title: Parental age and the risk of autism spectrum disorders: findings from a Swedish population-based cohort.
abstract: BACKGROUND
  The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID).
  
  
  METHODS
  The sample consisted of 417 303 Swedish children born 1984-2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD.
  
  
  RESULTS
  Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63-1.89] at ages 40-45. For fathers, compared with the median age of 32 years, the OR for ages 55-59 was 1.39 (1.29-1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40-45 (≥97.2th percentile) had an estimated 18.63 (95% CI: 17.25-20.01) ASD cases per 1000 births, whereas fathers aged 55-59 (≥99.7th percentile) had 16.35 (95% CI: 15.11-17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers ≤35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID.
  
  
  CONCLUSIONS
  We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age.
authors.affiliation: Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden, Neurodevelopmental Psychiatry Unit, Child and Youth Psychiatry, Stockholm County Council, Sweden, Centre for Epidemiology and Community Medicine, Stockholm County Council, Sweden, Huddinge Psychosis Outpatient Unit, Stockholm, Sweden, Academic Unit of Psychiatry, School of Social and Community Medicine, University of Bristol, Bristol, UK, Avon and Wiltshire Partnership NHS Mental Health Trust, Bristol, UK, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden, Department of Epidemiology and Biostatistics, Drexel University School of Public Health, Philadelphia, PA, USA and A.J. Drexel Autism Institute, Philadelphia, PA, USA.
authors.forename: Selma
authors.initials: S
authors.lastname: Idring
authors.forename: Cecilia
authors.initials: C
authors.lastname: Magnusson
authors.forename: Michael
authors.initials: M
authors.lastname: Lundberg
authors.forename: Mats
authors.initials: M
authors.lastname: Ek
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Rai
authors.forename: Anna C
authors.initials: AC
authors.lastname: Svensson
authors.forename: Christina
authors.initials: C
authors.lastname: Dalman
authors.forename: Håkan
authors.initials: H
authors.lastname: Karlsson
authors.forename: Brian K
authors.initials: BK
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology* / Q000209:etiology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000453:epidemiology; D008137:Longitudinal Studies; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D010290:Parents; D010331:Paternal Age; D011159:Population Surveillance; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors; D012959:Socioeconomic Factors; D013548:Sweden / Q000453:epidemiology
keywords: Autism spectrum disorders; intellectual disability; parental age; risk factors