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2.
Environ Sci Technol ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34817155

RESUMO

Urinary concentrations of phenols, parabens, and triclocarban have been extensively used as biomarkers of exposure. However, because these compounds are quickly metabolized and excreted in urine, characterizing participants' long-term average exposure from a few spot samples is challenging. To examine the variability of urinary concentrations of these compounds during pregnancy, we quantified four phenols, four parabens, and triclocarban in 357 first morning voids (FMVs) and 203 pooled samples collected during the second and third trimesters of 173 pregnancies. We computed intraclass correlation coefficients (ICCs) by the sample type (FMV and pool) across two trimesters and by the number of composite samples in pools, ranging from 2 to 4, within the same trimester. Among the three compounds detected in more than 50% of the samples, the ICCs across two trimesters were higher in pools (0.29-0.68) than in FMVs (0.17-0.52) and the highest ICC within the same trimester was observed when pooling either two or three composites. Methyl paraben and propyl paraben primarily exposed via cosmetic use had approximately 2-3 times higher ICCs than bisphenol A primarily exposed via diet. Our findings support that within-subject pooling of biospecimens can increase the reproducibility of pregnant women's exposure to these compounds and thus could potentially minimize exposure misclassification.

3.
Lancet Reg Health Am ; 2: 100027, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34642685

RESUMO

INTRODUCTION: Our understanding of the association between coronavirus disease 19 (COVID-19) and preterm or early term birth among racially and ethnically diverse populations and people with chronic medical conditions is limited. METHODS: We determined the association between COVID-19 and preterm (PTB) birth among live births documented by California Vital Statistics birth certificates between July 2020 and January 2021 (n=240,147). We used best obstetric estimate of gestational age to classify births as very preterm (VPTB, <32 weeks), PTB (< 37 weeks), early term (37 and 38 weeks), and term (39-44 weeks), as each confer independent risks to infant health and development. Separately, we calculated the joint effects of COVID-19 diagnosis, hypertension, diabetes, and obesity on PTB and VPTB. FINDINGS: COVID-19 diagnoses on birth certificates increased for all racial/ethnic groups between July 2020 and January 2021 and were highest for American Indian/Alaska Native (12.9%), Native Hawaiian/Pacific Islander (11.4%), and Latinx (10.3%) birthing people. COVID-19 diagnosis was associated with an increased risk of VPTB (aRR 1.6, 95% CI [1.4, 1.9]), PTB (aRR 1.4, 95% CI [1.3, 1.4]), and early term birth (aRR 1.1, 95% CI [1.1, 1.2]). There was no effect modification of the overall association by race/ethnicity or insurance status. COVID-19 diagnosis was associated with elevated risk of PTB in people with hypertension, diabetes, and/or obesity. INTERPRETATION: In a large population-based study, COVID-19 diagnosis increased the risk of VPTB, PTB, and early term birth, particularly among people with medical comorbidities. Considering increased circulation of COVID-19 variants, preventative measures, including vaccination, should be prioritized for birthing persons. FUNDING: UCSF-Kaiser Department of Research Building Interdisciplinary Research Careers in Women's Health Program (BIRCWH) National Institute of Child Health and Human Development (NICHD) and the Office of Research on Women's Health (ORWH) [K12 HD052163] and the California Preterm Birth Initiative, funded by Marc and Lynn Benioff.

4.
J Nutr ; 151(11): 3555-3569, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34494118

RESUMO

BACKGROUND: Inadequate or excessive intake of micronutrients in pregnancy has potential to negatively impact maternal/offspring health outcomes. OBJECTIVE: The aim was to compare risks of inadequate or excessive micronutrient intake in diverse females with singleton pregnancies by strata of maternal age, race/ethnicity, education, and prepregnancy BMI. METHODS: Fifteen observational cohorts in the US Environmental influences on Child Health Outcomes (ECHO) Consortium assessed participant dietary intake with 24-h dietary recalls (n = 1910) or food-frequency questionnaires (n = 7891) from 1999-2019. We compared the distributions of usual intake of 19 micronutrients from food alone (15 cohorts; n = 9801) and food plus dietary supplements (10 cohorts with supplement data; n = 7082) to estimate the proportion with usual daily intakes below their age-specific daily Estimated Average Requirement (EAR), above their Adequate Intake (AI), and above their Tolerable Upper Intake Level (UL), overall and within sociodemographic and anthropometric subgroups. RESULTS: Risk of inadequate intake from food alone ranged from 0% to 87%, depending on the micronutrient and assessment methodology. When dietary supplements were included, some women were below the EAR for vitamin D (20-38%), vitamin E (17-22%), and magnesium (39-41%); some women were above the AI for vitamin K (63-75%), choline (7%), and potassium (37-53%); and some were above the UL for folic acid (32-51%), iron (39-40%), and zinc (19-20%). Highest risks for inadequate intakes were observed among participants with age 14-18 y (6 nutrients), non-White race or Hispanic ethnicity (10 nutrients), less than a high school education (9 nutrients), or obesity (9 nutrients). CONCLUSIONS: Improved diet quality is needed for most pregnant females. Even with dietary supplement use, >20% of participants were at risk of inadequate intake of ≥1 micronutrients, especially in some population subgroups. Pregnancy may be a window of opportunity to address disparities in micronutrient intake that could contribute to intergenerational health inequalities.

5.
Metabolites ; 11(8)2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34436486

RESUMO

Maternal and cord plasma metabolomics were used to elucidate biological pathways associated with increased diagnosis risk for autism spectrum disorders (ASD). Metabolome-wide associations were assessed in both maternal and umbilical cord plasma in relation to diagnoses of ASD and other non-typical development (Non-TD) compared to typical development (TD) in the Markers of Autism risk in Babies: Learning Early Signs (MARBLES) cohort study of children born to mothers who already have at least one child with ASD. Analyses were stratified by sample matrix type, machine mode, and annotation confidence level. Dimensionality reduction techniques were used [i.e, principal component analysis (PCA) and random subset weighted quantile sum regression (WQSRS)] to minimize the high multiple comparison burden. With WQSRS, a metabolite mixture obtained from the negative mode of maternal plasma decreased the odds of Non-TD compared to TD. These metabolites, all related to the prostaglandin pathway, underscored the relevance of neuroinflammation status. No other significant findings were observed. Dimensionality reduction strategies provided confirming evidence that a set of maternal plasma metabolites are important in distinguishing Non-TD compared to TD diagnosis. A lower risk for Non-TD was linked to anti-inflammatory elements, thereby linking neuroinflammation to detrimental brain function consistent with studies ranging from neurodevelopment to neurodegeneration.

6.
Environ Sci Technol ; 55(16): 11155-11165, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34347462

RESUMO

Little is known about temporal trends of pregnant women's exposures to environmental phenols and parabens. We quantified four phenols [bisphenol A (BPA), bisphenol F, bisphenol S, and triclosan), four parabens [butyl paraben, ethyl paraben (ETPB), methyl paraben (MEPB), and propyl paraben (PRPB)], and triclocarban in 760 urine samples collected during 2007-2014 from 218 California pregnant women participating in a high-familial risk autism spectrum disorder cohort. We applied multiple regression to compute least square geometric means of urinary concentrations and computed average annual percent changes. We compared our urinary concentrations with those of other study populations to examine geographic variations in pregnant women's exposure to these target compounds. Urinary concentrations of BPA, MEPB, ETPB, and PRPB in this study population decreased over the study period [percent change per year (95% confidence interval): -5.7% (-8.2%, -3.2%); -13.0% (-18.1%, -7.7%); -5.5% (-11.0%, 0.3%); and -13.3% (-18.3%, -8.1%), respectively] and were consistently lower than those in pregnant women in other U.S. regions during the same study period. In recent years, certain phenols and parabens with known adverse health effects are being regulated or replaced with alternatives, which explains decreased body burdens observed in this study population. Either the national regulations or the advocacy campaigns in California may have influenced exposures or consumer product choices.


Assuntos
Transtorno do Espectro Autista , Parabenos , Carbanilidas , Exposição Ambiental/análise , Feminino , Humanos , Parabenos/análise , Fenol , Fenóis , Gravidez , Gestantes
7.
J Agric Food Chem ; 69(23): 6676-6689, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34098718

RESUMO

Existing methods for the analysis of pesticides in human breast milk involve multiple extraction steps requiring large sample and solvent volumes, which can be a major obstacle in large epidemiologic studies. Here, we developed a simple, low-volume method for extracting organophosphates, pyrethroids, carbamates, atrazine, and imidacloprid from 100 to 200 µL of human breast milk. Multiple extraction protocols were tested including microwave-assisted acid/base digestion and double-solvent extraction with 2 or 20 mL of 2:1 (v/v) dichloromethane/hexane, with or without subsequent solid-phase extraction (SPE) cleanup. Samples were analyzed by liquid chromatography tandem mass spectrometry. Analyte recoveries and reproducibility were highest when 100-200 µL of milk were extracted with 2 mL of dichloromethane/hexane without subsequent SPE steps. Analysis of 79 breast milk samples using this method revealed the presence of carbamates, organophosphates, pyrethroids, and imidacloprid at detection frequencies of 79-96, 53-90, 1-7, and 61%, respectively. This study demonstrates the feasibility of a simple low-volume extraction method for measuring pesticides in human breast milk.


Assuntos
Praguicidas , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Feminino , Humanos , Leite Humano/química , Praguicidas/análise , Reprodutibilidade dos Testes , Extração em Fase Sólida
8.
J Autism Dev Disord ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110557

RESUMO

We examined maternal prenatal vitamin use or supplemental folic acid intake during month one of pregnancy for association with autism spectrum disorder (ASD) in the Early Autism Risk Longitudinal Investigation, an enriched-risk pregnancy cohort. Total folic acid intake was calculated from monthly prenatal vitamins, multivitamins, and other supplement reports. Clinical assessments through age 3 years classified children as ASD (n = 38) or non-ASD (n = 153). In pregnancy month one, prenatal vitamin use (59.7%) was not significantly associated with odds of ASD (OR = 0.70, 95%CI 0.32, 1.53). Sample size was limited and residual confounding was possible. Given the estimated effect sizes in this and previous work, prenatal vitamin intake during early pregnancy could be a clinically useful preventative measure for ASD.

9.
Environ Res ; 196: 110939, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33647299

RESUMO

BACKGROUND/OBJECTIVE: Per- and polyfluoroalkyl substances (PFAS) have neurobehavioral toxicity in experimental studies. Evidence on associations between prenatal PFAS exposure and child's cognitive development is inconsistent partly due to differences in assessment time points and tools. We examined associations of prenatal maternal serum PFAS concentrations with child's cognitive development assessed at multiple time points in infancy and toddlerhood. METHODS: We included 140 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a longitudinal cohort of children with a first degree relative who was diagnosed with autism spectrum disorder followed from birth. Study children's cognitive development was assessed at 6, 12, 24, and 36 months of age using the Mullen Scales of Early Learning (MSEL) which provides an overall Early Learning Composite (normative mean of 100 and SD of 15) and four subscales (i.e., fine motor, visual reception, receptive language, and expressive language abilities; normative mean of 50 and SD of 10). Nine PFAS were quantified in maternal serum collected during pregnancy. We examined associations of log 2-transformed prenatal maternal serum PFAS concentrations with the MSEL Composite and each of the subscale scores at each time point as well as longitudinal changes in the scores over the four time points. We also classified trajectories into low- and high-score groups and fit Poisson regression models to estimate associations expressed as relative risks (RR). RESULTS: Among six PFAS detected in more than 60% of the samples, prenatal maternal serum perfluorooctanoate (PFOA) was inversely associated with child's Composite score at 24 months (ß = -5.22, 95% CI: -8.27, -2.17) and 36 months of age (ß = -5.18, 95% CI: -9.46, -0.91), while other five PFAS were not strongly associated with Composite score at any time points. When assessing longitudinal changes in the scores over the four time points, PFOA was associated with trajectories having a negative slope for Composite scores and all four subscales. When examining trajectories of the scores between low- and high-score groups, PFOA was associated with having lower and/or decreasing Composite scores (RR = 1.49, 95% CI: 1.09, 2.03). CONCLUSIONS: Prenatal PFOA appears to adversely affect child's cognitive development in toddlerhood in this study population. Because a large fraction of MARBLES children is at risk for atypical development, population-based studies are needed to confirm our findings.


Assuntos
Ácidos Alcanossulfônicos , Transtorno do Espectro Autista , Poluentes Ambientais , Fluorcarbonetos , Efeitos Tardios da Exposição Pré-Natal , Criança , Cognição , Poluentes Ambientais/toxicidade , Feminino , Fluorcarbonetos/toxicidade , Humanos , Lactente , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
11.
Environ Int ; 147: 106328, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33387879

RESUMO

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has shown potential to adversely affect child brain development, but epidemiologic evidence remains inconsistent. We examined whether prenatal exposure to PFAS was associated with increased risk of autism spectrum disorder (ASD). METHODS: Participants were 173 mother-child pairs from MARBLES (Markers of Autism Risk in Babies - Learning Early Signs), a high-risk ASD cohort. At 3 years old, children were clinically confirmed for ASD and classified into ASD (n = 57) and typical development (TD, n = 116). We quantified nine PFAS in maternal serum collected during pregnancy. We examined associations of ASD with individual PFAS as well as the combined effect of PFAS on ASD using scores of the first principal component (PC-1) accounting for the largest variance. RESULTS: Prenatal perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) showed positive associations (per 2 nanogram per milliliter increase: relative risk (RR) = 1.20, 95% CI: 0.90, 1.61 [PFOA]; RR = 1.24, 95% CI: 0.91, 1.69 [PFNA]), while perfluorohexane sulfonate (PFHxS) showed a negative association (RR = 0.88, 95% CI: 0.77, 1.01) with ASD risk. When examining associations of ASD with untransformed PFAS concentrations, PFOA, PFNA, and PC-1 were associated with increased ASD risk (per nanogram per milliliter increase: RR = 1.31, 95% CI: 1.04, 1.65; RR = 1.79, 95% CI: 1.13, 2.85; RR = 1.10, 95% CI: 0.97, 1.25, respectively), while the RR of PFHxS moved toward the null. CONCLUSIONS: From this high-risk ASD cohort, we observed increased risk of ASD in children exposed to PFOA and PFNA. Further studies should be conducted in the general population because this population may have a larger fraction of cases resulting from genetic sources.


Assuntos
Ácidos Alcanossulfônicos , Transtorno do Espectro Autista , Poluentes Ambientais , Fluorcarbonetos , Efeitos Tardios da Exposição Pré-Natal , Ácidos Alcanossulfônicos/toxicidade , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Carbonato de Cálcio , Criança , Pré-Escolar , Estudos de Coortes , Poluentes Ambientais/toxicidade , Feminino , Fluorcarbonetos/toxicidade , Humanos , Gravidez
12.
PLoS One ; 16(1): e0245064, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33418560

RESUMO

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.


Assuntos
Grupos Étnicos , Idade Gestacional , Idade Materna , Mães , Classe Social , Adulto , Feminino , Humanos , Recém-Nascido , Gravidez , Estados Unidos
13.
Autism Res ; 14(1): 11-28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33159718

RESUMO

The prenatal period is a critical window for the development of autism spectrum disorder (ASD). The relationship between prenatal nutrients and gestational gene expression in mothers of children later diagnosed with ASD or non-typical development (Non-TD) is poorly understood. Maternal blood collected prospectively during pregnancy provides insights into the effects of nutrition, particularly one-carbon metabolites, on gene pathways and neurodevelopment. Genome-wide transcriptomes were measured with microarrays in 300 maternal blood samples in Markers of Autism Risk in Babies-Learning Early Signs. Sixteen different one-carbon metabolites, including folic acid, betaine, 5'-methyltretrahydrofolate (5-MeTHF), and dimethylglycine (DMG) were measured. Differential expression analysis and weighted gene correlation network analysis (WGCNA) were used to compare gene expression between children later diagnosed as typical development (TD), Non-TD and ASD, and to one-carbon metabolites. Using differential gene expression analysis, six transcripts (TGR-AS1, SQSTM1, HLA-C, and RFESD) were associated with child outcomes (ASD, Non-TD, and TD) with genome-wide significance. Genes nominally differentially expressed between ASD and TD significantly overlapped with seven high confidence ASD genes. WGCNA identified co-expressed gene modules significantly correlated with 5-MeTHF, folic acid, DMG, and betaine. A module enriched in DNA methylation functions showed a suggestive protective association with folic acid/5-MeTHF concentrations and ASD risk. Maternal plasma betaine and DMG concentrations were associated with a block of co-expressed genes enriched for adaptive immune, histone modification, and RNA processing functions. These results suggest that the prenatal maternal blood transcriptome is a sensitive indicator of gestational one-carbon metabolite status and changes relevant to children's later neurodevelopmental outcomes. LAY SUMMARY: Pregnancy is a time when maternal nutrition could interact with genetic risk for autism spectrum disorder. Blood samples collected during pregnancy from mothers who had a prior child with autism were examined for gene expression and nutrient metabolites, then compared to the diagnosis of the child at age three. Expression differences in gene pathways related to the immune system and gene regulation were observed for pregnancies of children with autism and non-typical neurodevelopment and were associated with maternal nutrients.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno do Espectro Autista/genética , Carbono , Criança , Pré-Escolar , Epigênese Genética/genética , Feminino , Humanos , Lactente , Gravidez , Estudos Prospectivos
14.
Environ Res ; 194: 110495, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33220244

RESUMO

BACKGROUND: We assessed the relationships between prenatal pyrethroid pesticide exposure and autism spectrum disorders (ASD) or non-typical development (non-TD) at 3 years. METHODS: Participants were mother-child pairs (n = 201) in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) cohort. Because familial recurrence risk is high, MARBLES enrolls pregnant women with a family history of ASD. Children from these pregnancies were clinically assessed at 3 years of age and classified into 3 outcome categories: ASD, typically developing (TD), or non-TD (neither TD or ASD). Repeated maternal second and third trimester urine samples were analyzed for pyrethroid metabolite 3-phenoxybenzoic acid (3-PBA). Multinomial logistic regression was used to obtain relative risk ratios (RRR) linking 3-PBA concentrations averaged across each trimester and over pregnancy with child's outcome: ASD or non-TD vs. TD. Models were adjusted for specific gravity, maternal pre-pregnancy BMI, prenatal vitamin use, birth year, home-ownership, and pregnancy concentrations of TCPy (3,5,6-trichloro-2-pyridinol, a metabolite of chlorpyrifos). RESULTS: The median specific gravity corrected 3-PBA concentration of all samples was 1.46 ng/mL. Greater second trimester 3-PBA concentrations were associated with a relative risk ratio (RRR) for ASD of (RRR: 1.50 (95% CI 0.89 to 2.51), p = 0.12). There were no differences between non-TD and TD. CONCLUSIONS: This study found no evidence for differences in 3-PBA comparing non-TD with TD. A modestly elevated RRR was found comparing second trimester urinary 3-PBA concentrations for ASD versus TD; however, the confidence interval was wide and hence, these findings cannot be considered definitive.


Assuntos
Transtorno do Espectro Autista , Praguicidas , Piretrinas , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/epidemiologia , Carbonato de Cálcio , Criança , Estudos de Coortes , Feminino , Humanos , Praguicidas/toxicidade , Gravidez , Piretrinas/toxicidade
15.
Artigo em Inglês | MEDLINE | ID: mdl-33317014

RESUMO

BACKGROUND: Fetal development involves cellular differentiation and epigenetic changes-complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. HYPOTHESIS: We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. METHODS: In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. RESULTS: Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null -0.06% (95% CI: -0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). CONCLUSIONS: We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.


Assuntos
Metilação de DNA , Metilenotetra-Hidrofolato Redutase (NADPH2) , Criança , Metilação de DNA/genética , Feminino , Sangue Fetal , Genótipo , Humanos , Recém-Nascido , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Gravidez , Vitaminas
16.
Genome Med ; 12(1): 88, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054850

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes. METHODS: We performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females. RESULTS: We identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development. CONCLUSIONS: At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.


Assuntos
Transtorno do Espectro Autista/etiologia , Metilação de DNA , Epigenoma , Sangue Fetal , Genes Ligados ao Cromossomo X , Neurogênese , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/genética , Biomarcadores , Encéfalo/metabolismo , Pré-Escolar , Biologia Computacional/métodos , Epigênese Genética , Contagem de Eritrócitos , Feminino , Regulação da Expressão Gênica , Humanos , Lactente , Recém-Nascido , Aprendizado de Máquina , Masculino , Especificidade de Órgãos/genética , Prognóstico
17.
Environ Sci Technol ; 54(20): 13157-13166, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32940456

RESUMO

Phthalates with potential adverse health effects are being replaced by other phthalates or phthalate alternatives. Little is known about temporal trends of phthalate exposure in pregnant women in the United States. We quantified 16 metabolites of eight phthalates and di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) in 656 urine samples collected from 192 California pregnant women in 2007-2013 during their second and third trimesters of pregnancy who participated in the MARBLES (Markers of Autism Risk in Babies-Learning Early Signs) study. We used multiple regression to estimate least squares geometric means of phthalate biomarker concentrations and annual percent changes over the study period. Biomarker concentrations of diethyl phthalate (DEP) and three phthalates with known toxicity and adverse health effects (i.e., butyl benzyl phthalate [BBzP], dibutyl phthalate [DBP], di(2-ethylhexyl) phthalate [DEHP]) decreased, while those of di-isobutyl phthalate [DiBP], di-isononyl phthalate [DiNP], and di-n-octyl phthalate [DOP] increased in California pregnant women during our study period. To understand broad social forces that may influence temporal trends and geographic variations in phthalate exposure across countries, we compared our phthalate biomarker concentrations with those of other populations. We observed over a factor of 2 differences in exposure across countries for some phthalate biomarkers and between pregnant and nonpregnant women for DEP.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , California , Exposição Ambiental , Feminino , Humanos , Gravidez , Gestantes
18.
Autism Res ; 13(6): 998-1010, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32314879

RESUMO

Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well-defined etiology. We sought to determine parental age associations with ASD-related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced parental age with clinical ASD diagnosis, Social Responsiveness Scale, or Vineland Adaptive Behavior Scales scores. Instead, increased odds of ASD were found with paternal age < 30 years (adjusted odds ratio [AOR] = 2.83 and 95% confidence intervals [CI] = 1.14-7.02). Likewise, younger age (<30 years) for both parents was associated with decreases in Mullen Scales of Early Learning early learning composite (MSEL-ELC) scores (adjusted ß = -9.62, 95% CI = -17.1 to -2.15). We also found significant increases in cognitive functioning based on MSEL-ELC scores with increasing paternal age (adjusted ß associated with a 10-year increase in paternal age = 5.51, 95% CI = 0.70-10.3). Results suggest the potential for a different relationship between parental age and ASD-related outcomes in families with elevated ASD risk than has been observed in general population samples. Autism Res 2020, 13: 998-1010. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous work suggests that older parents have a greater likelihood of having a child with autism. We investigated this relationship in the younger siblings of families who already had a child with autism. In this setting, we found a higher likelihood of autism, as well as poorer cognitive scores, in the siblings with younger fathers, and higher cognitive scores in the siblings with older parents. These results suggest that parental age associations may differ based on children's familial risk for autism.


Assuntos
Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Idade Materna , Idade Paterna , Adulto , Transtorno Autístico/epidemiologia , Transtorno Autístico/genética , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos
19.
Autism ; 24(5): 1191-1200, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31958995

RESUMO

LAY ABSTRACT: Prior studies suggest that maternal polyunsaturated fatty acids intake during pregnancy may have protective effects on autism spectrum disorder in their children. However, they did not examine detailed timing of maternal polyunsaturated fatty acid intake during pregnancy, nor did they evaluate plasma concentrations. This study investigates whether maternal polyunsaturated fatty acids in defined time windows of pregnancy, assessed by both questionnaires and biomarkers, are associated with risk of autism spectrum disorder and other non-typical development in the children. Food frequency questionnaires were used to estimate maternal polyunsaturated fatty acid intake during the first and second half of pregnancy. Gas chromatography measured maternal plasma polyunsaturated fatty acid concentrations in the third trimester. In all, 258 mother-child pairs from a prospective cohort were included. All mothers already had a child with autism spectrum disorder and were planning a pregnancy or pregnant with another child. Children were clinically assessed longitudinally and diagnosed at 36 months. For polyunsaturated fatty acid intake from questionnaires, we only found mothers consuming more omega-3 in the second half of pregnancy were 40% less likely to have children with autism spectrum disorder. For polyunsaturated fatty acid concentrations in the third-trimester plasma, we did not observe any statistical significance in relation to the risk of autism spectrum disorder. However, our study confirmed associations from previous studies between higher maternal docosahexaenoic acid and eicosapentaenoic acid plasma concentrations in the late pregnancy and reduced risk for non-typical development. This study markedly advanced understandings of whether and when maternal polyunsaturated fatty acid intake influences risk for autism spectrum disorder and sets the stage for prevention at the behavioral and educational level.


Assuntos
Transtorno do Espectro Autista , Ácidos Graxos Ômega-3 , Carbonato de Cálcio , Ácidos Graxos Insaturados , Feminino , Humanos , Gravidez , Estudos Prospectivos
20.
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.


Assuntos
Transtorno Autístico/genética , Autoimunidade/genética , Cromatina/metabolismo , Meio Ambiente , Sangue Fetal/metabolismo , Adulto , Criança , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco
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