Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring
Authors: Carter Sarah A , Lin Jane C , Chow Ting , Yu Xin , Rahman Md Mostafijur , Martinez Mayra P , Feldman Klara , Eckel Sandrah P , Chen Jiu-Chiuan , Chen Zhanghua , Levitt Pat , Lurmann Frederick W , McConnell Rob , Xiang Anny H 
Published: September 2022

Gastrointestinal disturbances (GIDs) are relatively common in children diagnosed with autism spectrum disorder (ASD). This study assessed associations between maternal obesity, diabetes, preeclampsia, and asthma and likelihood of ASD with GIDs. This retrospective cohort study included 308,536 mother–child pairs of singletons born between 2001 and 2014 in a single integrated health care system. Social demographics, maternal health conditions during pregnancy, and child’s ASD and/or GID diagnosis by age 5 were extracted from electronic medical records. Child’s outcome was classified as: no ASD no GIDs; no ASD with GIDs; ASD no GIDs; and ASD with GIDs. Multinomial logistic regression was used to estimate odds ratios of child’s outcomes associated with maternal exposures, adjusting for covariates. Compared to children with neither disorder, each maternal condition was associated with higher odds of no ASD with GIDs, ASD no GIDs, and ASD with GIDs. Association was greatest for likelihood of ASD with GIDs (Maternal obesity odds ratio (95% confidence interval): 1.37 (1.22–1.54); Diabetes: 1.50 (1.28–1.76); Preeclampsia: 1.63 (1.36–1.95); Asthma: 1.39 (1.17–1.67); relative to no ASD no GIDs). Associations were robust to mutual adjustment for all maternal exposures. Maternal obesity, diabetes, preeclampsia, and asthma exposure during pregnancy may increase likelihood of both GIDs and ASD with or without co-occurring GIDs in offspring. This association was greatest in children diagnosed with ASD with co-occurring GIDs. Lay abstract Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.