Maternal Metals/Metalloid Blood Levels Are Associated With Lipidomic Profiles Among Pregnant Women in Puerto Rico.
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SUBMITTER: Kim C
PROVIDER: S-EPMC8790322 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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.
| S-EPMC7856269 | 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: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:IntroductionObjectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample.
| S-EPMC9015214 | 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: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: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
Project description:Given the potential adverse health effects related to toxic trace metal exposure and insufficient or excessive levels of essential trace metals in pregnant women and their fetuses, the present study characterizes biomarkers of metal and metalloid exposure at repeated time points during pregnancy among women in Puerto Rico. We recruited 1040 pregnant women from prenatal clinics and collected urine, blood, and questionnaire data on demographics, product use, food consumption, and water usage at up to three visits. All samples were analyzed for 16 metal(loid)s: arsenic (As), barium (Ba), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), cesium (Cs), copper (Cu), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), titanium (Ti), uranium (U), vanadium (V), and zinc (Zn). Urine samples were additionally analyzed for molybdenum (Mo), platinum (Pt), antimony (Sb), tin (Sn), and tungsten (W). Mean concentrations of most metal(loid)s were higher among participants compared to the general US female population. We found weak to moderate correlations for inter-matrix comparisons, and moderate to strong correlations between several metal(loid)s measured within each biological matrix. Blood concentrations of Cu, Zn, Mn, Hg, and Pb were shown to reflect reliable biomarkers of exposure. For other metals, repeated samples are recommended for exposure assessment in epidemiology studies. Predictors of metal(loid) biomarkers included fish and rice consumption (urinary As), fish and canned food (blood Hg), drinking public water (blood Pb), smoking (blood Cd), and iron/folic acid supplement use (urinary Cs, Mo, and Sb). Characterization of metal(loid) biomarker variation over time and between matrices, and identification of important exposure sources, may inform future epidemiology studies and exposure reduction strategies.
| S-EPMC7167342 | biostudies-literature
Project description:Background: The island of Vieques (a municipality of Puerto Rico) was used as a military practice range by the US Navy for more than 60 years. Many studies have reported the presence of toxic metals in soil samples taken from Vieques. The bombing range is only 18 km upwind from the Vieques residential area and inhalable resuspended particles resulting from bombing are known to reach the populated area. The current study reports for the first time, the presence of toxic metals' depuration profiles obtained from Vieques and Main Island Puerto Rico human subjects. Objectives: This study was designed to evaluate the distribution of toxic metals in a random population exposed to contaminants originating from military activities and comparing it to a non-exposed random population from Main Island Puerto Rico. Methods: A total of 83 subjects studied; 32 were from Vieques and 51 were from Main Island Puerto Rico. A physician administrated chelation therapy to all subjects and collected urine samples during a 24-h period. A total of 20 trace elements associated with military activities were measured in urine by induced coupled plasma mass spectrometry (ICP-MS). The results were compared between both population samples. Results: Significant differences in the levels of eight trace elements associated with military practices were found between Vieques and Main Island Puerto Rico. Lead (Pb), aluminum (Al), uranium (U) (p < 0.001), arsenic (As), cadmium (Cd) (p = 0.02), and gadolinium (Gd) (p = 0.03) were significantly higher in Vieques while niobium (Nb) and platinum (Pt) levels (p < 0.006) were lower in the Vieques samples. Discussion: Higher concentrations of Pb, Al, As, Cd, Gd, and U were found in Vieques residents' urine samples compared to Main Island. Nonetheless, Pt and Ga were present in Main Island at higher concentrations than in Vieques. Although limited by its sample size, this report should set a basis for the importance of health assessment in these subjects exposed to military activities remnants throughout the years and further evaluation of their effects on the overall health of the population.
| S-EPMC6994965 | biostudies-literature