Parental Age Linked to Increased Autism Spectrum Disorder Risk in Children

Zeyan Liew, PhD, MPH

Advanced parental age was independently associated with an increased risk of autism spectrum disorder in children, according to new findings.

Using data from Danish national health registries to estimate the associations between parental and grandparental age and autism spectrum disorder risk in children, Zeyan Liew, PhD, MPH, and colleagues reported that children with young maternal grandparents, and those with young and old paternal grandparents, had higher risk compared with children of grandparents who were 25-29 years old at the time of their parents' births.

“Although the association between advanced maternal and paternal age at childbirth and risk for autism spectrum disorder in the offspring is rather robust and observed in several populations, scientists are still trying to understand what are the mechanisms that might explain these associations,” Liew, from the Yale Center for Perinatal, Pediatric and Environmental Epidemiology, told HCPLive®.

Liew and the investigators constructed a parental age cohort to evaluate the association between parental age and autism spectrum disorder in 1,476,783 singleton children born between 1990-2013. The team also constructed a multigenerational cohort which included 362,438 fathers and 458,234 mothers born from 1973-1990, and had grandparental age information available.

Autism spectrum disorder diagnoses were determined from the Danish Psychiatric Central Register using the ICD-10. The disorder was typically diagnosed between 3-5 years old.

Of the nearly 1.5 million children (51.3% male) included in the parental age cohort, 1.9% had autism spectrum disorder (74.1% male) and 1.7% grandchildren in the multigenerational cohort had autism spectrum disorder. A majority of the mothers were from Denmark (87.1%) and had an upper secondary-level education or a bachelor’s degree or higher (76.9%).

Mean delivery age was higher for fathers compared with mothers (32.5 years old vs 29.8 years old) and the age of delivery increased in similar rates for the fathers and mothers from 1990-2013.

A majority of grandmothers were from Denmark (95.5%) and more than half (53.5%) had an upper secondary-level education or a bachelor’s degree. The mean delivery age for the grandparents (maternal grandfathers, 28.7 years old; maternal grandmothers, 25.9 years old; paternal grandfathers, 28.7 years old; paternal grandmothers, 25.9 years old) was lower than those of the parents.

Advanced paternal or maternal age >30 years old was monotonically associated with increased autism spectrum disorder risk (OR, 1.56; 95% CI, 1.45-1.68 for maternal age >40 years old; OR, 1.57; 95% CI, 1.39-1.78 for paternal age >50 years old), compared with parents 25-29 years old.

The investigators found that autism spectrum disorder risk was higher among grandchildren of younger (<19 years old) maternal grandmothers (OR, 1.68; 95% CI, 1.52-1.85); younger maternal grandfathers (OR, 1.5; 95% CI, 1.26-1.78); younger paternal grandmothers (OR, 1.18; 95% CI, 1.04-1.34); and older (>40 years old) paternal grandmothers (OR, 1.4; 95% CI, 1.03-1.9) compared to grandchildren of grandparents 25-29 years old at time of giving birth to the parents.

“Our findings of grandparents age at the time of the birth of the parents and future risk in autism spectrum disorder in the grandchild is novel, suggesting that possible transmission of autism spectrum disorder risk across generation should also be considered in future etiological research on autism spectrum disorder,” Liew said.

The study, “Association of Grandparental and Parental Age at Childbirth With Autism Spectrum Disorder in Children,” was published online in JAMA Network Open.