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

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
PEDIATRICS (Impact Factor: 5.47). 08/2011; 128(2):344-55. DOI: 10.1542/peds.2010-1036
Source: PubMed


The etiology of autism is unknown, although perinatal and neonatal exposures have been the focus of epidemiologic research for over 40 years.
To provide the first review and meta-analysis of the association between perinatal and neonatal factors and autism risk.
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 meta-regression was conducted to identify measured methodological factors that could explain between-study variability.
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.
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.

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    • "Most of the rodent models of ASD based on environmental factors are supported by strong epidemiological data (Newschaffer et al., 2007; Gardener et al., 2009; Veiby et al., 2013). Indeed, in addition to the role of genetic factors in ASD (Kim et al., 2014), there is extensive literature to show correlations between nonheritable factors and the disease. "
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    ABSTRACT: Autism spectrum disorders (ASD) are among the most severe developmental psychiatric disorders known today, characterized by impairments in communication and social interaction and stereotyped behaviors. However, no specific treatments for ASD are as yet available. By enabling selective genetic, neural, and pharmacological manipulations, animal studies are essential in ASD research. They make it possible to dissect the role of genetic and environmental factors in the pathogenesis of the disease, circumventing the many confounding variables present in human studies. Furthermore, they make it possible to unravel the relationships between altered brain function in ASD and behavior, and are essential to test new pharmacological options and their side-effects. Here, we first discuss the concepts of construct, face, and predictive validity in rodent models of ASD. Then, we discuss how ASD-relevant behavioral phenotypes can be mimicked in rodents. Finally, we provide examples of environmental and genetic rodent models widely used and validated in ASD research. We conclude that, although no animal model can capture, at once, all the molecular, cellular, and behavioral features of ASD, a useful approach is to focus on specific autism-relevant behavioral features to study their neural underpinnings. This approach has greatly contributed to our understanding of this disease, and is useful in identifying new therapeutic targets.
    Behavioural pharmacology 09/2015; 26(6):522-540. DOI:10.1097/FBP.0000000000000163 · 2.15 Impact Factor
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    • "Risk for an ASD diagnosis increases in individuals who suffered fetal distress, were birthed via cesarean, or had a low Apgar score at birth (Hultman & Sparén, 2004). Furthermore, gestational complications, nuchal cord, edema, and fetal distress are also associated with increased ASD diagnoses (Gardener et al., 2011; Zhang et al., 2010). All of these complications put the infant at greater risk for oxidative stress, which in turn may lead to an increased risk for ASD, particularly in individuals who are not already genetically susceptible (Dodds et al., 2011). "
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    ABSTRACT: This study focused on prenatal and perinatal factors related to Autism Spectrum Disorder (ASD). We hypothesized that mothers who exposed their infants to intrauterine toxicity or who had complications with labor or delivery would be more likely to give birth to individuals with lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. This clinical sample consisted of 33 children who presented for neuropsychological assessment with symptoms of ASD. Results indicated that individuals with a history of intrauterine toxicity had lower IQ scores than individuals who did not have a history of intrauterine toxicity. However, no significant effects were found for intrauterine toxicity and ASD or adaptive functioning. Results indicated that individuals with a history of complications during labor and delivery had lower IQ scores, higher scores on a measure of ASD, and lower scores on a measure of adaptive functioning. Findings may lend support the oxidative stress theory of ASD.
    The Journal of Genetic Psychology 11/2014; In Press. DOI:10.1080/00221325.2014.987201 · 0.69 Impact Factor
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    • "The etiology of autism is unknown, although perinatal and neonatal exposures have been the focus of recent epidemiologic research [57]. Exposure to certain medications such as perinatal medications, antiepileptic drugs, supplements, and SSRIs has been studied as well as drug exposure to cocaine and smoking. "
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    ABSTRACT: Autism is a neurodevelopmental disorder marked by severe deficits in social communication and interactions. It is a complex condition that lacks an established preventive method, warranting a need for research to identify possible environmental triggers. The identification of external factors particularly perinatal risk factors forms the initial critical step in preventing and alleviating risks. We conducted a literature review to assess evidence suggested in the worldwide literature. Perinatal risk factors that have a suggested association include íµí»½2 adrenergic receptor agonists, labor induction and augmentation, maternal infection and disease (i.e., antiphospholipid syndrome), antiepileptic drugs, cocaine use, and oral supplements. Smoking has not been found to have a direct association. Pollutants, selective serotonin reuptake inhibitors, artificial insemination, and fertility medications may have a link, but results are often conflicted. Factors related to the delivery room experience may be associated with meconium aspiration syndrome, birth weight, and labor time. Several risk factors during the pregnancy and labor periods have been associated with autism; yet further studies with large populations are needed to establish definitive associations. The fact that several risk factors during the prenatal and labor periods are implicated in autism should prompt the medical community to focus on the pregnancy and labor periods as preventive measures to curb the incidence of autism.
    International Scholarly Research Notices 10/2014; 2014(Article ID 290837). DOI:10.1155/2014/290837
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