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1.
Epigenetics ; : 1-9, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31538540

RESUMO

DNA methylation microarrays have been the platform of choice for epigenome-wide association studies in epidemiology, but declining costs have rendered targeted bisulphite sequencing a feasible alternative. Nonetheless, the literature for researchers seeking guidance on which platform to choose is sparse. To fill this gap, we conducted a comparison study in which we processed cord blood samples from four newborns in duplicates using both the Illumina HumanMethylationEPIC BeadChip and the Illumina TruSeq Methyl Capture EPIC Kit, and evaluated both platforms in regard to coverage, reproducibility, and identification of differential methylation. We conclude that with current analytic goals microarrays still outperform bisulphite sequencing for precise quantification of DNA methylation.

2.
Kidney Int ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31563333

RESUMO

In June 2018, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences sponsored a workshop to identify research gaps in an increasingly common form of chronic kidney disease in agricultural communities, often termed "CKDu." The organizers invited a broad range of experts who provided diverse expertise and perspectives, many of whom had never addressed this particular epidemic. Discussion was focused around selected topics, including identifying and mitigating barriers to research in CKDu, creating a case definition, and defining common data elements. All hypotheses regarding etiology were entertained, and meeting participants discussed potential research strategies, choices in study design, and novel tools that may prove useful in this disease. Achievements of the workshop included robust cross-disciplinary discussion and preliminary planning of research goals and design. Specific challenges in implementing basic and clinical research and interventions in low- and middle-income countries were recognized. A balanced approach to leveraging local resources and capacity building without overreaching was emphasized.

3.
Neurotoxicology ; 75: 105-115, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31513824

RESUMO

BACKGROUND: Lead is an established neurotoxicant and early life exposure to lead is associated with detrimental impacts on IQ and several neurobehavioral domains. Less is known, however, about effects of prenatal lead exposure below 5 µg/dL on executive function and on social, emotional and self-regulatory behaviors in childhood. OBJECTIVES: To examine the association between prenatal lead exposure and childhood executive function and social, emotional and self-regulatory behaviors. METHODS: We included 1006 mother-child pairs from the Project Viva prospective pre-birth cohort. We measured prenatal maternal lead in second-trimester erythrocytes. In mid-childhood (median 7.7 years), parents and teachers rated executive function related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ). We used multivariable linear regression models adjusted for maternal, paternal, and child characteristics and metal co-exposures. RESULTS: Mean maternal erythrocyte lead concentration was 1.2 µg/dL (interquartile range [IQR] 0.8-1.5 µg /dL), equivalent to approximately 0.4 µg/dL in whole blood. In adjusted models, associations with parent and teacher-rated scales were largely null, although effect estimates were consistently positive, suggesting worse scores with increasing lead levels. For an IQR increase in lead, BRIEF Global Executive Composite (GEC) was 0.73 (95% CI: -0.06, 1.52) points higher for parent-rated scores and 0.42 (95% CI: -0.39, 1.23) points higher for teacher-rated scores. Associations were strongest for parent-rated BRIEF plan/organize (ß = 0.85; 95% CI: 0.12, 1.59) and shift (ß = 0.88; 95% CI: 0.01, 1.75) subscales, as well as the SDQ emotional problems subscale (ß = 0.18; 95% CI: 0.03, 0.33). DISCUSSION: In this cohort with lead levels commonly experienced by U.S. women, there were few statistically significant associations with childhood executive function and behavior. However, there was a trend of worse neurobehavioral scores with increasing prenatal lead concentrations, in particular for childhood emotional problems and capacity to plan/organize and shift. Our results highlight the importance of continuing efforts to eliminate lead exposure in the general population.

4.
PLoS One ; 14(8): e0220790, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31412061

RESUMO

Maturational processes in the developing brain are disrupted by exposure to environmental toxicants, setting the stage for deviant developmental trajectories. Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure, particularly affecting the basal ganglia and prefrontal cortex. Both the intensity and timing of exposure matter; deciduous teeth can be used to retrospectively and objectively determine early-life windows of vulnerability. The aim of this pilot study was to examine associations between prenatal, early postnatal and childhood dentine Mn concentrations and intrinsic functional connectivity (iFC) of adolescents' brains. 14 adolescents (12-18 years; 6 girls) from northern Italian regions with either current, historic or no Mn contamination, completed a 10-minute resting state functional Magnetic Resonance Imaging (MRI) scan in an 1.5T MRI scanner. We estimated prenatal, early postnatal and childhood Mn concentrations in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses, focusing on six subcortical seeds (left and right caudate, putamen, pallidum) and one cortical seed (bilateral middle frontal gyrus) from Harvard-Oxford atlases. We examined linear and quadratic correlations between log-transformed Mn concentrations and seed-based iFC (Bonferroni-corrected p<0.0023), controlling for either socio-economic status, sex or age. Dentine Mn concentrations (Mn:Calcium ratio) were highest during the prenatal period (median = 0.48) and significantly declined during the early postnatal (median = 0.14) and childhood periods (median = 0.006). Postnatal Mn concentrations were associated with: 1) increased iFC between the middle frontal gyrus and medial prefrontal cortex; 2) decreased iFC between the right putamen and pre- and postcentral gyrus. Together, these findings suggest that early postnatal Mn concentrations are associated with increased iFC within cognitive control brain areas, but decreased iFC between motor areas in adolescents. Future studies should replicate these findings in larger samples, and link brain connectivity measures to cognitive and motor outcomes.

5.
Environ Int ; 132: 105012, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402058

RESUMO

BACKGROUND: Hepato- and nephrotoxicity of fluoride have been demonstrated in animals, but few studies have examined potential effects in humans. This population-based study examines the relationship between chronic low-level fluoride exposure and kidney and liver function among United States (U.S.) adolescents. This study aimed to evaluate whether greater fluoride exposure is associated with altered kidney and liver parameters among U.S. youth. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2013-2016). We analyzed data from 1983 and 1742 adolescents who had plasma and water fluoride measures respectively and did not have kidney disease. Fluoride was measured in plasma and household tap water. Kidney parameters included estimated glomerular filtration rate (calculated by the original Schwartz formula), serum uric acid, and the urinary albumin to creatinine ratio. Liver parameters were assessed in serum and included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, gamma-glutamyl transferase, and albumin. Survey-weighted linear regression examined relationships between fluoride exposure and kidney and liver parameters after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons. RESULTS: The average age of adolescents was 15.4 years. Median water and plasma fluoride concentrations were 0.48 mg/L and 0.33 µmol/L respectively. A 1 µmol/L increase in plasma fluoride was associated with a 10.36 mL/min/1.73 m2 lower estimated glomerular filtration rate (95% CI: -17.50, -3.22; p = 0.05), a 0.29 mg/dL higher serum uric acid concentration (95% CI: 0.09, 0.50; p = 0.05), and a 1.29 mg/dL lower blood urea nitrogen concentration (95%CI: -1.87, -0.70; p < 0.001). A 1 mg/L increase in water fluoride was associated with a 0.93 mg/dL lower blood urea nitrogen concentration (95% CI: -1.44, -0.42; p = 0.007). CONCLUSIONS: Fluoride exposure may contribute to complex changes in kidney and liver related parameters among U.S. adolescents. As the study is cross-sectional, reverse causality cannot be ruled out; therefore, altered kidney and/or liver function may impact bodily fluoride absorption and metabolic processes.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31443341

RESUMO

Child blood lead concentrations have been associated with measures of immune dysregulation in nationally representative study samples. However, response to vaccination-often considered the gold standard in immunotoxicity testing-has not been examined in relation to typical background lead concentrations common among U.S. children. The present study estimated the association between blood lead concentrations and antigen-specific antibody levels to measles, mumps, and rubella in a nationally representative sample of 7005 U.S. children aged 6-17 years. Data from the 1999-2004 cycles of the National Health and Nutrition Examination Survey (NHANES) were used. In the adjusted models, children with blood lead concentrations between 1 and 5 µg/dL had an 11% lower anti-measles (95% CI: -16, -5) and a 6% lower anti-mumps antibody level (95% CI: -11, -2) compared to children with blood lead concentrations <1 µg/dL. The odds of a seronegative anti-measles antibody level was approximately two-fold greater for children with blood lead concentrations between 1 and 5 µg/dL compared to children with blood lead concentrations <1 µg/dL (OR = 2.0, 95% CI: 1.4, 3.1). The adverse associations observed in the present study provide further evidence of potential immunosuppression at blood lead concentrations <5 µg/dL, the present Centers for Disease Control and Prevention action level.

7.
Environ Res ; 177: 108603, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31357156

RESUMO

BACKGROUND: Among highly exposed populations, arsenic exposure in utero may be associated with decreased birth weight, however less is known about potential effects of arsenic exposure in urban communities without contaminated sources such as drinking water. OBJECTIVE: Investigate the association of blood arsenic levels with birth weight-for-gestational age categories within a prospective birth cohort study. DESIGN/METHODS: We analyzed 730 mother-infant dyads within the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) cohort in Mexico City. Total arsenic was measured in maternal blood samples from the 2nd and 3rd trimesters, at delivery, as well as from infant umbilical cord blood samples. Multivariable, multinomial logistic regression models adjusting for maternal age at enrollment, pre-pregnancy body mass index, parity, infant sex, socioeconomic position, and prenatal environmental tobacco smoke exposure were used to calculate odds ratios of small-for-gestational age (<10th percentile, SGA) and large-for-gestational age (>90th percentile, LGA) compared to appropriate-for-gestational age (AGA) per unit increase of log-transformed arsenic. RESULTS: Median (IQR) blood arsenic levels for maternal second trimester were 0.72 (0.33) µg/L, maternal third trimester 0.75 (0.41) µg/L, maternal at delivery 0.85 (0.70) µg/L, and infant cord 0.78 (0.65) µg/L. Maternal delivery and infant cord blood samples were most strongly correlated (spearman r = 0.65, p < 0.0001). Maternal arsenic levels at delivery were associated with significantly higher odds of both SGA (adj. OR = 1.44, 95% CI: 1.08-1.93) and LGA (adj. OR = 2.03, 95% CI: 1.12-3.67) compared to AGA. Results were similar for cord blood. There were 130 SGA infants and 22 LGA infants. Earlier in pregnancy, there were no significant associations of arsenic and birth weight-for-gestational age. However, we observed non-significantly higher odds of LGA among women with higher arsenic levels in the 3rd trimester (adj. OR = 1.46, 95% CI: 0.67-3.12). CONCLUSION: We found that in a Mexico City birth cohort, higher maternal blood arsenic levels at delivery were associated with higher odds of both SGA and LGA. However, sources and species of arsenic were not known and the number of LGA infants was small, limiting the interpretation of this finding and highlighting the importance of future large studies to incorporate arsenic speciation. If our findings were confirmed in studies that addressed these limitations, determining modifiable factors that could be mitigated, such as sources of arsenic exposure, may be important for optimizing fetal growth to improve long-term health of children.

8.
Environ Int ; 130: 104908, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31233999

RESUMO

There is increasing evidence that environmental manganese (Mn) exposure early in life can have negative effects on children's neurodevelopment and increase the risk of behavioral problems, including attention deficit hyperactivity disorder (ADHD). Factors that may contribute to differences in sensitivity to Mn exposure are sex and genetic variation of proteins involved in the regulation of Mn concentrations. Here we investigate if sex and polymorphisms in Mn transporter genes SLC30A10 and SLC39A8 influence the association between Mn exposure and ADHD-related behavioral problems in children. The SNPs rs1776029 and rs12064812 in SLC30A10, and rs13107325 in SLC39A8 were genotyped by TaqMan PCR or pyrosequencing in a population of Italian children (aged 11-14 years; n = 645) with a wide range of environmental Mn exposure. Mn in surface soil was measured in situ using XRF technology or modeled by geospatial analysis. Linear regression models or generalized additive models (GAM) were used for analyzing associations between soil Mn and neurobehavioral problems assessed by the Conners' behavior rating scales (self-, and parent-reported). Gene-environment interactions (Mn transporter genotype x soil Mn) were evaluated using a genetic score in which genotypes for the three SNPs were combined based on their association with blood Mn, as an indication of their influence on Mn regulation. We observed differences in associations between soil Mn and neurobehavior between sexes. For several self-reported Conners' scales, girls showed U-shaped relationships with higher (worse) Conners' scoring at higher soil Mn levels, and several parent-reported scales showed positive linear relationships between increasing soil Mn and higher Conner's scores. For boys, we observed a positive linear relationship with soil Mn for one Conner's outcome only (hyperactivity, parent-reported). We also observed some interactions between soil Mn and the genetic score on Conner's scales in girls and girls with genotypes linked to high blood Mn showed particularly strong positive associations between soil Mn and parent-reported Conners' scales. Our results indicate that sex and polymorphisms in Mn transporter genes contribute to differences in sensitivity to Mn exposure from the environment and that girls that are genetically less efficient at regulating Mn, may be a particularly vulnerable group.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31181712

RESUMO

Evidence suggests that environmental exposures and socioeconomic factors may interact to produce metabolic changes in children. We assessed the influence of residential location and socioeconomic status (SES) on pediatric body mass index (BMI) Z-score and fasting blood glucose (FBG) concentration. Participants included 214 children aged 6-11 years who live near a large industrial complex in Taranto, Italy. Participants were grouped into residential zones based on the distance between their home address and the complex periphery (Zone 1: 0.000-4.999 km, Zone 2: 5.000-9.999 km, Zone 3: 10.000-15.000 km). BMI Z-scores were calculated via World Health Organization (WHO) pediatric reference curves. FBG was obtained via venous blood sampling. Closer residential location to the industrial complex on the order of 5.000 km was significantly associated with worsened metabolic outcomes, particularly in female children. Zone 1 participants had higher BMI-adjusted FBG than Zone 2 and 3 participants (p < 0.05 versus Zone 2; p < 0.01 versus Zone 3). SES did not significantly influence BMI-adjusted FBG. Moreover, BMI Z-scores indicated high rates of overweight (22.0%) and obesity (22.9%) in the cohort. BMI Z-score was not significantly associated with SES or residential zone but was negatively associated with maternal education level (p < 0.05). These results offer new evidence that residing near industrial activity may predict adverse effects on child metabolic health.

10.
Brain Behav Immun ; 80: 871-878, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158498

RESUMO

BACKGROUND: Identifying modifiable risk factors for neuropsychological correlates of attention deficit hyperactivity disorder (ADHD) in early childhood can inform prevention strategies. Prenatal inflammatory states, such as maternal asthma and other atopic disorders, have been increasingly linked to enhanced risk for neurobehavioral disorders in children, with some studies suggesting sex-specific effects. OBJECTIVES: To assess the association between maternal active asthma and/or atopy in the antenatal period and child symptoms of ADHD during mid-childhood and, given the male-bias in ADHD prevalence, to examine modifying effects of child sex. STUDY DESIGN: The study sample includes 250 maternal-child pairs enrolled in the Boston-based Asthma Coalition on Community, Environment and Social Stress (ACCESS) pregnancy cohort. We defined antenatal active atopy based on maternal report of current asthma, allergic rhinitis or atopic dermatitis during and/or in the year before pregnancy. When children were approximately 6 years old, mothers completed a battery of standardized child behavior rating scales designed for evaluating symptoms of ADHD. We used multivariable quantile regression to assess the relations between maternal antenatal atopy and symptoms of ADHD among children. RESULTS: In adjusted models, maternal atopy was significantly associated with greater risk for ADHD behaviors, as indicated by scores on the Conners' Parent Rating Scale-Revised ADHD index (ß = 3.32, 95% CI: 0.33, 6.32). In sex-stratified models this association was stronger among girls (5.96, 95% CI = 0.95, 10.96) compared to boys (-2.14, 95% CI = -5.75, 1.45, p-interaction = 0.01). Among girls, we observed a similar finding for the Behavior Assessment System for Children 2nd Edition Parent Rating Scale Attention Problems subscale (ß = 7.77, 95% CI = 1.57, 13.97). Results from other outcome subscales were similar in magnitude and direction, however, associations did not reach statistical significance at the p = 0.05 level. CONCLUSIONS: Maternal antenatal active atopy may be a risk factor for the development of ADHD-like symptoms, especially among girls.

11.
J Perinatol ; 39(7): 941-948, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31110244

RESUMO

OBJECTIVE: To determine whether prenatal sex hormones from maternal saliva are associated with birth-weight-for-gestational age. STUDY DESIGN: We measured salivary progesterone, testosterone, estradiol, dehydroepiandrosterone (DHEA), and cortisone in 504 pregnant women in a Mexico City cohort. We performed linear and modified Poisson regression to examine associations of log-transformed hormones with birth-weight-for-gestational age z-scores and the risk of small-for-gestational age (SGA) and large-for-gestational age (LGA) adjusting for maternal age, sex, BMI, parity, smoking, education, and socioeconomic status. RESULTS: In total, 15% of infants were SGA and 2% were LGA. Each interquartile range increment in testosterone/estradiol ratio was associated with a 0.12 decrement in birth-weight-for-gestational age z-score (95% CI: -0.27 to -0.02) and a 50% higher risk of SGA versus appropriate-for-gestational age (AGA) (95% CI: 1.13-1.99). CONCLUSION: Higher salivary testosterone/estradiol ratios may affect fetal growth, and identifying the predictors of hormone levels may be important to optimizing fetal growth.

12.
Nat Commun ; 10(1): 1893, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015461

RESUMO

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10-7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10-74) and BMI in pregnancy (3/914, p = 1.13x10-3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.


Assuntos
Peso ao Nascer/genética , DNA/metabolismo , Epigênese Genética , Genoma Humano , Adolescente , Adulto , Índice de Massa Corporal , Criança , Ilhas de CpG , DNA/genética , Metilação de DNA , Feminino , Desenvolvimento Fetal/genética , Feto , Ácido Fólico/sangue , Estudo de Associação Genômica Ampla , Humanos , Recém-Nascido , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Fumar/efeitos adversos , Fumar/sangue , Fumar/genética
13.
Environ Int ; 126: 484-493, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30849576

RESUMO

INTRODUCTION: Manganese (Mn) is an essential nutrient but also a toxicant at high exposures, when it can induce oxidative stress (OS). Mn uptake is inversely correlated with iron status, therefore anemic individuals may be more susceptible to Mn overload induced-OS, which can manifest as changes in mitochondrial DNA copy number (mtDNA CN). Our objectives were to: 1) determine stage-specific associations of prenatal Mn exposure with cord blood MtDNA CN; and 2) investigate effect modification by maternal anemia, ferritin, and mean corpuscular volume (MCV). MATERIALS AND METHODS: We measured whole blood Mn, hemoglobin, serum ferritin, and MCV in the 2nd and 3rd trimester, in maternal blood at birth, and in cord blood from a prospective birth cohort in Mexico City, Mexico (n = 485). We then extracted DNA from cord blood leukocytes to determine mtDNA CN. We used robust regression to measure associations between Mn and mtDNA CN at each trimester and at birth. Anemia (hemoglobin ≤11 g/dL), iron deficiency (ferritin ≤15 ng/mL) and MCV (stratified at median), were examined as effect modifiers. RESULTS: Mn levels increased throughout pregnancy, and Mn was inversely correlated with ferritin. We observed a positive association between Mn in the 3rd trimester and Mn in cord blood and mtDNA CN (ß = 0.04-0.05; 95% CI = 0.01, 0.08). Anemia significantly modified the association between mtDNA CN and Mn in the 2nd trimester. We found a positive association between 2nd trimester Mn and mtDNA CN in mothers with normal hemoglobin, and a negative association in those with low hemoglobin. (ßhigh = 0.06; 95% CI = 0.01, 0.11; p = 0.01 and ßlow = -0.06; 95% CI = 0.03, -0.13; p = 0.06). No associations were detected between anemia, iron deficiency and MCV and mtDNA CN. CONCLUSIONS: Maternal blood Mn in the 3rd trimester and in cord blood was positively associated with mtDNA CN, suggesting that higher late pregnancy prenatal Mn exposures can impact newborn mitochondria by promoting OS. Furthermore, 2nd trimester Mn was positively associated with mtDNA in non-anemic mother-child pairs but inversely associated in anemic individuals, indicating potential interactions between Mn and chronic anemia.

14.
Environ Res ; 172: 495-501, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852452

RESUMO

INTRODUCTION: In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences. METHODS: Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models. RESULTS: In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys. CONCLUSIONS: Increased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.

15.
Epidemiology ; 30(2): 263-273, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30720588

RESUMO

BACKGROUND: Trace metal concentrations may affect cardiometabolic risk, but the role of prenatal exposure is unclear. We examined (1) the relation between blood metal concentrations during pregnancy and child cardiometabolic risk factors; (2) overall effects of metals mixture (essential vs. nonessential); and (3) interactions between metals. METHODS: We measured 11 metals in maternal second-trimester whole blood in a prospective birth cohort in Mexico City. In children 4-6 years old, we measured body mass index (BMI), percent body fat, and blood pressure (N = 609); and plasma hemoglobin A1C (HbA1c), non-high-density lipoprotein (HDL) cholesterol, triglycerides, leptin, and adiponectin (N = 411). We constructed cardiometabolic component scores using age- and sex-adjusted z scores and averaged five scores to create a global risk score. We estimated linear associations of each metal with individual z scores and used Bayesian Kernel Machine Regression to assess metal mixtures and interactions. RESULTS: Higher total metals were associated with lower HbA1c, leptin, and systolic blood pressure, and with higher adiponectin and non-HDL cholesterol. We observed no interactions between metals. Higher selenium was associated with lower triglycerides in linear (ß = -1.01 z score units per 1 unit ln(Se), 95% CI = -1.84, -0.18) and Bayesian Kernel Machine Regression models. Manganese was associated with decreased HbA1c in linear models (ß = -0.32 and 95% CI = -0.61, -0.03). Antimony and arsenic were associated with lower leptin in Bayesian Kernel Machine Regression models. Essential metals were more strongly associated with cardiometabolic risk than were nonessential metals. CONCLUSIONS: Low essential metals during pregnancy were associated with increased cardiometabolic risk factors in childhood.


Assuntos
Doenças Cardiovasculares/epidemiologia , Metais/sangue , Adiponectina/sangue , Tecido Adiposo , Adolescente , Adulto , Teorema de Bayes , Pressão Sanguínea , Índice de Massa Corporal , Criança , Pré-Escolar , Colesterol/sangue , Feminino , Hemoglobina A Glicada/análise , Humanos , Leptina/sangue , Metais/classificação , México/epidemiologia , Gravidez , Segundo Trimestre da Gravidez/sangue , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Adulto Jovem
16.
Environ Int ; 125: 437-444, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30753999

RESUMO

INTRODUCTION: Lead (Pb) crosses the placenta and can cause oxidative stress, reduced fetal growth and neurological problems. The principal source of oxidative stress in human cells is mitochondria. Therefore, disruption of normal mitochondrial function during pregnancy may represent a primary mechanism behind the adverse effects of lead. We sought to assess the association of Pb exposure during pregnancy with mitochondrial DNA (mtDNA) content, a sensitive marker of mitochondrial function, in cord blood. MATERIALS AND METHODS: This study comprised mother-infant pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a prospective birth-cohort that enrolled 1050 pregnant women from Mexico City who were receiving prenatal care between December 2007 and July 2011. Quantitative PCR was used to calculate relative MtDNA content (mitochondrial-to-nuclear DNA ratio (mtDNA/nDNA)) in cord blood. Lead concentrations in both maternal blood (2nd and 3rd trimester and at delivery day) and in cord blood were measured by ICP-MS. Multivariable regression models adjusting for multiple confounders were fitted with 410 mother-infant pairs for whom complete data for mtDNA content, lead levels, and covariates were available. RESULTS: Maternal blood Pb measured in the second (mean 3.79 µg/dL, SD 2.63; ß = 0.059, 95% CI 0.008, 0.111) and third trimester (mean 3.90 µg/dL; SD 2.84; ß = 0.054, 95% CI 0.002, 0.107) during pregnancy and PB in cord blood (mean 3.50 µg/dL, SD 2.59; ß = 0.050, 95% CI 0.004; 0.096) were associated with increased cord blood mtDNA content (mean 1.46, SD 0.44). In two-way interaction analyses, cord blood Pb marginally interacted with gestational age leading to an increase in mtDNA content for pre-term births (Benjamini-Hochberg False Discovery Rate correction; BH-FDR = 0.08). CONCLUSION: This study shows that lead exposure in pregnancy alters mtDNA content in cord blood; therefore, alteration of mtDNA content might be a mechanism underlying the toxicity of lead.

17.
Stress ; 22(2): 228-235, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30767640

RESUMO

Women's experience of trauma may cause lifelong alterations in physiological stress regulation, which can be transmitted to offspring in utero. We investigated, in a prospective pregnancy cohort, associations among maternal lifetime interpersonal trauma (IPT) history, prenatal cortisol dysregulation, and children's memory domains. Sex-specific effects were also explored. Pregnant women were enrolled from Brigham & Women's Hospital and affiliated clinics near Boston, MA, in 2002-2007. IPT was assessed with the Revised Conflict Tactics Scale, short form. Salivary cortisol was measured at five time points on each of three days in one week at 29.0 ± 5.1 weeks gestation, and morning rise and diurnal slope were calculated. The Wide Range Assessment of Memory & Learning, 2nd Edition was administered at 6.5 ± 1.0 years and scores were generated for general memory and three sub-domains: verbal, visual, and attention/concentration. In total, 258 maternal-child dyads provided memory and IPT and/or cortisol data. IPT was positively associated with verbal memory in boys (ß ± SE: 4.6 ± 2.6) and inversely associated with visual memory score in girls (-6.5 ± 3.2). IPT did not predict prenatal cortisol, but prenatal cortisol modified the association between IPT history and child memory in varying coefficient models allowing for non-linear effect modification. The strongest evidence of interaction was for visual memory in boys: IPT history was associated with poorer visual memory only in those with flatter prenatal diurnal slope (interaction p = .005). Maternal lifetime IPT that leads to prenatal HPA dysregulation may have consequences for child memory, more so than either trauma or elevated cortisol alone. Boys may be more vulnerable to effects. Sex- and timing-specific effects require further investigation.

18.
Environ Int ; 124: 329-335, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30660846

RESUMO

BACKGROUND: The programming of sleep architecture begins in pregnancy and depends upon optimal in utero formation and maturation of the neural connectivity of the brain. Particulate air pollution exposure can disrupt fetal brain development but associations between fine particulate matter (PM2.5) exposure during pregnancy and child sleep outcomes have not been previously explored. METHODS: Analyses included 397 mother-child pairs enrolled in a pregnancy cohort in Mexico City. Daily ambient prenatal PM2.5 exposure was estimated using a validated satellite-based spatio-temporally resolved prediction model. Child sleep periods were estimated objectively using wrist-worn, continuous actigraphy over a 1-week period at age 4-5 years. Data-driven advanced statistical methods (distributed lag models (DLMs)) were employed to identify sensitive windows whereby PM2.5 exposure during gestation was significantly associated with changes in sleep duration or efficiency. Models were adjusted for maternal education, season, child's age, sex, and BMI z-score. RESULTS: Mother's average age was 27.7 years, with 59% having at least a high school education. Children slept an average of 7.7 h at night, with mean 80.1% efficiency. The adjusted DLM identified windows of PM2.5 exposure between 31 and 35 weeks gestation that were significantly associated with decreased sleep duration in children. In addition, increased PM2.5 during weeks 1-8 was associated with decreased sleep efficiency. In other exposure windows (weeks 39-40), PM2.5 was associated with increased sleep duration. CONCLUSION: Prenatal PM2.5 exposure is associated with altered sleep in preschool-aged children in Mexico City. Pollutant exposure during sensitive windows of pregnancy may have critical influence upon sleep programming.


Assuntos
Exposição Ambiental , Exposição Materna , Material Particulado/toxicidade , Transtornos do Sono-Vigília/etiologia , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Humanos , Masculino , México , Material Particulado/análise , Gravidez , Estações do Ano
19.
Acad Pediatr ; 19(4): 421-427, 2019 May - Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30639371

RESUMO

BACKGROUND: Environmental exposures contribute to multiple diseases in children; yet, few pediatricians have training in pediatric environmental health (PEH), and few academic health centers have PEH expertise. To build national capacity in PEH, the Academic Pediatric Association (APA) launched a professional development program that since 2002 has encouraged the establishment of post-residency/post-doctoral training programs, supported a special interest group, and convened an annual mentored retreat for PEH trainees. OBJECTIVE: Describe the APA's professional development program in PEH and assess its impact by tracking careers of former trainees. METHODS: Careers were tracked through interviews with trainees and program directors supplemented by searches of institutional websites. Publication listings were obtained through PubMed. Publication impact was assessed using bibliometric and altmetric measures. Grant histories were accessed through the National Institutes of Health RePORTER project. Information on advocacy work was obtained through interviews with program directors. RESULTS: Fifty-five trainees (36 physicians and 19 health scientists) completed PEH training and attended the APA retreat between 2002 and 2017. Forty-one (75%) are pursuing academic careers, 11 are associate or full professors, 11 are practicing general pediatrics or a pediatric subspecialty, 2 are Centers for Disease Control and Prevention epidemiologists, and 1 is a data scientist. Forty-two former trainees (76%) listed "environment" or "environmental" in their job titles or on their websites. Former trainees have published 632 scientific papers. These papers have been cited 3094times, have a relative citation ratio of 2.97, and have been read or viewed 1,274,388times. Twenty-one former trainees have been awarded 43 National Institutes of Health grants. Trainees have developed education and advocacy skills by teaching medical students and residents, presenting grand rounds, preparing policy papers, presenting legislative testimony, and making presentations to public audiences. CONCLUSIONS: The APA's professional development program has contributed to the expansion of national capacity in PEH. Former trainees are populating the field, generating new knowledge, and moving into leadership positions.

20.
Int J Hyg Environ Health ; 222(1): 68-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30146178

RESUMO

BACKGROUND: A child's adaptive ability is important for personal career and social development. Maternal self-esteem may help shape a child's behavior. This study aims to investigate whether maternal self-esteem measured when their children were toddlers predicts their children's adaptive skills at school age, and whether prenatal lead exposure modifies such a relationship. METHODS: We assessed prenatal lead exposure using cord blood lead and maternal bone lead around delivery (tibia and patella lead measured in vivo by K-x-ray-fluorescence) among 192 mother-child pairs investigated in Mexico from 1994 to 2011. Maternal self-esteem was measured using the Coopersmith-Self-esteem-Inventory when children were 2 years old. When children were 7-to-15 years old, we measured children's blood lead levels and administered the 2nd edition of Behavior-Assessment-System-for-Children (BASC-2) parent-rating-scales (PRS) and Self-Reports of Personality (SRP) to evaluate children's adaptive skills. RESULTS: Median (P25, P75) values for maternal patella and tibia lead, cord blood lead and children's current blood lead levels were 12.6 (3.2, 21.7) µg/g, 10.2 (4.1, 16.0) µg/g, 5.5 (3.5, 8.1) µg/dL and 2.7 (2.0, 4.0) µg/dL, respectively. In adjusted models, increased maternal self-esteem was associated with increased adaptive T-scores on the BASC-2 PRS and SRP scales. This relationship was weaker in high prenatal lead-exposure groups (high cord blood lead or patella lead groups, P25P100) compared with low prenatal lead-exposure (low cord blood lead or patella lead groups, P1P25) groups (P-interaction values < 0.10). No significant interactions between maternal tibia lead and self-esteem on children's adaptive T-scores were observed (P-interaction values > 0.10). CONCLUSIONS: Toddlers of mothers with high (vs. low) self-esteem have better adaptive abilities when they are of school-age. Prenatal lead exposure may attenuate or eliminate this positive association.


Assuntos
Adaptação Psicológica , Chumbo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Autoimagem , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Humanos , Gravidez , Adulto Jovem
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