Infections in childhood and subsequent diagnosis of autism spectrum disorders and intellectual disability: a register-based cohort study

Abstract

Objective. To explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID) and their co-occurrence. Methods. The association between specialized care for any infection, defined by ICD-codes and later ASD or ID was investigated in a register-based cohort of 556,732 individuals born 1987-2010, resident in Stockholm County, followed from birth to their 18th birthday or December 31, 2016. We considered as potential confounders childrens characteristics, family socioeconomic factors, obstetric complications, and parental histories of both treatment for infection and psychiatric disorders in survival analyses with extended Cox regression models. Residual confounding by shared familial factors was addressed in sibling analyses using within-strata estimation in Cox regression models. Sensitivity analyses with exclusion of congenital causes of ASD/ID and documented risk for infections were also performed. Results. Crude estimates indicated that infections during childhood were associated with later ASD and ID with largest risks observed for diagnoses involving ID. Inclusion of covariates, exclusion of congenital causes of ASD/ID from the population and sibling comparisons highlighted the potential for confounding by both heritable and non-heritable factors, though risks remained in all adjusted models. In adjusted sibling comparisons, excluding congenital causes, infections were associated with later ASD without ID (HR 1.24, 95%CI 1.15-1.33), ASD with ID (1.57, 1.35-1.82) and ID without ASD (2.01, 1.76-2.28). Risks associated with infections varied by age at exposure and by age at diagnosis of ASD/ID. Conclusions. Infections during childhood cannot be excluded in the etiology of ASD, particularly ASD with co-occurring ID.