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

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 and 22,993,128 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-minute Apgar 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.