The Complex Interplay of Adverse Prenatal and Neonatal Events, Genetic Predisposition, and Autism Spectrum Disorder: A Retrospective Analysis.

Researchers studied 77 children with severe autism to understand how genetics and pregnancy/birth complications work together. They found that over half the children had genetic changes, and those with genetic differences also had more complications during pregnancy and birth. Problems like low birth weight, jaundice, and early brain issues were more common in children with genetic changes. This suggests that genetics and birth complications may combine to increase autism risk.

This retrospective study of 77 children with Level 3 ASD from Sicily examined the relationship between genetic factors and prenatal/perinatal complications. The research found that 54.5% of children had positive genetic findings (chromosomal copy number variations or single-gene variants). All participants had at least one prenatal risk factor, with 48.1% experiencing postnatal complications. Children with genetic abnormalities, particularly those with chromosomal copy number variations, showed significantly higher numbers of prenatal and neonatal risk factors.

Low birth weight, hyperbilirubinemia, and early neurological complications were strongly associated with genetic findings. The study suggests a complex interplay between genetic predisposition and environmental factors in severe autism.

Findings support early genetic screening in children with severe autism, particularly those with multiple prenatal/perinatal complications. The study suggests integrating genetic testing with environmental risk assessment for comprehensive evaluation. Early identification may enable targeted interventions, though specific intervention recommendations require further research.

Single-center retrospective design limits generalizability. Small sample size of 77 children. Focus only on Level 3 ASD may not apply to milder autism presentations. Retrospective medical record review may have incomplete data.

To evaluate the interplay of genetic predispositions and prenatal, perinatal, and postnatal risk factors in children with Level 3 Autism Spectrum Disorder (ASD). This retrospective study included 77 children with Level 3-ASD from a Sicilian pediatric cohort. We systematically reviewed medical records to assess prenatal, perinatal, and postnatal risk factors, alongside genetic findings. Genetic testing included chromosomal microarray and next-generation sequencing for the identification of pathogenic or likely pathogenic variants.

Statistical analyses were performed to evaluate the correlation between cumulative risk factors and positive genetic findings, focusing on the role of chromosomal copy number variations (CNVs) and point mutations. Of the 77 children included, 54.5% showed a positive genetic finding, including CNVs or pathogenic single-gene variants. All patients had at least one prenatal risk factor, while postnatal complications were present in 48.1%. CNV carriers exhibited a significantly higher burden of both prenatal (mean = 6.70) and neonatal (mean = 2.40) risk factors compared to other groups (P < 0.001).

Genetically positive patients had a significantly higher cumulative risk factor load than genetically negative ones (P = 0.0006). Low birth weight, hyperbilirubinemia, and early neurological comorbidities were significantly associated with genetic findings (odds ratio = 10.0, 7.1, and 12.0, respectively). No single risk factor significantly differentiated CNV from single-gene cases. LASSO regression identified neurological comorbidities, hyperbilirubinemia, cesarean delivery, and hypoglycemia as independent predictors of genetic positivity.

Overall, genetic predisposition correlated with increased perinatal and neonatal complications. This study highlights the multifactorial nature of ASD and supports integrating genetic and environmental assessments into early diagnostic strategies. Early genetic screening and targeted interventions in infants with multiple risk factors may aid in reducing ASD risk and improving outcomes.