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April 5, 2007 — Advanced
maternal and paternal ages are independently linked with
risk for autism spectrum disorder (ASD) in children, according
to the results of a historical birth cohort study reported
in the April issue of the Archives of Pediatrics & Adolescent Medicine.
Lisa A. Croen, PhD, from the
Kaiser Permanente Medical Care Program in Oakland, California,
and colleagues studied all singleton children born at Kaiser
Permanente in Northern California from January 1, 1995,
to December 31, 1999, and they identified 593 children
who had ASD diagnoses (International
Classification of Diseases, Ninth Revision, Clinical Modification,
code 299.0 or 299.8) recorded twice or more in Kaiser Permanente
outpatient databases before May 2005. These 593 children
were compared with the remaining 132,251 singleton Kaiser
Permanente births.
Primary endpoints were relative
risks (RRs) for ASD, estimated from proportional hazards
regression models evaluating maternal and paternal ages,
adjusted for each other and for the sex, birth date, and
birth order of the child; maternal and paternal educational
levels; and maternal and paternal races/ethnicities.
The risk for 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).
Children with autistic disorder had increased adjusted
RRs for both maternal and paternal ages (maternal age:
RR, 1.18; 95% CI, 0.87 - 1.60; paternal age: RR, 1.34;
95% CI, 1.06 - 1.69), as did children with Asperger disorder
or pervasive developmental disorder not otherwise specified
(maternal age: RR, 1.45; 95% CI, 1.09 - 0.93; paternal
age: RR, 1.24; 95% CI, 0.99 - 0.55). Although sex differences
were not statistically significant, associations with parental
age were somewhat stronger for girls than for boys.
"We found that risk of ASD
was independently associated with advanced maternal and
paternal age in a contemporary cohort of California-born
children," the authors write. "Major strengths of this
study include a large population-based sample and prospective
collection of autism diagnoses and covariates, thus avoiding
biases due to differential reporting and recall by parents
of affected and unaffected children."
Study limitations include
possible underascertainment of ASDs, failure to control
for pregnancy complications, and possible confounding by
healthcare-seeking behavior measured in the first few years
of life.
"If the relationship between
parental age and ASD is causal, the fraction of autism
in this sample attributable to having a mother or father
older than 35 years is 4% to 13%," the authors conclude. "Future
investigations focused on the identification of both genetic
and environmental factors that correlate with advanced
parental age are warranted."
The Centers for Disease Control
and Prevention and the Kaiser Foundation Research Institute
funded this study in part. The authors have disclosed no
relevant financial relationships.
Arch Pediatr
Adolesc Med. 2007;161:334-340.
Clinical
Context
In the past few decades, the
prevalence of ASDs has increased significantly. The cause
of ASDs is unknown; however, there is evidence for a strong
genetic contribution. Advanced maternal age has been associated
with risk for autism in several studies, but the role of
paternal age in autism has been examined less frequently.
Currently, advanced paternal age has been associated with
adverse reproductive outcomes, such as miscarriage, fetal
death, childhood cancers, autoimmune disorders, schizophrenia,
and other neuropsychiatric disorders. These outcomes may
be explained by the age-associated increase in de novo
mutations in male germ cells.
The aim of the current study
was to explore the association between maternal and paternal
ages and risk for ASDs in offspring.
Study
Highlights
Pearls
for Practice
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