The risk of autism spectrum disorder (ASD) is increased in children with young maternal grandparents and young or old paternal grandmothers, compared with the grandchildren of grandparents who were between the ages of 25 and 29 years when they gave birth, according to findings of an epidemiologic study published in JAMA Network Open.
The prevalence of ASD has been increasing over the past few decades and depending on the region, it is estimated to occur in 1% to 2% of children. A number of factors have been suggested as possible contributors to this increase, including improved diagnostic efficiency and heightened awareness, as well as the trend toward postponing parenthood.
Yu Gao, PhD, of the department of environmental health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and colleagues used data from Danish national health registries to conduct this population-based multigenerational cohort study. They sought to evaluate the effect of parental age at childbirth and grandparental age at the time of the birth of the parent on risk for ASD.
The study included 1,476,783 children born in Denmark from 1990 to 2013 (51.3% boys; 1.9% diagnosed with ASD). The majority of those with ASD were boys (74.1%). The investigators found that a 5-year increase in maternal or paternal age was associated with a 9% increase in the odds for ASD in children. The highest odds ratio (OR) was observed for maternal age over 40 years (OR, 1.56; 95% CI, 1.45-1.68) and paternal age greater than 50 years (OR, 1.57; 95% CI, 1.39-1.78) when compared with parents aged 25 to 29 years.
The investigators observed a U-shaped curve for paternal grandparental age. Children whose fathers were born to young parents, defined as parenthood at age 19 years or younger, (OR, 1.18) or older parents, defined as parenthood at age 40 years or older, (OR, 1.40 and 1.11 for grandmothers and grandfathers, respectively) hade an increased risk of ASD. Children whose mothers were born to younger parents also had an increased risk of ASD (OR, 1.68 and 1.50 for grandmothers and grandfathers, respectively). However, the investigators found no associations with ASD risk for older maternal grandparents.
“A new hypothesis has recently been proposed that the association of parental age with the risk of ASD could persist across generations,” the study authors noted. They also conceded that age at delivery may be a marker for other risk factors for ASD.
The limited time period for study participant inclusion (children born 1990 to 2013 and parents born 1973 to 1990) may have introduced bias associated with truncated data, particularly for the youngest and oldest age categories. Study limitations also include the possibility of confounding by genetic risk for ASD and lack of data on grandparental psychiatric diagnoses.
The researchers concluded that “ASD risk in the grandchildren associated with younger and older grandparental age could be attributable to different social and biological mechanisms.”
Gao Y, Yu Y, Xiao J, et al. Association of grandparental and parental age at childbirth with autism spectrum disorder in children. JAMA Network Open. 2020;3:e202868. doi:10.1001/jamanetworkopen.2020.2868.