GASTROINTESTINAL SYMPTOMS AND THE GUT IN AUTISM SPECTRUM DISORDERS: BURDEN, MEASUREMENT, AND ETIOLOGIC RELEVANCE

Background: Individuals with ASD are more likely to experience gastrointestinal symptoms (GI). The goal of this dissertation was to shed light on the burden GI symptoms place on individuals with ASD and their families, improve the detection of GI symptoms, and assess the role of the gut as an etiologic risk factor for the incidence of ASD. Methods: The first study analyzed 12 qualitative interviews to summarize the experiences that families with a child with ASD and GI symptoms face. The second study reviewed the literature (n=144 studies between 1/1/1980 to 1/31/2017) on ASD and GI symptoms and described the range of approaches to ascertaining GI symptoms and conditions. The third study developed a questionnaire to assess GI symptoms in children with ASD and reported psychometric (n=537). The fourth study assessed for interaction between maternal immune activation and antibiotic use during pregnancy on the risk of ASD diagnosis in the offspring, in an enriched-risk prospective birth cohort (n= 142 ASD, 2,953 non-ASD). Results: Three themes emerged from qualitative interviews: Parents rely on behavioral indicators to detect GI symptoms in their child. GI symptoms are associated with poorer functioning and lower wellbeing and families tended to report negative experiences seeking healthcare for their child’s GI symptoms. In the second study, GI symptoms were assessed many ways, and the assessment tool was significantly associated with symptom estimates. In the third study, we developed an internally consistent 35-item tool for assessing the presence of GI symptoms. In the fourth study, we found that the association between flu in the second trimester on risk for ASD is modified by antibiotic use in pregnancy. Among women who did not receive an antibiotic during pregnancy, flu in the second trimester was associated with 4.4 times the odds of ASD diagnosis (OR=4.43 95% 1.13-14.69), but not among women who did receive an antibiotic (OR=1.06 95% 0.46-2.13). Conclusions: This work highlights the need for more work on the accurate measurement of GI symptoms in this population and the consideration of the gut as a risk factor for the development of ASD