Association between craniosynostosis and neurodevelopmental disorders: a nationwide claims database

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in children and have been increasing in recent years, the identification of risk factors and early intervention are important. Cranial deformities may be risk factors for these conditions, but the association with craniosynostosis, especially the non-syndromic form commonly seen in clinical practice, is unclear. Therefore, we examined this association using a nationwide database of 22 million people records. We conducted a retrospective cohort study using the JMDC claims database, identifying mother-child pairs born between January 2005 and March 2024 with at least three years of follow-up. Exposure was defined as a diagnosis of non-syndromic craniosynostosis (referred to as craniosynostosis), excluded syndromic such as Apert and Crouzon syndromes. Outcomes were incident ASD and ADHD classified by ICD-10 codes. Cox proportional hazard models adjusted for maternal psychiatric history and neonatal complications calculated hazard ratios (HRs), and a sibling subcohort analysis adjusted for genetic and environmental factors. Among 338,117 mother-child pairs, 1,145 children had craniosynostosis. Over a median follow-up of 6.0 years, 16,410 children were diagnosed with ASD and 7,325 ADHD. In adjusted models, craniosynostosis was associated with an increased risk of ASD (HR 2.18, 95% Confidence Interval (CI) 1.80–2.64) and ADHD (HR 2.40, 95%CI 1.77–3.24). Kaplan-Meier curves diverged from early childhood onward, and these findings persisted in sibling analyses. Craniosynostosis is significantly associated with the incidence of ASD and ADHD. Physicians and healthcare professionals should recognize cranial anomalies early and conduct careful follow-ups regarding children’s growth.