Childhood infections and autism spectrum disorders and/or intellectual disability: a register-based cohort study
Håkan Karlsson1, Hugo Sjöqvist2, Martin Brynge2
1Department of Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden. hakan.karlsson.2@ki.se.
Insights
Childhood infections are linked to later diagnoses of autism spectrum disorder (ASD) and intellectual disability (ID). Even after accounting for family factors, risks for ASD and ID remained, suggesting a potential contribution of infections to these neurodevelopmental conditions.
Area of Science:
- Neuroscience
- Epidemiology
- Public Health
Background:
- Childhood infections are common and can have long-term health implications.
- Autism spectrum disorder (ASD) and intellectual disability (ID) are complex neurodevelopmental conditions with multifactorial etiologies.
- Understanding potential environmental contributors, such as infections, is crucial for early identification and intervention.
Purpose of the Study:
- To investigate the association between childhood infections and the subsequent risk of autism spectrum disorder (ASD) and intellectual disability (ID).
- To examine the co-occurrence of ASD and ID in relation to prior childhood infections.
- To explore potential confounding factors and residual risks in this association.
Main Methods:
- A register-based cohort study of 556,732 individuals born between 1987 and 2010 in Stockholm County.
- Infection diagnoses were identified using ICD codes, and subsequent ASD/ID diagnoses were tracked until age 18 or December 31, 2016.
- Survival analyses using extended Cox regression models, including sibling analyses, were employed to control for confounders like child characteristics, socioeconomic factors, obstetric complications, and parental psychiatric history.
Main Results:
- Childhood infections were associated with an increased risk of later diagnoses of ASD and ID, with higher risks observed for ID.
- Adjusted sibling analyses, excluding congenital causes, showed significant associations: "ASD without ID" (HR 1.24), "ASD with ID" (HR 1.57), and "ID without ASD" (HR 2.01).
- The identified risks persisted after controlling for various confounders, indicating a potential independent contribution of infections, with risk varying by age at exposure and diagnosis.
Conclusions:
- Childhood infections may play a role in the etiology of intellectual disability and autism spectrum disorder.
- The findings underscore the importance of considering infections as a potential environmental factor in neurodevelopmental outcomes.
- Further research is warranted to elucidate the biological mechanisms underlying the observed associations.
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 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.
Results:
Crude 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.
Conclusions:
Infections during childhood may contribute to a later diagnosis of ID and ASD.
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