Modified Checklist for Autism in Toddlers in a Neonatal High-Risk Population.

Abstract

Autism spectrum disorder (ASD) is a chronic neurodevelopmental condition with both genetic and environmental origins. Early detection is crucial for successful clinical intervention, improving future health, and adaptive functioning. To assess the diagnostic accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) in a neonatal high-risk population using subsequent clinical ASD diagnoses as the reference standard and to identify factors associated with the checklist's accuracy within this group. This prospective, population-based cohort study identified children born in Sweden between January 1, 2013, and December 31, 2019, from the Swedish Neonatal Quality Register. Children were included if they were screened for autism using the checklist at corrected age 16 to 30 months. Follow-up for ASD in the National Patient Register extended from the day after inclusion or chronologic age 2 years, whichever occurred last, until December 31, 2022. Data were analyzed between June 6, 2024, and June 16, 2025. Autism screening with the M-CHAT at 24-month neonatal follow-up. The primary outcome was the first recorded ASD diagnosis within the Swedish health care system among children categorized into the following neonatal high-risk groups: extremely preterm, small for gestational age, morphologic brain damage, neonatal encephalopathy, or other severe morbidity at birth. Diagnostic accuracy of the checklist was estimated using sensitivity, specificity, positive predictive value, and negative predictive value. Among the 2178 children included in the study (median [IQR] corrected age at assessment, 26 [23-30] months; 1210 boys [55.6%]), 263 (12.1%) had positive screens. The overall sensitivity of the checklist was 62.4% (95% CI, 54.3%-69.7%); specificity, 91.2% (95% CI, 90.1%-92.4%), positive predictive value 31.4% (95% CI, 26.0%-37.1%), and negative predictive value 97.4% (95% CI, 96.7%-98.0%). Within the neonatal high-risk groups, children born extremely preterm had the highest proportion of positive screens and ASD diagnoses. This cohort study found that in high-risk neonates, the M-CHAT had high specificity but moderate sensitivity when evaluated against later ASD diagnoses, highlighting the need for additional tools to improve detection.