Background: Autism prevalence in California, based on individuals eligible for state-funded services, rose throughout the 1990s. The extent to which this trend is explained by changes in age at ...diagnosis or inclusion of milder cases has not been previously evaluated. Methods: Autism cases were identified from 1990 through 2006 in databases of the California Department of Developmental Services, which coordinates services for individuals with specific developmental disorders. The main outcomes were population incident cases younger than age 10 years for each quarter, cumulative incidence by age and birth year, age-specific incidence rates stratified by birth year, and proportions of diagnoses by age across birth years. Results: Autism incidence in children rose throughout the period. Cumulative incidence to 5 years of age per 10,000 births rose consistently from 6.2 for 1990 births to 42.5 for 2001 births. Age-specific incidence rates increased most steeply for 2- and 3-year olds. The proportion diagnosed by age 5 years increased only slightly, from 54% for 1990 births to 61% for 1996 births. Changing age at diagnosis can explain a 12% increase, and inclusion of milder cases, a 56% increase. Conclusions: Autism incidence in California shows no sign yet of plateauing. Younger ages at diagnosis, differential migration, changes in diagnostic criteria, and inclusion of milder cases do not fully explain the observed increases. Other artifacts have yet to be quantified, and as a result, the extent to which the continued rise represents a true increase in the occurrence of autism remains unclear.
Immune aberrations are often noted in children with autism spectrum disorder (ASD), but whether asthma and allergy are related to ASD is not well defined. This study examined asthma and allergies in ...association with ASD and phenotypic subsets. Participants were 560 children with confirmed ASD and 391 typically developing children from the CHildhood Autism Risks from Genetics and the Environment study. Maternally reported child asthma and allergy was compared between cases and controls, and in association with cognitive and behavioral test scores. Prevalence of asthma and overall allergies did not differ between cases and controls, but overall allergy in children with ASD was associated with higher stereotypy scores as measured by the Aberrant Behavior Checklist. In addition, reported food allergies were significantly associated with ASD (adjusted odds ratio = 2.23, 95% confidence interval 1.28, 3.89). Our results suggest food allergies and sensitivities may be more common in children with ASD, and that these issues may correlate with other behaviors.
CONTEXT Autism is a heterogeneous disorder with genetic and environmental factors likely contributing to its origins. Examination of hazardous pollutants has suggested the importance of air toxics in ...the etiology of autism, yet little research has examined its association with local levels of air pollution using residence-specific exposure assignments. OBJECTIVE To examine the relationship between traffic-related air pollution, air quality, and autism. DESIGN This population-based case-control study includes data obtained from children with autism and control children with typical development who were enrolled in the Childhood Autism Risks from Genetics and the Environment study in California. The mother's address from the birth certificate and addresses reported from a residential history questionnaire were used to estimate exposure for each trimester of pregnancy and first year of life. Traffic-related air pollution was assigned to each location using a line-source air-quality dispersion model. Regional air pollutant measures were based on the Environmental Protection Agency's Air Quality System data. Logistic regression models compared estimated and measured pollutant levels for children with autism and for control children with typical development. SETTING Case-control study from California. PARTICIPANTS A total of 279 children with autism and a total of 245 control children with typical development. MAIN OUTCOME MEASURES Crude and multivariable adjusted odds ratios (AORs) for autism. RESULTS Children with autism were more likely to live at residences that had the highest quartile of exposure to traffic-related air pollution, during gestation (AOR, 1.98 95% CI, 1.20-3.31) and during the first year of life (AOR, 3.10 95% CI, 1.76-5.57), compared with control children. Regional exposure measures of nitrogen dioxide and particulate matter less than 2.5 and 10 μm in diameter (PM2.5 and PM10) were also associated with autism during gestation (exposure to nitrogen dioxide: AOR, 1.81 95% CI, 1.37-3.09; exposure to PM2.5: AOR, 2.08 95% CI, 1.93-2.25; exposure to PM10: AOR, 2.17 95% CI, 1.49-3.16) and during the first year of life (exposure to nitrogen dioxide: AOR, 2.06 95% CI, 1.37-3.09; exposure to PM2.5: AOR, 2.12 95% CI, 1.45-3.10; exposure to PM10: AOR, 2.14 95% CI, 1.46-3.12). All regional pollutant estimates were scaled to twice the standard deviation of the distribution for all pregnancy estimates. CONCLUSIONS Exposure to traffic-related air pollution, nitrogen dioxide, PM2.5, and PM10 during pregnancy and during the first year of life was associated with autism. Further epidemiological and toxicological examinations of likely biological pathways will help determine whether these associations are causal.
Summary
This study compared parent‐reported sleep characteristics in 2‐ to 5‐year‐old children with autism spectrum disorders (ASD) to children with other developmental delays (DD) and typical ...development (TD). We included 529 children (303 ASD 167 males, 63 DD 46 males, and 163 TD 134 males) enrolled in the CHARGE study, an ongoing population‐based case–control study. The mean age of participants was 3.6 years (standard deviation, 0.8 years). ASD diagnosis was confirmed with Autism Diagnostic Interview‐Revised (ADI‐R) and Autism Diagnostic Observation Schedules (ADOS). Cognitive and adaptive functioning was assessed using Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS), respectively. Demographic, medical and sleep history information were ascertained from California birth records, telephone interview, medical assessments at clinic visit, and parent‐administered questionnaires. Fifty‐three percent of children with ASD had at least one frequent sleep problem, followed by 46% of children with DD, and 32% of the TD group (P < 0.0001). Exploratory factor analyses of sleep history data yielded two factors: sleep onset problems and night waking. Children with ASD had marginally higher sleep onset factor scores and significantly higher night waking factor scores compared with the TD group. Factor scores for children with DD were intermediate between the ASD and TD groups. Cognitive or adaptive development did not predict severity of sleep problems in the ASD group.
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.
Previous conceptualizations of autism have suggested that symptoms are evident either early in the first year of life or later in the second year, after a loss of previously acquired skills. New ...research suggests, however, that these two patterns do not capture all the different ways autism can emerge. For example, some children show a developmental plateau marked by failure to progress, while other children display mixed features, with both early delays and later losses evident. This article reviews the literature on autism onset, discusses problems with the traditional ways in which onset has been conceptualized, and provides recommendations for future research. We suggest that onset is better thought of as a dimensional process rather than dichotomous categories.
Background: Little is known about environmental causes and contributing factors for autism. Basic science and epidemiologic research suggest that oxidative stress and inflammation may play a role in ...disease development. Traffic-related air pollution, a common exposure with established effects on these pathways, contains substances found to have adverse prenatal effects. Objectives: We examined the association between autism and proximity of residence to freeways and major roadways during pregnancy and near the time of delivery, as a surrogate for air pollution exposure. Methods: Data were from 304 autism cases and 259 typically developing controls enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. The mother's address recorded on the birth certificate and trimester-specific addresses derived from a residential history obtained by questionnaire were geocoded, and measures of distance to freeways and major roads were calculated using ArcGIS software. Logistic regression models compared residential proximity to freeways and major roads for autism cases and typically developing controls. Results: Adjusting for sociodemographic factors and maternal smoking, maternal residence at the time of delivery was more likely be near a freeway (< 309 m) for cases than for controls odds ratio (OR) = 1.86; 95% confidence interval (CI), 1.04-3.45. Autism was also associated with residential proximity to a freeway during the third trimester (OR = 2.22; CI, 1.16–4.42). After adjustment for socioeconomic and sociodemographic characteristics, these associations were unchanged. Living near other major roads at birth was not associated with autism. Conclusions: Living near a freeway was associated with autism. Examination of associations with measured air pollutants is needed.
Sexual dimorphism in common disease is pervasive, including a dramatic male preponderance in autism spectrum disorders (ASDs). Potential genetic explanations include a liability threshold model ...requiring increased polymorphism risk in females, sex-limited X-chromosome contribution, gene-environment interaction driven by differences in hormonal milieu, risk influenced by genes sex-differentially expressed in early brain development, or contribution from general mechanisms of sexual dimorphism shared with secondary sex characteristics. Utilizing a large single nucleotide polymorphism (SNP) dataset, we identify distinct sex-specific genome-wide significant loci. We investigate genetic hypotheses and find no evidence for increased genetic risk load in females, but evidence for sex heterogeneity on the X chromosome, and contribution of sex-heterogeneous SNPs for anthropometric traits to ASD risk. Thus, our results support pleiotropy between secondary sex characteristic determination and ASDs, providing a biological basis for sex differences in ASDs and implicating non brain-limited mechanisms.
: Immune system development, particularly in the prenatal period, has far‐reaching consequences for health during early childhood, as well as throughout life. Environmental disturbance of the ...complex balances of Th1 and Th2 response mechanisms can alter that normal development. Dysregulation of this process or an aberrant trajectory or timing of events can result in atopy, asthma, a compromised ability to ward off infection, or other auto‐immune disease. A wide range of chemical, physical and biological agents appear to be capable of disrupting immune development. This MiniReview briefly reviews developmental milestones of the immune system in the prenatal period and early life, and then presents examples of environmentally induced alterations in immune markers. The first example involves a birth cohort study linked to an extensive programme of air pollution monitoring; the analysis shows prenatal ambient polycyclic aromatic hydrocarbons (PAH) and fine particle (PM2.5) exposures to be associated with altered lymphocyte immunophenotypic distributions in cord blood and possible changes in cord serum immunoglobulin E levels. The second example is a study of prenatal‐polychlorinated biphenyl (PCB) exposures and the foetal development of the thymus, the organ responsible for lymphocyte maturation. Mothers with higher serum concentrations of PCBs gave birth to neonates having smaller indices of thymus size. Finally, this report underscores the tight connection between development of the immune system and that of the central nervous system, and the plausibility that disruption of critical events in immune development may play a role in neurobehavioural disorders.
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