The CHARGE Study: An Epidemiologic Investigation of Genetic and EnvironmentalFactors Contributing to Autism

Hertz‐Picciotto, Irva; Croen, Lisa; Hansen, Robin; Jones, Caitlin G.; Water, Judith A Van de; Pessah, Isaac N.

doi:10.1289/ehp.8483

Cited by 376 publications

(334 citation statements)

References 71 publications

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“…Bands that were shown to be different between autism and controls were seen in more than a quarter of mothers who had children with autism. The fact that these bands were not found in all mothers of children with autism further emphasizes the heterogeneity that is widely reported in autism, and the variety of etiologic mechanisms that likely exist (Hertz-Picciotto et al, 2006). Furthermore, while none of the individual bands were noted exclusively in mothers of children with AU, the simultaneous presence of the 37kDa and 73kDa protein bands was unique to the AU group.…”

Section: Discussionmentioning

confidence: 89%

“…Institute at the University of California at Davis (Hertz-Picciotto et al, 2006). The CHARGE study population was sampled from three strata: children considered to have autism (AU), children selected from the general population who were typically developing (TD), and children with developmental disabilities without autism (DD).…”

Section: Study Subjectsmentioning

confidence: 99%

“…Detailed information regarding current autoimmune disease status for first-degree relatives was collected at the clinic visit by questionnaire (Hertz-Picciotto et al, 2006). A list of autoimmune conditions was reviewed with the parent by the clinician and descriptions were provided where needed.…”

Section: Study Subjectsmentioning

confidence: 99%

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Autism: Maternally derived antibodies specific for fetal brain proteins

et al. 2007

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Autism is a profound disorder of neurodevelopment with poorly understood biological origins. A potential role for maternal autoantibodies in the etiology of some cases of autism has been proposed in previous studies To investigate this hypothesis, maternal plasma antibodies against human fetal and adult brain proteins were analyzed by western blot in 61 mothers of children with autistic disorder and 102 controls matched for maternal age and birth year (62 mothers of typically developing children (TD) and 40 mothers of children with non-ASD developmental delays (DD)). We observed reactivity to two protein bands at approximately 73kDa and 37kDa in plasma from 7 of 61 (11.5%) mothers of children with autism (AU) against fetal but not adult brain, which was not noted in either control group (TD; 0/62 p=0.0061 and DD; 0/40 p=0.0401). Further, the presence of reactivity to these two bands correlated with a diagnosis of behavioral regression in the child when compared to the TD (p=0.0019) and DD (0.0089) groups. Individual reactivity to the 37kDa band was observed significantly more often in the AU population compared with TD (p=0.0086) and DD (p=0.002) mothers, yielding a 5.69-fold odds ratio (95% confidence interval 2.09 -15.51) associated with this band. The presence of these antibodies in the plasma of some mothers of children with autism, as well as the differential findings between mothers of children with early onset and regressive autism may suggest an association between the transfer of IgG autoantibodies during early neurodevelopment and the risk of developing of autism in some children.

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Section: Discussionmentioning

confidence: 89%

Section: Study Subjectsmentioning

confidence: 99%

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Autism: Maternally derived antibodies specific for fetal brain proteins

et al. 2007

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“…17 This population-based casecontrol investigation recruited children with ASD, with DDs other than ASD, and from the general population. CHARGE eligibility criteria included being 2 to 5 years old, born in California, having a parent who speaks English or Spanish, and living with at least 1 biological parent and in the study catchment area of specified California Regional Centers, which coordinate services for persons with developmental disabilities.…”

Section: Methodsmentioning

confidence: 99%

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

et al. 2014

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WHAT'S KNOWN ON THIS SUBJECT: Serotonin is critical in early brain development, creating concerns regarding prenatal exposure to factors influencing serotonin levels, like selective serotonin reuptake inhibitors (SSRIs). Prenatal SSRI use was recently associated with autism; however, its association with other developmental delays is unclear. WHAT THIS STUDY ADDS:This population-based case-control study in young children provides evidence that prenatal SSRI use may be a risk factor for autism and other developmental delays. However, underlying depression and its genetic underpinnings may be a confounder.abstract OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a populationbased case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information. RESULTS:Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98-11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62). Findings were similar among mothers with an anxiety or mood disorder history. CONCLUSIONS:In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.

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“…Other problems, not exclusive of autism, are attention-deficit and disturbed behaviors as etero-autolesivity. Thirty percent of children manifest epileptic seizures by late childhood or adolescence and 10% of cases are associated with several genetic disorders such as tuberous sclerosis, Angelman syndrome, phenylketonuria, and fragile X syndrome (6).…”

mentioning

confidence: 99%

Pregnancy risk factors in autism: a pilot study with artificial neural networks

Grossi¹,

Veggo

Narzisi

et al. 2015

Pediatr Res

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Background: Autism is a multifactorial condition in which a single risk factor can unlikely provide comprehensive explanation for the disease origin. Moreover, due to the complexity of risk factors interplay, traditional statistics is often unable to explain the core of the problem due to the strong inherent nonlinearity of relationships. The aim of this study was to assess the frequency of 27 potential risk factors related to pregnancy and peri-postnatal period. Methods: The mothers of 45 autistic children and of 68 typical developing children completed a careful interview. Twentyfour siblings of 19 autistic children formed an internal control group. results: A higher prevalence of potential risk factors was observed in 22 and 15 factors in external control and internal control groups, respectively. For six of them, the difference in prevalence was statistically significant. Specialized artificial neural networks (ANNs) discriminated between autism and control subjects with 80.19% global accuracy when the dataset was preprocessed with TWIST (training with input selection and testing) system selecting 16 out of 27 variables. Logistic regression applied to 27 variables gave unsatisfactory results with global accuracy of 46%. conclusion: Pregnancy factors play an important role in autism development. ANNs are able to build up a predictive model, which could represent the basis for a diagnostic screening tool.a utism is a specific neurodevelopmental condition that typically displays qualitative socio-communicative impairment and restricted, stereotyped interests and activities (1). Although a large proportion of children with autism manifests abnormal development during the first year of life, 15-62% of them show a regression between 18 and 24 mo of age after a period of apparently typical development (2,3).Approximately 70% of individuals with autism present a variable degree of intellectual disability (4) and expressive/ receptive language can be absent or very insufficient (5). Other problems, not exclusive of autism, are attention-deficit and disturbed behaviors as etero-autolesivity. Thirty percent of children manifest epileptic seizures by late childhood or adolescence and 10% of cases are associated with several genetic disorders such as tuberous sclerosis, Angelman syndrome, phenylketonuria, and fragile X syndrome (6).The etiopathogenesis of autism is not yet understood; the prevalence is undoubtedly rising, and it is not clear if this increase is linked to the diagnostic improvement or to a greater susceptibility of the population to the disease. Many twins and family studies point out the importance of inherited predisposition to the disorder even though epidemiologic research suggest the strong contribution of prenatal and early postnatal environmental factors. In fact, genetic factors alone account for no more than 20-30% of all cases, whereas other 70-80% are the result of a complex interaction between environmental risk factors and inherited or de novo genetic susceptibility (7).Many pregnancies and o...

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The CHARGE Study: An Epidemiologic Investigation of Genetic and EnvironmentalFactors Contributing to Autism

Cited by 376 publications

References 71 publications

Autism: Maternally derived antibodies specific for fetal brain proteins

Autism: Maternally derived antibodies specific for fetal brain proteins

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

Pregnancy risk factors in autism: a pilot study with artificial neural networks

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