Polybrominated diphenyl ethers (PBDEs), used as chemical flame retardants, are developmental osteotoxicants in mechanistic studies, but the effects of in utero exposure on adolescent bone health are unknown. We examined associations of gestational serum PBDE concentrations and BMD Z-scores in adolescence. Among 184 mother-adolescent pairs enrolled in the Health Outcomes and Measures of the Environment Study (Cincinnati, OH: 2003-2006), we quantified five PBDEs in maternal serum and four organophosphate ester (OPE) metabolites in maternal urine collected at 16- or 26-weeks gestation. At age 12 years, we conducted dual energy x-ray absorptiometry scans and calculated bone mineral density (BMD) Z-scores for six skeletal sites. We estimated covariate-adjusted associations per log10 increase in maternal serum PBDE concentrations using linear regression and assessed effect measure modification (EMM) by adolescent's sex using interaction terms. We also examined PBDE and OPE mixtures using quantile-based g-computation. In adjusted models, BDE-153 concentrations were associated with lower femoral neck BMD (β: -0.42; 95 % CI: -0.79, -0.05). Results were similar but weaker for other individual PBDEs and their mixture. The associations of BDEs-28, -47, and -100 with hip and femoral neck BMD Z-score were modified by adolescent's sex. For example, log10 BDE-28 was associated with total hip BMD Z-score differences of -0.75 (95 % CI: -1.50, 0.01) for males and 0.21 (95 % CI: -0.31, 0.74) for females (EMM p = 0.04). Higher quartiles of the PBDE + OPE mixture showed weak, site-specific associations with BMD, though all CIs crossed the null. In utero PBDE exposure may negatively affect adolescent bone health.

Background Organophosphate esters (OPEs) can be used as flame retardants and plasticizers in consumer products. Early life exposure may disrupt brain development by modifying brain structure and neurochemistry. Objectives To evaluate the associations between gestational and childhood OPE metabolite urinary concentrations and their mixtures with neurobehavioral outcomes, explore the potential mediation of brain structure and neurochemistry, and identify potential windows of susceptibility. Methods We employed quantile-based g-computation models to investigate the mixture associations of OPE metabolite concentrations with three distinct categories of outcomes within the HOME Study at age 12 years: 1) magnetic resonance imaging (MRI)-based morphometric measurements; 2) magnetic resonance spectroscopy (MRS)-derived neurochemical concentrations; and 3) neurobehavioral outcomes across four non-overlapping exposure windows: 1) gestational, 2) birth, 3) ages 1-3 years, and 4) ages 5-8 years. We identified outcomes associated with OPE metabolite concentrations. We conducted analyses to evaluate the potential mediation of changes in brain structure and neurochemistry. Results Urinary concentrations of the mixture of OPE metabolites were primarily associated with morphometric measurements compared to neurobehavioral outcomes and were seen across all windows investigated before adjusting for multiple comparisons. The OPE metabolite mixture in the 5-8 year window was associated with reduced cortical volume of the pars triangularis, which mediated 27% of the increase in dominant hand drops on the grooved pegboard test before adjusting for multiple comparisons. Discussion Cortical volume of the pars triangularis may mediate the adverse relationship between OPE metabolite mixture concentrations and adolescent visual motor function during the 5-8-year window.

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.

BACKGROUND AND AIM: Organophosphate esters (OPEs) flame retardants found in various consumer products, may be a risk factor of adverse reproductive health outcomes. No study has examined whether gestational exposure to OPEs alters maternal blood pressure (BP) during pregnancy. METHODS: We analyzed data from 346 women who had liveborn singletons without congenital abnormalities in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort (Cincinnati, OH, USA). The exposure variables were maternal urinary OPE metabolite concentrations at 16 weeks of gestation, standardized by specific gravity. We extracted the first two recorded maternal BP measures (20 weeks) to assess for chronic hypertension. We also extracted the two highest BP measures (≥20 weeks), and any diagnosis of hypertensive disorders of pregnancy (HDP: gestational hypertension, preeclampsia, and eclampsia) from medical charts. We defined HDP for this analysis as two BP140/90 or HDP noted in the chart at or after 20 weeks gestation. We used linear mixed models and modified Poisson regression with covariate adjustment to estimate associations between OPE concentrations with maternal BP and the risk of HDP. RESULTS:Diphenyl phosphate (DPHP) had the highest urinary geometric mean concentration (1.81 µg/L), followed by bis(1,3-dichloro-2-propyl) phosphate (BDCIPP; 0.80 µg/L), bis(2-chloroethyl) phosphate (BCEP; 0.61 µg/L), and di-n-butyl phosphate (DNBP; 0.26 µg/L). Thirty women (8.7%) were diagnosed with HDP. Every 10-fold increase of maternal BCEP concentrations was associated with 1.87 mmHg (95%CI 0.05-3.70) increase in the highest diastolic BP≥20 weeks. No urinary metabolites were associated with an increased risk of HDP (RR=1.17, 95%CI: 0.55-2.50 for DPHP; RR=1.68, 95%CI: 0.62-4.58 for BDCIPP; RR= 0.75, 95%CI 0.37-1.53 for BCEP; RR=2.34, 95% CI:0.88-6.24 for DNBP). CONCLUSIONS:Maternal urinary BCEP concentrations may be associated with increased diastolic BP. However, no associations were found between maternal urinary OPE metabolites and an increased risk of HDP. KEYWORDS: Endocrine disrupting chemicals, Pregnancy outcomes, Environmental epidemiology

Glycohemoglobin (GHB) is routinely used both as an index of mean glycemia and as a measure of risk for the development and progression of diabetes complications (1)(2). Because the prevalence of diabetes is higher for non-Hispanic blacks than in non-Hispanic whites (3) and at least 10% of black Americans have either hemoglobin S (HbS) or HbC trait (4), it is probable that at least 150 000 Americans with diabetes have HbS or HbC trait. Previous studies have shown that some GHB methods yield inaccurate results with samples heterozygous for HbS or HbC (5)(6)(7)(8)(9). Many of these interference studies have used boronate affinity chromatography as a reference method based on the assumption that this method should not be influenced by the presence of Hb variants (10). Because measurement of GHB by boronate affinity chromatography is based on the structure of the glycated component (cis-diol component of GHB), rather than differences in charge, it has been assumed that glycated HbS and/or HbC are included in the glycated fraction and that GHB results obtained …