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: 4.25). 04/2007; 161(4):334-40. DOI: 10.1001/archpedi.161.4.334
Source: PubMed

ABSTRACT 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.

  • 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.
    Frontiers in Neuroscience 07/2013; 7:123. DOI:10.3389/fnins.2013.00123 · 3.70 Impact Factor
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Age-associated accumulation of oxidative damage linked to decline of antioxidant defense mechanism, leads to impairment of cognitive function in many organisms. These damages can pass through generations and affect the cognitive quality of progenies. In Drosophila, classical olfactory conditioning results in the formation of different types of memory. Age-related memory impairment (AMI) causes reduction in middle term memory (MTM) and parental senescence causes decline in short-term memory (STM) of the offspring. We have further examined the neuromodulatory effect of Decalepis hamiltonii (Dh) root extract, which is a cocktail of novel antioxidant molecules, on the biochemical oxidative defenses in relation to cognitive ability of the aged flies and their offspring. There is a strong correlation between the age-related decline in the activity of the antioxidant enzymes and the lower cognitive ability of the aged flies and their offspring. Feeding of aged flies in the diet containing 0.1% Dh, markedly enhances the cognitive ability of both aged flies and their offspring which is associated with enhanced antioxidant defenses as evident for the activity of superoxide dismutase (SOD) and catalase. Our findings, for the first time, show that the antioxidant-rich Dh root extract attenuates the age-related decline in cognitive ability of Drosophila, and also shows ameliorative effect on the memory of the offspring.
    Behavioural brain research 04/2013; 249. DOI:10.1016/j.bbr.2013.04.017 · 3.39 Impact Factor
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to compare the reproductive parameters and the health-related, lifestyle and educational factors in middle-aged healthy men and male partners of infertile couples. Our patient group included 164 male partners of infertile couples with a preceding period of infertility of at least 12 months and 61 men attending a prostate health screening and considering themselves healthy. Significant differences between the groups were found in testicular volume, total sperm output, density and morphology as well as estradiol levels in serum. The analysis showed significant positive correlations between testicular volume and semen quality, while negative correlations were observed between gonadotropin levels and sperm parameters in both groups. Physical activity and sexual capability were higher in healthy men, while coital frequency and a history of sexually transmitted diseases were higher in male partners of infertile couples. The impact of physical activity and sexual capability on semen quality for all subjects was revealed. We can conclude that impaired reproductive function, that is, semen quality, in men >45 years is related not only with general male ageing but obvious differences between subjects of infertile couples and healthy middle-aged men can be seen. Their relations with lifestyle, environmental or physiological factors need further study.
    Andrologia 12/2012; 46(2). DOI:10.1111/and.12055 · 1.17 Impact Factor
Show more