The Association Between Congenital Heart Disease and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Congenital heart disease (CHD) is linked to an increased incidence of neurodevelopmental impairments in young patients. Given the number of published studies on this topic, a synthesis of the literature is timely and needed. We performed a systematic review and meta-analysis of the medical literature to assess the evidence linking CHD to incidence of autism spectrum disorder (ASD). A systematic review of studies on CHD and ASD in PubMed, Cochrane and Institute for Scientific Information (ISI) from 1965 to May 2021 was conducted. 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. We screened 2709 articles and 24 articles were included in this review. Among the 24 studies, there was a total of 348,771 subjects (12,114 CHD, 9829 ASD and 326,828 controls). Seven of 24 studies were eligible for the meta-analysis, which included information on a total of 250,611 subjects (3984 CHD, 9829 ASD, and 236,798 controls). The summary estimate indicated that having CHD is associated with almost double the odds of ASD compared with patients without CHD (OR 1.99, 95% CI 1.77-2.24, p < 0.01). Early developmental delay, perinatal factors, and genetics were potential risk factors and etiologies for the onset of ASD symptoms in CHD patients. Having CHD is associated with an increased risk of presenting with a diagnosis or symptoms suggestive of ASD.