Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 477-486.e1 |
| Number of pages | 11 |
| Journal | Journal of the American Academy of Child and Adolescent Psychiatry |
| Volume | 51 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2012 |
Keywords
- autism
- epidemiology
- maternal age
- meta-analysis
- perinatal
- SPECTRUM DISORDERS
- PATERNAL AGE
- OBSTETRIC COMPLICATIONS
- PERINATAL FACTORS
- INFANTILE-AUTISM
- CHILDREN BORN
- EPIDEMIOLOGY
- POPULATION
- CONSEQUENCES
- HEALTH