9 Congenital Heart Disease and Autism Spectrum Disorders: Is There a Link?

Abstract Background Congenital heart disease (CHD) has been linked to an increased incidence of intellectual disability and neurodevelopmental impairments in young patients. The relationship between CHD and autism spectrum disorders (ASD) is not well investigated. Objectives We performed a systematic review and meta-analysis of the medical literature to assess the evidence linking CHD to incidence of ASD. Design/Methods A systematic review of studies on CHD and ASD in PubMed, Cochrane and ISI from 1965 to May 2021 was conducted. Only retrospective or prospective cohort, case-control and cross-sectional human studies in the English language were included. Quantitative estimates of association between CHD and ASD were extracted from eligible studies for the meta-analysis. Pooled estimates were obtained using a random effect models fit by a generalised linear mixed model. Quantitative results not included in the meta-analysis were summarized using descriptive statistics. Results We screened 2,709 articles and 24 articles were included in this review. Among the 24 studies, there was a total of 348,771 subjects (12,114 CHD, 9,829 ASD and 326,828 controls). Patient age (range of 0 to 26 years) was reported in all studies. The proportion of males in CHD, ASD and controls were 50%, 80%, and 55%. CHD diagnosis ranged from non-specific (9/16), single ventricle lesion (2/16), dextro-transposition of the great arteries (2/16), and tetralogy of Fallot (1/16). Overall, seven articles reported a 4.66 times increase in the percentage of ASD cases in patients with CHD compared to the percentage of ASD cases in the general population: (5.87% vs 1.14% of ASD cases in CHD vs the general population). Seven of 24 studies were eligible for the meta-analysis, which included information on a total of 250,611 subjects (3,984 CHD, 9,829 ASD, and 236,798 controls). The summary estimate indicated that CHD patients are associated with almost double the odds of being diagnosed with autism compared with non-CHD patients: (OR 1.99, 95% CI 1.77-2.24, p<0.01). Early developmental delay, perinatal factors, genetics and neurological development were potential risk factors and etiologies for the onset of ASD in CHD patients. Suggestions for improvement of future clinical care include early identification and treatment of ASD among the CHD population. Limitations of this study include few articles explicitly exploring the link between CHD and ASD and lack of standardized ASD endpoints. Conclusion This review outlines that CHD patients are at an increased risk of presenting with a diagnosis or symptoms suggestive of ASD.