Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Medicine, 1–12. https://doi.org/10.1038/s41591-024-03479-5 Dr. Vahe Khachadourian et al.
Points
- This cohort study analyzed data from over 1.1 million children in Denmark (1998–2015) to examine the relationship between maternal health conditions during pregnancy and autism risk.
- Among 236 maternal conditions studied, 30 were significantly associated with autism after adjusting for confounders, including gestational diabetes (HR 1.19, 95% CI 1.08–1.31) and maternal depression (HR 1.49, 95% CI 1.27–1.75).
- Discordant sibling and paternal negative control analyses suggested that shared genetic and environmental factors contributed to the observed associations rather than maternal conditions directly causing autism.
- Maternal conditions affecting fetal health, such as pregnancy complications, were consistently linked to autism risk, suggesting they may serve as early indicators rather than causal factors.
- While maternal health conditions during pregnancy are associated with autism, these links are primarily driven by familial genetic and environmental factors rather than direct causation.
Summary
This cohort study examined the relationship between maternal health during pregnancy and the risk of autism in offspring, using data from 1,131,899 children born in Denmark between 1998 and 2015. The analysis included a wide range of maternal prenatal diagnoses (236 ICD-10-coded conditions), focusing on those with a prevalence greater than 0.1% of pregnancies. The study applied Cox proportional hazard regression models to estimate the likelihood of autism associated with maternal diagnoses, adjusting for sociodemographic factors, comorbidities, and disease chronicity. The results indicated that 18,374 (1.6%) of the children were diagnosed with autism by the end of the follow-up period. Thirty maternal diagnoses were significantly associated with autism after correction for confounders, with conditions such as diabetes during pregnancy (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.08–1.31) and depression (HR 1.49, 95% CI 1.27–1.75) showing a notable association.
However, familial confounding played a significant role in many of these associations. To address this, the study incorporated discordant sibling and paternal negative control designs, which indicated that genetic and environmental factors shared between family members likely accounted for the observed relationships. The analysis revealed that maternal conditions affecting the fetus, such as complications during pregnancy, were consistently associated with autism risk. The results suggest that these conditions may serve as early indicators of autism rather than causal factors.
In conclusion, the study highlights the pervasive associations between maternal health during pregnancy and autism in offspring. However, these associations were primarily attributed to familial confounding, emphasizing the need for further investigation into the genetic and environmental factors contributing to autism. The findings offer reassurance that maternal conditions during pregnancy, such as depression or diabetes, do not directly cause autism but may reflect underlying familial predispositions.
Link to the article: https://www.nature.com/articles/s41591-024-03479-5
References Khachadourian, V., Arildskov, E. S., Grove, J., O’Reilly, P. F., Buxbaum, J. D., Reichenberg, A., Sandin, S., Croen, L. A., Schendel, D., Hansen, S. N., & Janecka, M. (2025). Familial confounding in the associations between maternal health and autism. Nature Medicine, 1–12. https://doi.org/10.1038/s41591-024-03479-5
