Predictors of urinary and blood Metal(loid) concentrations among pregnant women in Northern Puerto Rico.
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ABSTRACT:
SUBMITTER: Ashrap P
PROVIDER: S-EPMC7167342 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Understanding important sources and pathways of exposure to common chemicals known or suspected to impact human health is critical to eliminate or reduce the exposure. This is particularly important in areas such as Puerto Rico, where residents have higher exposures to numerous chemicals, as well as higher rates of many adverse health outcomes, compared to the mainland US. OBJECTIVE:The aim of this study was to assess distributions, time trends, and predictors of urinary triclocarban, phenol, and paraben biomarkers measured at multiple times during pregnancy among women living in Northern Puerto Rico. METHODS:We recruited 1003 pregnant women between years 2010 and 2016 from prenatal clinics and collected urine samples and questionnaire data on personal care product use at up to three separate visits, between 16 and 28?weeks gestation. Urine samples were analyzed for triclocarban, seven phenols and four parabens: 2,4-dichlorophenol, 2,5-dichlorophenol, benzophenone-3, bisphenol A (BPA), bisphenol S (BPS), bisphenol F, triclosan, butylparaben, ethylparaben, methylparaben, and propylparaben. RESULTS:Detectable triclocarban, phenol and paraben concentrations among pregnant women were prevalent and tended to be higher than levels measured in women of reproductive age from the general US population, especially triclocarban, which had a median concentration 37 times higher in Puerto Rico participants (2.6 vs 0.07?ng/mL). A decreasing temporal trend was statistically significant for urine concentrations of BPA during the study period, while the BPA substitute BPS showed an increasing temporal trend. Significant and positive associations were found between biomarker concentrations with the products use in the past 48-h (soap, sunscreen, lotion, cosmetics). There was an increasing trend of triclocarban/triclosan urinary concentrations with increased concentrations of triclocarban/triclosan listed as the active ingredient in the bar soap/liquid soap products reported being used. CONCLUSION:Our results suggest several potential exposure sources to triclocarban, phenols, and parabens in this population and may help inform targeted approaches to reduce exposure.
| S-EPMC6361519 | biostudies-literature
Project description:Puerto Rico has higher rates of a range of endocrine-related diseases and disorders compared to the United States. However, little is known to date about human exposures to known or potential endocrine disrupting chemicals (EDCs) in Puerto Rico. We recruited 105 pregnant women in Northern Puerto Rico who provided urine samples and questionnaire data at three times (18 ± 2, 22 ± 2, and 26 ± 2 weeks) during gestation. We measured the urinary concentrations of five phenols and three parabens: 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP), benzophenone-3 (BP-3), bisphenol A (BPA), triclosan (TCS), butyl paraben (B-PB), methyl paraben (M-PB), and propyl paraben (P-PB). The frequent detection of these chemicals suggests that exposure is highly prevalent among these Puerto Rican pregnant women. Urinary concentrations of TCS, BP-3, and 25-DCP were higher than among women of reproductive age in the US general population, while concentrations of BPA, 24-DCP, and parabens were similar. Intraclass correlation coefficients (ICC) varied widely between biomarkers; BPA had the lowest ICC (0.24) and BP-3 had the highest (0.62), followed by 25-DCP (0.49) and TCS (0.47). We found positive associations between biomarker concentrations with self-reported use of liquid soap (TCS), sunscreen (BP-3), lotion (BP-3 and parabens), and cosmetics (parabens). Our results can inform future epidemiology studies and strategies to reduce exposure to these chemicals or their precursors.
| S-EPMC3638245 | biostudies-literature
Project description:Background/aimMatrix metalloproteinases (MMPs) are important regulators of uterine remodeling, a critical process for healthy pregnancies, and studies have revealed a link between an imbalance in MMPs and adverse birth outcomes. Toxicological studies have indicated that exposure to heavy metals can alter the levels of inflammatory cytokines, including MMPs. Despite growing evidence, the clear association between heavy metal exposure and MMPs has yet to be explored extensively in human populations. To have a better understanding of the association, in this study, we assessed associations between maternal blood metal levels with MMPs among 617 pregnant women in the Puerto Rico PROTECT birth cohort.MethodsWe measured blood concentrations for 11 metals in the first and/or second trimester of pregnancy using ICP-MS. MMPs (MMP1, MMP2, and MMP9) were quantified using a customized Luminex assay. Linear mixed effects models (LMEs) were used to regress MMPs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex effects were estimated using interaction terms between metal exposure variables and fetal sex indicators.ResultsWe observed significant associations between cesium, manganese, and zinc with all the MMPs that were measured. We also observed differences in metal-MMPs associations by fetal sex. Cobalt was positively associated with MMP1 only in women with male fetuses, and cesium was negatively associated with MMP1 only in women with female fetuses. MMP2 had significant associations with maternal blood metal concentrations only in women with female fetuses.ConclusionCertain metals were significantly associated with MMPs that are responsible for uterine remodeling and healthy pregnancies. Most of these associations differed by fetal sex. This study highlighted significant metal-MMPs associations that may inform research on new avenues for understanding heavy metal-induced adverse birth outcomes and the development of diagnostic tools.
| S-EPMC10443181 | biostudies-literature
Project description:Phenols and parabens are used in a multitude of consumer products resulting in ubiquitous human exposure. Animal and in vitro studies suggest that exposure to these compounds may be related to a number of adverse health outcomes, as well as potential mediators such as oxidative stress and inflammation. We examined urinary phenol (bisphenol A (BPA), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP)) and paraben (butyl paraben (B-PB), methyl paraben (M-PB), propyl paraben (P-PB)) concentrations measured three times during pregnancy in relation to markers of oxidative stress and inflammation among participants in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) project. Serum markers of inflammation (c-reactive protein (CRP), IL-1?, IL-6, IL-10, and tumor necrosis factor-? (TNF-?)) were measured twice during pregnancy (n=105 subjects, 187 measurements) and urinary markers of oxidative stress (8-hydroxydeoxyguanosine (OHdG) and isoprostane) were measured three times during pregnancy (n=54 subjects, 146 measurements). We used linear mixed models to assess relationships between natural log-transformed exposure and outcome biomarkers while accounting for within individual correlation across study visits. After adjustment for urinary specific gravity, study visit, maternal pre-pregnancy BMI, and maternal education, an interquartile range (IQR) increase in urinary BPA was associated with 21% higher OHdG (p=0.001) and 29% higher isoprostane (p=0.0002), indicating increased oxidative stress. The adjusted increase in isoprostane per IQR increase in marker of exposure was 17% for BP-3, 27% for B-PB, and 20% for P-PB (all p<0.05). An IQR increase in triclosan (TCS) was associated with 31% higher serum concentrations of IL-6 (p=0.007), a pro-inflammatory cytokine. In contrast, IQR increases in BP-3 and B-PB were significantly associated with 16% and 18% lower CRP, a measure of systemic inflammation. Our findings suggest that exposure to BPA, select parabens, and TCS during pregnancy may be related to oxidative stress and inflammation, potential mechanisms by which exposure to these compounds may influence birth outcomes and other adverse health effects, but additional research is needed.
| S-EPMC4323928 | biostudies-literature
Project description:Phthalates are ubiquitous environmental exposures that may be implicated in inflammatory processes, as demonstrated by previous in vivo and in vitro studies. Few human studies have substantiated these observations. This study sought to examine whether maternal phthalate exposures impact inflammatory processes, as measured by circulating inflammatory biomarkers, in the PROTECT cohort in northern Puerto Rico. Inflammatory biomarkers included matrix metalloproteinases 1, 2, and 9 (MMPs), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM), and intercellular cell adhesion molecule-1 (ICAM). Biomarkers were measured in maternal serum samples collected during pregnancy. 19 phthalate metabolites were assessed in urinary samples collected at three study visits across pregnancy. Phthalates with <50 % of measurements above the limit of detection were excluded from analysis. We utilized linear mixed effect models to estimate associations between interquartile range increases in phthalate metabolite concentrations and percent changes in inflammatory biomarkers. Our results revealed significant associations between mono-n-butyl phthalate (MBP) and higher MMP1 by 7.86 % (95 % CI: 0.49, 15.76) and between mono oxononyl phthalate (MONP) and higher MMP2 by 8.30 % (95 % CI: 2.22, 14.75). We observed negative or null associations between phthalate metabolites and MMP2, MMP9, ICAM, VCAM, and CRP. Many results were significantly modified by fetal sex, particularly those between di-2-ethylhexyl phthalate (DEHP) metabolites and MMP1 (p-interaction: MEHHP = 0.01, MEOHP = 0.04, MECPP = 0.01) and MMP2 (p-interaction: MEHHP = 0.03, MEOHP = 0.01, MECPP = 0.01), for which associations were positive among only women carrying female fetuses. MMPs have been previously associated with preeclampsia and hypertensive pregnancy disorders as mediators of artery remodeling. Hence, our findings suggest a potential role for phthalates in mediating the maternal inflammatory response, as well as significant sexual dimorphism in these relationships, which has implications for several adverse pregnancy outcomes.
| S-EPMC10323976 | biostudies-literature
Project description:Studies have revealed a link between aberrant levels of maternal C-reactive protein (CRP) and cell adhesion molecules (CAMs) with adverse birth outcomes. Some epidemiologic studies have indicated that long-term metal exposures can modulate the levels of CRP and CAMs, but the associations between prenatal metal exposures and the levels of CRP and CAMs have yet to be studied more extensively. In this study, we assessed associations between maternal blood metal levels and CRP/CAMs among 617 pregnant women in the Puerto Rico PROTECT birth cohort.MethodsBlood samples were collected from participants at 16-20 (visit 1) and 24-28 (visit 3) weeks gestation. We measured concentrations of 11 metals using inductively coupled plasma mass spectrometry (ICP-MS). From the blood samples, CRP and CAMs intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) were also quantified using a customized Luminex assay. Linear-mixed effects models (LMEs) were used to regress CRP and CAMs on metals and included random intercepts for study participants to account for correlated repeated outcome measures. Fetal sex and visit effects were estimated using interaction terms between metal exposure variables and fetal sex, as well as visit indicators, respectively.ResultsWe observed significant positive associations between nickel and CRP (Δ: 7.04, 95% CI = 0.75, 13.73) and between lead and VCAM (Δ: 4.57, 95% CI = 1.36, 7.89). The positive associations were mainly driven by mothers carrying male fetuses. We also observed various visit-specific associations. The significant associations between metals and CRP were predominantly driven by visit 3; however, the significant associations between metals and VCAM were mainly driven by visit 1.ConclusionCertain maternal blood metal levels were significantly associated with CRP and CAMs and most of these associations were differentially driven by fetal sex, as well as by timing in pregnancy. Future studies should further explore metal-CRP/CAMs associations for a better understanding of the underlying mechanism of metal-induced adverse birth outcomes.
| S-EPMC9374188 | biostudies-literature
Project description:BackgroundIn previous studies, exposures to heavy metals such as Pb and Cd have been associated with adverse birth outcomes; however, knowledge on effects at low levels of exposure and of other elements remain limited.MethodWe examined individual and mixture effects of metals and metalloids on birth outcomes among 812 pregnant women in the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort. We measured 16 essential and non-essential metal(loid)s in maternal blood collected at 16-20 and 24-28 weeks gestation. We used linear and logistic regression to independently examine associations between geometric mean (GM) concentrations of each metal across visits and gestational age, birthweight z-scores, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). We evaluated effect modification with infant sex*metal interaction terms. To identify critical windows of susceptibility, birth outcomes were regressed on visit-specific metal concentrations. Furthermore, average metal concentrations were divided into tertiles to examine the potential for non-linear relationships. We used elastic net (ENET) regularization to construct Environmental Risk Score (ERS) as a metal risk score and Bayesian Kernel Machine Regression (BKMR) to identify individual metals most critical to each outcome, accounting for correlated exposures.ResultsIn adjusted models, an interquartile range (IQR) increase in GM lead (Pb) was associated with 1.63 higher odds of preterm birth (95%CI = 1.17, 2.28) and 2 days shorter gestational age (95% CI = -3.1, -0.5). Manganese (Mn) and zinc (Zn) were also associated with higher odds of preterm birth and shorter gestational age; the associations were strongest among the highest tertile for Mn and among females for Zn. Mercury (Hg) was associated with higher risk of preterm birth at the later window of pregnancy. Ni measured later in pregnancy was associated with lower odds of SGA. ENET and BKMR models selected similar metals as "important" predictors of birth outcomes. The association between ERS and preterm birth was assessed and the third tertile of ERS was significantly associated with an elevated odds ratio of 2.13 (95% CI = 1.12, 5.49) for preterm birth compared to the first tertile.ConclusionAs the PROTECT cohort has lower Pb concentrations (GM = 0.33 μg/dL) compared to the mainland US, our findings suggest that low-level prenatal lead exposure, as well as elevated Mn and Zn exposure, may adversely affect birth outcomes. Improved understanding on environmental factors contributing to preterm birth, together with sustainable technologies to remove contamination, will have a direct impact in Puerto Rico and elsewhere.
| S-EPMC7198231 | biostudies-literature
Project description:BackgroundPhthalates have been reported to alter circulating lipid concentrations in animals, and investigation of these associations in humans will provide greater understanding of potential mechanisms for health outcomes.ObjectiveTo explore associations between phthalate metabolite biomarkers and lipidomic profiles among pregnant women (n = 99) in the Puerto Rico PROTECT cohort.MethodsWe measured 19 urinary phthalate metabolites during 24-28 weeks of pregnancy. Lipidomic profiles were identified from plasma samples by liquid chromatography-mass spectrometry-based shotgun lipidomics. Relationships between phthalate metabolites and lipid profiles were estimated using compound-by-compound comparisons in multiple linear regression and dimension reduction techniques. We derived sums for each lipid class and sub-class (saturated, mono-unsaturated, polyunsaturated) which were then regressed on phthalate metabolites. Associations were adjusted for false discovery.ResultsAfter controlling for multiple comparisons, 33 phthalate-lipid associations were identified (False discovery rate adjusted p value < 0.05), and diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1 were the most strongly associated with multiple phthalate metabolites. Metabolites of di-2-ethylhexyl phthalate, bis(2-ethylhexyl) phthalate, dibutyl phthalates, and diisobutyl phthalate were associated with increased ceramides, lysophosphatidylcholines, lysophosphatidylethanolamines, and triacylglycerols, particularly those containing saturated and mono-unsaturated fatty acid chains.SignificanceCharacterization of associations between lipidomic markers and phthalate metabolites during pregnancy will yield mechanistic insight for maternal and child health outcomes.ImpactThis study leverages emerging technology to evaluate lipidome-wide signatures of phthalate exposure during pregnancy. The greatest lipid signatures of phthalate exposure were observed for diacylglycerol 40:7 and plasmenyl-phosphatidylcholine 35:1. Polymerized glycerides are important for energy production and regulated through hormone signaling, while plasmenyl-phosphatidylcholines have been implicated in membrane dynamics and important for cell-to-cell signaling. Characterization of these mechanisms are relevant for informing the etiology of maternal and children's health outcomes.
| S-EPMC9124693 | biostudies-literature
Project description:BackgroundOrganophosphate esters (OPEs) are used as flame retardants and plasticizers. Oxidative stress, the imbalance of reactive oxygen species and antioxidants, measured prenatally has been associated with adverse birth outcomes including preeclampsia and preterm birth. We are the first study to investigate the relationship between OPEs and oxidative stress among pregnant women.MethodsPregnant women 18-40 yrs. were recruited in Northern Puerto Rico (n?=?47) between 2011 and 2015. OPE concentrations of: bis(2-chloroethyl) phosphate (BCEtP), bis(1-chloro-2-propyl) phosphate (BCPP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), dibutyl phosphate (DNBP), and diphenyl phosphate (DPHP) and biomarkers for oxidative stress, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine up to three times during pregnancy. Associations between oxidative stress biomarkers and OPEs were assessed using linear mixed models adjusted for specific gravity, age, BMI, and income.ResultsMetabolites BCEtP, BDCPP, and DPHP were frequently detected (>97%). OPE metabolite concentrations remained stable over time (Intraclass correlation coefficients (ICCs): 0.51-0.60). Metabolites BCEtP, BCPP, and DPHP were associated with an increase in 8-isoprostane and OHdG. An interquartile range (IQR) increase in BDCPP was associated with a 21% increase in 8-isoprostane (p?<?0.01), while and IQR increase in DPHP and BCPP was associated with a 12% increase (p?=?0.04, p?=?0.08, respectively). IQR increases in BDCPP and DPHP were also associated with an 18 and 19% increase in OHdG, respectively (p?<?0.01).ConclusionOPE metabolites were frequently detected and our results suggest that exposure to OPEs is associated with higher levels of oxidative stress. Further investigation into these relationships and birth outcomes is warranted.
| S-EPMC6954949 | biostudies-literature
Project description:BackgroundPuerto Rico has over 200 hazardous waste sites, as well as higher rates of several adverse health outcomes compared to the mainland US. In response to concerns of potential links between environmental contaminant exposure and preterm birth, the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) birth cohort was formed. Biomarkers of exposure for several contaminants have been found to be elevated in this cohort compared to women of child-bearing age in the National Health and Nutrition Examination Survey (NHANES). However, exposure to persistent organic pollutants (POPs) has not been evaluated.MethodsIn this preliminary analysis, we measured four classes of POPs, including perfluoroalkyl substances (PFASs), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and several persistent pesticides in serum samples collected at 16-20 weeks gestation from the first 48 women enrolled in PROTECT. We performed descriptive analyses for each analyte, assessed correlations between analytes using Spearman correlations, and compared serum levels in PROTECT women to levels in NHANES women aged 18-40.ResultsSeveral PFASs were detected in 96-100% of samples, with moderate to strong correlations between most PFASs (range r = 0.44-0.88). BDE47, BDE153, PCB 138-158, PCB153 and p,p'-dichlorodiphenyldichloroethene (p,p'-DDE) were detected in the majority of samples, with strong correlations between PCBs and p,p'-DDE (range r = 0.59-0.74). The median concentration for each analyte was lower than, sometimes by a factor of 4 (e.g. BDE47, p,p'-DDE), the median concentration reported in NHANES women aged 18-40.ConclusionAlthough participants in the ongoing PROTECT birth cohort have higher exposure to many environmental contaminants, this preliminary study suggests that they have lower exposure to several POPS, specifically PCBs, OCPs, PFASs, and PBDEs.
| S-EPMC6408968 | biostudies-literature