Pregnancy and Birth Complications in Autism and Liability to the Broader Autism Phenotype

Zwaigenbaum, Lonnie; Szatmári, Péter; Jones, Marshall B.; Bryson, Susan E.; MacLean, Joanna E.; Mahoney, William J.; Bartolucci, Giampiero; Tuff, Larry

doi:10.1097/00004583-200205000-00015

Cited by 86 publications

(62 citation statements)

References 28 publications

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“…In addition, probands with increased prenatal, perinatal, and neonatal complications had more family members with the broader autism phenotype, which was characterized as similar yet milder impairments in language, communication, and social skills or repetitive stereotyped interests and behaviors compared with diagnostic criteria for autism. However, this finding was not replicated in a second study by Zwaigenbaum et al 71 The shared-risk hypothesis also was supported by the findings in the Zwaigenbaum et al study that indicated more composite prenatal, perinatal, and neonatal adversity among unaffected siblings of children with pervasive developmental disorders that had high a Exposure data collection refers to the effect modification by exposure measurement (prospective versus retrospective). Diagnostic criteria refers to the effect modification by diagnostic criteria (narrow versus broad).…”

Section: Resultsmentioning

confidence: 93%

“…Confounding by birth order has been suggested because prenatal, perinatal, and neonatal complications are more often observed in first-, fourth-, and later-born offspring, and an increased risk of autism has been reported among those who are born first, fourth, and later. 50,71 Although some studies have shown that associations were attenuated and no longer significant after adjusting for parity, 39,59 other studies 50,71 have shown that the positive relationship persists.…”

Section: Resultsmentioning

confidence: 99%

“…71 Methodological limitations that may have impaired the precision and validity of the results of the studies in this review include small sample size, nonnormal control groups (eg, Down's syndrome), broad disease definition, and retrospective parental recall of exposures. Of 64 studies included, only 19 had over 80% power to detect an RR of 2 for an exposure with 10% prevalence.…”

Section: Resultsmentioning

confidence: 99%

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Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-Analysis

2011

PEDIATRICS

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WHAT'S KNOWN ON THIS SUBJECT:Autism etiology is unknown, although perinatal and neonatal exposures have been the focus of epidemiologic research for more than 40 years. Although studies show that obstetrical and neonatal complications may increase autism risk, the specific complications and magnitude of effect have been inconsistent. WHAT THIS STUDY ADDS: OBJECTIVE:To provide the first review and meta-analysis of the association between perinatal and neonatal factors and autism risk. METHODS:PubMed, Embase, and PsycInfo databases were searched for studies that examined the association between perinatal and neonatal factors and autism through March 2007. Forty studies were eligible for the meta-analysis. For each exposure, a summary effect estimate was calculated using a random-effects model. Heterogeneity in effect estimates across studies was examined, and, if found, a metaregression was conducted to identify measured methodological factors that could explain between-study variability. RESULTS:Over 60 perinatal and neonatal factors were examined. Factors associated with autism risk in the meta-analysis were abnormal presentation, umbilical-cord complications, fetal distress, birth injury or trauma, multiple birth, maternal hemorrhage, summer birth, low birth weight, small for gestational age, congenital malformation, low 5-minute Apgar score, feeding difficulties, meconium aspiration, neonatal anemia, ABO or Rh incompatibility, and hyperbilirubinemia. Factors not associated with autism risk included anesthesia, assisted vaginal delivery, postterm birth, high birth weight, and head circumference. CONCLUSIONS:There is insufficient evidence to implicate any 1 perinatal or neonatal factor in autism etiology, although there is some evidence to suggest that exposure to a broad class of conditions reflecting general compromises to perinatal and neonatal health may increase the risk. Methodological variations were likely sources of heterogeneity of risk factor effects across studies. Pediatrics 2011;128: 344-355

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-Analysis

2011

PEDIATRICS

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“…19,20 In addition, obstetric complications have been evoked as risk factor for autism, 21 although a causal relationship has not been demonstrated. 22,23 Genetic studies have shown linkage between autism and markers located in regions on several chromosomes. However, applying a threshold of 2.2 or 3.6 for the multipoint logarithm of the odds score (MLS), the proposed thresholds for suggestive and significant findings, respectively, 24 only few studies met these thresholds.…”

Section: Introductionmentioning

confidence: 99%

Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism

et al. 2005

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The identification of the candidate genes for autism through linkage and association studies has proven to be a difficult enterprise. An alternative approach is the analysis of cytogenetic abnormalities associated with autism. We present a review of all studies to date that relate patients with cytogenetic abnormalities to the autism phenotype. A literature survey of the Medline and Pubmed databases was performed, using multiple keyword searches. Additional searches through cited references and abstracts from the major genetic conferences from 2000 onwards completed the search. The quality of the phenotype (i.e. of the autism spectrum diagnosis) was rated for each included case. Available specific probe and marker information was used to define optimally the boundaries of the cytogenetic abnormalities. In case of recurrent deletions or duplications on chromosome 15 and 22, the positions of the low copy repeats that are thought to mediate these rearrangements were used to define the most likely boundaries of the implicated 'Cytogenetic Regions Of Interest' (CROIs). If no molecular data were available, the sequence position of the relevant chromosome bands was used to obtain the approximate molecular boundaries of the CROI. The findings of the current review indicate: (1) several regions of overlap between CROIs and known loci of significant linkage and/or association findings, and (2) additional regions of overlap among multiple CROIs at the same locus. Whereas the first finding confirms previous linkage/association findings, the latter may represent novel, not previously identified regions containing genes that contribute to autism. This analysis not only has confirmed the presence of several known autism risk regions but has also revealed additional previously unidentified loci, including 2q37, 5p15,

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“…Autism spectrum disorders could be due to heritable and nonheritable risk factors (Newschaffer et al 2002). For instance, thalidomide and anticonvulsants taken during pregnancy seem to elevate the risk of the disorder (Zwaigenbaum et al 2002;DeLong 1999). Similarly, intrauterine rubella (Chess 1997), cytomegalovirus (Iversson et al 1990;Stubbs et al 1984) infection, and premature birth with retinopathy of prematurity (Chase 1972) are implicated as risk factors.…”

Section: Environmental Factorsmentioning

confidence: 99%

Molecular genetics of autism spectrum disorders

Shastry

2003

J Hum Genet

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Autistic disorder belongs to a broad spectrum of pervasive developmental disorders. Autism is a clinically and genetically heterogeneous condition. It is characterized by impairment in a broad range of social interactions, communication, and repetitive patterns of behavior and interest. Although the exact etiology of the condition is not known, family and twin studies strongly support genetic factors in autism. Genome-wide scans suggest several susceptibility loci that may contain one or more predisposing genes. However, no such genes have been identified so far that predispose patients to autism. The condition is over 90% heritable, but the mode of inheritance is not clear. Moreover, it does not seem to be a single gene disorder. There is no cure for autism. Individualized structured education, family support services, and antipsychotic drugs are recommended. These may alleviate some behavioral problems. The identification of autism genes, an understanding of the neurobiology of the condition, and additional clinical studies may help to develop pharmacological interventions in the future.

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Pregnancy and Birth Complications in Autism and Liability to the Broader Autism Phenotype

Cited by 86 publications

References 28 publications

Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-Analysis

Perinatal and Neonatal Risk Factors for Autism: A Comprehensive Meta-Analysis

Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism

Molecular genetics of autism spectrum disorders

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