Objective To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum

Vol. 63 No. 9, September 2006 Archives
•





Advancing Paternal Age and Autism
Abraham Reichenberg, PhD; Raz Gross, MD, MPH; Mark Weiser, MD; Michealine Bresnahan, PhD; Jeremy Silverman, PhD; Susan Harlap, MBBS; Jonathan Rabinowitz, PhD; Cory Shulman, PhD; Dolores Malaspina, MD; Gad Lubin, MD; Haim Y. Knobler, MD; Michael Davidson, MD; Ezra Susser, MD, DrPH


Arch Gen Psychiatry. 2006;63:1026-1032.

Context Maternal and paternal ages are associated with neurodevelopmental disorders.

Objective To examine the relationship between advancing paternal age at birth of offspring and their risk of autism spectrum disorder (ASD).

Design Historical population-based cohort study.

Setting Identification of ASD cases from the Israeli draft board medical registry.

Participants We conducted a study of Jewish persons born in Israel during 6 consecutive years. Virtually all men and about three quarters of women in this cohort underwent draft board assessment at age 17 years. Paternal age at birth was obtained for most of the cohort; maternal age was obtained for a smaller subset. We used the smaller subset (n = 132 271) with data on both paternal and maternal age for the primary analysis and the larger subset (n = 318 506) with data on paternal but not maternal age for sensitivity analyses.

Main Outcome Measures Information on persons coded as having International Classification of Diseases, 10th Revision ASD was obtained from the registry. The registry identified 110 cases of ASD (incidence, 8.3 cases per 10 000 persons), mainly autism, in the smaller subset with complete parental age data.

Results There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age.

Conclusions Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.


Author Affiliations: Department of Psychiatry (Drs Reichenberg, Silverman, and Davidson) and Seaver Center for Autism Research (Dr Silverman), Mount Sinai School of Medicine; Department of Epidemiology, Mailman School of Public Health, Columbia University (Drs Gross, Bresnahan, Harlap, Malaspina, and Susser); New York State Psychiatric Institute (Drs Gross, Bresnahan, Malaspina, and Susser), New York; Institute of Psychiatry, King's College, London, England (Dr Reichenberg); and Department of Psychiatry, Chaim Sheba Medical Center, Tel Hashomer (Drs Weiser and Davidson); School of Social Work, Bar Ilan University, Ramat-Gan (Dr Rabinowitz); School of Social Work, Hebrew University, Jerusalem (Dr Shulman); and Medical Corps, Israel Defense Forces, Tel Aviv (Drs Lubin and Knobler), Israel.




RELATED ARTICLE


This Month in Archives of General Psychiatry
Arch Gen Psychiatry. 2006;63(9):954.
FULL TEXT






THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES


Is Schizophrenia a Syndrome of Accelerated Aging?
Kirkpatrick et al.
Schizophr Bull 2007;0:sbm140v1-sbm140.
ABSTRACT | FULL TEXT

Matched follow-up study of 5 8-year-old ICSI singletons: child behaviour, parenting stress and child (health-related) quality of life
Knoester et al.
Hum Reprod 2007;22:3098-3107.
ABSTRACT | FULL TEXT

Aberrant Epigenetic Regulation Could Explain the Relationship of Paternal Age to Schizophrenia
Perrin et al.
Schizophr Bull 2007;33:1270-1273.
ABSTRACT | FULL TEXT

Identification and Evaluation of Children With Autism Spectrum Disorders
Johnson et al.
Pediatrics 2007;120:1183-1215.
ABSTRACT | FULL TEXT

A unified genetic theory for sporadic and inherited autism
Zhao et al.
Proc. Natl. Acad. Sci. USA 2007;104:12831-12836.
ABSTRACT | FULL TEXT

Prenatal and Perinatal Risk Factors for Autism: A Review and Integration of Findings
Kolevzon et al.
Arch Pediatr Adolesc Med 2007;161:326-333.
ABSTRACT | FULL TEXT

Maternal and Paternal Age and Risk of Autism Spectrum Disorders
Croen et al.
Arch Pediatr Adolesc Med 2007;161:334-340.
ABSTRACT | FULL TEXT

Medical Implications of the Male Biological Clock.
Lewis et al.
JAMA 2006;296:2369-2371.
FULL TEXT

Improving Men's Health: Evidence and Opportunity.
Fontanarosa and Cole
JAMA 2006;296:2373-2375.
FULL TEXT

The neuropathology, medical management and dental implications of autism.
Friedlander et al.
Journal of the American Dental Association 2006;137:1517-1527.
ABSTRACT | FULL TEXT

Is Autism Associated with Advanced Parental Age?
JWatch Pediatrics 2006;2006:2-2.
FULL TEXT