Older Maternal Age Linked to Increased Risk for Autism in Children

From MedscapeCME Clinical Briefs

News Author: Caroline Cassels
CME Author: Hien T. Nghiem, MD

February 16, 2010 — Advanced maternal age significantly increases the risk of having a child with autism irrespective of paternal age, a large population-based study suggests.

The research, conducted by investigators at UC Davis Health System, Sacramento, California, shows that the incremental risk of having a child with autism increased by 18% for every 5-year increase in maternal age.

"These data show that the risk of having a child with full-syndrome autism increases with maternal age, but increased risk from advancing paternal age primarily occurs among younger mothers (<30)," the researchers, led by senior investigator Irva-Hertz-Picciotto, PhD, MPH, write.

According to lead study author Janie Shelton, a doctoral student, the study challenges the hypothesis that the father's age is a key factor in increasing autism risk.

"It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old.
Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism," Ms. Shelton said in a statement.

The study was published online February 8 in Autism Research.

According to the study, previous research on autism and paternal age have yielded conflicting results on whether mothers, fathers, or both contribute to an increased risk for autism in children.

To determine the independent or dependent effect from each parent, the researchers gathered electronic records for all births in California between January 1, 1990, and December 31, 1999. The records incorporated detailed demographic information, including the age of both parents.

To identify which children would subsequently develop autism, the investigators obtained electronic records identifying children born during the study period who later received an autism diagnosis from California's Department of Developmental Services. For the study, autism was defined as a diagnosis of full-syndrome autism at a California regional center.

The final study sample included 4.9 million births and 12,159 cases of autism. The researchers report that for older mothers there was a stepwise progression in the risk of having a child who would later be diagnosed as having autism, irrespective of the father's age.

"We demonstrate that advancing maternal age increases the risk of autism independent of father's age, while advancing father's age increases the risk of autism primarily for mothers under 30. Among mothers over 30, we observed a small increased risk only among fathers 40+; even at the highest age group, the increase was smaller and less precise than that for fathers 30-34 among younger mothers," the researchers write.

At this point, the reason parental age influences autism risk is not clear. "We still need to figure out what it is about older parents that puts their children at greater risk for autism and other adverse outcomes, so we can begin to design interventions," Dr. Hertz-Picciotto said in a statement.

The study authors have disclosed no relevant financial relationships.

Autism Res. Published online February 8, 2010.

Clinical Context

In recent decades, the diagnosis of autism has increased. Autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years. Between 1990 and 2001, there has been a 7-fold increase in cumulative incidence observed among 5-year-olds in California. Known factors can explain this finding such as changes in the diagnostic criteria and a shift towards younger age at diagnosis. Studies have linked advancing parental age as a risk factor for autism. However, reports on autism and parental age have yielded conflicting results on whether mothers, fathers, or both, contribute to increased risk.

The aim of this study was to analyze restricted strata of parental age in a 10-year California birth cohort to determine the independent or dependent effect from each parent.


Study Highlights

To establish the cohort of this study, the investigators linked autism cases from California Department of Developmental Services records to state birth files (1990-1999). Subsequently, only singleton births with complete data on parental age and education were included (n = 4,947,935; cases = 12,159).

The net effects of maternal and paternal age on the risk for autism after adjustment for potential confounders were modeled by logistic regression, with the parental age terms specified either as continuous or categoric.
aORs for the effects of advancing paternal (maternal) age were also estimated with use of stratified multivariate logistic regression in strata defined by narrow (5-year) maternal (paternal) age groups.
The covariates adjusted in all models were parental education, year of child's birth, race or ethnicity of mother and father, mother's parity, and insurance payment.

Results demonstrated that children with autism were more likely than control subjects to be men, to have older parents, and to be either non-Hispanic white or Asian vs children without autism.
In multivariate logistic regression models, advancing maternal age increased the risk for autism monotonically regardless of the paternal age.
Compared with mothers aged 25 to 29 years, the aOR for mothers older than 40 years was 1.51 (95% CI, 1.35 - 1.70) vs mothers younger than 25 years (aOR, 1.77; 95% CI, 1.56 - 2.00).
In contrast, autism risk was associated with advancing paternal age (> 40 years), primarily among mothers younger than 30 years (aOR, 1.59; 95% CI, 1.37 - 1.85) vs the reference group of fathers aged 25 to 29 years (aOR, 0.76; 95% CI, 0.70 - 0.82).
Among mothers 30 years and older, the aOR was 1.13 (95% CI, 1.01 - 1.27) for fathers 40 years and older vs fathers aged 25 to 29 years, almost identical to the aOR for fathers younger than 25 years.
Based on the first examination of heterogeneity in parental age effects, it appears that a women's risk of delivering a child who develops autism increases throughout her reproductive years, whereas the father's age (> 40 years) confers an increased risk for autism when the mother is younger than 30 years but has limited effect when the mother is older than 30 years.
Additionally, the recent trend towards delayed childbearing contributed approximately a 4.6% increase in autism diagnoses in California between 1990 and 1999.

Clinical Implications

According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, autism is a pervasive developmental disorder of which deficits in social skills and communication, as well as repetitive and restricted behaviors, occur before age 3 years.
The risk of having a child with autism increases with older maternal age, but the increased risk from advancing paternal age occurs when the mother is younger (age < 30 years).