Gastrointestinal Symptoms and Oral Antibiotic Use in Children with Autism Spectrum Disorder: Retrospective Analysis of a Privately Insured U.S. Population

Abstract

A retrospective analysis of administrative claims data from a large U.S. health insurer was performed to study a potential association between oral antibiotic use during early childhood and occurrence of later gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Among 3253 children with ASD, 37.0% had a GI-related diagnosis during the last 2 years of their 5-year health coverage enrollment period, compared to 20.0% of 278,370 children from the general population without an ASD diagnosis. Greater numbers of oral antibiotic fills during the first 3 years of enrollment were found to significantly increase the hazard rate of having a later GI-related diagnosis (adjusted hazard ratio 1.48; 95% confidence interval 1.34, 1.63) in children both with and without ASD.

Keywords: Administrative claims; Autism spectrum disorder; Gastrointestinal symptoms; Gut microbiome; Oral antibiotics; Retrospective analysis.

Figure 1.

Timeline of relevant dates in the study’s design. The index date (first date of coverage enrollment) must have been between January 1, 2000 and December 31, 2010 and within one year of a child’s birth year, which needed to be between the years 2000 and 2010. A minimum five years of continuous medical, pharmacy, and behavioral coverage were required to follow the index date for a child to be included in the study.

Figure 2.

Patterns of gastrointestinal (GI) episode occurrence in the autism spectrum disorder (ASD) cohort and the general population without an ASD diagnosis (POP) cohort: (a) relative frequency distributions for the number of GI episodes that occurred in members of each cohort during the late enrollment period; (b) proportion of the members in each cohort that experienced a GI episode during each three-month interval of the total five-year enrollment period. Each point represents the total proportion of individuals during the indicated three-month period.

Figure 3.

Trends in oral antibiotic use in the autism spectrum disorder (ASD) cohort and general population without an ASD diagnosis (POP) cohort, and in their subcohorts describing children with and without a gastrointestinal (GI) symptom diagnosed during the late enrollment period (+GI and −no GI subcohorts, respectively): (a) relative frequency distributions for the number of oral antibiotic fills during the early enrollment period for members of each GI subcohort and the primary cohorts; (b) proportion of the members in each cohort and GI subcohort that had an oral antibiotic fill during each three-month interval of the total five-year enrollment period. Each point represents the total proportion of individuals during the indicated three-month period.

Figure 4.

Proportion of oral antibiotics prescribed for different types of infections during the early enrollment period within the autism spectrum disorder (ASD) cohort and general population with no ASD diagnosis (POP) cohort, and within their subcohorts describing children with and without a gastrointestinal (GI) symptom diagnosed during the late enrollment period (+GI and −no GI subcohorts, respectively). The sum of proportions within each cohort/sub cohort may be greater than unity due to the occasional diagnosis of multiple infection types in one medical claim.