Objective To compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts.
Design Retrospective analysis of prospectively collected neonatal and follow-up data.
Setting Three population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2).
Patients Extremely preterm neonates of <28 weeks’ gestation in year 2011.
Main outcome measures Primary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness.
Results Overall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants’ baseline characteristics).
Conclusions Composite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.
Data availability statement
No data are available.
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Collaborators ANZNN Site Investigators: Kei Lui* Chair of ANZNN. Flinders Medical Centre, South Australia (SA): Peter Marshall. Gold Coast University Hospital, Queensland (QLD): Peter Schmidt. Blacktown District Hospital, New South Wales (NSW): Anjali Dhawan*. John Hunter Children’s Hospital, NSW: Larissa Korostenski, Javeed Travadi*. King Edward Memorial and Perth Children’s Hospitals, Western Australia (WA): Mary Sharp, Andy Gill*, Jane Pillow*. Liverpool Hospital, NSW: Jacqueline Stack. Mater Mothers' Hospital, QLD: Pita Birch, Karen Nothdurft*. Neonatal Retrieval Emergency Service Southern Queensland, QLD: Lucy Cooke*. Mercy Hospital for Women, Victoria (VIC): Dan Casalaz, Jim Holberton*. Monash Medical Centre, VIC: Alice Stewart. Nepean Hospital, NSW: Lyn Downe. Paediatric Infant Perinatal Emergency Retrieval (VIC): Michael Stewart. NSW Newborn & Paediatric Emergency Transport Service: Andrew Berry. Royal Children's Hospital, VIC: Rod Hunt*. Royal Darwin Hospital,
Northern Territory (NT): Peter Morris. Royal Hobart Hospital, Tasmania: Tony De Paoli. Royal Hospital for Women, NSW: Kei Lui* and Srinivas Bolisetty. Royal North Shore Hospital, NSW: Mary Paradisis. Royal Prince Alfred Hospital, NSW: Mark Greenhalgh. Royal Brisbane and Women's Hospital, QLD: Pieter Koorts. Royal Women's Hospital, VIC: Carl Kuschel, Sue Jacobs and Lex Doyle. SAAS MedSTAR Emergency Medical Retrieval Services: John Craven. Sydney Children's Hospital, NSW: Andrew Numa. The Canberra Hospital, ACT: Hazel Carlisle. The Children's Hospital at Westmead, NSW: Nadia Badawi and Himanshu Popat. The Townsville Hospital, QLD: Guan Koh. Neonatal Emergency Transport Service of Western Australia: Jonathan Davis. Westmead Hospital, NSW: Melissa Luig. Women's & Children's Hospital, SA: Bevan Headley and Chad Andersen*. Australian College of Neonatal Nurses: Linda Ng*. National Perinatal Epidemiology and Statistics Unit, University of New South Wales: Georgina Chambers*. New Zealand: Christchurch Women's Hospital: Nicola Austin and Adrienne Lynn. University of Otago, Christchurch: Brian Darlow. Dunedin Hospital: Liza Edmonds. Middlemore Hospital: Lindsay Mildenhall. Auckland City Hospital: Mariam Buksh and Malcolm Battin*. Waikato Hospital: Jutta van den Boom. Wellington Women's Hospital: Vaughan Richardson. Whangarei Hospital: David Barker*. Neonatal Nurses College Aotearoa: Barbara Hammond*. Singapore: KK Women's and Children's Hospital, Singapore: Victor Samuel Rajadurai*. Hong Kong: Prince of Wales Hospital: Simon Lam. United Christian Hospital: Genevieve Fung. Asterisk (*) denotes the ANZNN Executive Committee; The ANZNN Follow up Subcommittee members (regional representatives): Elizabeth Hurrion (Chair, Queensland), Peter Anderson (Developmental psychologist), Nicola Austin (New Zealand), Jeanie Cheong (Victoria), Vanessa Ellison (South Australia and Northern Territory), Mary Sharp (Western Australia) and Ingrid Rieger (New South Wales and Australian Capital Territory). Lex Doyle (Victoria) stepped down for Jeanie Cheong in 2020. CNN Site Investigators: Prakesh S Shah, MD, MSc (Director, Canadian Neonatal Network and Site Investigator), Mount Sinai Hospital, Toronto, Ontario; Marc Beltempo, MD (Associate Director, Canadian Neonatal Network and Site Investigator), Montreal Children’s Hospital at McGill University Health Centre, Montréal, Québec; Jaideep Kanungo, MD, Victoria General Hospital, Victoria, British Columbia; Joseph Ting, MD, British Columbia Women’s Hospital, Vancouver, British Columbia; Zenon Cieslak, MD, Royal Columbian Hospital, New Westminster, British Columbia; Rebecca Sherlock, MD, Surrey Memorial Hospital, Surrey, British Columbia; Ayman Abou Mehrem, MD, Foothills Medical Centre, Calgary, Alberta; Jennifer Toye, MD and Khalid Aziz, MBBS, Royal Alexandra Hospital, Edmonton, Alberta; Carlos Fajardo, MD, Alberta Children’s Hospital, Calgary, Alberta; Jaya Bodani, MD, Regina General Hospital, Regina, Saskatchewan; Lannae Strueby, MD, Royal University Hospital, Saskatoon, Saskatchewan; Mary Seshia, MBChB and Deepak Louis, MD, Winnipeg Health Sciences Centre, Winnipeg, Manitoba; Ruben Alvaro, MD, St. Boniface General Hospital, Winnipeg, Manitoba; Amit Mukerji, MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Orlando Da Silva, MD, MSc, London Health Sciences Centre, London, Ontario; Sajit Augustine, MD, Windsor Regional Hospital, Windsor, Ontario; Kyong-Soon Lee, MD, MSc, Hospital for Sick Children, Toronto, Ontario; Eugene Ng, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Brigitte Lemyre, MD, The Ottawa Hospital, Ottawa, Ontario; Thierry Daboval, MD, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Faiza Khurshid, MD, Kingston General Hospital, Kingston, Ontario; Victoria Bizgu, MD, Jewish General Hospital, Montréal, Québec; Keith Barrington, MBChB, Anie Lapointe, MD, and Guillaume Ethier, NNP, Hôpital Sainte-Justine, Montréal, Québec; Christine Drolet, MD, and Bruno Piedboeuf, MD, Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec; Martine Claveau, MSc, LLM, NNP, Montreal Children’s Hospital at McGill University Health Centre, Montréal, Québec; Marie St-Hilaire, MD, Hôpital Maisonneuve-Rosemont, Montréal, Québec; Valerie Bertelle, MD, and Edith Masse, MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec; Roderick Canning, MD, Moncton Hospital, Moncton, New Brunswick; Hala Makary, MD, Dr Everett Chalmers Hospital, Fredericton, New Brunswick; Cecil Ojah, MBBS, and Luis Monterrosa, MD, Saint John Regional Hospital, Saint John, New Brunswick; Julie Emberley, MD, Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland; Jehier Afifi, MB BCh, MSc, IWK Health Centre, Halifax, Nova Scotia; Andrzej Kajetanowicz, MD, Cape Breton Regional Hospital, Sydney, Nova Scotia; Shoo K Lee, MBBS, PhD (Chairman, Canadian Neonatal Network), Mount Sinai Hospital, Toronto, Ontario. CNFUN Site Investigators and Steering Committee: Thevanisha Pillay, MD, Victoria General Hospital, Victoria, British Columbia; Anne Synnes, MDCM, MHSC (director) and Ruth Grunau, PhD (steering committee) British Columbia Women’s Hospital, Vancouver, British Columbia; Jill Zwicker, PhD (steering committee); Rebecca Sherlock, MD, Surrey Memorial Hospital, Surrey, British Columbia; Miroslav Stavel, MD, Anitha Moodley, MD, Royal Columbian Hospital, New Westminister, British Columbia; Leonora Hendson, MB.BCH, MSc, Alberta’s Children’s Hospital, Foothills Medical Centre, Calgary, Alberta; Amber Reichert, MD, Matthew Hicks, MD, PhD, Glenrose Rehabilitation Hospital, Edmonton, Alberta; Jaya Bodani, MD, Regina General Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, Royal University Hospital, Saskatoon, Saskatchewan; Diane Moddemann, MD (steering committee), Cecilia de Cabo, MD, Winnipeg Health Sciences Centre, St. Boniface General Hospital, Winnipeg, Manitoba; Chukwuma Nwaesei, MD, Windsor Regional Hospital, Windsor, Ontario; Thierry Daboval, MD, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Sarah McKnight, MD, Kingston General Hospital, Kingston, Ontario; Kevin Coughlin, MD (steering committee), Lynn Whitty RN (steering committee), Children’s Hospital London Health Sciences Centre, London, Ontario; Linh Ly, MD, Hospital for Sick Children, Toronto, Ontario; Edmond Kelly, MD, Mount Sinai Hospital, Toronto, Ontario; Karen Thomas, MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Paige Church, MD, Rudaina Banihani MD (steering committee) Sunnybrook Health Sciences Centre, Toronto, Ontario; Ermelinda Pelausa, MD, Kim-Anh Nguyen MD, Jewish General Hospital, Montréal, Québec; May Khairy, MD, Marc Beltempo, MD, Montréal Children’s Hospital, Royal Victoria Hospital, Montréal, Québec; Veronique Dorval, MD, Thuy Mai Luu, MD, MSc (codirector), Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec; Charlotte Demers, MD, Alyssa Morin MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec; Sylvie Bélanger, MD, Centre Hospitalier Universitaire de Québec, Québec City, Québec; Roderick Canning, MD, Moncton Hospital, Moncton, New Brunswick; Luis Monterrosa, MD, Saint John Regional Hospital, Saint John, New Brunswick; Hala Makary, MD, Dr Everett Chalmers Hospital, Fredericton, New Brunswick; Jehier Afifi, MB BCh, MSc, (steering committee) IWK Health Centre, Halifax, Nova Scotia; Phil Murphy, Charles Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland. EPIPAGE-2 Study group – 2 years follow-up; Alsace: D Astruc, P Kuhn, B Langer, J Matis and C Ramousset; Aquitaine: X Hernandorena, P Chabanier, L Joly-Pedespan, M J Costedoat and A Leguen; Auvergne: B Lecomte, D Lemery and F Vendittelli; Basse-Normandie: G Beucher, M Dreyfus, B Guillois and Y Toure; Bourgogne: A Burguet, S Couvreur, J B Gouyon, P Sagot and N Colas; Bretagne: J Sizun, A Beuchée, P Pladys, F Rouget, R P Dupuy, D Soupre, F Charlot and S Roudaut; Centre: A Favreau, E Saliba and L Reboul; Champagne-Ardenne: N Bednarek, P Morville and V Verrière; Franche-Comté: G Thiriez and C Balamou; Haute-Normandie: L Marpeau, S Marret and C Barbier; Ile-de-France: G Kayem, X Durrmeyer, M Granier, M Ayoubi, O Baud, B Carbonne, L Foix L’Hélias, F Goffinet, P H Jarreau, D Mitanchez, P Boileau, C Duffaut, E Lorthe, L Cornu and R Moras; Languedoc-Roussillon: P Boulot, G Cambonie, H Daudé, A Badessi and N Tsaoussis; Limousin: A Bédu, F Mons and C Bahans; Lorraine: M H Binet, J Fresson, J M Hascoët, A Milton, O Morel, R Vieux and L Hilpert; Midi-Pyrénées: C Alberge, C Arnaud, C Vayssière and M Baron; Nord-Pas-de-Calais: M L Charkaluk, V Pierrat, D Subtil, P Truffert and S Akowanou; PACA et Corse: C D’Ercole, C Gire, U Simeoni, A Bongain and M Deschamps; Pays de Loire: B Branger, J C Rozé, N Winer, V Rouger and C Dupont; Picardie: J Gondry, G Krim and B Baby; Rhône-Alpes: M Debeir, O Claris, J C Picaud, S Rubio-Gurung, C Cans, A Ego, T Debillon, H Patural and A Rannaud; Guadeloupe: E Janky, A Poulichet, J M Rosenthal and E Coliné; Guyane: A Favre and N Joly; Martinique: S Châlons, J Pignol and P L Laurence; La Réunion: P Y Robillard, S Samperiz and D Ramful. Inserm UMR 1153: P Y Ancel, V Benhammou, B Blondel, M Bonet, A Brinis, A Coquelin, M Durox, M Kaminski, K Khemache, B Khoshnood, C Lebeaux, L Marchand-Martin, J Rousseau, M J Saurel-Cubizolles, D Tran and J Zeitlin.
Contributors All authors meet the four criteria: (1) substantial contributions to the conception or design of the work; or the acquisition, analysis or interpretation of data for the work; (2) drafting the work or revising it critically for important intellectual content; (3) final approval of the version to be published; and (4) agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors can identify which coauthors are responsible for specific other parts of the work. In addition, authors have confidence in the integrity of the contributions of their coauthors. MC conceptualised and designed the study, acquired and interpreted the data, drafted the manuscript and critically revised the manuscript for important intellectual content. JY conducted the statistical analysis, interpreted the data and critically revised the manuscript. PSS and TML conceptualised and designed the study, contributed to the statistical analysis and interpreted the data, critically revised the manuscript for important intellectual content and provided technical support and overall study supervision. TD, BAD, ARS, VP, EH, AE, PYA, and KL interpreted the study data and critically reviewed and revised the manuscript for important intellectual content.
Funding EPIPAGE-2 has been funded with support from the following organisations: The French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer and the National Solidarity Fund for Autonomy (CNSA); The National Research Agency through the French EQUIPEX program of investments in the future (ANR-11-EQPX-0038); the PREMUP Foundation; Fondation de France (00050329); Fondation pour la Recherche Médicale (SPF20160936356). The Australian and New Zealand Neonatal Network is predominantly funded by membership contributions from the participating centers. The Canadian Neonatal Network and the Canadian Neonatal Follow-Up Network are supported by the participating centers and receive organisational support from the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by a Canadian Institutes of Health Research team grant (CTP 87518), the Ontario Ministry of Health and Long-Term Care and Mount Sinai Hospital.
Disclaimer The funding bodies had no role in the design or conduct of the study; the collection, management, analysis or interpretation of the data; the preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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