{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:27:00Z","timestamp":1778840820595,"version":"3.51.4"},"reference-count":61,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hemostasis is a dynamic process that starts in utero. Neonates, especially those who are born preterm, are at high risk of bleeding. The coagulation system evolves with age, and the decreased levels of coagulation factors along with hypo-reactive platelets are counterbalanced with increased activity of von Willebrand factor, high hematocrit and mean corpuscular volume as well as low levels of coagulation inhibitors that promote hemostasis. Neonates with congenital bleeding disorders such as hemophilia are at even higher risk of bleeding complications. This review will focus upon one of the most devastating complications associated with neonatal bleeding: intracranial hemorrhages (ICH). While etiology may be multifactorial and impacted by maternal as well as fetal risk factors, the mode of delivery certainly plays an important role in the pathogenesis of ICH. We will address prematurity and congenital bleeding disorders such as hemophilia A and B and other rare bleeding disorders as risk factors and present an updated approach for treatment and possible prevention.<\/jats:p>","DOI":"10.1055\/s-0042-1756195","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:47:41Z","timestamp":1663282061000},"page":"409-415","source":"Crossref","is-referenced-by-count":8,"title":["Intracranial Hemorrhages in Neonates: Incidence, Risk Factors, and Treatment"],"prefix":"10.1055","volume":"49","author":[{"given":"Nadine G.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis and Department of Pediatric Hematology and Oncology, Sk\u00e5ne University Hospital, Malm\u00f6\/Lund, Sweden"},{"name":"Department of Clinical Sciences, Lund University, Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gili","family":"Kenet","sequence":"additional","affiliation":[{"name":"National Hemophilia Center, Institute of Thrombosis and Hemostasis and the Amalia Biron Research Institute, Sheba Medical Center, Tel-Hashomer, Israel"},{"name":"Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"issue":"03","key":"ref1","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1182\/blood.V88.3.900.900","article-title":"Evolution of blood coagulation activators and inhibitors in the healthy human fetus","volume":"88","author":"P Reverdiau-Moalic","year":"1996","journal-title":"Blood"},{"issue":"05","key":"ref2","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1182\/blood.V72.5.1651.1651","article-title":"Development of the human coagulation system in the healthy premature infant","volume":"72","author":"M Andrew","year":"1988","journal-title":"Blood"},{"issue":"02","key":"ref3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.blre.2009.12.001","article-title":"Hemostasis in neonates and children: pitfalls and dilemmas","volume":"24","author":"P Monagle","year":"2010","journal-title":"Blood Rev"},{"issue":"06","key":"ref4","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1016\/j.thromres.2015.10.034","article-title":"Differences in the mechanism of blood clot formation and nanostructure in infants and children compared with adults","volume":"136","author":"V Ignjatovic","year":"2015","journal-title":"Thromb Res"},{"issue":"01","key":"ref5","first-page":"9","article-title":"Age dependency for coagulation parameters in paediatric populations. Results of a multicentre study aimed at defining the age-specific reference ranges","volume":"116","author":"P Toulon","year":"2016","journal-title":"Thromb Haemost"},{"issue":"08","key":"ref6","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1182\/blood.V80.8.1998.1998","article-title":"Maturation of the hemostatic system during childhood","volume":"80","author":"M Andrew","year":"1992","journal-title":"Blood"},{"issue":"05","key":"ref7","first-page":"266","article-title":"Comparison of human normal, full-term, fetal and adult plasminogen by physical and chemical analyses","volume":"19","author":"L Summaria","year":"1989","journal-title":"Haemostasis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"627715","DOI":"10.3389\/fped.2021.627715","article-title":"Hemostatic challenges in neonates","volume":"9","author":"P Davenport","year":"2021","journal-title":"Front Pediatr"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.bcmd.2016.11.012","article-title":"Developmental hemostasis: a lifespan from neonates and pregnancy to the young and elderly adult in a European white population","volume":"67","author":"U Nowak-G\u00f6ttl","year":"2017","journal-title":"Blood Cells Mol Dis"},{"issue":"02","key":"ref10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1160\/TH09-05-0282","article-title":"Clot formation of neonates tested by thromboelastography correlates with gestational age","volume":"103","author":"T Strauss","year":"2010","journal-title":"Thromb Haemost"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bcmd.2016.12.013","article-title":"Activity of Von Willebrand factor and levels of VWF-cleaving protease (ADAMTS-13) in preterm and full term neonates","volume":"67","author":"T Strauss","year":"2017","journal-title":"Blood Cells Mol Dis"},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/MBC.0b013e32835975d6","article-title":"Diagnosis and treatment of intracranial hemorrhage in children with hemophilia","volume":"24","author":"K Nagel","year":"2013","journal-title":"Blood Coagul Fibrinolysis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e590","DOI":"10.1542\/peds.111.5.e590","article-title":"Risk factors for intraventricular hemorrhage in very low birth weight premature infants: a retrospective case-control study","volume":"111","author":"N Linder","year":"2003","journal-title":"Pediatrics"},{"issue":"02","key":"ref14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/2249-4847.134674","article-title":"A systematic review and meta-analysis of the timing of early intraventricular hemorrhage in preterm neonates: clinical and research implications","volume":"3","author":"S Y Al-Abdi","year":"2014","journal-title":"J Clin Neonatol"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1542\/peds.2013-0372","article-title":"Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants","volume":"133","author":"S Bolisetty","year":"2014","journal-title":"Pediatrics"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"e20201584","DOI":"10.1542\/peds.2020-1584","article-title":"Survival of ventilated extremely premature neonates with severe intraventricular hemorrhage","volume":"147","author":"K E McCauley","year":"2021","journal-title":"Pediatrics"},{"issue":"04","key":"ref17","doi-asserted-by":"crossref","first-page":"389.e1","DOI":"10.1016\/j.ajog.2020.09.043","article-title":"Epidemiology of coronavirus disease 2019 in pregnancy: risk factors and associations with adverse maternal and neonatal outcomes","volume":"224","author":"J S Brandt","year":"2021","journal-title":"Am J Obstet Gynecol"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1001\/jamapediatrics.2016.4151","article-title":"clinical characteristics, risk factors, and outcomes associated with neonatal hemorrhagic stroke: a population-based case-control study","volume":"171","author":"L Cole","year":"2017","journal-title":"JAMA Pediatr"},{"issue":"23","key":"ref19","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1056\/NEJM199912023412301","article-title":"Effect of mode of delivery in nulliparous women on neonatal intracranial injury","volume":"341","author":"D Towner","year":"1999","journal-title":"N Engl J Med"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0022-3476(85)80656-9","article-title":"Vitamin K in infancy","volume":"106","author":"P A Lane","year":"1985","journal-title":"J Pediatr"},{"issue":"03","key":"ref21","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1055\/s-2007-1000653","article-title":"Vitamin K deficiency bleeding in infants and children","volume":"21","author":"A H Sutor","year":"1995","journal-title":"Semin Thromb Hemost"},{"issue":"10","key":"ref22","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3324\/haematol.2018.209619","article-title":"Mode of delivery in hemophilia: vaginal delivery and Cesarean section carry similar risks for intracranial hemorrhages and other major bleeds","volume":"104","author":"N G Andersson","year":"2019","journal-title":"Haematologica"},{"issue":"04","key":"ref23","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1111\/j.1365-2141.2007.06949.x","article-title":"Intracranial haemorrhage in haemophilia A and B","volume":"140","author":"R C Ljung","year":"2008","journal-title":"Br J Haematol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/hae.12726","article-title":"Mode of delivery and cranial bleeding in newborns with haemophilia: a systematic review and meta-analysis of the literature","volume":"22","author":"J Davies","year":"2016","journal-title":"Haemophilia"},{"issue":"02","key":"ref25","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/j.1365-2141.2010.08469.x","article-title":"Associations between intracranial haemorrhage and prescribed prophylaxis in a large cohort of haemophilia patients in the United States","volume":"152","author":"C Witmer","year":"2011","journal-title":"Br J Haematol"},{"issue":"02","key":"ref26","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1111\/bjh.14844","article-title":"Intracranial haemorrhage in children and adolescents with severe haemophilia A or B - the impact of prophylactic treatment","volume":"179","author":"N G Andersson","year":"2017","journal-title":"Br J Haematol"},{"issue":"02","key":"ref27","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/hae.13081","article-title":"Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System","volume":"23","author":"R Kulkarni","year":"2017","journal-title":"Haemophilia"},{"issue":"04","key":"ref28","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/hae.13461","article-title":"Intracranial haemorrhage in children with inherited bleeding disorders in the UK 2003-2015: a national cohort study","volume":"24","author":"E A Chalmers","year":"2018","journal-title":"Haemophilia"},{"issue":"01","key":"ref29","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1111\/j.1365-2516.2006.01397.x","article-title":"Prevalence of sporadic and familial haemophilia","volume":"13","author":"C K Kasper","year":"2007","journal-title":"Haemophilia"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1111\/j.1365-2516.2011.02742.x","article-title":"Prenatal diagnosis for haemophilia: a nationwide survey among female carriers in the Netherlands","volume":"18","author":"D M Balak","year":"2012","journal-title":"Haemophilia"},{"issue":"02","key":"ref31","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1111\/j.1365-2141.2010.08545.x","article-title":"Guideline on the management of haemophilia in the fetus and neonate","volume":"154","author":"E Chalmers","year":"2011","journal-title":"Br J Haematol"},{"issue":"02","key":"ref32","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1055\/a-1141-1252","article-title":"Perinatal management of haemophilia","volume":"40","author":"W Streif","year":"2020","journal-title":"Hamostaseologie"},{"issue":"02","key":"ref33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1365-2516.2005.01072.x","article-title":"Management of neonates with inherited bleeding disorders\u2014survey of current UK practice","volume":"11","author":"E A Chalmers","year":"2005","journal-title":"Haemophilia"},{"issue":"02","key":"ref34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s00431-004-1542-6","article-title":"Haemophilia A in two premature infants","volume":"164","author":"C Bidlingmaier","year":"2005","journal-title":"Eur J Pediatr"},{"issue":"06","key":"ref35","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3109\/14767058.2013.825600","article-title":"Haemophilia in extreme immature preterm infants: increased risk for intracranial haemorrhage?","volume":"27","author":"S Fink","year":"2014","journal-title":"J Matern Fetal Neonatal Med"},{"issue":"S 09","key":"ref36","doi-asserted-by":"crossref","first-page":"29S","DOI":"10.1177\/1076029618807583","article-title":"A Practical Guide to the Management of the Fetus and Newborn With Hemophilia","volume":"24","author":"P C Moorehead","year":"2018","journal-title":"Clin Appl Thromb Hemost"},{"issue":"04","key":"ref37","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00043426-199907000-00009","article-title":"Intracranial and extracranial hemorrhages in newborns with hemophilia: a review of the literature","volume":"21","author":"R Kulkarni","year":"1999","journal-title":"J Pediatr Hematol Oncol"},{"issue":"02","key":"ref38","doi-asserted-by":"crossref","first-page":"e101","DOI":"10.1111\/bjh.16740","article-title":"Long-term follow-up of neonatal intracranial haemorrhage in children with severe haemophilia","volume":"190","author":"N G Andersson","year":"2020","journal-title":"Br J Haematol"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/MPH.0b013e31815b4c92","article-title":"Intracranial hemorrhage in newborns with hemophilia: the role of screening radiologic studies in the first 7 days of life","volume":"30","author":"A R Smith","year":"2008","journal-title":"J Pediatr Hematol Oncol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.pediatrneurol.2017.03.012","article-title":"Universal head ultrasound screening in full-term neonates: a retrospective analysis of 6771 infants","volume":"71","author":"E Ballardini","year":"2017","journal-title":"Pediatr Neurol"},{"issue":"03","key":"ref41","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1055\/s-0037-1604109","article-title":"Intracranial hemorrhage: a devastating outcome of congenital bleeding disorders-prevalence, diagnosis, and management, with a special focus on congenital factor XIII deficiency","volume":"44","author":"S ER Alavi","year":"2018","journal-title":"Semin Thromb Hemost"},{"issue":"05","key":"ref42","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1111\/j.1365-2516.2008.01814.x","article-title":"Intracranial haemorrhage in patients with congenital haemostatic defects","volume":"14","author":"P Mishra","year":"2008","journal-title":"Haemophilia"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jpeds.2018.04.020","article-title":"Incidence trends and risk factor variation in severe intraventricular hemorrhage across a population based cohort","volume":"200","author":"S C Handley","year":"2018","journal-title":"J Pediatr"},{"issue":"11","key":"ref44","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1111\/jth.13130","article-title":"Coagulation indices in very preterm infants from cord blood and postnatal samples","volume":"13","author":"E Neary","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"04","key":"ref45","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.tmrv.2016.07.001","article-title":"Neonatal plasma transfusion: an evidence-based review","volume":"30","author":"A K Keir","year":"2016","journal-title":"Transfus Med Rev"},{"issue":"02","key":"ref46","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/jp.2008.141","article-title":"Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system","volume":"29","author":"S E Wiedmeier","year":"2009","journal-title":"J Perinatol"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1203\/00006450-199004000-00004","article-title":"Deficient collagen-induced activation in the newborn platelet","volume":"27","author":"S J Israels","year":"1990","journal-title":"Pediatr Res"},{"issue":"01","key":"ref48","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1542\/peds.2007-2850","article-title":"Platelet transfusion practices among neonatologists in the United States and Canada: results of a survey","volume":"123","author":"C D Josephson","year":"2009","journal-title":"Pediatrics"},{"issue":"03","key":"ref49","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1056\/NEJMoa1807320","article-title":"Randomized trial of platelet-transfusion thresholds in neonates","volume":"380","author":"A Curley","year":"2019","journal-title":"N Engl J Med"},{"issue":"02","key":"ref50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s00431-008-0856-1","article-title":"Vitamin K, an update for the paediatrician","volume":"168","author":"M Van Winckel","year":"2009","journal-title":"Eur J Pediatr"},{"issue":"06","key":"ref51","doi-asserted-by":"crossref","first-page":"e273","DOI":"10.1111\/apa.12598","article-title":"Intracranial haemorrhage is linked to late onset vitamin K deficiency in infants aged 2-24 weeks","volume":"103","author":"M S Elalfy","year":"2014","journal-title":"Acta Paediatr"},{"issue":"03","key":"ref52","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1055\/s-0037-1614494","article-title":"Vitamin K deficiency bleeding (VKDB) in infancy","volume":"81","author":"A H Sutor","year":"1999","journal-title":"Thromb Haemost"},{"issue":"05","key":"ref53","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1111\/j.1365-2516.2012.02810.x","article-title":"Continuous infusion in haemophilia: current practice in Europe","volume":"18","author":"A Batorova","year":"2012","journal-title":"Haemophilia"},{"issue":"02","key":"ref54","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1111\/hae.14485","article-title":"Emicizumab in previously untreated and minimally treated infants","volume":"28","author":"E Hassan","year":"2022","journal-title":"Haemophilia"},{"issue":"16","key":"ref55","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1182\/blood.2020009217","article-title":"Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies","volume":"137","author":"M U Callaghan","year":"2021","journal-title":"Blood"},{"issue":"11","key":"ref56","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1182\/blood-2006-11-056291","article-title":"Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study","volume":"109","author":"S C Gouw","year":"2007","journal-title":"Blood"},{"issue":"20","key":"ref57","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1182\/blood-2012-09-457036","article-title":"Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study","volume":"121","author":"S C Gouw","year":"2013","journal-title":"Blood"},{"issue":"03","key":"ref58","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1111\/j.1365-2516.2007.01449.x","article-title":"A systematic approach to controlling problem bleeds in patients with severe congenital haemophilia A and high-titre inhibitors","volume":"13","author":"J Teitel","year":"2007","journal-title":"Haemophilia"},{"issue":"02","key":"ref59","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/j.1365-2516.2011.02612.x","article-title":"On-demand treatment of bleeds in haemophilia patients with inhibitors: strategies for securing and maintaining predictable efficacy with recombinant activated factor VII","volume":"18","author":"B S\u00f8rensen","year":"2012","journal-title":"Haemophilia"},{"key":"ref60","first-page":"CD004454","article-title":"Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth","volume":"12","author":"E McGoldrick","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"issue":"19","key":"ref61","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1080\/14767058.2020.1836148","article-title":"Delayed cord clamping for prevention of intraventricular hemorrhage in preterm neonates: a randomized control trial","volume":"35","author":"F Hemmati","year":"2022","journal-title":"J Matern Fetal Neonatal Med"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0042-1756195.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T23:29:01Z","timestamp":1683329341000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0042-1756195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":61,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2023,5,5]]},"published-print":{"date-parts":[[2023,6]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0042-1756195","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"value":"0094-6176","type":"print"},{"value":"1098-9064","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]}}}