Inhaled and systemic steroid exposure and neurodevelopmental outcome of preterm neonates

Abstract

Objectives: To compare death and/or neurodevelopmental outcomes of preterm infants exposed to inhaled and/or systemic steroids with those without exposure, and examine the impact of timing of exposure.

Methods: Retrospective study of infants born <29 weeks gestation and assessed at 18–21 months corrected age (CA). Neurodevelopmental impairment (NDI) was defined as any Bayley Scales of Infant and Toddler Development-III (BSID-III) score <85, cerebral palsy ≥ grade one, and visual or hearing impairment. Significant NDI (sNDI) was defined as any Bayley Scales of Infant Development (BSID-III) score <70, cerebral palsy ≥ grade three, or severe vision or hearing impairment.

Results: Of 2570 neonates, 1811 had no exposure, 125 were exposed to inhaled steroids, 522 to systemic steroids and 112 to both. Infants exposed to inhaled steroids had lower odds of bronchopulmonary dysplasia [adjusted odds ratio (AOR) 0.51, (0.33, 0.79)], and displayed no difference in death/NDI or death/significant neurodevelopmental impairment (sNDI), regardless of timing of exposure. Infants only exposed to systemic steroids before 4 weeks of age were at increased odds of death/NDI [AOR 1.83 (1.43, 2.34)] and death/sNDI [AOR 2.28 (1.76, 2.96)].

Conclusions: Exposure to inhaled steroids was not associated with increased odds of death/NDI or death/sNDI. Systemic steroids use before 4 weeks of age was associated with significantly worse outcomes.

Keywords:

• Bronchopulmonary dysplasia
• mortality
• neonates
• neurodevelopmental outcomes
• prematurity
• steroids

Acknowledgements

The authors gratefully acknowledge all site investigators of the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN). We also extend our thanks to the data abstractors of the CNN and CNFUN, as well as staff at the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital, Toronto, ON, for providing organizational, statistical, and editorial support for this project. MiCare is supported by a team grant from the Canadian Institutes of Health Research (CIHR, FRN87518, PBN150642) and in-kind support from Mount Sinai Hospital. Dr Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the CIHR (APR-126340).

Disclosure statement

No potential conflict of interest was reported by the authors, relevant to this article to disclose.

Canadian Neonatal Network Investigators

Prakesh S. Shah, MD, MSc (Director, Canadian Neonatal Network and site investigator), Mount Sinai Hospital, Toronto, Ontario; Adele Harrison, MD, MBChB, Victoria General Hospital, Victoria, British Columbia; Anne Synnes, MDCM, MHSC, and Joseph Ting, MD, BC Women’s Hospital and Health Centre, Vancouver, British Columbia; Zenon Cieslak, MD, Royal Columbian Hospital, New Westminster, British Columbia; Rebecca Sherlock, MD, Surrey Memorial Hospital, Surrey, British Columbia; Wendy Yee, MD, Foothills Medical Centre, Calgary, Alberta; Khalid Aziz, MBBS, MA, MEd, and Jennifer Toye, MD, Royal Alexandra Hospital, Edmonton, Alberta; Carlos Fajardo, MD, Alberta Children’s Hospital, Calgary, Alberta; Zarin Kalapesi, MD, Regina General Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, MBBS, and Sibasis Daspal, MD, Royal University Hospital, Saskatoon, Saskatchewan; Mary Seshia, MBChB, 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; Chuks Nwaesei, MD, Windsor Regional Hospital, Windsor, Ontario; Kyong-Soon Lee, MD, MSc, Hospital for Sick Children, Toronto, Ontario; Michael Dunn, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Brigitte Lemyre, MD, Children’s Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario; Kimberly Dow, MD, Kingston General Hospital, Kingston, Ontario; Ermelinda Pelausa, MD, Jewish General Hospital, Montréal, Québec; Keith Barrington, MBChB, Hôpital Sainte-Justine, Montréal, Québec; Christine Drolet, MD, and Bruno Piedboeuf, MD, Centre Hospitalier Universitaire de Québec, Sainte Foy Québec; Martine Claveau, NNP, LLM, MSc, and Marc Beltempo, MD, McGill University Health Centre, 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; Akhil Deshpandey, MBBS, MRCPI, 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.

Canadian Neonatal Follow-Up Network Investigators

Thevanisha Pillay, MD, Victoria General Hospital, Victoria, British Columbia; Anne Synnes, MDCM, MHSC (Director, CNFUN), B.C. Women’s Hospital and Health Centre, Vancouver, British Columbia; Reg Sauvé, MD, MPh, Leonora Hendson MBBCH, MSc, Alberta’s Children’s Hospital, Foothills Medical Centre, Calgary, Alberta; Amber Reichert, MD, Glenrose Rehabilitation Hospital, Edmonton, Alberta; Jaya Bodani, MD, Regina General Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, Royal University Hospital, Saskatoon, Saskatchewan; Diane Moddemann, MD, Winnipeg Health Sciences Centre, St. Boniface General Hospital, Winnipeg, Manitoba; Chuks Nwaesei, MD, Windsor Regional Hospital, Windsor, Ontario; Thierry Daboval, MD, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Kimberly Dow, Kingston General Hospital, Kingston, Ontario; David Lee, MD, 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; Salhab el Helou, MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Paige Church, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Ermelinda Pelausa, MD, Jewish General Hospital, Montréal, Québec; Patricia Riley, MD, Montréal Children’s Hospital, Royal Victoria Hospital, Montréal, Québec; Francine Levebrve, Centre Hospitalier Universitaire Sainte-Justine, Montréal, Québec; Charlotte Demers, 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; Michael Vincer, MD, IWK Health Centre, Halifax, Nova Scotia; Phil Murphy, Charles Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland.

Additional information

Funding

Organizational support was provided by the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, ON, Canada. MiCare is supported by team grants from the Canadian Institutes of Health Research (CIHR, FRN87518 and PBN150642) and in-kind support from Mount Sinai Hospital. Dr. P Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by CIHR (APR-126340).