Maternal and Paternal Age and Risk of Autism Spectrum Disorders

Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA 94612, USA.
Archives of Pediatrics and Adolescent Medicine (Impact Factor: 5.73). 04/2007; 161(4):334-40. DOI: 10.1001/archpedi.161.4.334
Source: PubMed


To explore the association between maternal and paternal age and risk of autism spectrum disorders (ASDs) in offspring.
Historical birth cohort study.
Kaiser Permanente (KP) in Northern California.
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.
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.
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.
Advanced maternal and paternal ages are independently associated with ASD risk.

Full-text preview

Available from:
    • "Advanced maternal age, however, was not associated with an increased risk of ASD in our cohort, which was also described in other reports [27, 28] . Nevertheless some previous studies showed that advanced maternal age conferred a significant risk of ASD in the offspring [7, 17, 19, 29]. Therefore, the association between advanced maternal age and ASD remains inconclusive. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder commonly prevalent in children worldwide including Thailand. However, there are very few studies thus far addressing risk factors for ASD in Thai children. This case-control study aims to investigate whether various risk factors especially socioeconomic status, advanced parental age (age >35 years), perinatal factors, maternal autoimmune diseases, and family history of neuropsychiatric illnesses were associated with the risk of having an offspring with ASD. There were 235 children with ASD (age 8.44 ± 3.37 years) and 235 controls (age 8.39 ± 3.37 years) enrolled in this study. The risk of developing ASD in these children included advanced paternal age (adjusted odds ratio (AOR) = 3.49, 95 % confidence interval (CI) = 2.05-5.96), family history of neuropsychiatric illnesses particularly if such disorders came from the paternal side of the child's family (AOR = 2.87, 95 % CI = 1.29-6.39), and having unemployed mothers (AOR = 1.65, 95 % CI = 1.08-2.54). This study supports previous findings of Western countries where risk factors for ASD tend to occur in children whose fathers were of advanced paternal age and in the families with neuropsychiatric illnesses particularly if such disorders came from the paternal side of the child's family. What is Known: • Family history of neuropsychiatric disorders and advanced paternal age are risk factors for ASD in the offspring previously identified in the studies in Europe and North America. What is New: • To our knowledge, this is the first study documenting risk factors for ASD in the Asian population. • Our study supports previous findings of Western countries where risk factors for ASD tend to occur in the families with neuropsychiatric illnesses particularly if such disorders came from the paternal side of the child's family.
    No preview · Article · Apr 2015 · European Journal of Pediatrics
  • Source
    • "Several environmental factors have been associated with the increase in ASD prevalence. Male as well as female parental age are factors, with the offspring of older mothers or older fathers having a higher risk for developing ASD than those of younger parents[6,7]. Also, ASD are more prevalent when parents are more highly educated and of higher socioeconomic status[8], there is maternal use of cocaine[9]or valproate during pregnan- cy[10], residence in urban areas[11]or in areas of high air pollution, living in proximity to toxic waste sites, and exposures to specific toxic chemicals and chemical classes[12]also increase the incidence of ASD. "

    Preview · Article · Mar 2015
  • Source
    • "For example, pregnancy stress results in the section of corticotrophin-releasing hormone (CRH) from the hypothalamus, and increased plasma levels of CRH have been linked to preterm labor (Hobel et al., 1999). While some evidence suggests that such maternal risk factors can contribute to the development of ASD (Rizzo et al., 1997; Croen et al., 2002, 2007; Hultman et al., 2002; Glasson et al., 2004; Beversdorf et al., 2005; Larsson et al., 2005; Lauritsen et al., 2005; Leonard et al., 2006; Reichenberg et al., 2006; Dionne et al., 2008; Durkin et al., 2008; Grant and Soles, 2009; Grether et al., 2009; King et al., 2009; Li et al., 2009a,b; Burstyn et al., 2010; James et al., 2010; Kalkbrenner et al., 2012; Meguid et al., 2010; Roza et al., 2010; Shelton et al., 2010; Dodds et al., 2011; Lee et al., 2012; Parner et al., 2012; Rai et al., 2012; Sandin et al., 2012; Schmidt et al., 2012), results remain largely mixed and are strongest for advanced maternal age. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.
    Full-text · Article · Jul 2013 · Frontiers in Neuroscience
Show more