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Preliminary assessment of exposure to persistent organic pollutants among pregnant women in Puerto Rico.

ABSTRACT: BACKGROUND:Puerto 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. METHODS:In 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. RESULTS:Several 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. CONCLUSION:Although 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.

SUBMITTER: Watkins DJ

PROVIDER: S-EPMC6408968 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Preliminary assessment of exposure to persistent organic pollutants among pregnant women in Puerto Rico.

Watkins Deborah J DJ Vélez-Vega Carmen M CM Rosario Zaira Z Cordero José F JF Alshawabkeh Akram N AN Meeker John D JD

International journal of hygiene and environmental health 20190207 2

<h4>Background</h4>Puerto 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 Nati ...[more]

PMID: 30738742

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Project description:BackgroundMetal(loid)s have been associated to adverse birth outcomes in experimental and epidemiological studies, but the underlying mechanism(s) are not well understood. Endocrine disruption may be a mechanism by which the metal(loid)s impact birth outcomes.MethodsPregnant women were recruited through the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT). Urine, blood, demographic and pregnancy-related data were collected at recruitment and subsequent visits. Sixteen metal(loid)s were analyzed in urine and blood samples, while nine maternal hormones (corticotropin-releasing hormone (CRH), sex-hormone binding globulin (SHBG), estriol (E3), progesterone, testosterone, thyroid-stimulating hormone (TSH), total triiodothyronine (T3), total thyroxine (T4), and free thyroxine (fT4)) were measured in serum samples from 815 singleton pregnancies. Linear mixed models with random intercepts were used to examine associations between metal(loid)s in blood and urine with hormone concentrations.ResultsArsenic blood concentrations were significantly associated with increased levels in CRH (%Δ: 23.0, 95%CI: 8.4-39.6) and decreased levels in testosterone (%Δ: -16.3, 95%CI: -26.2--5.1). Cobalt, manganese, and lead blood concentrations were associated with small increases in SHBG (%Δ range: 3.3-4.2), E3 (%Δ range: 3.9-8.7) and progesterone (%Δ range: 4.1-6.3) levels, respectively. Nickel blood concentration was inversely associated with testosterone levels (%Δ -13.3, 95%CI: -18.7--7.6). Significant interactions were detected for the association between nickel and study visit in relation to CRH (p < 0.02) and testosterone levels (p < 0.01).ConclusionOur analysis suggests that metal(loid)s may act as endocrine disruptors by altering prenatal hormone levels. This disruption may depend on specific windows of exposure during pregnancy. Additionally, some essential metal(loid)s such as managense and cobalt may be contributors to adverse maternal and fetal outcomes. The study of metal(loid)s as endocrine disruptors is in the early stages of epidemiological research and future studies are needed to further investigate these associations.

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.

Project description:ObjectiveEndocrine-disrupting chemicals (EDCs) adversely affect human health. Our objective was to determine the association of EDC exposure with earlier age of menopause.MethodsCross-sectional survey using National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2008 (n = 31,575 females). Eligible participants included: menopausal women >30 years of age; not currently pregnant, breastfeeding, using hormonal contraception; no history of bilateral oophorectomy or hysterectomy. Exposures, defined by serum lipid and urine creatinine-adjusted measures of EDCs, data were analyzed: > 90th percentile of the EDC distribution among all women, log-transformed EDC level, and decile of EDC level. Multi linear regression models considered complex survey design characteristics and adjusted for age, race/ethnicity, smoking, body mass index. EDCs were stratified into long (>1 year), short, and unknown half-lives; principle analyses were performed on those with long half-lives as well as phthalates, known reproductive toxicants. Secondary analysis determined whether the odds of being menopausal increased with EDC exposure among women aged 45-55 years.FindingsThis analysis examined 111 EDCs and focused on known reproductive toxicants or chemicals with half-lives >1 year. Women with high levels of ?-hexachlorocyclohexane, mirex, p,p'-DDE, 1,2,3,4,6,7,8-heptachlorodibenzofuran, mono-(2-ethyl-5-hydroxyhexyl) and mono-(2-ethyl-5-oxohexyl) phthalate, polychlorinated biphenyl congeners -70, -99, -105, -118, -138, -153, -156, -170, and -183 had mean ages of menopause 1.9 to 3.8 years earlier than women with lower levels of these chemicals. EDC-exposed women were up to 6 times more likely to be menopausal than non-exposed women.ConclusionsThis study of a representative sample of US women documents an association between EDCs and earlier age at menopause. We identified 15 EDCs that warrant closer evaluation because of their persistence and potential detrimental effects on ovarian function. Earlier menopause can alter the quantity and quality of a woman's life and has profound implications for fertility, human reproduction, and our global society.

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.

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.

Dataset Information

Preliminary assessment of exposure to persistent organic pollutants among pregnant women in Puerto Rico.

Publications

Preliminary assessment of exposure to persistent organic pollutants among pregnant women in Puerto Rico.

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