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In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

ABSTRACT: BACKGROUND:Low-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity. METHODS:This prospective study included 1442 mother-child pairs recruited at birth and followed up to age 15?years. Maternal Hg in red blood cells and plasma folate levels were measured in samples collected 1-3?days after delivery (a proxy for third trimester exposure). Adequate folate was defined as plasma folate ??20.4?nmol/L. Childhood OWO was defined as body mass index ??85% percentile for age and sex. RESULTS:The median (interquartile range) of maternal Hg levels were 2.11 (1.04-3.70) ?g/L. Geometric mean (95% CI) of maternal folate levels were 31.1 (30.1-32.1) nmol/L. Maternal Hg levels were positively associated with child OWO from age 2-15?years, independent of maternal pre-pregnancy OWO, diabetes, and other covariates. The relative risk (RR?=?1.24, 95% CI 1.05-1.47) of child OWO associated with the highest quartile of Hg exposure was 24% higher than those with the lowest quartile. Maternal pre-pregnancy OWO and/or diabetes additively enhanced Hg toxicity. The highest risk of child OWO was found among children of OWO and diabetic mothers in the top Hg quartile (RR?=?2.06; 95% CI 1.56-2.71) compared to their counterparts. Furthermore, adequate maternal folate status mitigated Hg toxicity. Given top quartile Hg exposure, adequate maternal folate was associated with a 34% reduction in child OWO risk (RR?=?0.66, 95% CI 0.51-0.85) as compared with insufficient maternal folate. There was a suggestive interaction between maternal Hg and folate levels on child OWO risk (p for interaction?=?0.086). CONCLUSIONS:In this US urban, multi-ethnic population, elevated in utero Hg exposure was associated with a higher risk of OWO in childhood, and such risk was enhanced by maternal OWO and/or diabetes and reduced by adequate maternal folate. These findings underscore the need to screen for Hg and to optimize maternal folate status, especially among mothers with OWO and/or diabetes.

SUBMITTER: Wang G

PROVIDER: S-EPMC6882077 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

Wang Guoying G DiBari Jessica J Bind Eric E Steffens Andrew M AM Mukherjee Jhindan J Bartell Tami R TR Bellinger David C DC Hong Xiumei X Ji Yuelong Y Wang Mei-Cheng MC Wills-Karp Marsha M Cheng Tina L TL Wang Xiaobin X

BMC medicine 20191128 1

<h4>Background</h4>Low-dose mercury (Hg) exposure has been associated with cardiovascular diseases, diabetes, and obesity in adults, but it is unknown the metabolic consequence of in utero Hg exposure. This study aimed to investigate the association between in utero Hg exposure and child overweight or obesity (OWO) and to explore if adequate maternal folate can mitigate Hg toxicity.<h4>Methods</h4>This prospective study included 1442 mother-child pairs recruited at birth and followed up to age 1 ...[more]

PMID: 31775748

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Project description:ImportanceThe first pediatric lead screening typically occurs at 1-year well-child care visits. However, data on the extent of maternal lead exposure and its long-term consequences for child health are lacking.ObjectiveTo investigate the associations between maternal red blood cell (RBC) lead levels and intergenerational risk of overweight or obesity (OWO) and whether adequate maternal folate status is associated with a reduction in OWO risk.Design, setting, and participantsProspective birth cohort study. The analysis was conducted from July 14, 2018, to August 2, 2019, at Johns Hopkins Bloomberg School of Public Health. This study included 1442 mother-child pairs recruited at birth from October 27, 2002, to October 10, 2013, and followed up prospectively at Boston Medical Center.Main outcomes and measuresChild body mass index (BMI) z score, calculated according to US national reference data, and OWO, defined as BMI at or exceeding the 85th percentile for age and sex. Maternal RBC lead levels and plasma folate levels were measured in samples obtained 24 to 72 hours after delivery; child whole-blood lead level was obtained from the first pediatric lead screening.ResultsThe mean (SD) age of mothers and children was 28.6 (6.5) years and 8.1 (3.1) years, respectively; 50.1% of children were boys. The median maternal RBC lead level and plasma folate level were 2.5 (interquartile range [IQR], 1.7-3.8) μg/dL and 32.2 (IQR, 22.1-44.4) nmol/L, respectively. The median child whole-blood lead level and child BMI z score were 1.4 (IQR, 1.4-2.0) μg/dL and 0.78 (IQR, -0.08 to 1.71), respectively. Maternal RBC lead level was associated with child OWO risk in a dose-response fashion, with an odds ratio (OR) of 1.65 (95% CI, 1.18-2.32) for high maternal RBC lead level (≥5.0 μg/dL) compared with low maternal RBC lead level (<2.0 μg/dL). Child OWO was highest among children of OWO mothers with high RBC lead levels (adjusted OR, 4.24; 95% CI, 2.64-6.82) compared with children of non-OWO mothers with low RBC lead levels. Children of OWO mothers with high RBC lead levels had 41% lower OWO risk (OR, 0.59; 95% CI, 0.36-0.95; P = .03) if their mothers had adequate plasma folate levels (≥20.4 nmol/L) compared with their counterparts.Conclusions and relevanceIn this sample of a US urban population, findings suggest that maternal elevated lead exposure was associated with increased risk of intergenerational OWO independent of postnatal blood lead levels. Adequate maternal folate status appeared to be associated with lower OWO risk. If confirmed by additional studies, these findings have implications for prenatal lead screening and management to minimize adverse health consequences on children.

Project description:Background/objectivesLow-level, in-utero exposure to toxic metals such as lead (Pb) and mercury (Hg) is widespread in the US and worldwide; and, individually, was found to be obesogenic in children. To address the literature gaps on the health effects of co-exposure to low-level toxic metals and the lack of intervention strategy, we aimed to investigate the association between in-utero co-exposure to Hg, Pb, cadmium (Cd) and childhood overweight or obesity (OWO) and whether adequate maternal micronutrients (selenium (Se) and folate) can be protective.Subjects/methodsThis study included 1442 mother-child pairs from the Boston Birth Cohort, a predominantly urban, low-income, Black, and Hispanic population, who were enrolled at birth and followed prospectively up to age 15 years. Bayesian kernel machine regression (BKMR) was applied to estimate individual and joint effects of exposures to metals and micronutrients on childhood OWO while adjusting for pertinent covariables. Stratified analyses by maternal OWO and micronutrient status were performed to identify sensitive subgroups.ResultsIn this sample of understudied US children, low-level in-utero co-exposure to Hg, Pb, and Cd was widespread. Besides individual positive associations of maternal Hg and Pb exposure with offspring OWO, BKMR clearly indicated a positive dose-response association between in-utero co-exposure to the three toxic metals and childhood OWO. Notably, the metal mixture-OWO association was more pronounced in children born to mothers with OWO; and in such a setting, the association was greatly attenuated if mothers had higher Se and folate levels.ConclusionsIn this prospective cohort of US children at high-risk of toxic metal exposure and OWO, we demonstrated that among children born to mothers with OWO, low-level in-utero co-exposure to Hg, Pb, and Cd increased the risk of childhood OWO; and that adequate maternal Se and folate levels mitigated the risk of childhood OWO.Clinical trial registry number and website where it was obtainedNCT03228875.

Project description:BackgroundAlthough previous studies suggest that exposure to traffic-related pollution during childhood increases the risk of childhood overweight or obesity (COWO), the role of early life exposure to fine particulate matter (aerodynamic diameter <2.5 ?m; PM2.5) and its joint effect with the mother’s prepregnancy body mass index (MPBMI) on COWO remain unclear.ObjectivesThe present study was conducted to examine the individual and joint effects of ambient PM2.5 exposures and MPBMI on the risk of COWO.MethodsWe estimated exposures to ambient PM2.5in utero and during the first 2 y of life (F2YL), using data from the U.S. Environmental Protection Agency’s (EPA’s) Air Quality System matched to residential address, in 1,446 mother–infant pairs who were recruited at birth from 1998 and followed up prospectively through 2012 at the Boston Medical Center in Massachusetts. We quantified the individual and joint effects of PM2.5 exposure with MPBMI on COWO, defined as the child’s age- and sex-specific BMI z-score ?85th?percentile at the last well-child care visit between 2 and 9 y of age. Additivity was assessed by estimating the reduced excess risk due to interaction.ResultsComparing the highest and lowest quartiles of PM2.5, the adjusted relative risks (RRs) [95% confidence intervals (CIs)] of COWO were 1.3 (95% CI: 1.1, 1.5), 1.2 (95% CI: 1.0, 1.4), 1.2 (95% CI: 1.0, 1.4), 1.3 (95% CI: 1.1, 1.6), 1.3 (95% CI: 1.1, 1.5) and 1.3 (1.1, 1.5) during preconception; the first, second, and third trimesters; the entire period of pregnancy; and F2YL, respectively. Spline regression showed a dose–response relationship between PM2.5 levels and COWO after a threshold near the median exposure (10.46 ?g/m3–10.89 ?g/m3). Compared with their counterparts, children of obese mothers exposed to high levels of PM2.5 had the highest risk of COWO [RR?2.0, relative excess risk due to interaction (RERI) not significant].ConclusionsIn the present study, we observed that early life exposure to PM2.5 may play an important role in the early life origins of COWO and may increase the risk of COWO in children of mothers who were overweight or obese before pregnancy beyond the risk that can be attributed to MPBMI alone. Our findings emphasize the clinical and public health policy relevance of early life PM2.5 exposure. https://doi.org/10.1289/EHP261

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In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

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In utero exposure to mercury and childhood overweight or obesity: counteracting effect of maternal folate status.

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