Maternal and paternal age and risk of autism spectrum disorders.

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.

[1]  Mark Weiser,et al.  Advancing paternal age and autism. , 2006, Archives of general psychiatry.

[2]  T. Bourgeron,et al.  Searching for ways out of the autism maze: genetic, epigenetic and environmental clues , 2006, Trends in Neurosciences.

[3]  B. Hamilton,et al.  Fertility and abortion rates in the United States, 1960-2002. , 2006, International journal of andrology.

[4]  E. Fombonne,et al.  Autism spectrum disorders associated with X chromosome markers in French-Canadian males , 2006, Molecular Psychiatry.

[5]  E. Guillén-Navarro,et al.  [Monogenic causes of X-linked mental retardation]. , 2006, Revista de neurologia.

[6]  M. Lauritsen,et al.  Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. , 2005, Journal of child psychology and psychiatry, and allied disciplines.

[7]  Y. Minabe,et al.  Advanced paternal age associated with an elevated risk for schizophrenia in offspring in a Japanese population , 2005, Schizophrenia Research.

[8]  P. Bolton,et al.  Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region , 2005, Psychiatric genetics.

[9]  Esben Agerbo,et al.  Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. , 2005, American journal of epidemiology.

[10]  T. Kemper,et al.  Neuroanatomic observations of the brain in autism: a review and future directions , 2005, International Journal of Developmental Neuroscience.

[11]  P. Andersen,et al.  Advanced paternal age and risk of fetal death: a cohort study. , 2004, American journal of epidemiology.

[12]  C. Lawler,et al.  Identifying environmental contributions to autism: provocative clues and false leads. , 2004, Mental retardation and developmental disabilities research reviews.

[13]  T. Olsson,et al.  Parental Age, Family Size, and Risk of Multiple Sclerosis , 2004, Epidemiology.

[14]  F. Rasmussen,et al.  Paternal age and schizophrenia: a population based cohort study , 2004, BMJ : British Medical Journal.

[15]  J. Hallmayer,et al.  Perinatal factors and the development of autism: a population study. , 2004, Archives of general psychiatry.

[16]  J. McGrath,et al.  Paternal and maternal age as risk factors for psychosis: findings from Denmark, Sweden and Australia , 2004, Schizophrenia Research.

[17]  M. Owen,et al.  Paternal age and risk for schizophrenia , 2003, British Journal of Psychiatry.

[18]  Laurence L. George,et al.  The Statistical Analysis of Failure Time Data , 2003, Technometrics.

[19]  E. Fombonne.  Epidemiological Surveys of Autism and Other Pervasive Developmental Disorders: An Update , 2003, Journal of autism and developmental disorders.

[20]  H. Ewald,et al.  Parental age and risk of schizophrenia: a case-control study. , 2003, Archives of general psychiatry.

[21]  Thomas Bourgeron,et al.  Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism , 2003, Nature Genetics.

[22]  W. Härdle,et al.  Does male age affect the risk of spontaneous abortion? An approach using semiparametric regression. , 2003, American journal of epidemiology.

[23]  C. Rice,et al.  Prevalence of autism in a US metropolitan area. , 2003, JAMA.

[24]  P. Allebeck,et al.  Paternal age and schizophrenia: further support for an association. , 2002, The American journal of psychiatry.

[25]  E. Susser,et al.  Paternal age and risk of schizophrenia in adult offspring. , 2002, The American journal of psychiatry.

[26]  Pär Sparén,et al.  Perinatal Risk Factors for Infantile Autism , 2002, Epidemiology.

[27]  S. Selvin,et al.  Descriptive Epidemiology of Autism in a California Population: Who Is at Risk? , 2002, Journal of autism and developmental disorders.

[28]  P. Thonneau,et al.  Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. , 2002, Human reproduction.

[29]  E. Susser,et al.  In utero infection and adult schizophrenia. , 2002, Mental retardation and developmental disabilities research reviews.

[30]  G. Draper,et al.  Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers. , 2001, International journal of epidemiology.

[31]  S. Folstein,et al.  Genetics of austim: complex aetiology for a heterogeneous disorder , 2001, Nature Reviews Genetics.

[32]  P. Decouflé,et al.  Prevalence of autism in a United States population: the Brick Township, New Jersey, investigation. , 2001, Pediatrics.

[33]  J. Dambrosia,et al.  Neuropeptides and neurotrophins in neonatal blood of children with autism or mental retardation , 2001, Annals of neurology.

[34]  E. Susser,et al.  Advancing paternal age and the risk of schizophrenia. , 2001, Archives of general psychiatry.

[35]  J. Chelly,et al.  Parental origin of de novo MECP2 mutations in Rett syndrome , 2001, European Journal of Human Genetics.

[36]  B. Leventhal,et al.  The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism , 2000, Journal of autism and developmental disorders.

[37]  P. Kyyrönen,et al.  Parental age as a risk factor of childhood leukemia and brain cancer in offspring. , 1999, Epidemiology.

[38]  Ursula Bellugi,et al.  Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome , 1999, Trends in Neurosciences.

[39]  P. Bolton,et al.  Obstetric complications in autism: consequences or causes of the condition? , 1997, Journal of the American Academy of Child and Adolescent Psychiatry.

[40]  S Arndt,et al.  Broader autism phenotype: evidence from a family history study of multiple-incidence autism families. , 1997, The American journal of psychiatry.

[41]  M. Byrne,et al.  Brief report: A case-control study of obstetric complications and later autistic disorder , 1996, Journal of autism and developmental disorders.

[42]  J. Crow.  Spontaneous mutation as a risk factor. , 1995, Experimental and clinical immunogenetics.

[43]  A. Couteur,et al.  Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders , 1994, Journal of autism and developmental disorders.

[44]  S. Folstein,et al.  The etiology of autism: pre-, peri- and neonatal factors. , 1993, Journal of the American Academy of Child and Adolescent Psychiatry.

[45]  S. E. Mouridsen,et al.  Brief report: Parental age in infantile autism, autistic-like conditions, and borderline childhood psychosis , 1993, Journal of autism and developmental disorders.

[46]  J. Rabe-Jabłońska,et al.  [Affective disorders in the fourth edition of the classification of mental disorders prepared by the American Psychiatric Association -- diagnostic and statistical manual of mental disorders]. , 1993, Psychiatria polska.

[47]  N. Krieger.  Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. , 1992, American journal of public health.

[48]  C. Lord,et al.  Pre- and perinatal factors in high-functioning females and males with autism , 1991, Journal of autism and developmental disorders.

[49]  W. McMahon,et al.  The UCLA-University of Utah epidemiologic survey of autism: prenatal, perinatal, and postnatal factors. , 1990, Pediatrics.

[50]  H. Steinhausen,et al.  Maternal Age and Autistic Children , 1984, Journal of developmental and behavioral pediatrics : JDBP.

[51]  M. Stewart,et al.  Etiological implication of maternal age and birth order in infantile autism , 1983, Journal of autism and developmental disorders.

[52]  Y. Hoshino,et al.  The Epidemiological Study of Autism in Fukushima‐ken , 1982, Folia psychiatrica et neurologica japonica.

[53]  C. Gillberg.  Maternal age and infantile autism , 1980, Journal of autism and developmental disorders.

[54]  J. Kalbfleisch,et al.  The Statistical Analysis of Failure Time Data , 1980 .

[55]  B. Quarrington,et al.  Pre-, peri-, and neonatal factors and infantile autism. , 1979, Journal of child psychology and psychiatry, and allied disciplines.

[56]  P. Moran,et al.  Raised Parental Age in Psychiatric Patients: Evidence for the Constitutional Hypothesis , 1979, British Journal of Psychiatry.

[57]  D. Treffert.  Epidemiology of infantile autism. , 1970, Archives of general psychiatry.

[58]  Victor Lotter,et al.  Epidemiology of autistic conditions in young children , 1967 .

[59]  L. Penrose.  Parental age and mutation. , 1955, Lancet.