Freepik

Autism spectrum disorder, or ASD, in children may be linked to the premature birth of their parents, according to a Yale School of Public Health study.

Assistant Professor of Epidemiology Zeyan Liew and graduate student Jingyuan Xiao GRD ’26 examined the medical records of nearly 400,000 mother-child and father-child pairs. The researchers found that children had nearly double the risk of ASD if their mothers and fathers were born at earlier than 32 gestational weeks compared to children whose parents were born at term. The study was published in the International Journal of Epidemiology on Jan. 7.

“The worldwide prevalence of autism spectrum disorder (ASD) is increasing, but scientific understandings regarding the etiology of this multifactorial and complex neurodevelopmental conditions are still limited,” Liew and Xiao wrote in an email to the News. “We conducted this study to evaluate whether adverse birth characteristics of the parents … could influence ASD risk in their offspring.”

The researchers analyzed data from a cohort of 230,174 mother-child and 157,926 father-child pairs in Denmark to examine the multigenerational risk factors that might contribute to the prevalence of ASD.

The scientists also collected data on the grandparents’ and parents’ sociodemographic factors, age when pregnant, geographical location and mental health to include in their statistical models. They said that Denmark’s national health care and centralized medical records system helped make this type of longitudinal family linkage research possible.

The researchers used a pregnancy term of 37 weeks and a birth weight of 2,500 grams as a baseline reference. They found that mothers and fathers who were born prematurely — at fewer than 37 weeks of gestation — or with a low birthweight had a 30 to 40 percent higher risk of having children with ASD. Meanwhile, parents born at fewer than 32 gestational weeks had nearly double the risk of later having children with ASD, compared to parents born at term.

In the past, many studies on ASD have focused on environmental risk factors such as prenatal exposure to air pollution. Additionally, studies of family members of children living with ASD have largely centered on siblings instead of multigenerational data, the scientists said.

“It is known that certain genetics and fetal exposure to environmental risk factors contribute to the risk of ASD, but these known factors don’t fully explain the occurrence of all ASD cases in populations,” wrote Xiao and Liew. “Recently, new hypotheses regarding multigenerational risk for ASD have been proposed in animal models, but epidemiological evidence is still lacking.”

The Autism Center for Excellence Program at Yale, or ACE, led by professor Katarzyna Chawarska, currently has ongoing projects examining the brain connectivity of school-age siblings of children with autism to better comprehend how this relates to the severity of autism symptoms. Another ACE project aims to identify genetic markers linked to autism by studying the biological differences during early development of the brain in sibling pairs where one or both siblings are diagnosed with ASD.

Chawarska said she was “peripherally” involved in contributing to Liew and Xiao’s study but declined to comment further.

Xiao and Liew noted that additional studies are required to elucidate how ASD is transmitted across generations.

“It might be important to study specific grandparental and environmental factors that can directly impact on parental in-utero development,” Xiao and Liew wrote.

The scientists explained that prior research on multigenerational factors and ASD suggests that grandmaternal smoking and the use of diethylstilbestrol — a compound given to pregnant women between 1938 to 1971 to prevent pregnancy complications — potentially hinder neurodevelopmental health in grandchildren.

Xiao and Liew said that future studies should follow the development of parents born with adverse birth characteristics, such as low birthweight or preterm birth, to identify other postnatal factors that may have contributed to ASD in their children. The researchers hope these paths for future investigation could be a means to mitigate ASD transmission pathways within families.

The Centers for Disease Control and Prevention estimates that 1 in 54 children has been diagnosed with ASD in the United States.

Sydney Gray | sydney.gray@yale.edu