An association between advanced paternal age at birth and risk for autism spectrum disorders and the underlying biological mechanisms

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Background and aim. Paternal age at birth has been suggested to be associated with autism spectrum disorder (ASD). In this study, we aimed at replicating the association in a Japanese sample in a retrospective manner, and at investigating biological mechanisms underlying this association using a birth cohort. A potential candidate for this mechanism is a use of artificial reproductive technique.Method 1. "Retrospective study" : 84 individuals with high-functioning ASD and 208 typically developed control individuals were enrolled. A statistical association was sought between diagnosis of ASD and paternal age at birth, while controlling for gender, parity, and maternal age at birth.Method 2. "Prospective study" : 780 pregnant women and their babies were enrolled as a part of an ongoing birth cohort study who were born during the period of 19 November, 2007 and 1 July, 2009. The participating mother-and-child dyads were followed up until the end of 2010 to examine whether any aberrant dev … More elopmental trajectories would be found ; such outcome measures include scores of Mullen Scales of Early Learning, developmental milestones, and suspected diagnosis of ASD. We also examined a risk of suspected ASD in association with paternal age at birth, and artificial reproductive technique as well. Result 1. "Retrospective study" : The association between paternal age at birth and a risk for ASD was confirmed after controlling for covariates. The dose-response relationship was also found.Result 2. "Prospective study" : In univariate analyses, paternal age at birth did not predict delay in motor/language development, in achievement of developmental milestones, and suspected diagnosis of ASD. On the other hand, artificial reproductive technique appeared to predict delayed development and ASD, although the associations did not reach statistical significance. Due to lack of statistical power, we were unable to seek for interaction between paternal age at birth and artificial reproductive therapy in association with a risk for ASD.Conclusion. Although firm conclusions are awaited, this study suggested relevance of artificial reproductive techniques as an underlying biological mechanism for the association between paternal age at birth and ASD. Less