Risk of intracranial hemorrhage in neonates with hemophilia: a systematic review and meta-analysis

Abstract Background Intracranial hemorrhage (ICH) represents one of the most severe and potentially devastating complications in neonates with hemophilia. Although ICH is well recognized as a major cause of early morbidity and mortality in children with hemophilia, the true incidence during the neonatal period remains uncertain due to fragmented reporting and heterogeneous study designs. Methods We conducted a systematic review and meta-analysis to estimate the cumulative incidence of neonatal ICH in infants with hemophilia. PubMed, Embase, and Scopus were searched from inception to November 2025. Studies reporting ICH within the first 28 days of life among live-born neonates with hemophilia were eligible. Pooled incidence estimates were calculated using random-effects meta-analysis. Results Thirteen studies encompassing 5845 live-born neonates with hemophilia were included. A total of 131 neonatal ICH events were identified. The pooled cumulative incidence of neonatal ICH was 2.10% (95% CI: 1.4–2.79), with substantial between-study heterogeneity. Fatal ICH was rare, with a pooled mortality estimate of approximately 0.2% (95% CI 0.0–1.2). Conclusions Neonatal ICH in hemophilia, although uncommon, remains a clinically significant complication with potential long-term consequences. These findings highlight the importance of early diagnosis, careful perinatal management, and avoidance of traumatic delivery techniques, and the use of prophylaxis in at-risk populations. Dedicated neonatal-focused registries and prospective studies are needed to refine risk stratification and guide preventive strategies.