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Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN.

ABSTRACT: BACKGROUND:Comprehensive examinations of placental metal concentrations and correlations with infant parameters are under-investigated. Chattanooga, Tennessee's consistently high incidence of low birth weight and potential for metal exposure provides an ideal opportunity to investigate potential correlations. OBJECTIVES:To investigate the associations between a wide variety of metals in placental tissue and multiple infant parameters. METHODS:A total of 31 elements were screened via ICP-MS in 374 individual placental samples. Of those, 14 were quantifiable in >?86% of the samples. We examined correlations between metal concentrations and infant parameters (birth weight, gestational age, birth weight centile, placental weight, birth length and head circumference). We fit multivariable regression models to estimate the covariate-adjusted associations of birth weight with ln-transformed concentrations of each of the 14 metals and used generalized additive models to examine nonlinear relationships. RESULTS:Some of the strongest relationships with infant parameters came from several lesser-studied metals. Placental rhodium concentrations were negatively correlated with almost all infant parameters. In the fully adjusted regression model, birth weight was significantly associated with several metals. On an IQR (25th to the 75th percentile) basis, estimated changes in birthweight were: for cobalt (82.5?g, IQR=6.05?µg/kg, p?=?0.006), iron (-51.5?g, IQR?=?171800?µg/kg, p?=?0.030), manganese (-27.2?g, IQR=152.1?µg/kg, p?=?0.017), lead (-72.7?g, IQR=16.55?µg/kg, p?=?0.004) and rhodium (-1365.5?g, IQR?=?0.33?µg/kg, p?

SUBMITTER: Mikelson CK

PROVIDER: S-EPMC6288679 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN.

Mikelson Colleen K CK Troisi Jacopo J LaLonde Amy A Symes Steven J K SJK Thurston Sally W SW DiRe Lauren M LM David Adair C C Miller Richard K RK Richards Sean M SM

Environmental research 20180907

<h4>Background</h4>Comprehensive examinations of placental metal concentrations and correlations with infant parameters are under-investigated. Chattanooga, Tennessee's consistently high incidence of low birth weight and potential for metal exposure provides an ideal opportunity to investigate potential correlations.<h4>Objectives</h4>To investigate the associations between a wide variety of metals in placental tissue and multiple infant parameters.<h4>Methods</h4>A total of 31 elements were scr ...[more]

PMID: 30296639

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Project description:OBJECTIVE:Damage to locus ceruleus neurons could play a part in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis because of impairment of the blood-brain barrier and enhanced neuroinflammation. The locus ceruleus has connections throughout the brain and spinal cord, so the characteristic widespread multifocal pathology in these disorders could be due to damage to different subsets of locus ceruleus neurons. Previous studies have shown that only certain locus ceruleus neurons accumulate the neurotoxic metal mercury. To find out if concentrations of other toxic metals or of essential trace elements also vary between individual locus ceruleus neurons, we used synchrotron X-ray fluorescence microscopy on frozen sections of locus ceruleus neurons taken from people with multiple sclerosis, in whom the locus ceruleus is structurally intact. MATERIALS AND METHODS:Paraffin embedded sections containing the locus ceruleus from seven people with multiple sclerosis were stained with autometallography that demonstrates accumulations of mercury, silver and bismuth. These were compared to maps of multiple elements obtained from frozen sections of locus ceruleus neurons from the same people using X-ray fluorescence microscopy. Neurons in the anterior pons from three of these donors were used as internal controls. RESULTS:Autometallography staining was observed in scattered locus ceruleus neurons from three of the seven donors. X-ray fluorescence microscopy showed variations among individual locus ceruleus neurons in levels of mercury, selenium, iron, copper, lead, bromine, and rubidium. Variations between donors of locus ceruleus neuronal average levels of mercury, iron, copper, and bromine were also detected. Anterior pons neurons contained no mercury, had varied levels of iron, and had lower copper levels than locus ceruleus neurons. CONCLUSIONS:Individual human locus ceruleus neurons contain varying levels of toxic metals and essential trace elements. In contrast, most toxic metals are absent or at low levels in nearby anterior pons neurons. The locus ceruleus plays a role in numerous central nervous system functions, including maintaining the blood-brain-barrier and limiting neuroinflammation. Toxic metals, or alterations in essential trace metals within individual locus ceruleus neurons, could be one factor determining the non-random destruction of locus ceruleus neurons in normal aging and neurodegenerative diseases, and subsequently the sites of the widespread multifocal central nervous system pathology in these disorders.

Project description:BACKGROUND:Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. METHODS:This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12-20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants. RESULTS:The 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0-1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (? 2 episodes of symptomatic malaria or ? 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80-111.6) and 4.06 (1.73-9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32-8.12) and aRR = 7.07 (2.84-17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46-21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy. CONCLUSION:Higher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes. Trial Registration Current Controlled Trials Identifier NCT02163447.

Project description:BackgroundPrenatal cadmium (Cd) exposure has been recognized to restrict growth, and male and female fetuses may have differential susceptibility to the developmental toxicity of Cd. Imprinted genes, which exhibit monoallelic expression based on parent of origin, are highly expressed in placental tissues. The function of these genes is particularly critical to fetal growth and development, and some are expressed in sex-specific patterns.ObjectivesWe aimed to examine whether prenatal Cd associates with the expression of imprinted placental genes, overall or in fetal sex-specific patterns, across two independent epidemiologic studies.MethodsWe tested for Cd–sex interactions in association with gene expression, then regressed the placental expression levels of 74 putative imprinted genes on placental log-Cd concentrations while adjusting for maternal age, sex, smoking history, and educational attainment. These models were performed within study- and sex-specific strata in the New Hampshire Birth Cohort Study (NHBCS; [Formula: see text]) and the Rhode Island Child Health Study (RICHS; [Formula: see text]). We then used fixed-effects models to estimate the sex-specific and overall associations across strata and then examine heterogeneity in the associations by fetal sex.ResultsWe observed that higher Cd concentrations were associated with higher expression of distal-less homeobox 5 (DLX5) ([Formula: see text]), and lower expression of h19 imprinted maternally expressed transcript (H19) ([Formula: see text]) and necdin, MAGE family member (NDN) ([Formula: see text]) across study and sex-specific strata, while three other genes [carboxypeptidase A4 (CPA4), growth factor receptor bound protein 10 (GRB10), and integrin-linked kinase (ILK)] were significantly associated with Cd concentrations, but only among female placenta ([Formula: see text]). Additionally, the expression of DLX5, H19, and NDN, the most statistically significant Cd-associated genes, were also associated with standardized birth weight z-scores.DiscussionThe differential regulation of a set of imprinted genes, particularly DLX5, H19, and NDN, in association with prenatal Cd exposure may be involved in overall developmental toxicity, and some imprinted genes may respond to Cd exposure in a manner that is specific to infant gender. https://doi.org/10.1289/EHP4264.

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Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN.

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Placental concentrations of essential, toxic, and understudied metals and relationships with birth outcomes in Chattanooga, TN.

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