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Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population.

ABSTRACT: BACKGROUND:Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exposures with birth outcomes and cord blood adipokine and insulin concentrations. METHODS:We analyzed five OPE metabolites in urine samples collected at up to three visits during pregnancy from 90 women enrolled in the ORigins of Child Health And Resilience in Development (ORCHARD) pregnancy cohort in Baltimore, MD from 2017 to 2019. To quantify the variability of metabolite concentrations during pregnancy, we calculated intraclass correlation coefficients (ICCs) for each metabolite using mixed effects regression models. Using self-reported questionnaire data collected during gestation, we assessed possible sociodemographic and environmental/behavioral predictors of each OPE metabolite using generalized estimating equations to account for repeated exposure measures. We ascertained birth outcomes of 76 offspring from medical records, including weight-for-gestational age, length, ponderal index, and gestational age. In a subset of 37 infants, we measured cord blood concentrations of leptin, adiponectin, and insulin. To account for repeated exposure measures, we used linear structural equation models to assess the relations of standard deviation (SD) increases in prenatal OPE metabolite factor scores with continuous birth outcomes and cord blood biomarker concentrations. RESULTS:ICCs ranged from 0.09 for isopropylphenyl-phenyl phosphate (ip-PPP) to 0.59 for bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). We observed little consistency in environmental or behavioral predictors of OPE exposures, although concentrations were generally lower for samples collected in the afternoon compared to morning and winter compared to other seasons. In adjusted analyses, a SD increase in BDCIPP concentration was associated with a 0.06?g/cm3 (95% CI: 0.00, 0.12) greater ponderal index. A SD increase in BDCIPP was associated with a 0.37 (95% CI: -?0.62, -?0.13) SD lower insulin concentration and 0.24 (95% CI: -?0.39, -?0.08) SD lower leptin concentration. Other OPEs were not associated with infant outcomes. CONCLUSIONS:These findings suggest some OPEs may be metabolic disruptors warranting investigation in larger studies.

SUBMITTER: Kuiper JR

PROVIDER: S-EPMC7247187 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population.

Kuiper Jordan R JR Stapleton Heather M HM Wills-Karp Marsha M Wang Xiaobin X Burd Irina I Buckley Jessie P JP

Environmental health : a global access science source 20200524 1

<h4>Background</h4>Organophosphate esters (OPEs) are synthetic chemicals used as flame retardants and plasticizers in a variety of goods. Despite ubiquitous human exposures and laboratory evidence that prenatal OPE exposures may disrupt offspring metabolism, perinatal studies of OPE health effects are limited. The objectives of this study were to: 1) Determine predictors and reproducibility of urinary OPE biomarker concentrations during pregnancy, and 2) Estimate the relation of prenatal OPE exp ...[more]

PMID: 32448197

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Project description:BackgroundUltra-processed foods are highly processed foods which are manufactured with industrial substances to increase convenience and palatability. Some organophosphate esters (OPEs) are used as flame retardants and plasticizers and have been detected in food samples, particularly processed foods. However, little is known about dietary sources of OPEs or whether higher consumption of ultra-processed foods increases exposures.ObjectivesWe evaluated whether higher consumption of ultra-processed food is associated with urinary OPE metabolite concentrations in a nationally representative sample of US children and adults.MethodsAmong 2242 participants (?6 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014, we used the NOVA classification system to calculate percent of total energy from ultra-processed food using a 24 h dietary recall. Concentrations of 7 OPE metabolites, including diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), di-p-cresyl phosphate (DPCP), 2,3,4,5-tetrabromobenzoic acid (TBBA), and bis(1-chloro-2-propyl) phosphate (BCPP) were measured in urine. We used multivariable linear or logistic regressions to examine associations per 10% higher total energy from ultra-processed foods with percent changes or prevalence of detectable levels of creatinine-standardized OPEs.ResultsIn a model adjusting for only urinary creatinine, each 10% higher total energy from ultra-processed food was associated with 3.5% (95% CI: 0.7%, 6.3%) higher DPHP and 8.2% (95% CI: 4.6, 11.9%) higher BDCPP concentrations. However, none of the OPE metabolites was associated with ultra-processed food consumption in models adjusted for sociodemographic characteristics, health behaviors, and BMI (all p-values >0.05). Ultra-processed breads and tortillas; sauces, dressing, and gravies; and milk-based drinks were associated with higher concentrations of BDCPP while frozen and shelf-stable plate meals were associated with lower concentrations. Reconstituted meat or fish products and ultra-processed milk-based desserts were associated with greater odds of detectable levels of BCPP.ConclusionWhile some food groups were associated with urinary OPE metabolite concentrations, ultra-processed foods do not appear to be a major source of current OPE exposure in the US.

Project description:OBJECTIVE:To evaluate whether urinary concentrations of organophosphate flame retardant (PFR) metabolites are associated with pregnancy loss among women conceiving with assisted reproductive technology (ART). DESIGN:Prospective preconception cohort of subfertile women. SETTING:Academic hospital fertility center in Boston, Massachusetts. PATIENT(S):A total of 155 women conceiving 179 pregnancies with ART. INTERVENTION(S):None. Mean exposure to each of five PFR metabolites was estimated by averaging the specific-gravity adjusted natural log concentrations from two urine samples collected during the ART cycle of conception. MAIN OUTCOME MEASURE(S):Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for biochemical and total pregnancy loss (all losses <20 weeks' gestation) by quartiles of PFR metabolite concentrations were estimated using a repeated measures log-binomial model, accounting for multiple pregnancies per woman. RESULT(S):Of the 179 pregnancies, 31% ended in pregnancy loss (12% in biochemical loss). Among the three metabolites with high detection frequency [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), and isopropylphenyl phenyl phosphate (ip-PPP)], an increased risk of biochemical loss was observed for women with DPHP concentrations in the fourth vs. first quartile (RR 1.64; 95% CI 0.61-4.39). Also found was an elevated risk of biochemical pregnancy loss among women in the highest quartile of the molar sum of urinary PFR metabolites compared with the lowest (RR 1.89; 95% CI 0.64-5.58). Urinary concentrations of ip-PPP and BDCIPP were not associated with either outcome. CONCLUSION(S):Among subfertile women, urinary DPHP metabolite concentrations measured during the ART cycle of conception may be associated with early pregnancy loss. Although this study is uniquely designed to investigate early markers of pregnancy success and maintenance, the small sample size likely contributed to imprecision. Given their increasing use as replacement chemicals for traditional flame retardants, exposure to PFRs may increase, and more studies will be needed to investigate their potential to impact pregnancy and reproduction.

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Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population.

Publications

Predictors and reproducibility of urinary organophosphate ester metabolite concentrations during pregnancy and associations with birth outcomes in an urban population.

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