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Title: The role of maternal age in the aetiology of autism using population based studies
Author: Sandin, Sven
ISNI:       0000 0004 5357 5676
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2014
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Autism Spectrum Disorders (ASD) are neurodevelopmental syndromes affecting 1%-2% of all children. The aetiology of ASD is unknown, yet evidence supports a role for both genetic and non-genetic, including environmental, factors in aetiology. This thesis includes four related studies examining the role of maternal factors, and in particular maternal age, in the aetiology of ASD. Using methods of meta-analysis, national Swedish health registers, as well as a multinational cohort combining national registers from five countries this thesis examined: (a) the hypothesis that advancing maternal age is associated with ASD in the offspring ; (b) the hypothesis that maternal reproductive treatments are associated with ASD risk; and (c) the familial risk for ASD. The meta-analysis provided support for the hypothesis that advancing maternal age is associated with risk for ASD in the offspring. Risk for ASD was 1.3 fold higher (95%CI:1.2-1.4) for offspring of mothers 35 years old or older compared with mothers 25-29. The multinational cohort provided further support for the hypothesis demonstrating an independent effects of paternal and maternal age on risk for ASD. In addition, in addition to the effect of advancing age this study showed an increased risk with increasing differences in age between the spouses. Fertility treatments, overall, were not associated with risk for autism [RR=1.1; 95% 0.9-1.4]. However, in treatments for the most severe form of male infertility there was a strong association RR=4.6 (95%CI: 2.1-9.9). Our family study demonstrated that genetic factors explain half of the liability to ASD (h2=50%, 95% CI:). Factors related to maternal intrauterine environment do not seem to play a substantial role in autism aetiology. In conclusion, maternal age represents a moderate risk factor for autism. The mechanisms underlying this effect may involve both genomic and social factors, and should be rigorously examined in future studies.
Supervisor: Reichenberg, Abraham; Hultman, Christina Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available