Prenatal and Early Life Exposure to Stressful Life Events and Risk of Autism Spectrum Disorders: Population-Based Studies in Sweden and England

Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
PLoS ONE (Impact Factor: 3.23). 06/2012; 7(6):e38893. DOI: 10.1371/journal.pone.0038893
Source: PubMed


Exposure to stressful life events during pregnancy has been suggested as a potential risk factor for offspring Autism Spectrum Disorders (ASD), but the literature is limited and inconsistent. We tested the hypothesis that maternal exposure to stressful life events would be associated with increased risks of offspring ASD, and that these risks would be highest for exposures during the prenatal period.
We used prospectively collected data from two large population based studies in Sweden and England. In the Swedish study of 4429 ASD cases and 43277 controls, our exposure comprised the occurrence of any severe life event before and during pregnancy and the child's early life. In the English study (maximum n = 11554, ASD n = 72), we studied the risk of offspring ASD in relation to a combined maternal exposure to multiple (up to 42) common and rare life events, as well as their perceived impact upon the mother during pregnancy and early life. In crude and adjusted regression analyses in both studies, we found no evidence of an association between prenatal life events, or their number and perceived impact and the risk of offspring ASD. Sub-group analysis of ASD with and without intellectual disability in the Swedish study yielded similar results.
We found no evidence to support the hypotheses that exposure to stressful life events during the prenatal period is associated with an increased risk of offspring ASD.

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Available from: Cecilia Magnusson, Jan 27, 2014
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    • "Another theory posits prenatal maternal stress as a major contributing factor to the development of ASD (Beversdorf et al., 2005; Ward, 1990). However, a recent study by Rai et al. (2012) could demonstrate no explicit relationship between prenatal life events and the risk for developing ASD. It is difficult to resolve these competing theories because prenatal stress is well known to decrease exposure to prenatal testosterone (Ward et al., 2003). "
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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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    • "As hypothesized, and consistent with some prior literature evidencing that autism spectrum traits (Ronald et al., 2011) and autismprevalence rates (Kinney et al., 2008a) increased with exposure to increasingly severe stress exposure, the current study found both objective hardship and subjective distress were associated with more severe autism-like traits, although most children scored in the subclinical range. Findings are not, however, consistent with two recent population studies (Li et al., 2009; Rai et al., 2012). This discrepancy may be attributable to differences in nature of stress exposure (e.g., sudden-onset of uniform natural disaster versus variable stressors with more diffuse onset). "
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    ABSTRACT: Research implicates prenatal maternal stress (PNMS) as a risk factor for neurodevelopmental disorders; however few studies report PNMS effects on autism risk in offspring. We examined, prospectively, the degree to which objective and subjective elements of PNMS explained variance in autism-like traits among offspring, and tested moderating effects of sex and PNMS timing in utero. Subjects were 89 (46F/43M) children who were in utero during the 1998 Quebec Ice Storm. Soon after the storm, mothers completed questionnaires on objective exposure and subjective distress, and completed the Autism Spectrum Screening Questionnaire (ASSQ) for their children at age 6½. ASSQ scores were higher among boys than girls. Greater objective and subjective PNMS predicted higher ASSQ independent of potential confounds. An objective-by-subjective interaction suggested that when subjective PNMS was high, objective PNMS had little effect; whereas when subjective PNMS was low, objective PNMS strongly affected ASSQ scores. A timing-by-objective stress interaction suggested objective stress significantly affected ASSQ in first-trimester exposed children, though less so with later exposure. The final regression explained 43% of variance in ASSQ scores; the main effect of sex and the sex-by-PNMS interactions were not significant. Findings may help elucidate neurodevelopmental origins of non-clinical autism-like traits from a dimensional perspective.
    Psychiatry Research 05/2014; 219(2). DOI:10.1016/j.psychres.2014.04.034 · 2.47 Impact Factor
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    • "Rare genetic variants , and copy number variants in particular, have been shown to play a major role in ASD (Heil and Schaaf 2013). In addition to autism-related genes, various environmental events are thought to act as triggering factors in the development of ASD, including obstetric complications (Arndt et al. 2005; Libbey et al. 2005; Patterson 2009); prenatal influenza, rubella, and cytomegalovirus infections (Pardo et al. 2005); maternal stress during pregnancy (Beversdorf et al. 2005; but also see Rai et al. 2012); and maternal use of thalidomide (Strömland et al. 1994), misoprostol, and especially valproic acid during pregnancy (Landrigan 2010; Christensen et al. 2013). People with ASD typically show disrupted social motivation (Chevallier et al. 2012; Stavropoulos and Carver 2013). "
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    ABSTRACT: Objective: Little is known about the effectiveness of pharmacological interventions on autism spectrum disorder (ASD). This is a systematic review of the randomized controlled trials (RCTs) of oxytocin interventions in autism, made from January 1990 to September 2013. Method: A search of computerized databases was supplemented by manual search in the bibliographies of key publications. The methodological quality of the studies included in the review was evaluated independently by two researchers, according to a set of formal criteria. Discrepancies in scoring were resolved through discussion. Results: The review yielded seven RCTs, including 101 subjects with ASD (males=95) and 8 males with Fragile X syndrome. The main categories of target symptoms tested in the studies were repetitive behaviors, eye gaze, and emotion recognition. The studies had a medium to high risk of bias. Most studies had small samples (median=15). All the studies but one reported statistically significant between-group differences on at least one outcome variable. Most findings were characterized by medium effect size. Only one study had evidence that the improvement in emotion recognition was maintained after 6 weeks of treatment with intranasal oxytocin. Overall, oxytocin was well tolerated and side effects, when present, were generally rated as mild; however, restlessness, increased irritability, and increased energy occurred more often under oxytocin. Conclusions: RCTs of oxytocin interventions in autism yielded potentially promising findings in measures of emotion recognition and eye gaze, which are impaired early in the course of the ASD condition and might disrupt social skills learning in developing children. There is a need for larger, more methodologically rigorous RCTs in this area. Future studies should be better powered to estimate outcomes with medium to low effect size, and should try to enroll female participants, who were rarely considered in previous studies. Risk of bias should be minimized. Human long-term administration studies are necessary before clinical recommendations can be made.
    Journal of child and adolescent psychopharmacology 03/2014; 24(2):54-68. DOI:10.1089/cap.2013.0040 · 2.93 Impact Factor
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