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Infections in Children with Autism Spectrum Disorder: Study to Explore Early Development
Immune system abnormalities have been widely reported as a component of autism spectrum disorder (ASD); childhood infections may be an expected outcome of these abnormalities. In addition, there have been some limited studies linking childhood infections, including ear infections and specific viral infections, to autism. However, these studies have provided mixed results. Further, potential differences in infection risk in regressive versus non-regressive ASD have not been extensively examined.
Objectives:
We examined caregiver report of clinically diagnosed infections in (1) children with ASD compared to non-ASD developmentally delayed/disordered (DD) controls and to non-ASD population (POP) controls and (2) children with regressive ASD compared to children with non-regressive ASD.
Methods:
The Study to Explore Early Development is a multi-site case-control study of ASD that enrolled children aged 30-68 months. ASD cases (n=707) were determined using standardized diagnostic instruments including the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview, Revised. DD controls (n=690) were recruited from educational or clinical settings. POP controls (n=898) were ascertained from birth certificates. Children with regressive ASD (n=310) were identified using Early Development Questionnaire (EDQ) scores. Whether the child ever had a clinically diagnosed infection in the first 3 years of life was reported by the child’s primary caregiver. Associations between ASD and having ever had an infection were examined using multivariable logistic regression models adjusted for child sex, birthweight and gestational age, maternal race/ethnicity and education, and number of children in the home. Associations between regressive ASD and having ever had an infection were examined using multivariable logistic regression models, adjusted for child sex and maternal race/ethnicity and education. All analyses included a random intercept for enrollment site.
Results:
At least one clinically diagnosed infection in the first 3 years of life was reported for 51.5% of children with ASD, 40.3% of POP controls and 49.2% of DD controls; 34.6%, 33.4% and 37.2% of ASD, POP, and DD children, respectively, had more than one such infection. The odds of ever having had a clinically diagnosed infection were 1.6 times higher in ASD cases compared to POP controls (adjusted OR [aOR] = 1.6 [95% CI: 1.3, 2.0]). ASD cases and DD controls did not differ in their odds of ever having a clinically diagnosed infection before the age of 3 (aOR = 1.9 [0.9, 1.4]).
Among ASD cases, 50.9% of those with regressive ASD had ever had an infection compared to 53.9% of those with non-regressive ASD, while 33.1% and 37.1% of regressive ASD cases and non-regressive ASD cases, respectively, had more than one infection in the first 3 years of life. Those with regressive ASD did not differ in their odds of ever having an infection compared to those without non-regressive ASD (aOR = 1.2 [0.9, 1.6]).
Conclusions:
These results support earlier reports of greater infectious disease risk in children with ASD, but the risk does not appear to be unique to ASD overall, or regressive ASD specifically. An increased risk for childhood infections may be a shared feature among children with adverse neurodevelopmental outcomes.