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

Dheeraj Rai,Christina Dalman,Glyn Lewis,Colin Steer,Cecilia Magnusson,Jean Golding,Andrew Whitehouse

doi:10.1371/journal.pone.0038893

Abstract

Background and AimExposure 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.Methods and ResultsWe 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.ConclusionWe 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.

Highlights

Autism spectrum disorders (ASDs) are developmental disorders characterized by impairments in reciprocal social interaction, communication, restricted patterns of interests and stereotyped behaviours [1]
In logistic regression analysis conditioned on age and sex, we found no evidence of any relationships between prenatal life events and offspring autism spectrum disorders as a group in either crude or adjusted models (Table 2)
We found similar results when ASDs were grouped by intellectual disability, point estimates of risk when life events occurred during pregnancy were higher for ASD without intellectual disability [OR 1.21 95% CI (0.67–2.20)] than those for ASD with intellectual disability [OR 0.47 95% CI (0.17–1.31), Table 3]

Summary

Introduction

Autism spectrum disorders (ASDs) are developmental disorders characterized by impairments in reciprocal social interaction, communication, restricted patterns of interests and stereotyped behaviours [1]. Maternal exposure to stressful life events during pregnancy has been suggested as a potential risk factor for ASD [7,8]. Animal experiments have found that exposure to stress during pregnancy may adversely affect the neurodevelopment of the offspring, including in domains relevant to autism (for review see Kinney et al, 2008) [7] Mechanisms such as DNA methylation [9], or programming of the hypothalamic-pituitary-adrenal axis have been proposed as potential pathways by which psychological stress could affect neurodevelopment [7]. 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

Methods

Results

Discussion

Conclusion