TY - JOUR
T1 - Advancing maternal age is associated with increasing risk for autism
T2 - A review and meta-analysis
AU - Sandin, Sven
AU - Hultman, Christina M.
AU - Kolevzon, Alexander
AU - Gross, Raz
AU - MacCabe, James H.
AU - Reichenberg, Abraham
N1 - Funding Information:
This study was supported by the Beatrice and Samuel A. Seaver Foundation and Autism Speaks.
PY - 2012/5
Y1 - 2012/5
N2 - Objective: We conducted a meta-analysis of epidemiological studies investigating the association between maternal age and autism. Method: 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 to 29, the adjusted relative risk (RR) for autism in the offspring was 1.52 (95% CI = 1.12-1.92). 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.
AB - Objective: We conducted a meta-analysis of epidemiological studies investigating the association between maternal age and autism. Method: 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 to 29, the adjusted relative risk (RR) for autism in the offspring was 1.52 (95% CI = 1.12-1.92). 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.
KW - autism
KW - epidemiology
KW - maternal age
KW - meta-analysis
KW - perinatal
UR - http://www.scopus.com/inward/record.url?scp=84860223780&partnerID=8YFLogxK
U2 - 10.1016/j.jaac.2012.02.018
DO - 10.1016/j.jaac.2012.02.018
M3 - Article
AN - SCOPUS:84860223780
SN - 0890-8567
VL - 51
SP - 477-486.e1
JO - Journal of the American Academy of Child and Adolescent Psychiatry
JF - Journal of the American Academy of Child and Adolescent Psychiatry
IS - 5
ER -