Advanced parental age and autism risk in children: a systematic review and meta-analysis.

Advanced parental age has raised additional concern as a risk factor of autism. We conducted a meta-analysis of observational studies investigating the association between advanced parental age and risk of autism. PubMed, EMBASE, and Web of Science were searched for reports published up to November 11, 2015. Risk estimates from individual studies were pooled using random-effects models. Twenty-seven studies were included in the meta-analysis. Compared with the reference points, the lowest parental age category was associated with a reduced risk of autism in the offspring, with adjusted odds ratios (ORs) 0.89 (95% confidence intervals [CIs] 0.75-1.06) and 0.81 (95% CI 0.73-0.89) for mother and father, respectively, and the highest parental age category was associated with an increased risk of autism in the offspring, with adjusted ORs 1.41 (95% CI 1.29-1.55) and 1.55 (95% CI 1.39-1.73) for mother and father respectively. Dose-response meta-analysis indicated that an increase of 10 years in maternal and paternal age was associated with an 18% and 21% higher risk of autism. Advanced parental age was associated with an increased risk of autism in the offspring. More mechanistic studies are needed to further explain this positive association.