Advancing Parental Age and Increased Autism Risk

Advancing Parental Age and Increased Autism Risk

According to a national survey conducted jointly by the Health Resources and Services Administration and the Center for Disease Control and Prevention, the prevalence of Autism Spectrum Disorders (ASDs) in the United States is approximately 1 in 91 children, with male children being four times more likely to have an ASD than females (Kogan et al., 2009). Autistic disorder/autism, is a developmental disorder typically manifesting prior to three years of age, and is marked by severe impairments in social interaction, emotional reciprocity and communicative ability, as well as, the presence of stereotyped behaviors, routinized behavioral repertoires, and/or perseverative and restricted interests (American Psychiatric Association [Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision], 2000). Although the etiology of autism is, as yet, largely unknown, contemporary researchers overwhelming concur that the risk of giving birth to a child with autism is likely a complex interaction of polygenic and environmental factors; however, the specific underlying mechanisms by which this occurs remain vastly elusive.

One particular line of epidemiological research has focused upon the relationship of prenatal risk factors in the development of autism, and more specifically, the possible association of advanced maternal and paternal age as contributing factors to an increased risk of producing a child with autism. Accordingly, a group of researchers representing the California Department of Public Health conducted a comparative investigation aimed at determining the potential influence of increasing parental ages at time of birth and the development of autism in the parents’ respective offspring (Grether, Anderson, Croen, Smith, & Windham, 2009). Following from previous mixed research findings (as cited in Grether et al., 2009) relating increased maternal age alone, paternal age alone, and both maternal and paternal ages in tandem to increased autism risk, Grether and colleagues, believing the aforementioned inconsistencies to be largely resultant of small sample sizes and research methodology, aimed to assist in the clarification of such inconsistencies via the utilization of an extremely large study population consisting of nearly 7,550,026 singletons born in California, USA between January 1, 1989 and December 31, 2002. In the event that the inconsistencies evidenced in earlier research did, in fact, reflect actual differences across the varying populations studied, the researchers included within their analyses a number of potential covariates available from participant birth certificates, such as: gender, year of birth, maternal and paternal education, maternal and paternal race/ethnicity, child’s birth-weight and gestational age, parity, and a rough estimate of socioeconomic status as derived from method of payment for hospital services. With respect to the overarching rationale and purpose in conducting the following investigation, the researchers state that “due to the fact that age related reproductive mechanisms differ between men and women, disentangling the interrelations between risk of autism and age of mothers and fathers is likely to be helpful in the search for etiological factors” (Grether et al., 2009; p. 1118).

Children with autism were identified for the study via the California Department of Developmental Services (DDS), a statewide system responsible for the coordination of services for individuals with intellectual and developmental disabilities, including autism. In order to fulfill DDS eligibility requirements for services due to autism, individuals must have met the criteria for a diagnosis of autistic disorder/autism as put forth in the DSM-III-TR prior to 1994, or the DSM-IV beginning in 1994 and onward. Birth certificates were utilized to obtain parental ages at the time of the child’s birth for the entire study population, however, cases falling beyond the ranges of 15-44 years for maternal age and 15-64 years for paternal age were excluded, as considered misrepresentative and/or improbable ages (e.g., reported maternal ages ranged from 7 to 96 years, paternal ages from 0 to 97 years). Following the exclusion of a number of observations resultant to implausible parental ages and missing data, the remaining group of individuals with DDS-reported autism (n = 20,701) were ultimately compared with the remaining group of individuals without autism (n = 6,506,555) with respect to parental age at the time of the child’s birth.

The results obtained by Grether et al. (2009), via the utilization of logistic regression and odds ratios for a series of unadjusted models, as well as models adjusted to examine potential covariates and control for the other parent’s age, indicate that, within the large and diverse population employed within their current investigation, the risk of giving birth to a child with autism was independently related to both increasing maternal and increasing paternal age. The researchers determined that the odds of having a child with autism increased 38% with respect to maternal age and 22% with respect to paternal age for each ten year increment in the parents’ respective ages. Furthermore, the observed maternal and paternal age effects remained relatively constant within the defined subgroups of gender, race/ethnicity, maternal and paternal educational levels, birth-weight, and gestational age. The effects of maternal age on the risk of autism was found to be slightly greater among children of lower socioeconomic status, as well as those born in the earlier, as opposed to later, years included within the study, a finding the researchers posited as likely resulting from changes in the diagnostic criteria for DDS services following the implementation of the DSM-IV in 1994.

Grether et al. (2009) offer several biological explanations by which increasing parental age may potentially impact fetal neurodevelopment and subsequently the emergence of autism. With respect to maternal age, explanations include (1) the possibility of an altered in utero environment resultant to hormonal factors associated with aging, (2) as women age, they become more likely to experience infertility, and therefore, exposure to assisted reproductive technologies may increase autism risks, (3) unstable genetic mutations; wherein the DNA for the specific disease-related genes are repeatedly duplicated (i.e., nucleotide repeat instability) and (4) an increase in the stress to a women’s body resultant to cumulative build-up of environmental toxins. With respect to paternal age effects, the researchers posit that the most likely explanation for an increased autism risk is the result of increased de novo mutations (i.e., a novel mutation that occurs in a germ cell and is then passed on to an offspring) in the sperm of aging men; a likely result of years of collective toxic build-up in the body. According to the researchers, de novo mutations may account for cases of autism in which there appears to be no identifiable link to heredity.

In the search for the etiological factors that contribute to autism, the preceding study conducted by Grether et al. (2009) provides plausible evidence in support of an association between increasing parental ages and an increased risk of giving birth to a child with autism. Clearly, further studies are necessary to determine the exact biological mechanisms by which this linkage of autism with increased parental ages occurs, however, the above study provides rigorous support to a preexisting genetic risk explanation to the etiology of autism.

The preceding study is significantly strengthened by the large sample size employed, and hence, the statistical analyses and precision afforded by such; however, limitations nonetheless constrain the generalizability of the findings. Most notably, the above analyses were limited to persons enrolled within the California DDS, and therefore, California residents only. Future research is warranted to determine if the findings of the current study are replicated in varying regions of dissimilar population dynamics. Furthermore, as DDS services are limited to individuals with diagnosed autistic disorder/autism, phenotypic subgroups of the autism spectrum were excluded from study. Future research should aim to ascertain a greater representational sampling of individuals from varying degrees of the autism spectrum in an attempt to determine the significance of advanced reproductive age and autism spectrum risk across phenotypic subtypes.

References:

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (Revised 4th ed.). Washington, DC: Author.
Grether, J. K., Anderson, M. C., Croen, L. A., Smith, D., & Windham, G. C. (2009). Risk of autism and increasing maternal and paternal age in a large North American population. American Journal of Epidemiology, 170,(9), 1118-1126.
Kogan, M. D., Blumberg, S. J., Schieve, L. A., Boyle, C. A., Perrin, J. M., Ghandour, R. M. (2009). Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics, 124,(5), 1395-1403.