Neonates with hypoxic-ischemic encephalopathy treated with hypothermia: Observations in a large Canadian population and determinants of death and/or brain injury

Article type: Research Article

Authors: Xu, E.H.^a | Claveau, M.^a | Yoon, E.W.^b | Barrington, K.J.^c | Mohammad, K.^d | Shah, P.S.^{b; e} | Wintermark, P.^{a; *} | Canadian Neonatal Network

Collaborators: Shah, Prakesh S | Kanungo, Jaideep | Ting, Joseph | Cieslak, Zenon | Sherlock, Rebecca | Yee, Wendy | Toye, Jennifer | Fajardo, Carlos | Kalapesi, Zarin | Sankaran, Koravangattu | Daspal, Sibasis | Seshia, Mary | Alvaro, Ruben | Mukerji, Amit | Da Silva, Orlando | Nwaesei, Chuks | Lee, Kyong-Soon | Dunn, Michael | Lemyre, Brigitte | Dow, Kimberly | Pelausa, Ermelinda | Barrington, Keith | Lapoint, Anie | Drolet, Christine | Piedboeuf, Bruno | Claveau, Martine | Beltempo, Marc | Bertelle, Valerie | Masse, Edith | Canning, Roderick | Makary, Hala | Ojah, Cecil | Monterrosa, Luis | Emberley, Julie | Afifi, Jehier | Kajetanowicz, Andrzej | Lee, Shoo K

Affiliations: Mount Sinai Hospital, Toronto, Ontario | Victoria General Hospital, Victoria, British Columbia | B.C. Women’s Hospital and Health Centre, Vancouver, British Columbia | Royal Columbian Hospital, New Westminster, British Columbia | Surrey Memorial Hospital, Surrey, British Columbia | Foothills Medical Centre, Calgary, Alberta | Royal Alexandra Hospital, Edmonton, Alberta | Alberta Children’s Hospital, Calgary, Alberta | Regina General Hospital, Regina, Saskatchewan | Royal University Hospital, Saskatoon, Saskatchewan | Winnipeg Health Sciences Centre, Winnipeg, Manitoba | St. Boniface General Hospital, Winnipeg, Manitoba | Hamilton Health Sciences Centre, Hamilton, Ontario | London Health Sciences Centre, London, Ontario | Windsor Regional Hospital, Windsor, Ontario | Hospital for Sick Children, Toronto, Ontario | Sunnybrook Health Sciences Centre, Toronto, Ontario | Children’s Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario | Kingston General Hospital, Kingston, Ontario | Jewish General Hospital, Montréal, Québec | Hôpital Sainte-Justine, Montréal, Québec | Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec | Montreal Children’s Hospital at McGill University Health Centre, Montréal, Québec | Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec | Moncton Hospital, Moncton, New Brunswick | Dr. Everett Chalmers Hospital, Fredericton, New Brunswick | Saint John Regional Hospital, Saint John, New Brunswick | Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland | IWK Health Centre, Halifax, Nova Scotia | Cape Breton Regional Hospital, Sydney, Nova Scotia | (Chairman, Canadian Neonatal Network), Mount Sinai Hospital, Toronto, Ontario | [a] Department of Pediatrics, Division of Newborn Medicine, Montreal Children’s Hospital, McGill University, Montreal, Québec, Canada | [b] Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada | [c] Department of Pediatrics, Division of Neonate Medicine, University of Montreal, Montreal, Québec, Canada | [d] Department of Pediatrics, Division of Neonatology, University of Calgary, Calgary, Canada | [e] Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada | Mount Sinai Hospital, Toronto, Ontario | Victoria General Hospital, Victoria, British Columbia | B.C. Women’s Hospital and Health Centre, Vancouver, British Columbia | Royal Columbian Hospital, New Westminster, British Columbia | Surrey Memorial Hospital, Surrey, British Columbia | Foothills Medical Centre, Calgary, Alberta | Royal Alexandra Hospital, Edmonton, Alberta | Alberta Children’s Hospital, Calgary, Alberta | Regina General Hospital, Regina, Saskatchewan | Royal University Hospital, Saskatoon, Saskatchewan | Winnipeg Health Sciences Centre, Winnipeg, Manitoba | St. Boniface General Hospital, Winnipeg, Manitoba | Hamilton Health Sciences Centre, Hamilton, Ontario | London Health Sciences Centre, London, Ontario | Windsor Regional Hospital, Windsor, Ontario | Hospital for Sick Children, Toronto, Ontario | Sunnybrook Health Sciences Centre, Toronto, Ontario | Children’s Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario | Kingston General Hospital, Kingston, Ontario | Jewish General Hospital, Montréal, Québec | Hôpital Sainte-Justine, Montréal, Québec | Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec | Montreal Children’s Hospital at McGill University Health Centre, Montréal, Québec | Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec | Moncton Hospital, Moncton, New Brunswick | Dr. Everett Chalmers Hospital, Fredericton, New Brunswick | Saint John Regional Hospital, Saint John, New Brunswick | Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland | IWK Health Centre, Halifax, Nova Scotia | Cape Breton Regional Hospital, Sydney, Nova Scotia | (Chairman, Canadian Neonatal Network), Mount Sinai Hospital, Toronto, Ontario

Correspondence: [*] Address for correspondence: Pia Wintermark, Montreal Children’s Hospital, Division of Neonate Medicine, Research Institute of the McGill University Health Centre, 1001boul. Décarie, Site Glen Block E, EM0.3244, Montréal, QC H4A 3J1, Canada. Tel.: (514) 412 4452; Fax: (514) 412 4356; E-mail: pia.wintermark@gmail.com.

Note: [1] A complete list of the Canadian Neonatal Network Investigators appears in the Supplementary Information.

Abstract: BACKGROUND:Birth asphyxia in term neonates remains a serious condition that causes significant mortality and long-term neurodevelopmental sequelae despite hypothermia treatment. The objective of this study was to review therapeutic hypothermia practices in a large population of neonates with hypoxic-ischemic encephalopathy (HIE) across Canada and to identify determinants of adverse outcome. METHODS:Our retrospective observational cohort study examined neonates≥36 weeks, admitted to the Canadian Neonatal Network NICUs between 2010 and 2014, diagnosed with HIE, and treated with hypothermia. Adverse outcome was defined as death and/or brain injury. Maternal, birth, and postnatal characteristics were compared between neonates with adverse outcome and those without. The association between the variables which were significantly different (p < 0.05) between the two groups and adverse outcome were further tested, while adjusting for gestational age, birth weight, gender, and initial severity of encephalopathy. RESULTS:A total of 2187 neonates were admitted for HIE; 52% were treated with hypothermia and 40% developed adverse outcome. Initial severity of encephalopathy (moderate, p = 0.006; severe, p < 0.0001), hypotension treated with inotropes (p = 0.001), and renal failure (p = 0.007) were significantly associated with an increased risk of death and/or brain injury. CONCLUSIONS:In asphyxiated neonates treated with hypothermia, not only their initial severity of encephalopathy on admission, but also their cardiac and renal complications during the first days after birth were significantly associated with risk of death and/or brain injury. Careful monitoring and cautious management of these complications is warranted.

Keywords: Birth asphyxia, hypoxic-ischemic encephalopathy, brain injury, magnetic resonance imaging

DOI: 10.3233/NPM-190368

Journal: Journal of Neonatal-Perinatal Medicine, vol. 13, no. 4, pp. 449-458, 2020