hit reaction curve, were also observed with 10-fold increases in BDE-153 during the prenatal period and throughout childhood (Prenatal: β=15.0 milliseconds (ms) [95% CI: -15.8, 45.8]; 5years: β=20.6ms [95% CI: -20.8, 61.9]; 8years: β=28.6ms [95% CI: -12.1, 69.4]). Significant impairment in discriminability, as indicated by detectability (d'), between targets and non-targets was also noted with 5 and 8-year PBDE concentrations. Associations between PBDEs and inattention significantly differed by child sex, with males performing more poorly than females with regard to omission errors and measures of reaction times. Collectively, these results do not strongly support that PBDEs are associated with poorer impulse and attention control among 8year old children. However, there may be a possible relationship between prenatal and concurrent PBDEs and inattention, which requires additional research.
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http://dx.doi.org/10.1016/j.ntt.2017.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693687PMC
November 2017

Childhood polybrominated diphenyl ether (PBDE) exposure and neurobehavior in children at 8 years.

Environ Res 2017 10 19;158:677-684. Epub 2017 Jul 19.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Background: Prenatal polybrominated diphenyl ether (PBDE) exposure has been associated with decrements in IQ and increased attention deficit/hyperactivity disorder related behaviors in children; however, data are limited for the role of postnatal exposures.

Objectives: We investigated the association between a series of childhood PBDE concentrations and Full-Scale Intelligence Quotient (FSIQ) and externalizing problems at 8 years.

Methods: We used data from 208 children in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort. Child serum PBDEs were measured at 1, 2, 3, 5, and 8 years; missing serum PBDE concentrations were estimated via multiple imputation. The Wechsler Intelligence Scales for Children-IV and the Behavior Assessment System for Children-2 was used to assess intelligence and externalizing behavior, respectively, in children at 8 years. We used multiple informant models to estimate associations between repeated lipid-adjusted PBDEs and child neurobehavior and to test for windows of susceptibility.

Results: Postnatal exposure to PBDE congeners (- 28, - 47, - 99, - 100, and - 153) at multiple ages was inversely associated with FSIQ at 8 years. For instance, a 10-fold increase in BDE-153 concentrations at 2, 3, 5, and 8 years were all related to lower FSIQ at age 8 (β for 3 years: - 7.7-points, 95% CI - 12.5, - 2.9; β for 8 years: - 5.6-points, 95% CI - 10.8, - 0.4). Multiple PBDE congeners at 8 years were associated with increased hyperactivity and aggressive behaviors at 8 years.

Conclusions: Postnatal PBDE exposure was associated with decrements in FSIQ and increases in hyperactivity and aggressive behaviors.
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http://dx.doi.org/10.1016/j.envres.2017.07.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5567986PMC
October 2017

Calpain-2/p35-p25/Cdk5 pathway is involved in the neuronal apoptosis induced by polybrominated diphenyl ether-153.

Toxicol Lett 2017 Aug 27;277:41-53. Epub 2017 May 27.

Department of Occupational Health, Shanxi Medical University, Taiyuan 030001, China.

Polybrominated diphenyl ethers (PBDEs) have been demonstrated to induce neurotoxicity in experimental rats and mice, with neuronal apoptosis as one of the major mechanisms, however, the mechanisms underlying PBDEs-induced neuronal apoptosis remain unclear. In this study, we aimed to investigate the role of calpain/p35-p25/Cdk5 pathway in BDE-153-induced neuronal apoptosis in the hippocampus and primary neurons in rats. Results showed that compared to the controls, neuronal apoptosis was significantly increased in vivo and ex vivo, as manifested by the increased hippocampus TUNEL-positive cell rates, apoptotic neurons in Hoechst and AO/EB staining, and the increased LDH activity and percentage of Annexin V-positive cells in rat hippocampus and primary neurons. Calpain activity was significantly increased in all the BDE-153-treated groups in vivo and ex vivo when compared to non-treatment controls. In addition, we showed that calpain-2 accounted for the calpain activation instead of calpain-1, as demonstrated by the up-regulated mRNA and protein expressions in calpain-2 but not calpain-1. Activated calpain truncated p35 into p25, which resulted in the p25/Cdk5 formation and activation. Calpain inhibitor PD150606 or p25/Cdk5 inhibitor Roscovitine relieved neuronal apoptosis mainly via inhibiting the p25/Cdk5 activation. Overall, the findings suggested that calpain-2/p35-p25/Cdk5 pathway was involved in BDE-153-induced neuronal apoptosis, which provides novel insight into the mechanisms of PBDE neurotoxicity.
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http://dx.doi.org/10.1016/j.toxlet.2017.05.027DOI Listing
August 2017

Prenatal and postnatal polybrominated diphenyl ether exposure and visual spatial abilities in children.

Environ Res 2017 Feb 1;153:83-92. Epub 2016 Dec 1.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Polybrominated diphenyl ethers (PBDEs) are associated with impaired visual spatial abilities in toxicological studies, but no epidemiologic study has investigated PBDEs and visual spatial abilities in children. The Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003-2006, Cincinnati, OH), was used to examine prenatal and childhood PBDEs and visual spatial abilities in 199 children. PBDEs were measured at 16±3 weeks gestation and at 1, 2, 3, 5, and 8 years using gas chromatography/isotope dilution high-resolution mass spectrometry. We used the Virtual Morris Water Maze to measure visual spatial abilities at 8 years. In covariate-adjusted models, 10-fold increases in BDE-47, -99, and -100 at 5 years were associated with shorter completion times by 5.2s (95% Confidence Interval [CI] -9.3, -1.1), 4.5s (95% CI -8.1, -0.9), and 4.7s (95% CI -9.0, -0.3), respectively. However, children with higher BDE-153 at 3 years had longer completion times (β=5.4s, 95% CI -0.3, 11.1). Prenatal PBDEs were associated with improved visual spatial memory retention, with children spending a higher percentage of their search path in the correct quadrant. Child sex modified some associations between PBDEs and visual spatial learning. Longer path lengths were observed among males with increased BDE-47 at 2 and 3 years, while females had shorter paths. In conclusion, prenatal and postnatal BDE-28, -47, -99, and -100 at 5 and 8 years were associated with improved visual spatial abilities, whereas a pattern of impairments in visual spatial learning was noted with early childhood BDE-153 concentrations.
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http://dx.doi.org/10.1016/j.envres.2016.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5222735PMC
February 2017

Prenatal Polybrominated Diphenyl Ether Exposure and Body Mass Index in Children Up To 8 Years of Age.

Environ Health Perspect 2016 12 10;124(12):1891-1897. Epub 2016 Jun 10.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Background: Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen.

Objectives: We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and ΣPBDEs during pregnancy were associated with anthropometric measures in children aged 1-8 years.

Methods: We examined 318 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1-8 years), weight (1-8 years), body mass index (BMI) (2-8 years), waist circumference (4-8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures.

Results: We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = -0.36; 95% CI: -0.60, -0.13) at 2-8 years, smaller waist circumference (β = -1.81 cm; 95% CI: -3.13, -0.50) at 4-8 years, and lower percent body fat (β = -2.37%; 95% CI: -4.21, -0.53) at 8 years. A decrease in waist circumference at 4-8 years was observed with a 10-fold increase in BDE-100 (β = -1.50 cm; 95% CI: -2.93, -0.08) and ΣPBDEs (β = -1.57 cm; 95% CI: -3.11, -0.02).

Conclusions: Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat. Citation: Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891-1897; http://dx.doi.org/10.1289/EHP139.
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http://dx.doi.org/10.1289/EHP139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132628PMC
December 2016

Physician Recommendation of Diabetes Clinical Protocols.

Hosp Top 2016 ;94(1):15-21

a School of Public Health, Texas A&M Health Science Center, College Station , Texas , USA.

The authors examined the responses of 63 primary care physicians to diabetes clinical protocols (DCPs) for the management of type II diabetes (T2DM). We measured physician demographics, current diabetes patient loads, and responses to DCPs (physician attitudes, physician familiarity, and physician recommendation of DCPs) using a 20-question electronic survey. Results of the survey indicate that primary care physicians may be unfamiliar with the benefits of diabetes clinical protocols for the self-management of T2DM. Given the importance of diabetes self-management education in controlling T2DM, those interested in implementing DCPs should address the beliefs and attitudes of primary care physicians.
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http://dx.doi.org/10.1080/00185868.2016.1142313DOI Listing
March 2017

Prenatal Exposure to Nitrosatable Drugs, Dietary Intake of Nitrites, and Preterm Birth.

Am J Epidemiol 2016 Apr 6;183(7):634-42. Epub 2016 Mar 6.

Prenatal exposure to nitrosatable drugs, including secondary or tertiary amines, has been associated with preterm birth. Associations may be accentuated by higher intakes of dietary nitrites because of the increased formation of N-nitroso compounds. Using data from mothers of babies without major birth defects (controls) from the National Birth Defects Prevention Study, we examined the relationship between nitrosatable drug exposure in conjunction with dietary nitrite intake and preterm birth among 496 mothers of preterm infants and 5,398 mothers with full-term deliveries in 1997-2005. A protective association was observed with a high intake of plant nitrites (adjusted hazard ratio (AHR) = 0.72, 95% confidence interval (CI): 0.53, 0.97). Secondary amines in conjunction with high nitrite intake were associated with preterm birth during the first (AHR = 1.84, 95% CI: 1.14, 2.98), second (AHR = 1.89, 95% CI: 1.17, 3.07), and third (AHR = 2.00, 95% CI: 1.22, 3.29) trimesters. The adjusted hazard ratios for tertiary amine use in the third trimester by increasing tertiles of nitrite intake were 0.67 (95% CI: 0.35, 1.31), 1.25 (95% CI: 0.71, 2.19), and 2.02 (95% CI: 1.17, 3.49). Prenatal exposure to nitrosatable drugs, particularly secondary and tertiary amines, in conjunction with higher levels of dietary nitrite intake may increase the risk of preterm birth.
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http://dx.doi.org/10.1093/aje/kwv250DOI Listing
April 2016

Prenatal polybrominated diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children.

Environ Res 2016 May 28;147:556-64. Epub 2016 Jan 28.

Division of Epidemiology, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address:

Executive function is a critical behavioral trait rarely studied in relation to potential neurotoxicants. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) has been associated with adverse neurodevelopment, but there is limited research on executive function. Data from 256 mother-child pairs in the Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003-2006, Cincinnati, OH), was used to examine maternal serum PBDEs and PFASs and executive function in children ages 5 and 8 years. Maternal serum PBDEs and PFASs were measured at 16±3 weeks gestation. Executive function was assessed with the parent-rated Behavior Rating Inventory of Executive Function (BRIEF), which yields composite measures: behavioral regulation index, metacognition index, and global executive composite. Higher BRIEF scores indicate executive function impairments. Linear mixed models and generalized estimating equations were used to estimate covariate-adjusted associations between PBDEs and PFASs and executive function. A 10-fold increase in BDE-153 was associated with poorer behavior regulation (β=3.23, 95% CI 0.60, 5.86). Higher odds of having a score ≥60 in behavior regulation (OR=3.92, 95% CI 1.76, 8.73) or global executive functioning (OR=2.34, 95% CI 1.05, 5.23) was observed with increased BDE-153. Each ln-unit increase in perfluorooctane sulfonate (PFOS) was associated with poorer behavior regulation (β=3.14, 95% CI 0.68, 5.61), metacognition (β=3.10, 95% CI 0.62, 5.58), and global executive functioning (β=3.38, 95% CI 0.86, 5.90). However, no association was observed between perfluorooctanoate (PFOA) and executive function. Prenatal exposures to BDE-153 and PFOS may be associated with executive function deficits in school-age children.
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http://dx.doi.org/10.1016/j.envres.2016.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821747PMC
May 2016

Gestational Weight Gain Trend and Population Attributable Risks of Adverse Fetal Growth Outcomes in Ohio.

Paediatr Perinat Epidemiol 2015 Jul 5;29(4):346-50. Epub 2015 Jun 5.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine and Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.

Background: The trend of gestational weight gain (GWG) in relation to the Institute of Medicine (IOM) guidelines and the population attributable risks (PARs) of GWG on fetal growth outcomes remain unclear.

Methods: We analysed Ohio birth certificates from 2006 to 2012 to examine GWG trend by prepregnancy body mass index, to calculate the risk of small- and large-for-gestational age (SGA and LGA), and macrosomia (birthweight >4000 g or >4500 g) infants, and to estimate the PARs of GWG below or above the guidelines.

Results: Of 869,531 women who delivered singleton live births at 22-44 weeks of gestation, 4.5% were underweight, 48.9% were normal weight, 23.9% were overweight, and 22.7% were obese before pregnancy. About 36.5% of underweight, 52.6% of normal weight, 72.5% of overweight, and 62.4% of obese women gained weight above the guidelines, with only slight changes from 2006 to 2012. Also, 34.9% of underweight, 20.1% of normal weight, 16.3% of overweight, and 27.0% of obese women gained weight below the guidelines. The PAR of GWG below or above the guidelines was -13% for SGA, 32.6% for LGA, 28.1% for macrosomia >4000 g, and 48.3% for macrosomia >4500 g, mostly driven by currently GWG above the guidelines in normal weight, overweight, and obese women.

Conclusions: A high percentage of pregnant women gained weight outside of the current IOM GWG guidelines; however, changes from 2006 to 2012 were small. GWG above the IOM guidelines significantly contributed to a large proportion of LGA and macrosomic infants in the general population.
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http://dx.doi.org/10.1111/ppe.12197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5141288PMC
July 2015
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