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Abstract
Objective To assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).
Methods In this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18–24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO.
Results Of the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18–24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12).
Conclusions In preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18–24 months CA.
- intensive care units, neonatal
- neonatology
- paediatrics
- infant development
Data availability statement
Data are available upon reasonable request.
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Data availability statement
Data are available upon reasonable request.
Footnotes
Collaborators 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; Jonathan Wong, MD, British Columbia Women’s Hospital, Vancouver, British Columbia; Miroslav Stavel, 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 Joseph Ting, MD, Royal Alexandra Hospital and University of Alberta Hospital, Edmonton, Alberta; Carlos Fajardo, MD, Alberta Children’s Hospital, Calgary, Alberta; Jaya Bodani, MD, Regina General Hospital, Regina, Saskatchewan; Lannae Strueby, MD, Jim Pattison Children’s Hospital, Saskatoon, Saskatchewan; Mary Seshia, MBChB, and Deepak Louis, MD, Winnipeg Health Sciences Centre, Winnipeg, Manitoba; Ruben Alvaro, MD, and Ann Yi, 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, 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; Caio Barbosa de Oliveira, MD, Moncton Hospital, Moncton, New Brunswick; Hala Makary, MD, Dr. Everett Chalmers Hospital, Fredericton, New Brunswick; Cecil Ojah, MBBS, and Alana Newman, MD, Saint John Regional Hospital, Saint John, New Brunswick; Jo-Anna Hudson, 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; Bruno Piedboeuf, MD (Chairman, Canadian Neonatal Network), Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec. Canadian Preterm Birth Network (CPTBN) Participating Site Investigators: Leanne Dahlgren, MD, Children's & Women's Health Centre of BC, Vancouver, British Columbia; Stephen Wood, MD, Amy Metcalfe, PhD, Candace O’Quinn, MD, Foothills Medical Centre, Calgary, Alberta; Michael Helewa, MD, St. Boniface General Hospital, Winnipeg, Manitoba; Fatima Taboun, MD, Windsor Regional Hospital, Windsor, Ontario; Nir Melamed, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Haim Abenhaim, MD, Jewish General Hospital, Montréal, Québec; Karen Wou, MDCM, Rob Gratton, MD, McGill University Health Centre, Montréal, Québec; Isabelle Boucoiran, MD, MSc, Catherine Taillefer, MD, Hôpital Sainte-Justine, Montréal, Québec; Katherine Theriault, MD, Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec; Vicky Allen, MD, IWK Health Centre, Halifax, Nova Scotia. CNFUN Participating Site Investigators: Thevanisha Pillay MD, Victoria General Hospital, Victoria, British Columbia; Jessie VanDyk MD, British Columbia Children's Hospital, Vancouver, British Columbia; Rebecca Sherlock MD, Surrey Memorial Hospital, Surrey, British Columbia; Miroslav Stavel MD, Anitha Moodley MD, Royal Columbian Hospital, New Westminister, British Columbia; Leonora Hendson MD, Amina Benlamri MD, Alberta Children's Hospital/Foothills Medical Centre, Calgary, Alberta; Amber Reichert MD, Amy Shafey MD, Glenrose Rehabilitation Hospital, Edmonton, Alberta; Diane Moddemann MD MEd, Cecilia de Cabo MD, Winnipeg Health Sciences Centre, St. Boniface General Hospital, Winnipeg, Manitoba; Judy Seesahai MD, Windsor Regional Hospital, Windsor, Ontario; Sarah McKnight MD, Kingston General Hospital, Kingston, Ontario; Kevin Coughlin MD, Children's Hospital London Health Sciences Centre, London, Ontario; Linh Ly, MD, Hospital for Sick Children, Toronto, Ontario; Kamini Raghuram MD, Mount Sinai Hospital, Toronto, Ontario; Karen Thomas MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Rudaina Banihani MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Kim-Anh Nguyen MD, Jewish General Hospital, Montréal, Québec; May Khairy, MD, Jarred Garfinkle MD, Montréal Children's Hospital, Montréal, Québec; Thuy Mai Luu MD MSc,(Director), Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec; Alyssa Morin MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec; Sylvie Bélanger MD, Centre Hospitalier Universitaire de Québec, Québec City, Québec; Jehier Afifi MB BCh, MSc, (Co-director), IWK Health Centre, Halifax, Nova Scotia.
Contributors SKRGV and ASS conceptualised and designed the study, interpreted the data, drafted the initial manuscript, and critically reviewed and revised the final manuscript. ALo, MH, AJ, ALa, HM, JK, K-SL and PSS participated in the study design and data interpretation, and critically reviewed and revised the manuscript. XY participated in the study design, conducted data analysis, and interpreted data and critically reviewed and revised the final manuscript. ASS and PSS are guarantors.
Funding This study was supported by a Canadian Institutes of Health Research (CIHR) grant funding the Canadian Preterm Birth Network (PBN 150642). Organisational support for the Canadian Neonatal Network, the Canadian Preterm Birth Network, and the CNFUN was provided by the Maternal-infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by Mount Sinai Hospital, a CIHR Team Grant (CTP 87518), CIHR (SCA-145104), CHILD-BRIGHT Network funding partners, and participating hospitals.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.