Prenatal Lead Exposure, Type 2 Diabetes, and Cardiometabolic Risk Factors in Mexican Children at Age 10-18 Years.
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ABSTRACT: Context
Several cross-sectional studies have assessed the association of lead exposure with type 2 diabetes and cardiometabolic risk factors in adults; however, studies of such associations in childhood are rare.Objective
We assessed the prospective associations of prenatal exposure to lead with type 2 diabetes and cardiometabolic risk factors in children.Design
The Early Life Exposure in Mexico to Environmental Toxicants is a birth cohort study of pregnant women and their offspring.Setting
Public hospitals in Mexico City.Patients or other participants
Women were recruited during pregnancy; their offspring were recruited for a follow-up visit at age 10 to 18 years (n = 369).Main outcome measures
We measured fasting serum markers of type 2 diabetes and cardiometabolic risk factors in children, including fasting glucose, insulin, and lipids. The index of insulin resistance was calculated.Results
The geometric mean of maternal blood lead levels (BLLs) during pregnancy was 4.3 µg/dL (95% confidence interval [CI]): 4.0-4.6 µg/dL) in the entire sample. In boys, those with maternal BLLs ≥ 5 µg/dL (compared with those with BLLs < 5 µg/dL) had significantly lower z scores for total cholesterol (β = -0.41, 95% CI: -0.71, -0.12), high-density lipoprotein cholesterol (β = -0.32, 95% CI: -0.59, -0.05), and low-density lipoprotein cholesterol (β = -0.52, 95% CI: -0.81, -0.22), adjusting for covariates. No associations were detected in girls.Conclusions
In our study, we found that higher prenatal exposure to lead was associated with lower levels of cholesterol in children following a sex-specific pattern. Further studies with a larger sample size that examine whether sex is a potential modifier are needed to confirm our findings.
SUBMITTER: Liu Y
PROVIDER: S-EPMC7037075 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms. METHODS:A subsample (n = 1,311) of the Avon Longitudinal Study of Parents and Children (Bristol, UK) was selected, and mercury (Hg) concentrations were measured in freeze-dried umbilical cord tissue as a measure of MeHg exposure. A total of 1135 children had available data on 247 single-nucleotide polymorphisms (SNPs) within relevant genes, as well as the Wechsler Intelligence Scale for Children Intelligence Quotient (IQ) scores at age 8 years. Multivariate regression models were used to assess the associations between MeHg exposure and IQ and to determine possible gene-environment interactions. RESULTS:Hg concentrations indicated low background exposures (mean = 26 ng/g, standard deviation = 13). Log10-transformed Hg was positively associated with IQ, which attenuated after adjustment for nutritional and sociodemographic cofactors. In stratified analyses, a reverse association was found in higher social class families (for performance IQ, P value for interaction = 0.0013) among whom there was a wider range of MeHg exposure. Among 40 SNPs showing nominally significant main effects, MeHg interactions were detected for rs662 (paraoxonase 1) and rs1042838 (progesterone receptor) (P < 0.05) and for rs3811647 (transferrin) and rs2049046 (brain-derived neurotrophic factor) (P < 0.10). CONCLUSIONS:In this population with a low level of MeHg exposure, there were only equivocal associations between MeHg exposure and adverse neuropsychological outcomes. Heterogeneities in several relevant genes suggest possible genetic predisposition to MeHg neurotoxicity in a substantial proportion of the population. Future studies need to address this possibility.
| S-EPMC6477679 | biostudies-literature
Project description:Importance:Although antibiotics are associated with obesity in animal models, the evidence in humans is conflicting. Objective:To assess whether antibiotic exposure during pregnancy and/or early childhood is associated with the development of childhood obesity, focusing particularly on siblings and twins. Design, Setting, and Participants:This cross-sectional national study included 284 211 participants (132 852 mothers and 151 359 children) in New Zealand. Data analyses were performed for 150 699 children for whom data were available, 30 696 siblings, and 4188 twins using covariate-adjusted analyses, and for 6249 siblings and 522 twins with discordant outcomes using fixed-effects analyses. Data analysis was performed November 2017 to March 2019. Exposure:Exposure to antibiotics during pregnancy and/or early childhood. Main Outcomes and Measures:The main outcome is odds of obesity at age 4 years. Anthropometric data from children born between July 2008 and June 2011 were obtained from the B4 School Check, a national health screening program that records the height and weight of 4-year-old children in New Zealand. These data were linked to antibiotics (pharmaceutical records) dispensed to women before conception and during all 3 trimesters of pregnancy and to their children from birth until age 2 years. Results:The overall study population consisted of 132 852 mothers and 151 359 children (77 610 [51.3%] boys) who were aged 4 to 5 years when their anthropometrical measurements were assessed. Antibiotic exposure was common, with at least 1 course dispensed to 35.7% of mothers during pregnancy and 82.3% of children during the first 2 years of life. Results from covariate-adjusted analyses showed that both prenatal and early childhood exposures to antibiotics were independently associated with obesity at age 4 years, in a dose-dependent manner. Every additional course of antibiotics dispensed to the mothers yielded an adjusted odds ratio (aOR) of obesity in their children (siblings) of 1.02 (95% CI, 0.99-1.06), which was similar to the odds across pregnancy for the whole population (aOR, 1.06; 95% CI, 1.04-1.07). For the child's exposure, the aOR for the association between antibiotic exposure and obesity was 1.04 (95% CI, 1.03-1.05) among siblings and 1.05 (95% CI, 1.02-1.09) among twins. However, fixed-effects analyses of siblings and twins showed no associations between antibiotic exposure and obesity, with aORs of 0.95 (95% CI, 0.90-1.00) for maternal exposure, 1.02 (95% CI, 0.99-1.04) for child's exposure, and 0.91 (95% CI, 0.81-1.02) for twins' exposure. Conclusions and Relevance:Although covariate-adjusted analyses demonstrated an association between antibiotic exposure and odds of obesity, further analyses of siblings and twins with discordant outcomes showed no associations. Thus, these discordant results likely reflect unmeasured confounding factors.
| S-EPMC6991276 | biostudies-literature
Project description:BackgroundPrevious reports suggest that prenatal phthalate exposure is associated with lower scores on measures of motor skills in infants and toddlers. Whether these associations persist into later childhood or preadolescence has not been studied.MethodsIn a follow up study of 209 inner-city mothers and their children the concentrations of mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monomethyl phthalate (MEP), mono-carboxy-isooctyl phthalate (MCOP), and four di-2-ethylhexyl phthalate metabolites (ΣDEHP) were measured in spot urine sample collected from the women in late pregnancy and from their children at ages 3, 5, and 7 years. The Bruininks-Oseretsky Test of Motor Proficiency short form (BOT-2) was administered at child age 11 to assess gross and fine motor skills.ResultsThe total number of children included in the study was 209. Of the 209 children, 116(55.5%) were girls and 93 were (45%) boys. Among girls, prenatal MnBP(b=-2.09; 95%CI: [-3.43, -0.75]), MBzP (b=-1.14; [95%CI: -2.13, -0.14]), and MiBP(b=-1.36; 95%CI: [-2.51, -0.21] and MEP(b=-1.23 [95%CI: -2.36, -0.11]) were associated with lower total BOT-2 composite score. MnBP (b= -1.43; 95% CI: [-2.44, -0.42]) was associated with lower fine motor scores and MiBP(b = -0.56; 95% CI: [-1.12, -0.01]) and MEP (b = -0.60; 95% CI: [-1.14, -0.06])was associated with lower gross motor scores. Among boys, prenatal MBzP (b = -0.79; 95% CI: [-1.40, -0.19]) was associated with lower fine motor composite score. The associations between MEP measured at age 3 and the BOT-2 gross motor, fine motor and total motor score differed by sex. In boys, there was an inverse association between ΣDEHP metabolites measured in childhood at ages 3 (b = -1.30; 95% CI: [-2.34, -0.26]) and 7 years (b = -0.96; 95% CI: [-1.79, -0.13]), and BOT-2 fine motor composite scores.ConclusionsHigher prenatal exposure to specific phthalates was associated with lower motor function among 11- year old girls while higher postnatal exposure to ΣDEHP metabolites was associated with lower scores among boys. As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development.
| S-EPMC6814270 | biostudies-literature
Project description:BackgroundAirborne polycyclic aromatic hydrocarbons (PAH) are widespread urban air pollutants from fossil fuel burning and other combustion sources. We previously reported that a broad spectrum of combustion-related DNA adducts in cord blood was associated with attention problems at 6-7 years of age in the Columbia Center for Children's Environmental Health (CCCEH) longitudinal cohort study.ObjectivesWe evaluated the relationship between behavioral problems and two different measures of prenatal exposure--both specific to PAH--in the same cohort.MethodsChildren of nonsmoking African-American and Dominican women in New York City (NYC) were followed from in utero to 6-7 years. Prenatal PAH exposure was estimated by personal air monitoring of the mothers during pregnancy as well as by the measurement of DNA adducts specific to benzo[a]pyrene (BaP), a representative PAH, in maternal and cord blood. At 6-7 years of age, child behavior was assessed using the Child Behavior Checklist (CBCL) (n = 253). Generalized linear models were used to test the association between prenatal PAH exposure and behavioral outcomes.ResultsIn multivariate analyses, high prenatal PAH exposure, whether characterized by personal air monitoring (greater than the median of 2.27 ng/m³) or maternal and cord adducts (detectable or higher), was positively associated with symptoms of Anxious/Depressed and Attention Problems (p ? 0.05).ConclusionThese results provide additional evidence that environmental levels of PAH encountered in NYC air can adversely affect child behavior.
| S-EPMC3385432 | biostudies-literature
Project description:BackgroundEmerging evidence suggests that phthalate exposure may be associated with behavior problems in children and that these associations may be sex specific.MethodsIn a follow up study of 411 inner-city minority mothers and their children, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monethyl phthalate (MEP) and four di-2-ethylhexyl phthalate metabolites (DEHP) were quantified in maternal urine samples collected during the third trimester and in child urine samples at ages 3 and 5 years. The Conners' Parent Rating Scale-Revised: Long Form (CPRS) and Child Behavior Checklist (CBCL) were administered to the mothers to assess children's behavior problems at 7 years of age. The analysis included children with available measures of CBCL, CPRS and phthalates measured in maternal urine. We performed both Quasi-Poisson regression and a mixture analysis using Weighted Quantile Sum(WQS) regression to assess the risk for CPRS scores and for internalizing and externalizing behaviors (from the CBCL) following intra-uterine exposure to the phthalate metabolites for boys and girls separately.ResultsAmong boys, increases in in anxious-shy behaviors were associated with prenatal exposure to MBzP (Mean Ratio [MR] = 1.20, 95%CI 1.05-1.36) and MiBP (Mean Ratio (MR) = 1.22, 95%CI 1.02-1.47). Among girls, increases in perfectionism were associated with MBzP (MR = 1.15, 95%CI 1.01-1.30). In both boys and girls, increases in psychosomatic problems were associated with MiBP (MR = 1.28, 95%CI 1.02-1.60), and MnBP (MR = 1.28, 95%CI 1.02-1.59), respectively. Among girls, decreased hyperactivity was associated with two DEHP metabolites, mono(2-ethyl-5-oxohexyl) phthalate (MR = 0.83, 95%CI 0.71-0.98) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MR = 0.85, 95%CI 0.72-0.99). Using weighted Quantile Sum logistic regression, no associations were found between the Weighted Quantile Sum (WQS) of phthalate metabolites and CPRS scores or externalizing and internalizing behaviors. Nonetheless, when the analysis was performed separately for DEHP and non-DEHP metabolites significant associations were found between the WQS of DEHP metabolites and social problems in boys (OR = 2.15, 95%CI 1.13-4.06, p-value = 0.02) anxious-shy problems in girls (OR = 2.19, 95%CI 1.15-4.16, p = 0.02), and emotional lability problems in all children (OR = 0.61, 95%CI 0.38-0.97, p = 0.04). MEHP and MEOHP were the most highly weighted DEHP metabolites in WQS mixture. The analysis performed with CBCL scale corroborated these associations.ConclusionConcentration of non-DEHP metabolites was associated with anxious-shy behaviors among boys. DEHP phthalate metabolites were associated with decreased hyperactivity and impulsivity among girls on CPRS scores. These findings lend further support to the adverse associations between prenatal phthalate exposure and childhood outcomes, and clearly suggest that such associations are sex and mixture specific.
| S-EPMC7867029 | biostudies-literature
Project description:BackgroundGestational lead (Pb) exposure can adversely affect offspring health through multiple mechanisms, including epigenomic alterations via DNA methylation (5mC) and hydroxymethylation (5hmC), an intermediate in oxidative demethylation. Most current methods do not distinguish between 5mC and 5hmC, limiting insights into their individual roles.ObjectiveOur study sought to identify the association of trimester-specific (T1, T2, T3) prenatal Pb exposure with 5mC and 5hmC levels at multiple cytosine-phosphate-guanine sites within gene regions previously associated with prenatal Pb (HCN2, NINJ2, RAB5A, TPPP) in whole blood leukocytes of children ages 11-18 years of age.MethodsParticipants from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) birth cohorts were selected (n=144) for pyrosequencing analysis following oxidative or standard sodium bisulfite treatment. This workflow directly quantifies total methylation (5mC+5hmC) and 5mC only; 5hmC is estimated by subtraction.ResultsParticipants were 51% male, and mean maternal blood lead levels (BLL) were 6.43±5.16μg/dL in Trimester 1 (T1), 5.66±5.21μg/dL in Trimester 2 (T2), and 5.86±4.34μg/dL in Trimester 3 (T3). In addition, 5hmC levels were calculated for HCN2 (mean±standard deviation(SD), 2.08±4.18%), NINJ2 (G/C: 2.01±5.95; GG: 0.90±3.97), RAB5A (0.66±0.80%), and TPPP (1.11±6.67%). Furthermore, 5mC levels were measured in HCN2 (81.3±9.63%), NINJ2 (heterozygotes: 38.6±7.39%; GG homozygotes: 67.3±9.83%), RAB5A (1.41±1.21%), and TPPP (92.5±8.03%). Several significant associations between BLLs and 5mC/5hmC were identified: T1 BLLs with 5mC in HCN2 (β=-0.37, p=0.03) and 5hmC in NINJ2 (β=0.49, p=0.003); T2 BLLs with 5mC in HCN2 (β=0.37, p=0.03) and 5hmC in NINJ2 (β=0.27, p=0.008); and T3 BLLs with 5mC in HCN2 (β=0.50, p=0.01) and NINJ2 (β=-0.35, p=0.004) and 5hmC in NINJ2 (β=0.45, p<0.001). NINJ2 5mC was negatively correlated with gene expression (Pearson r=-0.5, p-value=0.005), whereas 5hmC was positively correlated (r=0.4, p-value=0.04).DiscussionThese findings suggest there is variable 5hmC in human whole blood and that prenatal Pb exposure is associated with gene-specific 5mC and 5hmC levels at adolescence, providing evidence to consider 5hmC as a regulatory mechanism that is responsive to environmental exposures. https://doi.org/10.1289/EHP8507.
| S-EPMC8216410 | biostudies-literature
Project description:Abstract Objective Obesity in pregnancy and gestational diabetes (GDM) increase cardiometabolic disease risk but are difficult to disentangle. This study aimed to test the hypothesis that 4–10 years after a pregnancy complicated by overweight/obesity and GDM (OB‐GDM), women and children would have greater adiposity and poorer cardiometabolic health than those with overweight/obesity (OB) or normal weight (NW) and no GDM during the index pregnancy. Methods In this cross‐sectional study, mother‐child dyads were stratified into three groups based on maternal health status during pregnancy (OB‐GDM = 67; OB = 76; NW = 76). Weight, height, waist and hip circumferences, and blood pressure were measured, along with fasting glucose, insulin, HbA1c, lipids, adipokines, and cytokines. Results Women in the OB and OB‐GDM groups had greater current adiposity and poorer cardiometabolic health outcomes than those in the NW group (p < 0.05). After adjusting for current adiposity, women in the OB‐GDM group had higher HbA1c, glucose, HOMA‐IR and triglycerides than NW and OB groups (p < 0.05). Among children, adiposity was greater in the OB‐GDM versus NW group (p < 0.05), but other indices of cardiometabolic health did not differ. Conclusions Poor cardiometabolic health in women with prior GDM is independent of current adiposity. Although greater adiposity among children exposed to GDM is evident at 4–10 years, differences in cardiometabolic health may not emerge until later.
| S-EPMC9535673 | biostudies-literature
Project description:BackgroundPrior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.MethodsIn a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP), butylbenzyl phthalate (BBzP), di-isobutyl phthalate (DiBP), di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ).ResultsChild full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b?=?-2.69 (95% confidence interval [CI]?=?-4.33, -1.05) and b?=?-2.69 (95% CI?=?-4.22, -1.16) per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI?=?1.9, 11.4) and 7.6 (95% CI?=?3.2, 12.1) points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.ConclusionMaternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.
| S-EPMC4262205 | biostudies-literature
Project description:ObjectiveTo examine relationships between prenatal perfluoroalkyl substance (PFAS) exposure and adiposity in children born to women who lived downstream from a fluoropolymer manufacturing plant.MethodsData are from a prospective cohort in Cincinnati, Ohio (HOME Study). Perfluorooctanoic (PFOA), perfluorooctane sulfonic (PFOS), perfluorononanoic (PFNA), and perfluorohexane sulfonic (PFHxS) acids were measured in prenatal serum samples. Differences were measured in body mass index z-scores (BMI), waist circumference, and body fat at 8 years of age (n = 204) and BMI between 2-8 years of age (n = 285) according to PFAS concentrations.ResultsChildren born to women in the top two PFOA terciles had greater adiposity at 8 years than children in the 1st tercile. For example, waist circumference (cm) was higher among children in the 2nd (4.3; 95% CI: 1.7, 6.9) and 3rd tercile (2.2; 95% CI: -0.5, 4.9) compared to children in the 1st tercile. Children in the top two PFOA terciles also had greater BMI gains from 2 to 8 years compared to children in the 1st tercile (P < 0.05). PFOS, PFNA, and PFHxS were not associated with adiposity.ConclusionsIn this cohort, higher prenatal serum PFOA concentrations were associated with greater adiposity at 8 years and a more rapid increase in BMI between 2-8 years.
| S-EPMC4688224 | biostudies-literature
Project description:Neurodevelopmental delays can interfere with children's engagement with the world and further development, and may have negative consequences into adulthood. Mercury is highly toxic and may negatively influence neurodevelopment because it can freely cross the placenta and accumulate in the fetal brain. We searched four publication databases (Embase, PsycINFO, PubMed/MEDLINE, Scopus) for studies examining the relationship between early life mercury exposure and scores on neurodevelopmental performance measures in children aged 0 to 5 years old. Study quality was assessed using the National Institutes of Health (NIH) Quality Assessment Tool. Thirty-two prospective studies were included in the review. Neurodevelopmental performance was measured using 23 different scales, most commonly the Bayley Scales of Infant and Toddler Development (BSID). In most cases, the evidence for an association between mercury and neurodevelopment was weak. There did not appear to be exceptions for particular childhood ages, outcome scales, or mercury levels. The small number of results to the contrary were more likely to be studies which did not meet our high-quality criteria, and could be a consequence of multiple testing, selection bias, or incomplete confounder adjustment. Based on current evidence, dietary mercury exposure during pregnancy is unlikely to be a risk factor for low neurodevelopmental functioning in early childhood.
| S-EPMC8871549 | biostudies-literature