A quarterly publication of the Autism Research Institute
Winter 2025 | Number 1, Volume 39
While a number of studies have associated maternal health problems during pregnancy with autism spectrum disorders (ASD) in offspring, a large-scale study sheds new light on these findings.
Vahe Khachadourian and colleagues examined medical data on all children born in Denmark between 1998 and 2015, as well as data on their mothers and fathers. Focusing on maternal illnesses occurring around the time of pregnancy, the researchers estimated the likelihood of autism in offspring associated with each illness. In addition, they looked at data for siblings who were exposed to the same maternal illnesses in utero as the children with ASD. The researchers note that if a mother had the same medical condition during pregnancies of children with and without autism, it would suggest that factors other than the medical condition were involved.
They report, “Among the 1,131,899 individuals in our sample, 18,374 (1.6%) were diagnosed with autism by the end of follow up. Across 236 maternal diagnoses we tested, 30 were significantly associated with autism after accounting for sociodemographic factors, disorder chronicity and comorbidity, and correction for multiple testing. This included obstetric, cardiometabolic and psychiatric disorders (for example, diabetes in pregnancy and depression), previously shown to be associated with autism.”
However, the researchers say that after accounting for familial factors such as genetics and exposure to environmental pollutants, the only maternal diagnosis still strongly associated with autism was that of pregnancy complications related to the fetus. “Our interpretation is that these fetal diagnoses likely do not cause autism, but are instead early signs of it,” lead study author Magdalena Janecka comments. “The predominant hypothesis is that autism re ally starts prenatally. Even before a child receives a diagnosis for autism, developmental changes have been happening the entire time.”
Another interesting finding was that many paternal diagnoses were as closely related to ASD in children as maternal diagnoses. Again, this points to familial factors, since fathers have little direct effect on a fetus in utero.
The researchers conclude, “While our results diminish the possibility of direct causal contributions of many of these maternal diagnoses to autism and implicate the contributions of underlying familial factors, these findings still offer important etiological insights. ‘Familial confounding’ should not be conflated with ‘irrelevant.’ Instead, a more granular understanding of the nature of this confounding—including what familial factors, genetic and nongenetic, are confounding the observational associations and how they influence neurodevelopment—will be critical for a fuller understanding of autism etiology.”
“Familial confounding in the associations between maternal health and autism,” Vahe Khachadourian, Elias Speleman Arildskov, Jakob Grove, Paul F. O’Reilly, Joseph D. Buxbaum, Abraham Reichenberg, Sven Sandin, Lisa A. Croen, Diana Schendel, Stefan Nygaard Hansen, and Magdalena Janecka, Nature Medicine, January 31, 2025 (free online). Address: Magdalena Janecka, Department of Child and Adolescent Psychiatry, NYU Grossman School of Medicine, New York, NY 10016, [email protected].
—and—
“Study finds no evidence that maternal sickness during pregnancy causes autism,” news release, NYU Langone Health, January 31, 2025.
