Neonatal risk factors associated with autism spectrum disorders: an umbrella review

Abstract

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by severe social communication deficits and stereotypical repetitive behaviors.Purpose: This umbrella review assessed neonatal risk factors associated with ASD using meta-analyses and systematic reviews.Methods: We conducted a systematic search of interna- tional databases including PubMed, Scopus, and Web of Science for studies published through April 2022 utilizing pertinent keywords. A random-effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI). Substantial heterogeneity was considered at values of I2≥50%. A quality assessment of the included studies was performed using the A MeaSurement Tool to Assess Systematic Reviews (AMSTAR2) checklist.Results: A total of 207,221 children with ASD and22,993,128 neurotypical children were included. Six meta- analyses were included in this umbrella review. The factors of congenital heart disease (OR, 1.35; 95% CI, 1.17–1.52),macrosomia (OR, 1.11; 95% CI, 1.05–1.18), low birth weight (OR, 1.63; 95% CI, 1.48–1.81), very low birth weight (OR, 2.25; 95% CI, 1.79–2.83), small for gestational age (OR,1.17; 95% CI, 1.09–1.24), jaundice (OR, 1.74; 95% CI, 1.42–2.12), male sex (OR, 1.47; 95% CI, 1.39–1.55) and 1-minuteApgar score <7 (OR, 1.40; 95% CI, 1.26–1.55) were graded as suggestive evidence (class III). Only 3 studies reported heterogeneity (I2<50%). Based on the AMSTAR2 analysis, the methodological quality was critically low in 3 meta- analyses, low in 2, and moderate in 1.Conclusion: Based on these results, clinicians should consider the risk factors for ASD and screen children in clinics.