An exploratory analysis of urinary organophosphate ester metabolites and oxidative stress among pregnant women in Puerto Rico

Ingle, Mary E.; Watkins, Deborah J.; Rosario, Zaira; Vélez-Vega, Carmen M.; Calafat, Antònia M.; Ospina, María; Ferguson, Kelly K.; Cordero, José F.; Alshawabkeh, Akram N.; Meeker, John D.

doi:10.1016/j.scitotenv.2019.134798

Cited by 49 publications

(17 citation statements)

References 47 publications

(62 reference statements)

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“…Concentrations of BDCIPP and DPHP in our study were comparable to those reported in a recent study of adult National Health and Nutrition Examination Survey (NHANES) 2013-2014 participants [44] while other studies of OPE concentrations during pregnancy had similar concentrations of BDCIPP [19] and DPHP [2,45]. However, concentrations for all other metabolites were generally lower in our study population compared to other studies of pregnant women [1,2,13,57,94]. While we have no explanation for this observation, differences in participant SES, occupation, and residential characteristics may be possibilities.…”

Section: Discussionsupporting

confidence: 83%

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

et al. 2020

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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.

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Section: Discussionsupporting

confidence: 83%

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

et al. 2020

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“…We used linear mixed models (LMM) with a random intercept for subject ID to model each prostanoid measure as the dependent variable, with separate models for each exposure biomarker. The crude models included the metal concentration as the exposure and specific gravity as a covariate to adjust for urinary dilution [ 48 , 59 , 60 ]. The final set of covariates were selected based on a priori knowledge and if their inclusion appreciably changed the effect estimates of metal exposure.…”

Section: Methodsmentioning

confidence: 99%

Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

et al. 2021

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Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9% for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

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“…We used linear mixed models (LMM) with a random intercept for subject ID to model each prostanoid measure as the dependent variable, with separate models for each exposure biomarker. The crude models included the metal concentration as the exposure and specific gravity as a covariate to adjust for urinary dilution [43,60,61]. The final set of covariates were selected based on a priori knowledge and if their inclusion appreciably changed the effect estimates of metal exposure.…”

Section: Methodsmentioning

confidence: 99%

Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

Ashrap¹,

Watkins²,

Milne³

et al. 2020

Preprint

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Metal exposure has been associated with a wide range of adverse birth outcomes and oxidative stress is a leading hypothesis of the mechanism of action of metal toxicity. We assessed the relationship between maternal exposure to essential and non-essential metals and metalloids in pregnancy and oxidative stress markers, and sought to identify windows of vulnerability and effect modification by fetal sex. In our analysis of 215 women from the PROTECT birth cohort study, we measured 14 essential and non-essential metals in urine samples at three time points during pregnancy. The oxidative stress marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite 2,3-dinor-5,6-dihydro-15-15-F2t-IsoP, as well as prostaglandin F2α (PGF2α), were also measured in the same urine samples. Using linear mixed models, we examined the main effects of metals on markers of oxidative stress as well as the visit-specific and fetal sex-specific effects. After adjustment for covariates, we found that a few urinary metal concentrations, most notably cesium (Cs) and copper (Cu), were associated with higher 8-iso-PGF2α with effect estimates ranging from 7.3 to 14.9 % for each interquartile range, increase in the metal concentration. The effect estimates were generally in the same direction at the three visits and a few were significant only among women carrying a male fetus. Our data show that higher urinary metal concentrations were associated with elevated biomarkers of oxidative stress. Our results also indicate a potential vulnerability of women carrying a male fetus.

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An exploratory analysis of urinary organophosphate ester metabolites and oxidative stress among pregnant women in Puerto Rico

Cited by 49 publications

References 47 publications

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

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

Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

Maternal Urinary Metal and Metalloid Concentrations in Association with Oxidative Stress Biomarkers

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