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Lisa A. Croen, PhD; Daniel V. Najjar, MS; Bruce Fireman, MA; Judith K. Grether, PhD

Arch Pediatr Adolesc Med. 2007;161(4):334-340.

Objective  To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring.

Design  Historical birth cohort study.

Setting  Kaiser Permanente (KP) in Northern California.

Participants  All singleton children born at KP from January 1, 1995, to December 31, 1999, were included in the study. We identified 593 children who had ASD diagnoses (International Classification of Diseases, Ninth Revision, Clinical Modification, code 299.0 or 299.8) recorded 2 or more times in KP outpatient databases before May 2005. These children were compared with all 132 251 remaining singleton KP births.

Main Exposures  Maternal and paternal age at birth of offspring.

Main Outcome Measures  Relative risks (RRs) estimated from proportional hazards regression models. Risk of ASDs evaluated in relation to maternal and paternal age, adjusted for each other and for the sex, birth date, and birth order of the child, maternal and paternal educational level, and maternal and paternal race/ethnicity.

Results  Risk of ASDs increased significantly with each 10-year increase in maternal age (adjusted RR, 1.31; 95% confidence interval [CI], 1.07-1.62) and paternal age (RR, 1.28; 95% CI, 1.09-1.51). Adjusted RRs for both maternal and paternal age were elevated for children with autistic disorder (maternal age: RR, 1.18; 95% CI, 0.87-1.60; paternal age: RR, 1.34; 95% CI, 1.06-1.69) and children with Asperger disorder or pervasive developmental disorder not otherwise specified (maternal age: RR, 1.45; 95% CI, 1.09-1.93; paternal age: RR, 1.24; 95% CI, 0.99-1.55). Associations with parental age were somewhat stronger for girls than for boys, although sex differences were not statistically significant.

Conclusion  Advanced maternal and paternal ages are independently associated with ASD risk.

Author Affiliations: Division of Research, Kaiser Permanente Medical Care Program (Northern California Region), Oakland (Dr Croen and Messrs Najjar and Fireman); and California Department of Health Services, Richmond (Dr Grether).

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