Paternal and maternal age at pregnancy and autism spectrum disorders in offspring

Main Article Content

Luh Putu Rihayani Budi
Mei Neni Sitaresmi
I Gusti Ayu Trisna Windiani


Background The prevalence of autism spectrum disorders (ASDs) has increased 10 times over the past half century, while paternal and maternal age at pregnancy has also increased. Studies looking for an association between paternal or maternal age at pregnancy and ASDs in offspring have not been conclusive. Objective To assess for possible associations between paternal and maternal age at pregnancy and ASDs in offspring. Methods This case-control study had 50 case and 100 control subjects, each case was matched for age and gender to two controls. Case subjects were obtained by consecutive sampling of patients aged 18 months to 7 years who visited the Developmental Behavioral & Community Pediatrics Outpatient Clinic and private growth and development centers from January to April 2013, while control group were children of the same age range and same gender who visited pediatric outpatient clinic at Sanglah Hospital mostly due to acute respiratory tract infection, without ASDs as assessed by the DSM-IV-TR criteria. We interviewed parents to collect the following data: maternal and paternal age at pregnancy, child’s birth weight, history of asphyxia, hospital admission during the neonatal period, pathological labor, maternal smoking during pregnancy, paternal smoking, and gestational age. Data analysis was performed with Chi-square and Fisher’s exact tests. Results Multivariable analysis showed that higher paternal age at pregnancy was associated with ASDs in offspring (OR 6.3; 95%CI 2.0 to 19.3; P 0.001). However, there was no significant association between maternal age during pregnancy and the incidence of ASDs. Asphyxia and paternal smoking were also associated with higher incidence of ASDs in the offspring (OR 10.3; 95%CI 1.9 to 56.5; P 0.007 and OR 3.2; 95%CI 1.5 to 6.9; P 0.003, respectively). Conclusion Paternal age >=40 years increased the risk of ASDs in offspring by 6.3 times. In addition, paternal smoking increased the risk of ASDs in offspring by 3.2 times and asphyxia increased the risk of ASDs in offspring by 10.3 times.

Article Details

How to Cite
Budi LP, Sitaresmi M, Windiani IGA. Paternal and maternal age at pregnancy and autism spectrum disorders in offspring. PI [Internet]. 30Nov.2016 [cited 21Jul.2019];55(6):345-1. Available from:
Received 2016-02-12
Accepted 2016-02-12
Published 2016-11-30


1. Newschaffer CJ, Fallin D, Lee NL. Heritable and nonheritable risk factors for autism spectrum disorders. Epidemiol Rev. 2002;24:137-53.
2. Blaxill MF. What’s going on? The question of time trends in Luh Putu Rihayani Budi et al: Parental age at pregnancy and autism spectrum disorders in offspring autism. Public Health Rep. 2004;119:536-51.
3. National Dissemination Center for Children With Disabilities [homepage on the internet]. Washington: Briefing papers; 1998 [cited 2010 Jan 12]. Pervasive developmental disorder; [about 16 screens]. Available from:
4. Johnson CP, Myers SM, American Academy of Pediatrics Council on Children with Disabilities. Identification and evaluation of children with autism spectrum disorders. Pediatrics. 2007;120:1183-215.
5. Soedarsono Djamaluddin SU. Model layanan Pendidikan anak autistik. In: Sutandi R, editor. Penatalaksanaan holistic autisme. Jakarta: Pusat Informasi dan Penerbitan Bagian Ilmu Penyakit Dalam FK Universitas Indonesia; 2003. p. 420-433.
6. Watts TJ. The pathogenesis of autism. Clin Med Pathol. 2008;1:99-103.
7. Wargasetia TL. Aspek genetik pada autisme. In: Sutandi R, editor. Penatalaksanaan holistik autism. Jakarta: Pusat Informasi dan Penerbitan Bagian Ilmu Penyakit Dalam FK Universitas Indonesia; 2003. p. 13-23.
8. Bilder D, Pinborough-Zimmerman J, Miller J, McMahon W. Prenatal, perinatal, and neonatal factors associated with autism spectrum disorders. Pediatrics. 2009;123:1293-300.
9. Bray I, Gunnell D, Davey Smith G. Advanced paternal age: how old is too old? J Epidemiol Community Health. 2006;60:851–3.
10. Durkin MS, Maenner MJ, Newschaffer CJ, Lee LC, Cunniff CM, Daniels JL, et al. Advanced parental age and the risk of autism spectrum disorder. Am J Epidemiol. 2008;168:1268- 76.
11. Crow JF. The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A. 1997;94:8380-6.
12. Risch N, Reich EW, Wishnick MM, McCarthy JG. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987;41:218-48.
13. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, fourth edition, text revision. Washington DC: American Psychiatric Association; 2000. p. 69-84.
14. Sastroasmoro S, Ismael S. Dasar-dasar metodologi penelitian klinis. 3rd ed. Jakarta: Bagian Ilmu Kesehatan Anak Fakultas Kedokteran Universitas Indonesia; 2008. p. 127-45.
15. Damanik SM. Klasifikasi bayi menurut berat lahir dan masa gestasi. In: Kosim MS, Yunanto A, Dewi R, Sarosa GI, Usman A, editors. Buku ajar neonatologi. Jakarta: Ikatan Dokter Anak Indonesia; 2009. p. 11-30.
16. Croen LA, Najjar DV, Fireman B, Grether JK. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med. 2007;161:334-40.
17. Reichenberg A, Gross R, Weiser M, Bresnahan M, Silverman J, Harlap S, et al. Advancing paternal age and autism. Arch Gen Psychiatry. 2006;63:1026-32.
18. Tsuchiya KJ, Matsumoto K, Miyachi T, Tsuji M, Nakamura K, Takagai S, et al. Paternal age at birth and high-functioning autistic-spectrum disorder in offspring. Br J Psychiatry. 2008;193:316-21.
19. Juul-Dam N, Townsend J, Courchesne E. Prenatal, perinatal, and neonatal factors in autism, pervasive developmental disorder-not otherwise specified, and the general population. Pediatrics. 2001;107:E63.
20. Larsson HJ, Eaton WW, Madsen KM, Vestergaard M, Olesen AV, Agerbo E, et al. Risk factors for autism: perinatal factors, parental psychiatric history, and socioeconomic status. Am J Epidemiol. 2005;161:916-25.
21. Buchmayer S, Johansson S, Johansson A, Hultman CM, Sparen P, Cnattingius S. Can association between preterm birth and autism be explained by maternal or neonatal morbidity? Pediatrics. 2009;124:817-25.
22. Indredavik MS, Brubakk A, Romundstad P, Vik T. Prenatal smoking exposure and psychiatric symptoms in adolescence. Acta Paediatr. 2007;96:377-82.