Abstract
ObjectiveTo explore the associations between childhood infections and subsequent diagnoses of autism spectrum disorder (ASD), intellectual disability (ID), and their co-occurrence.MethodsThe 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 children’s characteristics, family socioeconomic factors, obstetric complications, and parental histories of 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 the exclusion of congenital causes of ASD/ID and documented risk for infections were also performed.ResultsCrude estimates indicated that infections during childhood were associated with later ASD and ID with the 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.ConclusionsInfections during childhood may contribute to a later diagnosis of ID and ASD.
Highlights
IntroductionThe relative contributions of these plausibly causal factors appear to vary across diagnostic sub-groups based on co-occurring diagnoses [2,3,4]
The etiology of autism spectrum disorders (ASD) remains elusive but appears to involve common, rare, and de novo genetic variants as well as environmental exposures [1].The relative contributions of these plausibly causal factors appear to vary across diagnostic sub-groups based on co-occurring diagnoses [2,3,4]
All investigated covariates differed significantly (p
Summary
The relative contributions of these plausibly causal factors appear to vary across diagnostic sub-groups based on co-occurring diagnoses [2,3,4]. ASD is diagnosed throughout childhood and age at diagnosis appears to be determined by both internal (severity, sex) and external factors (parental educational level, access to care) [11]. While parents often report deviations from normal developmental trajectories at an early age, the pattern of onset varies substantially. It remains to be established if the childhood environment contributes to a trajectory towards ASD in vulnerable children [12, 13] Identification of modifiable early life environmental factors is key to the development of prevention strategies for ASD
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