Association of maternal endometriosis with autism spectrum disorder in offspring: a retrospective cohort study

With the increasing incidence of autism spectrum disorder (ASD), various risk factors for ASD have been identified. Among them, maternal immune activation (MIA), which can be triggered by inflammation via elevated proinflammatory cytokines, has recently been reported as a risk factor for ASD in offspring. We assessed the association of maternal endometriosis, a chronic gynecological inflammation that may induce MIA, with ASD in offspring. In this retrospective cohort study, we used the data from a large-scale public health insurance database across Japan to identify dyads of mothers and their firstborn children, delivered between January 2005 and May 2022. Mothers with multiple pregnancies were excluded. The proportions of children diagnosed with ASD at 3 years old were compared between eligible mothers with endometriosis and those without a diagnosis of endometriosis prior to delivery. Multivariable logistic regression analysis was performed to evaluate the association of maternal endometriosis with ASD in children, after adjusting for maternal and peripartum characteristics. We identified 30,020 eligible dyads of mothers and their firstborn children. Among them, 3,496 mothers had endometriosis. The proportions of ASD in the offspring of the group of mothers without and with endometriosis were 2.7% (720/26,524) and 2.9% (102/3,496), respectively. Logistic regression analysis revealed no significant association of maternal endometriosis with ASD in their children (adjusted odds ratio, 1.04; 95% confidence interval, 0.84–1.29). No significant association of maternal endometriosis with ASD in offspring was detected in this study. These findings suggest children whose mothers have an antepartum history of endometriosis alone may not need to be closely monitored for ASD, and health care providers or people involved with children may need to consider other reported backgrounds related to ASD.