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Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

ABSTRACT: Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL).We studied 476 mother-infant pairs whose archived blood specimens were genotyped for TF P570S, HFE H63D and HFE C282Y. MBL and UCBL were collected within 12 hours of delivery. Linear regression models were used to examine the association between log-transformed MBL and UCBL, examine for confounding and collinearity, and explore gene-environment interactions.The geometric mean MBL was 0.61 ?g/dL (range 0.03, 3.2) and UCBL 0.42 (<0.02, 3.9). Gene variants were common with carrier frequencies ranging from 12-31%; all were in Hardy-Weinberg equilibrium. In an adjusted linear regression model, log MBL was associated with log UCBL (??=?0.92, 95% CI: 0.82, 1.03; p?

SUBMITTER: Karwowski MP

PROVIDER: S-EPMC4271345 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

Karwowski Mateusz P MP Just Allan C AC Bellinger David C DC Jim Rebecca R Hatley Earl L EL Ettinger Adrienne S AS Hu Howard H Wright Robert O RO

Environmental health : a global access science source 20141006

<h4>Background</h4>Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL).<h4>Methods</h4>We studied 476 mother-infant pairs whose archived bloo ...[more]

PMID: 25287020

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Project description:BACKGROUND:Lead toxicity is a cause of intellectual disability in children and majority of affected children live in developing countries. Its adverse effect on pregnancy outcome has also been documented. OBJECTIVES:To assess the relationship between maternal blood lead levels and umbilical cord blood lead levels in their corresponding newborn infants; to determine factors associated with high blood lead levels and the pregnancy outcome in participants. MATERIALS AND METHODS:This was a cross-sectional descriptive study carried out at a tertiary Teaching Hospital, Lagos, Nigeria. Four hundred and forty pregnant women and their respective newborns delivered at the study centre. Blood samples were obtained from the mothers and umbilical cord of the newborns at delivery and analysed by atomic absorption spectrophotometry. Socio-demographic and obstetric data was obtained by questionnaires administered to the mothers. The anthropometric measurements of the babies were taken at birth and clinical data recorded. Main outcome measures were blood lead levels in mother and baby pair, socio-demographic factors, birth weight, gestational age, length, occipito-frontal circumference. RESULTS:The median maternal and umbilical blood lead level was 64.3μg/dl and 39.2μg/dl respectively. The levels were above 5μg/dl in 75.6% and 66.8% of mothers and umbilical cord respectively. There was a strong positive correlation between the maternal and umbilical cord blood lead levels (rs = 0.80). Use of calcium supplements during pregnancy was significantly associated with a lower maternal blood lead level (p = 0.010) while recent painting and renovation of residential accommodation were associated with a higher umbilical cord blood lead level (p = 0.025). There were no statistically significant associations between the maternal and umbilical cord blood lead levels and the gestational age and anthropometry of the newborns at birth. CONCLUSIONS:The blood lead levels in newborns of women residing in Lagos, Nigeria are high and administration of antenatal calcium is associated with lower blood lead levels.

Project description:BackgroundStudies have evaluated environmental exposure to toxic metals such as arsenic (As), cadmium (Cd), manganese (Mn), or lead (Pb) on birth size; however, information on potential effects of exposures to metal mixtures is limited.ObjectivesWe assessed the association between metal mixtures (As, Cd, Mn, Pb) in umbilical cord blood and neonate size in Bangladeshi children.MethodsIn this birth cohort study, pregnant women who were ≥18 years of age with an ultrasound-confirmed singleton pregnancy of ≤16wk gestation were recruited from two Bangladesh clinics between 2008 and 2011. Neonate size metrics were measured at the time of delivery. Metals in cord blood were measured using inductively coupled plasma mass spectrometry. We employed multivariable linear regression and Bayesian kernel machine regression (BKMR) to estimate associations of individual metals and metal mixtures with birth size parameters.ResultsData from 1,088 participants was assessed. We found a significant negative association between metal mixture and birth length and head circumference when all metal concentrations were above the 60th and 55th percentiles, respectively, compared with the median. An interquartile range (IQR) increase in log Cd concentration {log[Cd (in micrograms per deciliter)] IQR=2.51} was associated with a 0.13-standard deviation (SD) decrease in mean birth length (95% CI: -0.25, -0.02) and a 0.17-SD decrease in mean head circumference (95% CI: -0.28, -0.05), based on linear regression models adjusted for covariates and the other metals. An IQR increase in log Mn concentration {log[Mn (in micrograms per deciliter)] IQR=0.69} was associated with a 0.07-SD decrease in mean birth weight (95% CI: -0.15, 0.002).DiscussionMetal mixtures in cord blood were associated with reduced birth size in Bangladeshi children. Results from linear regression models adjusted and the BKMR mixtures analyses suggest adverse effects of Cd and Mn, as individual metal exposures, on birth size outcomes. https://doi.org/10.1289/EHP7502.

Project description:BackgroundInorganic arsenic (iAs) is a ubiquitous metalloid and drinking water contaminant. Prenatal exposure is associated with birth outcomes across multiple studies. During metabolism, iAs is sequentially methylated to mono- and di-methylated arsenical species (MMAs and DMAs) to facilitate whole body clearance. Inefficient methylation (e.g., higher urinary % MMAs) is associated with increased risk of certain iAs-associated diseases. One-carbon metabolism factors influence iAs methylation, modifying toxicity in adults, and warrant further study during the prenatal period. The objective of this study was to evaluate folate, vitamin B12, and homocysteine as modifiers of the relationship between biomarkers of iAs methylation efficiency and birth outcomes.MethodsData from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort (2011-2012) with maternal urine and cord serum arsenic biomarkers and maternal serum folate, vitamin B12, and homocysteine concentrations were utilized. One-carbon metabolism factors were dichotomized using clinical cutoffs and median splits. Multivariable linear regression models were fit to evaluate associations between each biomarker and birth outcome overall and within levels of one-carbon metabolism factors. Likelihood ratio tests of full and reduced models were used to test the significance of statistical interactions on the additive scale (α = 0.10).ResultsAmong urinary biomarkers, % U-MMAs was most strongly associated with birth weight (β = - 23.09, 95% CI: - 44.54, - 1.64). Larger, more negative mean differences in birth weight were observed among infants born to women who were B12 deficient (β = - 28.69, 95% CI: - 53.97, - 3.42) or experiencing hyperhomocysteinemia (β = - 63.29, 95% CI: - 154.77, 28.19). Generally, mean differences in birth weight were attenuated among infants born to mothers with higher serum concentrations of folate and vitamin B12 (or lower serum concentrations of homocysteine). Effect modification by vitamin B12 and homocysteine was significant on the additive scale for some associations. Results for gestational age were less compelling, with an approximate one-week mean difference associated with C-tAs (β = 0.87, 95% CI: 0, 1.74), but not meaningful otherwise.ConclusionsTissue distributions of iAs and its metabolites (e.g., % MMAs) may vary according to serum concentrations of folate, vitamin B12 and homocysteine during pregnancy. This represents a potential mechanism through which maternal diet may modify the harms of prenatal exposure to iAs.

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Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

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Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study.

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