title: Autism risk associated with parental age and with increasing difference in age between the parents.
abstract: Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers⩾50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.|Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.|Departments of Psychiatry and Preventive Medicine, Seaver Autism Center for Research and Treatment, Friedman Brain Institute, and Mindich Child Health Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-6994-4884
authors.initials: S
authors.lastname: Sandin
authors.affiliation: Department of Public Health, Institute of Epidemiology and Social Medicine, Aarhus University, Aarhus, Denmark.|Department of Economics and Business, National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.|Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark.
authors.forename: D
authors.initials: D
authors.lastname: Schendel
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Magnusson
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Karolinska, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Hultman
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Surén
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: E
authors.initials: E
authors.lastname: Susser
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Grønborg
authors.affiliation: National Institute for Health and Welfare, Helsinki, Finland.|Nordic School of Public Health, Gothenburg, Sweden.|Department of Child Psychiatry, Turku University and Turku University Hospital, Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Gissler
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Gunnes
authors.affiliation: Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv, Israel.|Division of Psychiatry, Chaim Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Gross
authors.affiliation: Public Healthcare, Västra Götaland County, Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Henning
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.|New York State Psychiatric Institute, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Bresnahan
authors.affiliation: Department of Child Psychiatry, Turku University and Turku University Hospital, Turku, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Sourander
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.|Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: M
authors.identifier: http://orcid.org/0000-0001-7572-3092
authors.initials: M
authors.lastname: Hornig
authors.affiliation: Telethon Kids Institute, University of Western Australia, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Carter
authors.affiliation: Telethon Kids Institute, University of Western Australia, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Francis
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Parner
authors.affiliation: Telethon Kids Institute, University of Western Australia, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Leonard
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.|Public Health Research & Scientific Review, Autism Speaks, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Rosanoff
authors.affiliation: Norwegian Institute of Public Health, Oslo, Norway.|Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: C
authors.initials: C
authors.lastname: Stoltenberg
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK.|Departments of Psychiatry and Preventive Medicine, Seaver Autism Center for Research and Treatment, Friedman Brain Institute, and Mindich Child Health Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Reichenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001321:Autistic Disorder / Q000453:epidemiology*; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D007557:Israel; D016015:Logistic Models; D008297:Male; D008423:Maternal Age; D008875:Middle Aged; D009664:Norway; D010331:Paternal Age; D012042:Registries; D012306:Risk; D012307:Risk Factors; D012737:Sex Factors; D013548:Sweden; D014904:Western Australia; D055815:Young Adult