title: Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis.
abstract: OBJECTIVE
  We conducted a meta-analysis of epidemiological studies investigating the association between maternal age and autism.
  
  
  METHODS
  Using recommended guidelines for performing meta-analyses, we systematically selected, and extracted results from, epidemiological scientific studies reported before January 2012. We calculated pooled risk estimates comparing categories of advancing maternal age with and without adjusting for possible confounding factors. We investigated the influence of gender ratio among cases, ratio of infantile autism to autism spectrum disorder (ASD), and median year of diagnosis as effect moderators in mixed-effect meta-regression.
  
  
  RESULTS
  We found 16 epidemiological papers fulfilling the a priori search criteria. The meta-analysis included 25,687 ASD cases and 8,655,576 control subjects. Comparing mothers ≥ 35 years with mothers 25 to 29 years old, the crude relative risk (RR) for autism in the offspring was 1.52 (95% confidence interval [CI] = 1.12-1.92). Comparing mothers ≥ 35 with mothers 25-29, [corrected] the adjusted relative risk (RR) for autism in the offspring was 1.31 (95% CI = 1.19-1.45). [corrected] For mothers <20 compared with mothers 25 to 29 years old, there was a statistically significant decrease in risk (RR = 0.76; 95% confidence interval = 0.60-0.97). Almost all studies showed a dose-response effect of maternal age on risk of autism. The meta-regression suggested a stronger maternal age effect in the studies with more male offspring and for children diagnosed in later years.
  
  
  CONCLUSIONS
  The results of this meta-analysis support an association between advancing maternal age and risk of autism. The RR increased monotonically with increasing maternal age. The association persisted after the effects of paternal age and other potential confounders had been considered, supporting an independent relation between higher maternal age and autism.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-171 77 Stockholm, Sweden. sven.sandin@ki.se
authors.forename: Sven
authors.initials: S
authors.lastname: Sandin
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hultman
authors.forename: Alexander
authors.initials: A
authors.lastname: Kolevzon
authors.forename: Raz
authors.initials: R
authors.lastname: Gross
authors.forename: James H
authors.initials: JH
authors.lastname: MacCabe
authors.forename: Abraham
authors.initials: A
authors.lastname: Reichenberg
mesh_terms: D000293:Adolescent; D001321:Autistic Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology*; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D006801:Humans; D007223:Infant; D008423:Maternal Age; D012307:Risk Factors; D012744:Sex Ratio