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.

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    • "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. "
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    Frontiers in Neuroscience 07/2013; 7(7):123. DOI:10.3389/fnins.2013.00123 · 3.66 Impact Factor
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    • "Cognitive issues which can be disrupted by the age of parents have been demonstrated in case of autism and schizophrenia [5] [6]. Increase in paternal age leads to greater likelihood of schizophrenia and autism [6] [7]. There appears to be an inverse correlation between the parental age and the offspring intelligence in human beings [8] [9]. "
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    • "An increased number of births in men aged >35 years has been described in Europe, the United States and also in Eastern countries (Lambert et al., 2006; Martin et al., 2007; Nieschlag & Behre, 2010) with predicted growth over the next decade. Despite the fact that increasing paternal age is associated with prolonged time to pregnancy (Hassan & Killick, 2003) , decreased sperm quality (Hellstrom et al., 2006), fertility (Dunson et al., 2004) and the risk of genetic diseases in offspring (Dzurova & Pikhart, 2005; Croen et al., 2007), a significantly larger proportion of men father a child in their 50s (Sartorius & Niesclag, 2010; Stewart & Kim, 2011). At the same time, men older than 45 years have been under-represented in clinical studies (Sartorius & Niesclag, 2010; Stewart & Kim, 2011), which limits statistical power and prevents the determination of the shape of relationships between age and reproductive quality. "
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