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1.
Neurotoxicology ; 87: 51-61, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478771

RESUMO

INTRODUCTION: Understanding the neurodevelopmental effects of manganese (Mn) is complicated due to its essentiality for growth and development. While evidence exists for the harmful effects of excess Mn, pediatric epidemiologic studies have observed inconsistent associations between Mn and child cognition. OBJECTIVE: We sought to estimate prospective associations between Mn measured in three different early-life time windows with adolescent cognition using deciduous teeth biomarkers. METHODS: Deciduous teeth were collected from 195 participants (ages 10-14 years) of the Public Health Impact of Manganese Exposure (PHIME) study in Brescia, Italy. Measurements of tooth Mn represented prenatal (∼14 weeks gestation - birth), early postnatal (birth - 1.5 years) and childhood (∼1.5 - 6 years) time windows. Neuropsychologists administered the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III), to obtain composite IQ and subtest scores. Associations between tooth Mn at each time window and adolescent WISC-III scores were estimated using multivariable linear regression. We tested differences in associations between Mn and outcomes across time windows using multiple informant models. Sex-specific associations were explored in stratified models. RESULTS: Adjusted associations between tooth Mn and composite IQ scores were positive in the prenatal period and negative in the childhood period. Associations were strongest for subtest scores that reflect working memory, problem solving, visuospatial ability and attention: prenatal Mn was positively associated with Digits backward [SD change in score per interquartile range increase in Mn: ß = 0.20 (95 % CI: 0.02, 0.38)] and Block design [ß = 0.21 (0.01, 0.41)] and early postnatal Mn was positively associated with Digits forward [ß = 0.24 (0.09, 0.40)], while childhood Mn was negatively associated with Coding [ß = -0.14 (-0.28, -0.001)]. Sex-stratified analyses suggested different Mn-cognition associations for boys and girls and was also dependent on the time window of exposure. CONCLUSION: Our results suggest that exposure timing is critical when evaluating Mn associations between Mn and cognition. Higher prenatal Mn was beneficial for adolescent cognition; however, these beneficial associations shifted towards harmful effects in later time windows. Cognitive domains most sensitive to Mn across time windows included visuospatial ability, working memory, attention and problem-solving.

2.
Neurotoxicology ; 87: 86-93, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34478773

RESUMO

Foods and beverages provide a source of fluoride exposure in Mexico. While high fluoride concentrations are neurotoxic, recent research suggests that exposures within the optimal range may also pose a risk to the developing brain. This prospective study examined whether dietary fluoride intake during pregnancy is associated with toddlers' neurodevelopment in 103 mother-child pairs from the PROGRESS cohort in Mexico City. Food and beverage fluoride intake was assessed in trimesters 2 and 3 using a food frequency questionnaire and Mexican tables of fluoride content. We used the Bayley-III to evaluate cognitive, motor, and language outcomes at 12 and 24 months of age. Adjusted linear regression models were generated for each neurodevelopment assessment time point (12 and 24 months). Mixed-effects models were used to consider a repeated measurement approach. Interactions between maternal fluoride intake and child sex on neurodevelopmental outcomes were tested. Median (IQR) dietary fluoride intake during pregnancy was 1.01 mg/d (0.73, 1.32). Maternal fluoride intake was not associated with cognitive, language, or motor outcomes collapsing across boys and girls. However, child sex modified the association between maternal fluoride intake and cognitive outcome (p interaction term = 0.06). A 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.50-point lower cognitive outcome in 24-month old boys (95 % CI: -6.58, -0.42); there was no statistical association with girls (ß = 0.07, 95 % CI: -2.37, 2.51), nor on the cognitive outcome at 12-months of age. Averaging across the 12- and 24-month cognitive outcomes using mixed-effects models revealed a similar association: a 0.5 mg/day increase in overall dietary fluoride intake was associated with a 3.46-point lower cognitive outcome in boys (95 % CI: -6.23, -0.70). These findings suggest that the development of nonverbal abilities in males may be more vulnerable to prenatal fluoride exposure than language or motor abilities, even at levels within the recommended intake range.

3.
Environ Res ; 204(Pt B): 112062, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537199

RESUMO

Air pollution exposure, especially particulate matter ≤2.5 µm in diameter (PM2.5), is associated with poorer kidney function in adults and children. Perinatal exposure may occur during susceptible periods of nephron development. We used distributed lag nonlinear models (DLNMs) to examine time-varying associations between early life daily PM2.5 exposure (periconceptional through age 8 years) and kidney parameters in preadolescent children aged 8-10 years. Participants included 427 mother-child dyads enrolled in the PROGRESS birth cohort study based in Mexico City. Daily PM2.5 exposure was estimated at each participant's residence using a validated satellite-based spatio-temporal model. Kidney function parameters included estimated glomerular filtration rate (eGFR), serum cystatin C, and blood urea nitrogen (BUN). Models were adjusted for child's age, sex and body mass index (BMI) z-score, as well as maternal education, indoor smoking report and seasonality (prenatal models were additionally adjusted for average first year of life PM2.5 exposure). We also tested for sex-specific effects. Average perinatal PM2.5 was 22.7 µg/m3 and ranged 16.4-29.3 µg/m3. Early pregnancy PM2.5 exposures were associated with higher eGFR in preadolescence. Specifically, we found that PM2.5 exposure between weeks 1-18 of gestation was associated with increased preadolescent eGFR, whereas exposure in the first 14 months of life after birth were associated with decreased eGFR. Specifically, a 5 µg/m3 increase in PM2.5 during the detected prenatal window was associated with a cumulative increase in eGFR of 4.44 mL/min/1.732 (95%CI: 1.37, 7.52), and during the postnatal window we report a cumulative eGFR decrease of -10.36 mL/min/1.732 (95%CI: -17.68, -3.04). We identified perinatal windows of susceptibility to PM2.5 exposure with preadolescent kidney function parameters. Follow-up investigating PM2.5 exposure with peripubertal kidney function trajectories and risk of kidney disease in adulthood will be critical.

4.
Environ Res ; 204(Pt B): 112111, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34563522

RESUMO

BACKGROUND/AIM: Adiposity trajectories reflect dynamic process of growth and may predict later life health better than individual measures. Prenatal phthalate exposures may program later childhood adiposity, but findings from studies examining these associations are conflicting. We investigated associations between phthalate biomarker concentrations during pregnancy with child adiposity trajectories. METHODS: We followed 514 mother-child pairs from the Mexico City PROGRESS cohort from pregnancy through twelve years. We measured concentrations of nine phthalate biomarkers in 2nd and 3rd trimester maternal urine samples to create a pregnancy average using the geometric mean. We measured child BMI z-score, fat mass index (FMI), and waist-to-height ratio (WHtR) at three study visits between four and 12 years of age. We identified adiposity trajectories using multivariate latent class growth modeling, considering BMI z-score, FMI, and WHtR as joint indicators of latent adiposity. We estimated associations of phthalates biomarkers with class membership using multinomial logistic regression. We used quantile g-computation to estimate the potential effect of the total phthalate mixture and assessed effect modification by sex. RESULTS: We identified three trajectories of child adiposity, a "low-stable", a "low-high", and a "high-high" group. A doubling of the sum of di (2-ethylhexyl) phthalate metabolites (ΣDEHP), was associated with 1.53 (1.08, 2.19) greater odds of being in the "high-high" trajectory in comparison to the "low-stable" group, whereas a doubling in di-isononyl phthalate metabolites (ΣDiNP) was associated with 1.43 (1.02, 2.02) greater odds of being in the "low-high" trajectory and mono (carboxy-isononyl) phthalate (MCNP) was associated with 0.66 (0.45, 97) lower odds of being in the "low-high" trajectory. No sex-specific associations or mixture associations were observed. CONCLUSIONS: Prenatal concentrations of urinary DEHP metabolites, DiNP metabolites, and MCNP, a di-isodecyl phthalate metabolite, were associated with trajectories of child adiposity. The total phthalate mixture was not associated with early life child adiposity.

5.
Environ Res ; 204(Pt A): 112014, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34506780

RESUMO

BACKGROUND: Early-life renal maturation is susceptible to nephrotoxic environmental chemicals. Given the widespread consumption of fluoride and the global obesity epidemic, our main aim was to determine whether childhood fluoride exposure adversely affects kidney function in preadolescence, and if adiposity status modifies this association. METHODS: Our study included 438 children from the PROGRESS cohort. Urinary fluoride (uF) was assessed at age 4 by diffusion analysis; outcomes studied included estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), selected kidney proteins and blood pressure measured at age 8-12 years. We modeled the relationship between uF and outcomes, and adjusted for body mass index (BMI), age, sex, and socioeconomic status. RESULTS: The median uF concentration was 0.67 µg/mL. We observed null associations between 4-year uF and preadolescent eGFR, although effect estimates were in the expected inverse direction. A single unit increase in ln-transformed uF was associated with a 2.2 mL/min decrease in cystatin C-based eGFR (95% CI: 5.8, 1.4; p = 0.23). We observed no evidence of sex-specific effects or effect modification by BMI status. Although uF was not associated with BMI, among children with obesity, we observed an inverse association (ß: 4.8; 95% CI: 10.2, 0.6; p = 0.08) between uF and eGFR. CONCLUSIONS: Low-level fluoride exposure in early childhood was not associated with renal function in preadolescence. However, given the adverse outcomes of chronic fluoride consumption it is possible that the preadolescent age was too young to observe any effects. Longitudinal follow-up in this cohort and others is an important next step.

6.
Epigenetics ; 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34569420

RESUMO

DNA methylation (DNAm) is vulnerable to dysregulation by environmental exposures during epigenetic reprogramming that occurs in embryogenesis. Sexual dimorphism in environmentally induced DNAm dysregulation has been identified and therefore it is important to understand sex-specific DNAm patterns. DNAm at several autosomal sites has been consistently associated with sex in cord blood and placental fetal tissues. However, there is limited research comparing sex-specific DNAm across tissues, particularly differentially methylated regions (DMRs). This study leverages DNAm data measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify autosomal DMRs and differentially methylated positions (DMPs). A replication analyses was conducted in an independent cohort (GEO Accession GSE129841). We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively. Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis (NKAPL, PIWIL2, AURKC) and X-inactivation (LRIF1). In replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall DMRs and DMPs had higher methylation levels among females in cord blood and artery samples, but higher methylation levels among males in placenta samples. Further research is necessary to understand biological mechanisms that contribute to differences in sex-specific DNAm signatures across tissues, as well as to determine if sexual dimorphism in the epigenome impacts response to environmental stressors.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34444524

RESUMO

The aim of this study was to examine changes in depression, stress and social support levels before and during the COVID-19 pandemic in women living in Mexico City. We studied 466 women enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study who completed the Edinburgh Depression Scale (EDS) questionnaire prior (2018-2019) and during the lockdown period of the pandemic (May-November 2020). Psychosocial stress and social support for both time periods were ascertained using the Crisis in Family Systems (CRISYS) questionnaire and the Social Support Network (SSN) Scale, respectively. Associations between stress, social support and change in EDS score/depression were analyzed using generalized linear models adjusting for covariates. Higher stress (>median) during the pandemic was associated with an increase in EDS score (ß: 2.13; 95% CI (1.06, 3.19), p < 0.001), and higher odds of depression (OR: 3.75; 95% CI (2.17, 6.50), p < 0.001), while social support was associated with lower odds of depression (OR: 0.56, 95% CI (0.32, 0.97), p = 0.037). Higher levels of stress during the pandemic were associated with depression. Social support may act as a buffer for the effects of psychosocial stress. Future studies should examine the long-term effects of stress associated with the pandemic on mental and overall health.


Assuntos
COVID-19 , Pandemias , Ansiedade , Controle de Doenças Transmissíveis , Depressão/epidemiologia , Feminino , Humanos , México/epidemiologia , SARS-CoV-2 , Apoio Social
8.
Environ Res ; 202: 111651, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246643

RESUMO

INTRODUCTION: Prenatal exposure to fine particulate matter air pollution (PM2.5) is an important, under-studied risk factor for neurodevelopmental dysfunction. We describe the relationships between prenatal PM2.5 exposure and vigilance and inhibitory control, executive functions related to multiple health outcomes in Mexico City children. METHODS: We studied 320 children enrolled in Programming Research in Obesity, GRowth, Environment and Social Stressors, a longitudinal birth cohort study in Mexico City. We used a spatio-temporal model to estimate daily prenatal PM2.5 exposure at each participant's residential address. At age 9-10 years, children performed three Go/No-Go tasks, which measure vigilance and inhibitory control ability. We used Latent class analysis (LCA) to classify performance into subgroups that reflected neurocognitive performance and applied multivariate regression and distributed lag regression modeling (DLM) to test overall and time-dependent associations between prenatal PM2.5 exposure and Go/No-Go performance. RESULTS: LCA detected two Go/No-Go phenotypes: high performers (Class 1) and low performers (Class 2). Predicting odds of Class 1 vs Class 2 membership based on prenatal PM2.5 exposure timing, logistic regression modeling showed that average prenatal PM2.5 exposure in the second and third trimesters correlated with increased odds of membership in low-performance Class 2 (OR = 1.59 (1.16, 2.17), p = 0.004). Additionally, DLM analysis identified a critical window consisting of gestational days 103-268 (second and third trimesters) in which prenatal PM2.5 exposure predicted poorer Go/No-Go performance. DISCUSSION: Increased prenatal PM2.5 exposure predicted decreased vigilance and inhibitory control at age 9-10 years. These findings highlight the second and third trimesters of gestation as critical windows of PM2.5 exposure for the development of vigilance and inhibitory control in preadolescent children. Because childhood development of vigilance and inhibitory control informs behavior, academic performance, and self-regulation into adulthood, these results may help to describe the relationship of prenatal PM2.5 exposure to long-term health and psychosocial outcomes. The integrative methodology of this study also contributes to a shift towards more holistic analysis.

9.
Environ Res ; 201: 111540, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34166661

RESUMO

BACKGROUND: Lead (Pb), manganese (Mn), selenium (Se) and methylmercury (MeHg) can be neurotoxic individually, despite Mn and Se also being essential elements. Little is known about the joint effects of essential and non-essential elements on neurobehavior, particularly for prenatal exposures. OBJECTIVES: To evaluate associations of prenatal exposure to multiple elements with executive function and neurobehavior in children. METHODS: Participants included 1009 mother-child pairs from the Project Viva pre-birth cohort. We estimated maternal erythrocyte Pb, Mn, Se, and Hg concentrations prenatally. In 6-11-year old children (median 7.6 years), parents and teachers rated children's executive function-related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. We evaluated associations of element mixtures with neurobehavior using Bayesian kernel machine regression (BKMR), multivariable linear regression, and quantile g-computation. RESULTS: Median erythrocyte Pb, Mn, Se, and Hg concentrations were 1.1 µg/dL, 33.1 µg/L, 204.5 ng/mL, and 3.1 ng/g, respectively. Findings from BKMR and quantile g-computation models both showed worse (higher) parent-rated BRIEF and SDQ z-scores with higher concentrations of the mixture, although estimates were imprecise. When remaining elements were set at their median within BKMR models, increases in Pb and Se from the 25th to 75th percentile of exposure distributions were associated with 0.08 (95% CI: 0.02, 0.19) and 0.07 (95% CI: 0.03, 0.16) standard deviation increases in parent-rated BRIEF scores, and 0.08 (95% CI: 0.02, 0.17) and 0.05 (95% CI: 0.03, 0.13) standard deviation increases in SDQ scores, respectively. There was no evidence of element interactions. DISCUSSION: Although associations were small in magnitude, we found a trend of worsening neurobehavioral ratings with increasing prenatal exposure to an element mixture. However, we may be observing a limited range of dose-dependent impacts given the levels of exposure within our population.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Teorema de Bayes , Criança , Estudos de Coortes , Função Executiva , Feminino , Humanos , Manganês/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
10.
Environ Int ; 155: 106690, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34120006

RESUMO

Metals are involved in glucose metabolism, and some may alter glycemic regulation. However, joint effects of essential and non-essential metals on glucose concentrations during pregnancy are unclear. This study explored the joint associations of pregnancy exposures to essential (copper, magnesium, manganese, selenium, zinc) and non-essential (arsenic, barium, cadmium, cesium, lead, mercury) metals with gestational glucose concentrations using 1,311 women enrolled 1999-2002 in Project Viva, a Boston, MA-area pregnancy cohort. The study measured erythrocyte metal concentrations from 1st trimester blood samples and used glucose concentrations measured 1 h after non-fasting 50-gram glucose challenge tests (GCT) from clinical gestational diabetes screening at 26-28 weeks gestation. Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation were applied to model the associations of metal mixtures-including their interactions-with glucose concentrations post-GCT. We tested for reproducibility of BKMR results using generalized additive models. The BKMR model showed an inverse U-shaped association for barium and a linear inverse association for mercury. Specifically, estimated mean glucose concentrations were highest around 75th percentile of barium concentrations [2.1 (95% confidence interval: -0.2, 4.4) mg/dL higher comparing to the 25th percentile], and each interquartile range increase of erythrocyte mercury was associated with 1.9 mg/dL lower mean glucose concentrations (95% credible interval: -4.2, 0.4). Quantile g-computation showed joint associations of all metals, essential-metals, and non-essential metals on gestational glucose concentrations were all null, however, we observed evidences of interaction for barium and lead. Overall, we found early pregnancy barium and mercury erythrocytic concentrations were associated with altered post-load glucose concentrations in later pregnancy, with potential interactions between barium and lead.


Assuntos
Diabetes Gestacional , Teorema de Bayes , Feminino , Glucose , Humanos , Gravidez , Segundo Trimestre da Gravidez , Reprodutibilidade dos Testes
11.
Environ Int ; 156: 106714, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34147999

RESUMO

BACKGROUND: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. OBJECTIVES: To estimate individual and joint effects of metal mixture components on birth outcomes. METHODS: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. RESULTS: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. DISCUSSION: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.


Assuntos
Arsênio , Arsênio/análise , Arsênio/toxicidade , Teorema de Bayes , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Lactente , Masculino , Exposição Materna/efeitos adversos , Gravidez , Estudos Prospectivos
12.
Front Public Health ; 9: 653599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178917

RESUMO

Background: An untargeted chemical analysis of bio-fluids provides semi-quantitative data for thousands of chemicals for expanding our understanding about relationships among metabolic pathways, diseases, phenotypes and exposures. During the processing of mass spectral and chromatography data, various signal thresholds are used to control the number of peaks in the final data matrix that is used for statistical analyses. However, commonly used stringent thresholds generate constrained data matrices which may under-represent the detected chemical space, leading to missed biological insights in the exposome research. Methods: We have re-analyzed a liquid chromatography high resolution mass spectrometry data set for a publicly available epidemiology study (n = 499) of human cord blood samples using the MS-DIAL software with minimally possible thresholds during the data processing steps. Peak list for individual files and the data matrix after alignment and gap-filling steps were summarized for different peak height and detection frequency thresholds. Correlations between birth weight and LC/MS peaks in the newly generated data matrix were computed using the spearman correlation coefficient. Results: MS-DIAL software detected on average 23,156 peaks for individual LC/MS file and 63,393 peaks in the aligned peak table. A combination of peak height and detection frequency thresholds that was used in the original publication at the individual file and the peak alignment levels can reject 90% peaks from the untargeted chemical analysis dataset that was generated by MS-DIAL. Correlation analysis for birth weight data suggested that up to 80% of the significantly associated peaks were rejected by the data processing thresholds that were used in the original publication. The re-analysis with minimum possible thresholds recovered metabolic insights about C19 steroids and hydroxy-acyl-carnitines and their relationships with birth weight. Conclusions: Data processing thresholds for peak height and detection frequencies at individual data file and at the alignment level should be used at minimal possible level or completely avoided for mining untargeted chemical analysis data in the exposome research for discovering new biomarkers and mechanisms.


Assuntos
Metabolômica , Software , Cromatografia Líquida , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Espectrometria de Massas
13.
Environ Int ; 155: 106612, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33965768

RESUMO

BACKGROUND: Pregnancy induces numerous cardiovascular and metabolic changes. Alterations in these sensitive processes may precipitate long-term post-delivery health consequences. Studies have reported associations between phthalates and metabolic complications of pregnancy, but no study has investigated metabolic outcomes beyond pregnancy. OBJECTIVES: To examine associations of exposure to phthalates during pregnancy with post-delivery metabolic health. DESIGN: We quantified 15 urinary phthalate biomarker concentrations during the second and third trimesters among 618 pregnant women from Mexico City. Maternal metabolic health biomarkers included fasting blood measures of glycemia [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance [HOMA-IR], % hemoglobin A1c (HbA1c%)] and lipids (total, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, triglycerides), at 4-5 and 6-8 years post-delivery. To estimate the influence of the phthalates mixture, we used Bayesian weighted quantile sum regression and Bayesian kernel machine regression; for individual biomarkers, we used linear mixed models. RESULTS: As a mixture, higher urinary phthalate biomarker concentrations during pregnancy were associated with post-delivery concentrations of plasma glucose (interquartile range [IQR] difference: 0.13 SD, 95%CrI: 0.05, 0.20), plasma insulin (IQR difference: 0.06 SD, 95%CrI: -0.02, 0.14), HOMA-IR (IQR difference: 0.08 SD, 95% CrI: 0.01, 0.16), and HbA1c% (IQR difference: 0.15 SD, 95%CrI: 0.05, 0.24). Associations were primarily driven by mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) and the sum of dibutyl phthalate biomarkers (∑DBP). The phthalates mixture was associated with lower HDL (IQR difference: -0.08 SD, 95%CrI: -0.16, -0.01), driven by ∑DBP and monoethyl phthalate (MEP), and higher triglyceride levels (IQR difference: 0.15 SD, 95%CrI: 0.08, 0.22), driven by MECPTP and MEP. The overall mixture was not associated with total cholesterol and LDL. However, ∑DBP and MEP were associated with lower and higher total cholesterol, respectively, and MECPTP and ∑DBP were associated with lower LDL. CONCLUSIONS: Phthalate exposure during pregnancy is associated with adverse long-term changes in maternal metabolic health. A better understanding of timing of the exact biological changes and their implications on metabolic disease risk is needed.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Teorema de Bayes , Biomarcadores , Glicemia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Feminino , Humanos , Lipídeos , Ácidos Ftálicos/toxicidade , Gravidez
14.
Environ Res ; 201: 111338, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34051199

RESUMO

BACKGROUND: Phthalate exposure has been associated with increased childhood behavioral problems. Existing studies failed to include phthalate replacements and did not account for high correlations among phthalates. Phthalates' exposure is higher in Mexico than in U.S. locations, making it an ideal target population for this study. AIM: To examine associations between 15 maternal prenatal phthalate metabolite concentrations and children's behavioral problems. METHODS: We quantified phthalate metabolites in maternal urine samples from maternal-child dyads (n = 514) enrolled in the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) birth cohort in Mexico City. We performed least absolute shrinkage and selection operator (LASSO) regressions to identify associations between specific-gravity adjusted log2-transformed phthalate metabolites and parent-reported 4-6 year old behavior on the Behavior Assessment System for Children (BASC-2), accounting for metabolite correlations. We adjusted for socio-demographic and birth-related factors, and examined associations stratified by sex. RESULTS: Higher prenatal mono-2-ethyl-5-carboxypentyl terephthalate (MECPTP) urinary concentrations were associated with increased hyperactivity scores in the overall sample (ß = 0.57, 95% CI = 0.17, 1.13) and in girls (ß = 0.54, 95% CI = 0.16, 1.08), overall behavioral problems in boys (ß = 0.58, 95% CI = 0.20, 1.15), and depression scores in boys (ß = 0.44, 95% CI = 0.06, 0.88). Higher prenatal monobenzyl phthalate (MBzP) concentrations were associated with reduced hyperactivity scores in girls (ß = -0.54, 95% CI = -1.08, -0.21). DISCUSSION: Our findings suggested that prenatal concentrations of phthalates and their replacements altered child neurodevelopment and those associations may be influenced sex.


Assuntos
Ácidos Ftálicos/urina , Efeitos Tardios da Exposição Pré-Natal , Comportamento Problema , Criança , Pré-Escolar , Feminino , Humanos , Masculino , México , Obesidade , Gravidez , Estresse Psicológico
15.
Am J Clin Nutr ; 114(2): 540-549, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34038956

RESUMO

BACKGROUND: Dietary sources of metals are not well established among pregnant women in the United States. OBJECTIVE: We aimed to perform a diet-wide association study (DWAS) of metals during the first trimester of pregnancy. METHODS: In early pregnancy (11.3 ± 2.8 weeks of gestation), 1196 women from Project Viva (recruited 1999-2002 in eastern Massachusetts) completed a validated FFQ (135 food items) and underwent measurements of erythrocyte metals [arsenic (As), barium, cadmium, cesium (Cs), copper, mercury (Hg), magnesium, manganese, lead (Pb), selenium (Se), zinc]. The DWAS involved a systematic evaluation and visualization of all bivariate relations for each food-metal combination. For dietary items with strong associations with erythrocyte metals, we applied targeted maximum likelihood estimations and substitution models to evaluate how hypothetical dietary interventions would influence metals' concentrations. RESULTS: Participants' mean ± SD age was 32.5 ± 4.5 y and prepregnancy BMI was 24.8 ± 5.4 kg/m2; they were mostly white (75.9%), college graduates (72.4%), married or cohabitating (94.6%), had a household income >$70,000/y (63.5%), and had never smoked (67.1%). Compared with other US-based cohorts, the overall diet quality of participants was above average, and concentrations of erythrocyte metals were lower. The DWAS identified significant associations of several food items with As, Hg, Pb, Cs, and Se; for example, As was higher for each SD increment in fresh fruit (11.5%; 95% CI: 4.9%, 18.4%), white rice (17.9%; 95% CI: 9.4%, 26.9%), and seafood (50.9%; 95% CI: 42.8%, 59.3%). Following the guidelines for pregnant women to consume ≤3 servings/wk of seafood was associated with lower As (-0.55 ng/g; 95% CI: -0.82, -0.28 ng/g) and lower Hg (-2.67 ng/g; 95% CI: -3.55, -1.80 ng/g). Substituting white rice with bread, pasta, tortilla, and potato was also associated with lower As (35%-50%) and Hg (35%-70%). CONCLUSIONS: Our DWAS provides a systematic evaluation of diet-metals relations. Prenatal diet may be an important source of exposures to metals.


Assuntos
Dieta , Exposição Ambiental , Eritrócitos/química , Contaminação de Alimentos , Metais/química , Adulto , Anatomia Transversal , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Gravidez
16.
Environ Int ; 154: 106414, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33678412

RESUMO

BACKGROUND: For the developing kidney, the prenatal period may represent a critical window of vulnerability to environmental insults resulting in permanent nephron loss. Given that the majority of nephron formation is complete in the 3rd trimester, we set out to test whether 1) prenatal lead exposure is associated with decreased preadolescent kidney function and 2) whether preadolescent obesity acts synergistically with early life lead exposure to reduce kidney function. METHODS: Our study included 453 mother-child pairs participating in the PROGRESS birth cohort. We assessed prenatal blood lead levels (BLLs) in samples collected in the 2nd and 3rd trimesters and at delivery, as well as tibial and patellar bone lead measures assessed one-month postpartum. Preadolescent estimated glomerular filtration rate (eGFR) was derived from serum levels of creatinine and/or cystatin C measured at age 8-12 years. We applied linear regression to assess the relationship between prenatal bone and BLL with preadolescent eGFR, and adjusted for covariates including age, sex, BMI z-score, indoor tobacco smoke exposure, and socioeconomic status. We also examined sex-specific associations and tested for effect modification by BMI status. RESULTS: We observed null associations between prenatal lead exposure and eGFR. However, in interaction analyses we found that among overweight children, there was an inverse association between BLL (assessed at 2nd and 3rd trimester and at delivery) and preadolescent eGFR. For example, among overweight participants, a one ln-unit increase in 2nd trimester BLL was associated with a 10.5 unit decrease in cystatin C-based eGFR (95% CI: -18.1, -2.8; p = 0.008). Regardless of lead exposure, we also observed null relationships between BMI z-score and eGFR overall, as well as among overweight participants. However, among participants with preadolescent obesity, we observed a significant 5.9-unit decrease in eGFR. We observed no evidence of sex-specific effects. CONCLUSIONS: Our findings, if confirmed in other studies, suggest a complex interplay between the combined adverse effects of adiposity and perinatal lead exposure as they relate to adolescent kidney function. Future studies will assess kidney function and adiposity trajectories through adolescence to better understand environmental risk factors for kidney function decline.


Assuntos
Chumbo , Adolescente , Índice de Massa Corporal , Criança , Creatinina , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Chumbo/toxicidade , Masculino , Gravidez
17.
Artigo em Inglês | MEDLINE | ID: mdl-33652701

RESUMO

Exposure to PM2.5 has been associated with the prevalence of obesity. In the Greater Mexico City Area (GMCA), both are ranked among the highest in the world. Our aim was to analyze this association in children, adolescents, and adults in the GMCA. We used data from the 2006 and 2012 Mexican National Surveys of Health and Nutrition (ENSANUT). Participants' past-year exposure to ambient PM2.5 was assessed using land use terms and satellite-derived aerosol optical depth estimates; weight and height were measured. We used survey-adjusted logistic regression models to estimate the odds ratios (ORs) of obesity (vs. normal-overweight) for every 10 µg/m3 increase in annual PM2.5 exposure for children, adolescents, and adults. Using a meta-analysis approach, we estimated the overall odds of obesity. We analyzed data representing 19.3 million and 20.9 million GMCA individuals from ENSANUT 2006 and 2012, respectively. The overall pooled estimate between PM2.5 exposure and obesity was OR = 1.96 (95% CI: 1.21, 3.18). For adolescents, a 10 µg/m3 increase in PM2.5 was associated with an OR of 3.53 (95% CI: 1.45, 8.58) and 3.79 (95% CI: 1.40, 10.24) in 2006 and 2012, respectively. More studies such as this are recommended in Latin American cities with similar air pollution and obesity conditions.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Adolescente , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Cidades/epidemiologia , Exposição Ambiental/análise , Humanos , México/epidemiologia , Obesidade/epidemiologia , Material Particulado/análise , Prevalência
18.
Int J Hyg Environ Health ; 233: 113695, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33582606

RESUMO

BACKGROUND: Recent studies have reported that air pollution exposure may have neurotoxic properties. OBJECTIVE: To examine longitudinal associations between prenatal particles less than 2.5 µm in diameter (PM2.5) exposure and neurodevelopment during the first two years of children's life. METHODS: Analysis was conducted in PROGRESS, a longitudinal birth cohort between 2007 and 2013 in Mexico City. We used satellite data to predict daily PM2.5 concentrations at high spatial resolution. Multivariate mixed-effect regression models were adjusted to examine cognitive, language and motor scores in children up to 24 months of age (n = 740) and each trimester-specific and whole pregnancy exposure to PM2.5. RESULTS: Models adjusted by child sex, gestational age, birth weight, smoking and mother's IQ, showed that each increase of 1 µg/m3 of PM2.5 was associated with a decreased language function of -0.38 points (95% CI: -0.77, -0.01). PM2.5 exposure at third trimester of pregnancy contributed most to the observed association. CONCLUSION: Our findings suggest that language development up to 24 months of age may be particularly sensitive to PM2.5 exposure during pregnancy.

19.
Epigenomics ; 13(7): 499-512, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33635093

RESUMO

Aims: The authors sought to examine associations between urinary exosomal miRNAs (exo-miRs), emerging biomarkers of renal health, and cardiorenal outcomes in early childhood. Materials & methods: The authors extracted exo-miRs in urine from 88 healthy Mexican children aged 4-6 years. The authors measured associations between 193 exo-miRs and cardiorenal outcomes: systolic/diastolic blood pressure, estimated glomerular filtration rate and urinary sodium and potassium levels. The authors adjusted for age, sex, BMI, socioeconomic status, indoor tobacco smoke exposure and urine specific gravity. Results: Multiple exo-miRs were identified meeting a false discovery rate threshold of q < 0.1. Specifically, three exo-miRs had increased expression with urinary sodium, 17 with urinary sodium-to-potassium ratio and one with decreased estimated glomerular filtration rate. Conclusions: These results highlight urinary exo-miRs as early-life biomarkers of children's cardiorenal health.

20.
Mol Psychiatry ; 26(6): 1832-1845, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33414500

RESUMO

Maternal anxiety during pregnancy is associated with adverse foetal, neonatal, and child outcomes, but biological mechanisms remain unclear. Altered foetal DNA methylation (DNAm) has been proposed as a potential underlying mechanism. In the current study, we performed a meta-analysis to examine the associations between maternal anxiety, measured prospectively during pregnancy, and genome-wide DNAm from umbilical cord blood. Sixteen non-overlapping cohorts from 12 independent longitudinal studies of the Pregnancy And Childhood Epigenetics Consortium participated, resulting in a combined dataset of 7243 mother-child dyads. We examined prenatal anxiety in relation to genome-wide DNAm and differentially methylated regions. We observed no association between the general symptoms of anxiety during pregnancy or pregnancy-related anxiety, and DNAm at any of the CpG sites, after multiple-testing correction. Furthermore, we identify no differentially methylated regions associated with maternal anxiety. At the cohort-level, of the 21 associations observed in individual cohorts, none replicated consistently in the other cohorts. In conclusion, contrary to some previous studies proposing cord blood DNAm as a promising potential mechanism explaining the link between maternal anxiety during pregnancy and adverse outcomes in offspring, we found no consistent evidence for any robust associations between maternal anxiety and DNAm in cord blood. Larger studies and analysis of DNAm in other tissues may be needed to establish subtle or subgroup-specific associations between maternal anxiety and the foetal epigenome.


Assuntos
Metilação de DNA , Epigenoma , Ansiedade/genética , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Feminino , Humanos , Gravidez
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