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1.
Mol Autism ; 10: 36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673306

RESUMO

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children. Methods: Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis. Results: While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions. Limitations: ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder. Conclusions: This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.

2.
Transl Psychiatry ; 9(1): 243, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582732

RESUMO

Although developmental delays affect learning, language, and behavior, some evidence suggests the presence of disturbances in metabolism are associated with psychiatric disorders. Here, the plasma metabolic phenotype of children with autism spectrum disorder (ASD, n = 167), idiopathic-developmental delay (i-DD, n = 51), and Down syndrome (DS, n = 31), as compared to typically developed (TD, n = 193) controls was investigated in a subset of children from the case-control Childhood Autism Risk from Genetics and the Environment (CHARGE) Study. Metabolome profiles were obtained using nuclear magnetic resonance spectroscopy and analyzed in an untargeted manner. Forty-nine metabolites were identified and quantified in each sample that included amino acids, organic acids, sugars, and other compounds. Multiple linear regression analysis revealed significant associations between 11 plasma metabolites and neurodevelopmental outcome. Despite the varied origins of these developmental disabilities, we observed similar perturbation in one-carbon metabolism pathways among DS and ASD cases. Similarities were also observed in the DS and i-DD cases in the energy-related tricarboxylic acid cycle. Other metabolites and pathways were uniquely associated with DS or ASD. By comparing metabolic signatures between these conditions, the current study expands on extant literature demonstrating metabolic alterations associated with developmental disabilities and provides a better understanding of overlapping vs specific biological perturbations associated with these disorders.

3.
Environ Res ; 179(Pt A): 108719, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31627027

RESUMO

BACKGROUND: Environmental phenols and parabens are endocrine disrupting chemicals (EDCs) with the potential to affect child neurodevelopment including autism spectrum disorders (ASD). Our aim was to assess whether exposure to environmental phenols and parabens during pregnancy was associated with an increased risk of clinical ASD or other nontypical development (non-TD). METHODS: This study included mother-child pairs (N = 207) from the Markers of Autism Risks in Babies - Learning Early Signs (MARBLES) Cohort Study with urinary phenol and paraben metabolites analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) from repeated pregnancy urine samples. Because family recurrence risks in siblings are about 20%, MARBLES enrolls pregnant women who already had a child with ASD. Children were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, non-TD, or typically developing (TD). Single analyte analyses were conducted with trinomial logistic regression and weighted quantile sum (WQS) regression was used to test for mixture effects. RESULTS: Regression models were adjusted for pre-pregnancy body mass index, prenatal vitamin use (yes/no), homeowner status (yes/no), birth year, and child's sex. In single chemical analyses phenol exposures were not significantly associated with child's diagnosis. Mixture analyses using trinomial WQS regression showed a significantly increased risk of non-TD compared to TD (OR = 1.58, 95% CI: 1.04, 2.04) with overall greater prenatal phenol and paraben metabolites mixture. Results for ASD also showed an increased risk, but it was not significant. DISCUSSION: This is the first study to provide evidence that pregnancy environmental phenol exposures may increase the risk for non-TD in a high-risk population.

4.
Occup Environ Med ; 76(9): 644-651, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31248991

RESUMO

OBJECTIVES: The aim of this study is to determine if parental occupational exposure to 16 agents is associated with autism spectrum disorder (ASD). METHODS: Demographic, health and parental occupational data were collected as part of the CHildhood Autism Risks from Genetics and Environment study. The workplace exposure assessment was conducted by two experienced industrial hygienists for the parents of 537 children with ASD and 414 typically developing (TD) children. For each job, frequency and intensity of 16 agents were assessed and both binary and semi-quantitative cumulative exposure variables were derived. Logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) to assess associations between parental occupational exposures 3 months pre-pregnancy until birth. RESULTS: The OR of ASD in the children of mothers exposed to any solvents was 1.5 times higher than the mothers of TD children (95% CI=1.01-2.23). Cumulative exposure indicated that the OR associated with a moderate level of solvent exposure in mothers was 1.85 (95% CI=1.09, 3.15) for children with ASD compared with TD children. No other exposures were associated with ASD in mothers, fathers or the parents combined. CONCLUSION: Maternal occupational exposure to solvents may increase the risk for ASD. These results are consistent with a growing body of evidence indicating that environmental and occupational exposures may be associated with ASD. Future research should consider specific types of solvents, larger samples and/or different study designs to evaluate other exposures for potential associations with ASD.

5.
JAMA ; 321(17): 1702-1715, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31063572

RESUMO

Importance: Both low and high gestational weight gain have been associated with adverse maternal and infant outcomes, but optimal gestational weight gain remains uncertain and not well defined for all prepregnancy weight ranges. Objectives: To examine the association of ranges of gestational weight gain with risk of adverse maternal and infant outcomes and estimate optimal gestational weight gain ranges across prepregnancy body mass index categories. Design, Setting, and Participants: Individual participant-level meta-analysis using data from 196 670 participants within 25 cohort studies from Europe and North America (main study sample). Optimal gestational weight gain ranges were estimated for each prepregnancy body mass index (BMI) category by selecting the range of gestational weight gain that was associated with lower risk for any adverse outcome. Individual participant-level data from 3505 participants within 4 separate hospital-based cohorts were used as a validation sample. Data were collected between 1989 and 2015. The final date of follow-up was December 2015. Exposures: Gestational weight gain. Main Outcomes and Measures: The main outcome termed any adverse outcome was defined as the presence of 1 or more of the following outcomes: preeclampsia, gestational hypertension, gestational diabetes, cesarean delivery, preterm birth, and small or large size for gestational age at birth. Results: Of the 196 670 women (median age, 30.0 years [quartile 1 and 3, 27.0 and 33.0 years] and 40 937 were white) included in the main sample, 7809 (4.0%) were categorized at baseline as underweight (BMI <18.5); 133 788 (68.0%), normal weight (BMI, 18.5-24.9); 38 828 (19.7%), overweight (BMI, 25.0-29.9); 11 992 (6.1%), obesity grade 1 (BMI, 30.0-34.9); 3284 (1.7%), obesity grade 2 (BMI, 35.0-39.9); and 969 (0.5%), obesity grade 3 (BMI, ≥40.0). Overall, any adverse outcome occurred in 37.2% (n = 73 161) of women, ranging from 34.7% (2706 of 7809) among women categorized as underweight to 61.1% (592 of 969) among women categorized as obesity grade 3. Optimal gestational weight gain ranges were 14.0 kg to less than 16.0 kg for women categorized as underweight; 10.0 kg to less than 18.0 kg for normal weight; 2.0 kg to less than 16.0 kg for overweight; 2.0 kg to less than 6.0 kg for obesity grade 1; weight loss or gain of 0 kg to less than 4.0 kg for obesity grade 2; and weight gain of 0 kg to less than 6.0 kg for obesity grade 3. These gestational weight gain ranges were associated with low to moderate discrimination between those with and those without adverse outcomes (range for area under the receiver operating characteristic curve, 0.55-0.76). Results for discriminative performance in the validation sample were similar to the corresponding results in the main study sample (range for area under the receiver operating characteristic curve, 0.51-0.79). Conclusions and Relevance: In this meta-analysis of pooled individual participant data from 25 cohort studies, the risk for adverse maternal and infant outcomes varied by gestational weight gain and across the range of prepregnancy weights. The estimates of optimal gestational weight gain may inform prenatal counseling; however, the optimal gestational weight gain ranges had limited predictive value for the outcomes assessed.


Assuntos
Índice de Massa Corporal , Ganho de Peso na Gestação , Complicações na Gravidez , Resultado da Gravidez , Adulto , Peso ao Nascer , Cesárea/estatística & dados numéricos , Diabetes Gestacional , Feminino , Humanos , Hipertensão Induzida pela Gravidez , Recém-Nascido , Obesidade , Gravidez , Nascimento Prematuro
6.
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
7.
Hum Mol Genet ; 28(16): 2659-2674, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31009952

RESUMO

DNA methylation acts at the interface of genetic and environmental factors relevant for autism spectrum disorder (ASD). Placenta, normally discarded at birth, is a potentially rich source of DNA methylation patterns predictive of ASD in the child. Here, we performed whole methylome analyses of placentas from a prospective study MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) of high-risk pregnancies. A total of 400 differentially methylated regions (DMRs) discriminated placentas stored from children later diagnosed with ASD compared to typically developing controls. These ASD DMRs were significantly enriched at promoters, mapped to 596 genes functionally enriched in neuronal development, and overlapped genetic ASD risk. ASD DMRs at CYP2E1 and IRS2 reached genome-wide significance, replicated by pyrosequencing and correlated with expression differences in brain. Methylation at CYP2E1 associated with both ASD diagnosis and genotype within the DMR. In contrast, methylation at IRS2 was unaffected by within DMR genotype but modified by preconceptional maternal prenatal vitamin use. This study therefore identified two potentially useful early epigenetic markers for ASD in placenta.

8.
Environ Int ; 126: 363-376, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826615

RESUMO

BACKGROUND: Prenatal air pollution exposure has been linked to many adverse health conditions in the offspring. However, little is known about the mechanisms underlying these associations. Epigenetics may be one plausible biologic link. Here, we sought to identify site-specific and global DNA methylation (DNAm) changes, in developmentally relevant tissues, associated with prenatal exposure to nitrogen dioxide (NO2) and ozone (O3). Additionally, we assessed whether sex-specific changes in methylation exist and whether DNAm changes are consistently observed across tissues. METHODS: Genome-scale DNAm measurements were obtained using the Infinium HumanMethylation450k platform for 133 placenta and 175 cord blood specimens from Early Autism Risk Longitudinal Investigation (EARLI) neonates. Ambient NO2 and O3 exposure levels were based on prenatal address locations of EARLI mothers and the Environmental Protection Agency's AirNOW monitoring network using inverse distance weighting. We computed sample-level aggregate methylation measures for each of 5 types of genomic regions including genome-wide, open sea, shelf, shore, and island regions. Linear regression was performed for each genomic region; per-sample aggregate methylation measures were modeled as a function of quantitative exposure level with covariate adjustment. In addition, bumphunting was performed to identify differentially methylated regions (DMRs) associated with prenatal O3 and NO2 exposures in each tissue and by sex, with adjustment for technical and biological sources of variation. RESULTS: We identified global and locus-specific changes in DNA methylation related to prenatal exposure to NO2 and O3 in 2 developmentally relevant tissues. Neonates with increased prenatal O3 exposure had lower aggregate levels of DNAm at CpGs located in open sea and shelf regions of the genome. We identified 6 DMRs associated with prenatal NO2 exposure, including 3 sex-specific. An additional 3 sex-specific DMRs were associated with prenatal O3 exposure levels. DMRs initially detected in cord blood samples (n = 4) showed consistent exposure-related changes in DNAm in placenta. However, the DMRs initially detected in placenta (n = 5) did not show DNAm differences in cord blood and, thus, they appear to be tissue-specific. CONCLUSIONS: We observed global, locus, and sex-specific methylation changes associated with prenatal NO2 and O3 exposures. Our findings support DNAm is a biologic target of prenatal air pollutant exposures and highlight epigenetic involvement in sex-specific differential susceptibility to environmental exposure effects in 2 developmentally relevant tissues.


Assuntos
Poluição do Ar/análise , Metilação de DNA , Troca Materno-Fetal , Poluentes Atmosféricos/análise , Saúde da Criança , Epigenômica , Feminino , Humanos , Saúde do Lactente , Recém-Nascido , Masculino , Exposição Materna , Dióxido de Nitrogênio/análise , Ozônio/análise , Placenta/química , Gravidez
9.
PLoS Med ; 16(2): e1002744, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30742624

RESUMO

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.


Assuntos
Índice de Massa Corporal , Análise de Dados , Ganho de Peso na Gestação/fisiologia , Obesidade Pediátrica/epidemiologia , Austrália/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , América do Norte/epidemiologia , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Obesidade Pediátrica/diagnóstico , Gravidez , Fatores de Risco
10.
Am J Public Health ; 109(4): 550-554, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30789769

RESUMO

Evidence is growing on the adverse neurodevelopmental effects of exposure to combustion-related air pollution. Project TENDR (Targeting Environmental Neurodevelopmental Risks), a unique collaboration of leading scientists, health professionals, and children's and environmental health advocates, has identified combustion-related air pollutants as critical targets for action to protect healthy brain development. We present policy recommendations for maintaining and strengthening federal environmental health protections, advancing state and local actions, and supporting scientific research to inform effective strategies for reducing children's exposures to combustion-related air pollution. Such actions not only would improve children's neurological development but also would have the important co-benefit of climate change mitigation and further improvements in other health conditions.

11.
Environ Health ; 17(1): 85, 2018 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518373

RESUMO

BACKGROUND: Evidence from experimental and observational studies suggests that prenatal phthalate exposures may be associated with autism spectrum disorder (ASD). We examined whether prenatal phthalate exposures were associated with an increased risk of ASD. METHODS: We quantified 14 metabolites of eight phthalates in 636 multiple maternal urine samples collected during 2nd and 3rd trimesters of pregnancy from 201 mother-child pairs in MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD longitudinal cohort. At 3 years old, children were clinically assessed for ASD and classified into three diagnostic categories: ASD (n = 46), non-typical development (Non-TD, n = 55), and typical development (TD, n = 100). We used multinomial logistic regression to evaluate the association of phthalate metabolite concentrations with ASD and Non-TD. RESULTS: Most associations of phthalate biomarkers with both ASD and Non-TD were null, with the exception that monoethyl phthalate (MEP) was significantly associated with an increased risk of Non-TD (per 2.72-fold relative increase in concentration: Relative risk ratio (RRR) = 1.38; 95% confidence interval (CI): 1.01, 1.90). When stratified by prenatal vitamin use during the first month of pregnancy, among mothers who took vitamins, ASD risk was inversely associated with mono-isobutyl phthalate (MiBP, RRR = 0.44; 95% CI: 0.21, 0.88), mono(3-carboxypropyl) phthalate (MCPP, RRR = 0.41; 95% CI: 0.20, 0.83) and mono-carboxyisooctyl phthalate (MCOP, RRR = 0.49; 95% CI: 0.27, 0.88), but among mothers who did not take prenatal vitamins, Non-TD risk was positively associated with MCPP (RRR = 5.09; 95% CI: 2.05, 12.6), MCOP (RRR = 1.86; 95% CI: 1.01, 3.39), and mono-carboxyisononyl phthalate (MCNP, RRR = 3.67; 95% CI: 1.80, 7.48). When stratified by sex, among boys, MEP, monobenzyl phthalate, MCPP, MCNP, and sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP) were positively associated with Non-TD risk, but associations with ASD were null. Among girls, associations with both ASD and Non-TD were null. CONCLUSIONS: Our study showed that phthalate exposures in mid- to late pregnancy were not associated with ASD in children from this high-risk ASD cohort. Further studies should be conducted in the general population without high-risk genes to confirm our findings.

12.
Artigo em Inglês | MEDLINE | ID: mdl-30520558

RESUMO

Autism spectrum disorder (ASD) is a markedly heterogeneous condition with a varied phenotypic presentation. Its high concordance among siblings, as well as its clear association with specific genetic disorders, both point to a strong genetic etiology. However, the molecular basis of ASD is still poorly understood, although recent studies point to the existence of sex-specific ASD pathophysiologies and biomarkers. Despite this, little is known about how exactly sex influences the gene expression signatures of ASD probands. In an effort to identify sex-dependent biomarkers and characterize their function, we present an analysis of a single paired-end postmortem brain RNA-Seq data set and a meta-analysis of six blood-based microarray data sets. Here, we identify several genes with sex-dependent dysregulation, and many more with sex-independent dysregulation. Moreover, through pathway analysis, we find that these sex-independent biomarkers have substantially different biological roles than the sex-dependent biomarkers, and that some of these pathways are ubiquitously dysregulated in both postmortem brain and blood. We conclude by synthesizing the discovered biomarker profiles with the extant literature, by highlighting the advantage of studying sex-specific dysregulation directly, and by making a call for new transcriptomic data that comprise large female cohorts.

13.
BMC Med ; 16(1): 201, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30396358

RESUMO

BACKGROUND: Gestational weight gain differs according to pre-pregnancy body mass index and is related to the risks of adverse maternal and child health outcomes. Gestational weight gain charts for women in different pre-pregnancy body mass index groups enable identification of women and offspring at risk for adverse health outcomes. We aimed to construct gestational weight gain reference charts for underweight, normal weight, overweight, and grades 1, 2 and 3 obese women and to compare these charts with those obtained in women with uncomplicated term pregnancies. METHODS: We used individual participant data from 218,216 pregnant women participating in 33 cohorts from Europe, North America, and Oceania. Of these women, 9065 (4.2%), 148,697 (68.1%), 42,678 (19.6%), 13,084 (6.0%), 3597 (1.6%), and 1095 (0.5%) were underweight, normal weight, overweight, and grades 1, 2, and 3 obese women, respectively. A total of 138, 517 women from 26 cohorts had pregnancies with no hypertensive or diabetic disorders and with term deliveries of appropriate for gestational age at birth infants. Gestational weight gain charts for underweight, normal weight, overweight, and grade 1, 2, and 3 obese women were derived by the Box-Cox t method using the generalized additive model for location, scale, and shape. RESULTS: We observed that gestational weight gain strongly differed per maternal pre-pregnancy body mass index group. The median (interquartile range) gestational weight gain at 40 weeks was 14.2 kg (11.4-17.4) for underweight women, 14.5 kg (11.5-17.7) for normal weight women, 13.9 kg (10.1-17.9) for overweight women, and 11.2 kg (7.0-15.7), 8.7 kg (4.3-13.4) and 6.3 kg (1.9-11.1) for grades 1, 2, and 3 obese women, respectively. The rate of weight gain was lower in the first half than in the second half of pregnancy. No differences in the patterns of weight gain were observed between cohorts or countries. Similar weight gain patterns were observed in mothers without pregnancy complications. CONCLUSIONS: Gestational weight gain patterns are strongly related to pre-pregnancy body mass index. The derived charts can be used to assess gestational weight gain in etiological research and as a monitoring tool for weight gain during pregnancy in clinical practice.

14.
Environ Int ; 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30477814

RESUMO

BACKGROUND: Because phthalates are quickly metabolized and excreted in urine, and human exposures tend to be episodic, phthalate metabolite concentrations measured in a maternal spot urine sample are only indicative of recent exposure. OBJECTIVE: To examine temporal variability of pregnant women's phthalate exposure using multiple first morning voids (FMV) and pooled samples. METHODS: We quantified 14 metabolites of eight phthalates in 577 urine samples collected from 188 pregnancies in the MARBLES (Markers of Autism Risk in Babies - Learning Early Signs) study. We calculated intraclass correlation coefficients (ICCs) using two samples of the same urine type (i.e., two FMVs or two pools) collected across the 2nd and 3rd trimesters. We also calculated ICCs and FMV/pool concentration ratios using two samples (i.e., two FMVs or one FMV and one pool) collected within the same trimester. RESULTS: Overall, ICCs were higher in pooled samples (0.24-0.87) than in FMVs (0.08-0.69). Regardless of the sample type, ICCs tended to be higher for metabolites for which exposure sources are personal care products or indoor residential materials than those for which diet is an important exposure source. ICCs tended to increase and FMV/pool ratios tended to decrease with an increasing number of composite samples in the pools. CONCLUSIONS: Our study helped determine the number of samples needed to capture moderate to high reproducibility of individual's average exposure to phthalates and the average exposure can be differently characterized depending on the number of samples in the pools.

15.
Environ Health Perspect ; 126(11): 117004, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30465702

RESUMO

BACKGROUND: Until recently, environmental factors in autism spectrum disorder (ASD) were largely ignored. Over the last decade, altered risks from lifestyle, medical, chemical, and other factors have emerged through various study designs: whole population cohorts linked to diagnostic and/or exposure-related databases, large case-control studies, and smaller cohorts of children at elevated risk for ASD. OBJECTIVES: This study aimed to introduce the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) prospective study and its goals, motivate the enhanced-risk cohort design, describe protocols and main exposures of interest, and present initial descriptive results for the study population. METHODS: Families having one or more previous child with ASD were contacted before or during a pregnancy, and once the woman became pregnant, were invited to enroll. Data and biological samples were collected throughout pregnancy, at birth, and until the child's third birthday. Neurodevelopment was assessed longitudinally. The study began enrolling in 2006 and is ongoing. RESULTS: As of 30 June 2018, 463 pregnant mothers have enrolled. Most mothers ([Formula: see text]) were thirty years of age or over, including 7.9% who are fourty years of age or over. The sample includes 22% Hispanic and another 25% nonHispanic Black, Asian, or multiracial participants; 24% were born outside the United States. Retention is high: 84% of participants whose pregnancies did not end in miscarriage completed the study or are still currently active. Among children evaluated at 36 months of age, 24% met criteria for ASD, and another 25% were assessed as nonASD nontypical development. CONCLUSION: Few environmental studies of ASD prospectively obtain early-life exposure measurements. The MARBLES study fills this gap with extensive data and specimen collection beginning in pregnancy and has achieved excellent retention in an ethnically diverse study population. The 24% familial recurrence risk is consistent with recent reported risks observed in large samples of siblings of children diagnosed with ASD. https://doi.org/10.1289/EHP535.

16.
PLoS Med ; 15(10): e1002671, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30356230

RESUMO

In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures.

17.
Child Care Health Dev ; 44(6): 916-925, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30136409

RESUMO

BACKGROUND: This study aimed to describe parental perceptions of the causes of autism spectrum disorder (ASD) in an ethnically diverse sample and explore whether these perceptions relate to treatment choices. METHODS: The sample consisted of White (n = 224), Hispanic (n = 85), and Asian (n = 21) mothers of a child with ASD. A mixed methods approach was used in this secondary analysis focusing on parental perceptions about the causes of ASD and the relationship of these to utilization of services and treatment. RESULTS: Environmental and genetic factors were most often believed to be the cause or one of the causes of ASD by mothers across all ethnic groups studied. Asian mothers were more likely to cite multiple causes. Environmental causes were associated with receiving 20 or more hours of autism-related services per week, whereas belief in environmental exposures and vaccines and medications as causes were associated with complementary-alternative medicine (CAM) use. CONCLUSION: Our findings suggest that ethnic differences in autism causal beliefs and treatment choices may exist. Future research should be conducted to specifically confirm the findings, to understand parental motivation behind their service and treatment choices, and to gain more insight into the types, usage, and sources of CAM treatments. Clinicians can use parental autism causal beliefs in discussions about treatment recommendations.

18.
Environ Res ; 165: 400-409, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29860212

RESUMO

BACKGROUND: Variability of short-lived urinary pesticide metabolites during pregnancy raises challenges for exposure assessment. OBJECTIVES: For urinary metabolite concentrations 3-phenoxybenzoic acid (3-PBA) and 3,5,6-trichloro-2-pyridinol (TCPy), we assessed: (1) temporal variability; (2) variation of two urine specimens within a trimester; (3) reliability for pesticide concentrations from a single urine specimen to classify participants into exposure tertiles; and (4) seasonal or year variations. METHODS: Pregnant mothers (N = 166) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) Study provided urine specimens (n = 528). First morning void (FMV), pooled, and 24-h specimens were analyzed for 3-PBA and TCPy. For 9 mothers (n = 88 specimens), each urine specimen was analyzed separately (not pooled) to estimate within- and between-person variance components expressed as intraclass correlation coefficients (ICC). Pesticide concentrations from two specimens within a trimester were also assessed using ICC's. Agreement for exposure classifications was assessed with weighted Cohen's kappa statistics. Longitudinal mixed effect models were used to assess seasonal or year variations. RESULTS: Urinary pesticide metabolites were detected in ≥ 93% of specimens analyzed. The highest ICC from repeated individual specimens was from specific gravity-corrected FMV specimens for 3-PBA (ICC=0.13). Despite high within-person variability, the median concentrations did not differ across trimesters. Concentrations from pooled specimens had substantial agreement predicting exposure categories for TCPy (K = 0.67, 95% CI (0.59, 0.76)) and moderate agreement for 3-PBA (K = 0.59, 95% CI (0.49, 0.69)). TCPy concentrations significantly decreased from 2007 to 2014. CONCLUSIONS: Pooled specimens may improve exposure classification and reduce laboratory costs for compounds with short biological half-lives in epidemiological studies.

19.
Environ Int ; 115: 267-278, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29605679

RESUMO

BACKGROUND AND AIMS: There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA). METHODS: We used PCB 153, p,p'-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997-2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy. RESULTS: Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04-1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04-1.14]) than in boys (OR of 1.03 [95% CI: 1.03-1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01-1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85-0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11-1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97-2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02-2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61-0.72]) (p-interaction = 0.0004). No significant associations were found for p,p'-DDE. CONCLUSIONS: Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways.

20.
Autism Res ; 11(4): 554-586, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29573218

RESUMO

The complexity of neurodevelopment, the rapidity of early neurogenesis, and over 100 years of research identifying environmental influences on neurodevelopment serve as backdrop to understanding factors that influence risk and severity of autism spectrum disorder (ASD). This Keynote Lecture, delivered at the May 2016 annual meeting of the International Society for Autism Research, describes concepts of causation, outlines the trajectory of research on nongenetic factors beginning in the 1960s, and briefly reviews the current state of this science. Causal concepts are introduced, including root causes; pitfalls in interpreting time trends as clues to etiologic factors; susceptible time windows for exposure; and implications of a multi-factorial model of ASD. An historical background presents early research into the origins of ASD. The epidemiologic literature from the last fifteen years is briefly but critically reviewed for potential roles of, for example, air pollution, pesticides, plastics, prenatal vitamins, lifestyle and family factors, and maternal obstetric and metabolic conditions during her pregnancy. Three examples from the case-control CHildhood Autism Risks from Genes and the Environment Study are probed to illustrate methodological approaches to central challenges in observational studies: capturing environmental exposure; causal inference when a randomized controlled clinical trial is either unethical or infeasible; and the integration of genetic, epigenetic, and environmental influences on development. We conclude with reflections on future directions, including exposomics, new technologies, the microbiome, gene-by-environment interaction in the era of -omics, and epigenetics as the interface of those two. As the environment is malleable, this research advances the goal of a productive and fulfilling life for all children, teen-agers and adults. Autism Res 2018, 11: 554-586. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This Keynote Lecture, delivered at the 2016 meeting of the International Society for Autism Research, discusses evidence from human epidemiologic studies of prenatal factors contributing to autism, such as pesticides, maternal nutrition and her health. There is no single cause for autism. Examples highlight the features of a high-quality epidemiology study, and what comprises a compelling case for causation. Emergent research directions hold promise for identifying potential interventions to reduce disabilities, enhance giftedness, and improve lives of those with ASD.

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