Risk of autism and increasing maternal and paternal age in a large North American population. American Journal of Epidemiology, 170, 1118-1126

Environmental Health Investigations Branch, California Department of Public Health, Richmond, California 94804, USA.
American journal of epidemiology (Impact Factor: 4.98). 09/2009; 170(9):1118-26. DOI: 10.1093/aje/kwp247
Source: PubMed

ABSTRACT Previous studies are inconsistent regarding whether there are independent effects of maternal and paternal age on the risk of autism. Different biologic mechanisms are suggested by maternal and paternal age effects. The study population included all California singletons born in 1989-2002 (n = 7,550,026). Children with autism (n = 23,311) were identified through the California Department of Developmental Services and compared with the remainder of the study population, with parental ages and covariates obtained from birth certificates. Adjusted odds ratios and 95% confidence intervals were used to evaluate the risk of autism associated with increasing maternal and paternal age. In adjusted models that included age of the other parent and demographic covariates, a 10-year increase in maternal age was associated with a 38% increase in the odds ratio for autism (odds ratio = 1.38, 95% confidence interval: 1.32, 1.44), and a 10-year increase in paternal age was associated with a 22% increase (odds ratio = 1.22, 95% confidence interval: 1.18, 1.26). Maternal and paternal age effects were seen in subgroups defined by race/ethnicity and other covariates and were of greater magnitude among first-born compared with later-born children. Further studies are needed to help clarify the biologic mechanisms involved in the independent association of autism risk with increasing maternal and paternal age.

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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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    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
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    • "Further studies indicate that the father's age is of similar importance given that men transmit a much higher number of mutations to their children than women (Kong et al., 2012) and that the age of the father is the dominant factor in determining the number of de novo mutations in the child (Kong et al., 2012). Thus, advanced paternal age was similarly associated with increased risk of ASDs in offspring (Croen et al., 2007; Grether et al., 2009; Reichenberg et al., 2010; Shelton et al., 2010; Buizer-Voskamp et al., 2011; van Balkom et al., 2012). However, advanced paternal and maternal age may act as risk factors through different mechanisms. "
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    ABSTRACT: Autism is a neurodevelopmental disorders characterized by impairments in communication and social behavior, and by repetitive behaviors. Although genetic factors might be largely responsible for the occurrence of autism they cannot fully account for all cases and it is likely that in addition to a certain combination of autism-related genes, specific environmental factors might act as risk factors triggering the development of autism. Thus, the role of environmental factors in autism is an important area of research and recent data will be discussed in this review. Interestingly, the results show that many environmental risk factors are interrelated and their identification and comparison might unveil a common scheme of alterations on a contextual as well as molecular level. For example, both, disruption in the immune system and in zinc homeostasis may affect synaptic transmission in autism. Thus, here, a model is proposed that interconnects the most important and scientifically recognized environmental factors. Moreover, similarities in how these risk factors impact synapse function are discussed and a possible influence on an already well described genetic pathway leading to the development of autism via zinc homeostasis is proposed.
    Frontiers in Psychiatry 11/2012; 3:118. DOI:10.3389/fpsyt.2012.00118
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    • "However, these studies have yielded contradictory results, with some reporting only paternal age as a risk factor for ASD (Sasanfar et al. 2010; Gabis et al. 2010; Reichenberg et al. 2006; Tsuchiya et al. 2008; Zhang et al. 2010). Another set of investigators reported only maternal age as a risk factor for ASD (Bilder et al. 2009; Croen et al. 2002; Glasson et al. 2004; Gillberg 1980; Tsai and Stewart 1983), and others have reported both paternal and maternal age as risk factors for ASD (Larsson et al. 2005; Shelton et al. 2010; Croen et al. 2007; Durkin et al. 2008; King et al. 2009; Grether et al. 2009). "
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    ABSTRACT: Several studies have reported maternal and paternal age as risk factors for having a child with Autism Spectrum Disorder (ASD), yet the results remain inconsistent. We used data for 68 age- and sex-matched case-control pairs collected from Jamaica. Using Multivariate General Linear Models (MGLM) and controlling for parity, gestational age, and parental education, we found a significant (p < 0.0001) joint effect of parental ages on having children with ASD indicating an adjusted mean paternal age difference between cases and controls of [5.9 years; 95% CI (2.6, 9.1)] and a difference for maternal age of [6.5 years; 95% CI (4.0, 8.9)]. To avoid multicollinearity in logistic regression, we recommend joint modeling of parental ages as a vector of outcome variables using MGLM.
    Journal of Autism and Developmental Disorders 01/2012; 42(9):1928-38. DOI:10.1007/s10803-011-1438-z · 3.06 Impact Factor
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