ORIGINAL ARTICLE The incidence, risk and functional outcomes of intracranial haemorrhage in children with inherited bleeding disorders at one haemophilia center M. BLADEN,* E. MAIN, † 1 K. KHAIR,* N. HUBERT,* E. KOUTOUMANOU † and R. LIESNER* *Great Ormond Street Hospital for Children NHS Foundation Trust, Haemophilia Centre; and †Institute of Child Health, University College London, London, UK Introduction: Intracranial haemorrhage (ICH) is the most serious bleeding event for patients with inherited bleeding disorders (IBD). The risks and long-term consequences remain unknown. Aim: This single-centre service evaluation aimed to identify the incidence, risks and long-term outcomes following ICH in patients with IBD. Methods: The IBD database and medical notes between 1987 and 2013 were reviewed. Children without apparent neurological deficit following ICH completed standardized assessments and supplementary information sheets. Results: ICH was confirmed in 38/1111 children with IBD. The overall risk of ICH amongst children with IBD was 3.4% (95% CI: 2.5, 4.7%). However, 27/38 had an ICH in the first year of life, 18 of which were in the neonatal period. In children with IBD who had an ICH, the risks of ICH in the neonatal period or first year of life were 18/38 (47%) (95% CI: 32, 63%) and 27/38 (71%) (95% CI: 55, 83%) respectively. Mortality risk from ICH in children with an IBD was 5/38 (13%) (95% CI: 5.8, 27.3 %). Ten of 32 survivors had known neurological sequelae including motor disorder deficits (MDD) while 22 had no documented evidence of neurological impairment or MDD. Re-evaluation was possible in 17/22 children, 8 of whom demonstrated evidence of MDD. After re-evaluation, the risk of significant neurological MDD from ICH increased from 31% CI (95% CI: 18, 49%) to 56% CI (95% CI: 39, 72%). Conclusion: Risks and consequences of ICH in IBD were highest within the neonatal period and first year of life. MDD after ICH was not reliably identified in early life and ongoing monitoring in the first decade of life will facilitate educational support or physical rehabilitation. Keywords: children, inherited bleeding disorder, intracranial haemorrhage, neonates, outcomes Introduction An intracranial haemorrhage (ICH) is the most serious type of bleeding event for patients with inherited bleeding disorders (IBD). While prophylactic factor replacement therapy has significantly reduced ICH events in these patients [1], the perinatal period remains a high risk time for newborns with severe IBDs because it precedes diagnosis in some cases and prophylaxis in all cases. While haemarthrosis remains the most common significant bleeding occurrence in IBD, ICH is responsible for the most deaths [2,3]. The long-term functional, cognitive and behavioural conse- quences in survivors of ICH impact on quality of life [4–9]. Patients with haemophilia are at greater risk of ICH than the general population [4,10,11], with the preva- lence of ICH in haemophilia being estimated at 3.5– 4.0%. However the true prevalence of ICH is likely to be underestimated, as asymptomatic babies with ICH may not be investigated or reported [11,12]. Risk fac- tors for ICH in infants with haemophilia may include: unknown carrier status, prematurity, traumatic birth history and negative family history (FH) [13–16]. Pub- lished figures of mortality resulting from ICH in hae- mophilia have been as high as 20%, with more recent estimates of 2.5% [3,10,17]. Given that 30% of all patients with haemophilia may have no FH, mortality rates from perinatal ICH in haemophilia may be underestimated if the correct testing is not done prior to demise of an affected baby. Publications related to ICH in patients with IBDs are mainly case studies Correspondence: Melanie Bladen, Haemophilia Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Tel.: +44207 7626778; fax: +44207 8298872; e-mail: melanie.bladen@gosh.nhs.uk 1 Joint first authorship. Accepted after revision 8 February 2016 © 2016 John Wiley & Sons Ltd 1 Haemophilia (2016), 1–8 DOI: 10.1111/hae.12938