Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology.
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ABSTRACT:
SUBMITTER: Frye RE
PROVIDER: S-EPMC8159748 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Ambient air pollution and maternal diabetes may affect common biological pathways underlying adverse neurodevelopmental effects. However, joint effects of maternal diabetes and air pollution on autism spectrum disorder (ASD) have not been studied. OBJECTIVE:We evaluated whether prenatal and early-life air pollution exposure interacts with maternal diabetes status to affect ASD risk. METHODS:This retrospective cohort study included 246,420 singleton children born in Kaiser Permanente Southern California hospitals in 1999-2009. Children were followed from birth until age 5, during which 2471 ASD cases were diagnosed. Ozone (O3), particulate matter?<?2.5??m (PM2.5) and <10??m in aerodynamic diameter, and nitrogen dioxide measured at regulatory air monitoring stations were interpolated to estimate exposures during preconception and each pregnancy trimester, and first year of life at each child's birth address. Hazard ratios (HRs) for ASD were estimated adjusting for birth year, KPSC service areas, and relevant maternal and child characteristics. For each exposure window, interactions were tested between pollutants and a 4-category maternal diabetes variable (none, GDM???24 and <24?weeks' gestation, and pre-existing type 2 diabetes). For an exposure window with statistically significant global interaction between pollutant and diabetes (p?<?0.05), pollutant-associated HRs were estimated separately for each category of maternal diabetes. RESULTS:There were associations of ASD with preconception, first and third trimesters, and first year of life PM2.5, but not with other pollutants. There were, however, interactions of maternal diabetes with first trimester and first year of life O3. Increased ASD risk was associated with first trimester O3 among mothers with GDM?<?24?weeks' gestation [adjusted HR 1.50 per 15.7?ppb O3 (95% CI: 1.08-2.09)]. No O3 associations with ASD were observed in other categories of maternal diabetes. CONCLUSIONS:GDM onset early in pregnancy may increase children's susceptibility to prenatal O3-associated ASD risk. These novel findings merit further investigation.
| S-EPMC7250244 | biostudies-literature
Project description:ImportanceThe etiology of autism spectrum disorder (ASD) is poorly understood, but prior studies suggest associations with airborne pollutants.ObjectiveTo evaluate the association between prenatal exposures to airborne pollutants and ASD in a large population-based cohort.Design, setting, and participantsThis population-based cohort encompassed nearly all births in Metro Vancouver, British Columbia, Canada, from 2004 through 2009, with follow-up through 2014. Children were diagnosed with ASD using a standardized assessment with the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. Monthly mean exposures to particulate matter with a diameter less than 2.5 µm (PM2.5), nitric oxide (NO), and nitrogen dioxide (NO2) at the maternal residence during pregnancy were estimated with temporally adjusted, high-resolution land use regression models. The association between prenatal air pollution exposures and the odds of developing ASD was evaluated using logistic regression adjusted for child sex, birth month, birth year, maternal age, maternal birthplace, and neighborhood-level urbanicity and income band. Data analysis occurred from June 2016 to May 2018.ExposuresMean monthly concentrations of ambient PM2.5, NO, and NO2 at the maternal residence during pregnancy, calculated retrospectively using temporally adjusted, high-resolution land use regression models.Main outcomes and measuresAutism spectrum disorder diagnoses based on standardized assessment of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The hypothesis being tested was formulated during data collection.ResultsIn a cohort of 132 256 births, 1307 children (1.0%) were diagnosed with ASD by the age of 5 years. The final sample size for the PM2.5-adjusted model was 129 439 children, and for NO and NO2, it was 129 436 children; of these, 1276 (1.0%) were diagnosed with ASD. Adjusted odds ratios for ASD per interquartile range (IQR) were not significant for exposure to PM2.5 during pregnancy (1.04 [95% CI, 0.98-1.10] per 1.5 μg/m3 increase [IQR] in PM2.5) or NO2 (1.06 [95% CI, 0.99-1.12] per 4.8 ppb [IQR] increase in NO2) but the odds ratio was significant for NO (1.07 [95% CI, 1.01-1.13] per 10.7 ppb [IQR] increase in NO). Odds ratios for male children were 1.04 (95% CI, 0.98-1.10) for PM2.5; 1.09 (95% CI, 1.02-1.15) for NO; and 1.07 (95% CI, 1.00-1.13) for NO2. For female children, they were for 1.03 (95% CI, 0.90-1.18) for PM2.5; 0.98 (95% CI, 0.83-1.13) for NO; and 1.00 (95% CI, 0.86-1.16) for NO2.Conclusions and relevanceIn a population-based birth cohort, we detected an association between exposure to NO and ASD but no significant association with PM2.5 and NO2.
| S-EPMC6583438 | biostudies-literature
Project description:Genetic studies in ASD have mostly focused on the proband, with no clear understanding of parental genetic contributions to fetal neurodevelopment. Among parental etiological factors, perinatal maternal inflammation secondary to autoimmunity, infections, and toxins is associated with ASD. However, the inherent impact of maternal genetics on in-utero inflammation and fetal neurodevelopment in the absence of strong external inflammatory exposures is not known. We used the PtenWT/m3m4 mouse model for ASD to demonstrate the impact of maternal genetics on the penetrance of ASD-like phenotypes in the offspring. PtenWT/m3m4 (Momm3m4) or PtenWT/WT (MomWT) females, their offspring, and placental interface were analyzed for inflammatory markers, gene expression, and cellular phenotypes at E17.5. Postnatal behavior was tested by comparing pups from Momm3m4 vs. MomWT. Mothers of the PtenWT/m3m4 genotype (Momm3m4) showed inadequate induction of IL-10 mediated immunosuppression during pregnancy. Low IL-10 in the mother was directly correlated with decreased complement expression in the fetal liver. Fetuses from Momm3m4 had increased breakdown of the blood-brain-barrier, neuronal loss, and lack of glial cell maturation during in-utero stages. This impact of maternal genotype translated to a postnatal increase in the risk of newborn mortality, visible macrocephaly and ASD-like repetitive and social behaviors. Depending on maternal genotype, non-predisposed (wildtype) offspring showed ASD-like phenotypes, and phenotypic penetrance was decreased in predisposed pups from MomWT. Our study introduces the concept that maternal genetics alone, without any added external inflammatory insults, can modulate fetal neurodevelopment and ASD-related phenotypes in the offspring via alteration of IL-10 mediated materno-fetal immunosuppression.
| S-EPMC8179926 | biostudies-literature
Project description:BackgroundStudies have shown that air pollution exposures during pregnancy are associated with an increased risk of autism spectrum disorder (ASD) in children, and the risk appears to be greater for boys. However, studies assessing gestational windows of susceptibility have been mostly limited by trimesters.ObjectiveWe identified sensitive windows of exposure to regional air pollution and risk of ASD and examined sex differences in a large birth cohort.MethodsThis population-based retrospective cohort study included 294,937 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California (KPSC) hospitals from 2001 to 2014. Children were followed using electronic medical records until clinical ASD diagnosis, non-KPSC membership, death, or 31 December 2019, whichever came first. Weekly mean fine particulate matter [PM with an aerodynamic diameter of ≤2.5μm (PM2.5)], nitrogen dioxide (NO2), and ozone (O3) pregnancy exposures were estimated using spatiotemporal prediction models. Cox proportional hazard models with distributed lags were used to estimate weekly pollutant exposure associations with ASD risk for the entire cohort, and separately for boys and for girls. Models were adjusted for child sex (for full cohort), maternal race/ethnicity, maternal age at delivery, parity, maternal education, maternal comorbidities, medical center, census tract median household income, birth year, and season.ResultsThere were 5,694 ASD diagnoses (4,636 boys, 1,058 girls). Sensitive PM2.5 exposure windows associated with ASD were found early in pregnancy, statistically significant throughout the first two trimesters [1-27 wk of gestation, cumulative hazard ratio (HR)=1.14 [95% confidence interval (CI): 1.06, 1.23] per interquartile range (IQR) (7.4-μg/m3) increase]. O3 exposure during 34-37 wk of gestation was associated with increased risk [HR=1.06 (95% CI: 1.01, 1.11) per IQR (17.4 ppb) increase] but with reduced risk during 20-28 wk of gestation [HR=0.93 (95% CI: 0.89, 0.98)]. No associations were observed with NO2. Sex-stratified early gestational PM2.5 associations were stronger among boys [boys HR=1.16 (95% CI: 1.08, 1.26); girls HR=1.06 (95% CI: 0.89, 1.26)]. O3 associations in later gestation were observed only in boys [boys HR=1.10 (95% CI: 1.04, 1.16); girls HR=0.94 (95% CI: 0.84, 1.05)].ConclusionsExposures to PM2.5 in the first two gestational trimesters were associated with increased ASD risk in children, with stronger associations observed for boys. The role of O3 exposure on ASD risk merits further investigation. https://doi.org/10.1289/EHP9509.
| S-EPMC8765363 | biostudies-literature
Project description:BackgroundStudies from the United States indicate that exposure to air pollution in early life is associated with autism spectrum disorders (ASD) in children, but the evidence is not consistent with European data.ObjectiveWe aimed to investigate the association between exposure to air pollution from road traffic and the risk of ASD in children, with careful adjustment for socioeconomic and other confounders.MethodChildren born and residing in Stockholm, Sweden, during 1993-2007 with an ASD diagnosis were identified through multiple health registers and classified as cases (n = 5,136). A randomly selected sample of 18,237 children from the same study base constituted controls. Levels of nitrogen oxides (NOx) and particulate matter with diameter ? 10 ?m (PM10) from road traffic were estimated at residential addresses during mother's pregnancy and the child's first year of life by dispersion models. Odds ratios (OR) and 95% confidence intervals (CI) for ASD with or without intellectual disability (ID) were estimated using logistic regression models after conditioning on municipality and calendar year of birth as well as adjustment for potential confounders.ResultAir pollution exposure during the prenatal period was not associated with ASD overall (OR = 1.00; 95% CI: 0.86, 1.15 per 10-?g/m3 increase in PM10 and OR = 1.02; 95% CI: 0.94, 1.10 per 20-?g/m3 increase in NOx during mother's pregnancy). Similar results were seen for exposure during the first year of life, and for ASD in combination with ID. An inverse association between air pollution exposure and ASD risk was observed among children of mothers who moved to a new residence during pregnancy.ConclusionEarly-life exposure to low levels of NOx and PM10 from road traffic does not appear to increase the risk of ASD. Citation: Gong T, Dalman C, Wicks S, Dal H, Magnusson C, Lundholm C, Almqvist C, Pershagen G. 2017. Perinatal exposure to traffic-related air pollution and autism spectrum disorders. Environ Health Perspect 125:119-126;?http://dx.doi.org/10.1289/EHP118.
| S-EPMC5226686 | biostudies-literature
Project description:BackgroundResidual confounding is a major concern for causal inference in observational studies on air pollution-autism spectrum disorder (ASD) associations. This study is aimed at assessing confounding in these associations using negative control exposures.MethodsThis nested case-control study included all children diagnosed with ASD (detected through 31 December 2016) born during 2007-2012 in Israel and residing in the study area (N = 3,843), and matched controls of the same age (N = 38,430). We assigned individual house-level exposure estimates for each child. We estimated associations using logistic regression models, mutually adjusted for all relevant exposure periods (prepregnancy, pregnancy, and postnatal). We assessed residual confounding using postoutcome negative control exposure at age 28-36 months.ResultsIn mutually adjusted models, we observed positive associations with ASD for postnatal exposures to NOx (odds ratio per interquartile range, 95% confidence interval: 1.19, 1.02-1.38) and NO2 (1.20, 1.00-1.43), and gestational exposure to PM2.5-10 (1.08, 1.01-1.15). The result for the negative control period was 1.04, 0.99-1.10 for PM2.5, suggesting some residual confounding, but no associations for PM2.5-10 (0.98, 0.81-1.18), NOx (1.02, 0.84-1.25), or NO2 (0.98, 0.81-1.18), suggesting no residual confounding.ConclusionsOur results further support a hypothesized causal link with ASD that is specific to postnatal exposures to traffic-related pollution.
| S-EPMC8478838 | biostudies-literature
Project description:Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
2023-11-04 | GSE246534 | GEO
Project description:Traffic-related air pollution exposure may influence brain development and function and thus be related to neurobehavioral problems in children, but little is known about windows of susceptibility.Examine associations of gestational and childhood exposure to traffic-related pollution with executive function and behavior problems in children.We studied associations of pre- and postnatal pollution exposures with neurobehavioral outcomes in 1212 children in the Project Viva pre-birth cohort followed to mid-childhood (median age 7.7years). Parents and classroom teachers completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ). Using validated spatiotemporal models, we estimated exposure to black carbon (BC) and fine particulate matter (PM2.5) in the third trimester of pregnancy, from birth to 3years, from birth to 6years, and in the year before behavioral ratings. We also measured residential distance to major roadways and near-residence traffic density at birth and in mid-childhood. We estimated associations of BC, PM2.5, and other traffic exposure measures with BRIEF and SDQ scores, adjusted for potential confounders.Higher childhood BC exposure was associated with higher teacher-rated BRIEF Behavioral Regulation Index (BRI) scores, indicating greater problems: 1.0 points (95% confidence interval (CI): 0.0, 2.1) per interquartile range (IQR) increase in birth-age 6BC, and 1.7 points (95% CI: 0.6, 2.8) for BC in the year prior to behavioral ratings. Mid-childhood residential traffic density was also associated with BRI score (0.6, 95% CI: 0.1, 1.1). Birth-age 3BC was not associated with BRIEF or SDQ scores. Third trimester BC exposure was not associated with teacher-rated BRI scores (-0.2, 95% CI: -1.1, 0.8), and predicted lower scores (fewer problems) on the BRIEF Metacognition Index (-1.2, 95% CI: -2.2, -0.2) and SDQ total difficulties (-0.9, 95% CI: -1.4, -0.4). PM2.5 exposure was associated with teacher-rated BRIEF and SDQ scores in minimally adjusted models but associations attenuated with covariate adjustment. None of the parent-rated outcomes suggested adverse effects of greater pollution exposure at any time point.Children with higher mid-childhood exposure to BC and greater near-residence traffic density in mid-childhood had greater problems with behavioral regulation as assessed by classroom teachers, but not as assessed by parents. Prenatal and early childhood exposure to traffic-related pollution did not predict greater executive function or behavior problems; third trimester BC was associated with lower scores (representing fewer problems) on measures of metacognition and behavioral problems.
| S-EPMC5056808 | biostudies-literature
Project description:Independent studies report association of autism spectrum disorder with air pollution exposure and a functional promoter variant (rs1858830) in the MET receptor tyrosine kinase (MET) gene. Toxicological data find altered brain Met expression in mice after prenatal exposure to a model air pollutant. Our objective was to investigate whether air pollution exposure and MET rs1858830 genotype interact to alter the risk of autism spectrum disorder.We studied 252 cases of autism spectrum disorder and 156 typically developing controls from the Childhood Autism Risk from Genetics and the Environment Study. Air pollution exposure was assigned for local traffic-related sources and regional sources (particulate matter, nitrogen dioxide, and ozone). MET genotype was determined by direct resequencing.Subjects with both MET rs1858830 CC genotype and high air pollutant exposures were at increased risk of autism spectrum disorder compared with subjects who had both the CG/GG genotypes and lower air pollutant exposures. There was evidence of multiplicative interaction between NO2 and MET CC genotype (P= 0.03).MET rs1858830 CC genotype and air pollutant exposure may interact to increase the risk of autism spectrum disorder.
| S-EPMC4019012 | biostudies-literature
Project description:Background:Previous autism spectrum disorder (ASD) and air pollution studies focused on pregnancy exposures, but another vulnerable period is immediate postnatally. Here, we examined early life exposures to air pollution from the pre- to the postnatal period and ASD/ASD subtypes in the Danish population. Methods:With Danish registers, we conducted a nationwide case-control study of 15,387 children with ASD born 1989-2013 and 68,139 population controls matched by birth year and sex identified from the birth registry. We generated air dispersion model (AirGIS) estimates for NO2, SO2, PM2.5 and PM10 at mothers' home from 9 months before to 9 months after pregnancy and calculated odds ratios (OR) and 95% confidence intervals (CI), adjusting for parental age, neighborhood socio-economic indicators, and maternal smoking using conditional logistic regression. Results:In models that included all exposure periods, we estimated adjusted ORs for ASD per interquartile range (IQR) increase for 9 month after pregnancy with NO2 of 1.08 (95% CI: 1.01, 1.15) and with PM2.5 of 1.06 (95% CI: 1.01, 1.11); associations were smaller for PM10 (1.04; 95% CI: 1.00, 1.09) and strongest for SO2 (1.21; 95% CI: 1.13, 1.29). Also, associations for pollutants were stronger in more recent years (2000-2013) and in larger cities compared with provincial towns/rural counties. For particles and NO2, associations were only specific to autism and Asperger diagnoses. Conclusion:Our data suggest that air pollutant exposure in early infancy but not during pregnancy increases the risk of being diagnosed with autism and Asperger among children born in Denmark.
| S-EPMC6474375 | biostudies-literature