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Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?
  1. Jarred Garfinkle1,
  2. Eugene W Yoon2,
  3. Ruben Alvaro3,
  4. Chuks Nwaesei4,
  5. Martine Claveau5,
  6. Shoo K Lee1,2,6,7,8,
  7. Prakesh S Shah1,2,6,9
  8. on behalf of the Canadian Neonatal Network Investigators
    1. 1 Department of Pediatrics, University of Toronto, Toronto, Canada
    2. 2 Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
    3. 3 Department of Pediatrics and Child Health, University of Manitoba, Winnepeg, Manitoba, Canada
    4. 4 Department of Pediatrics, Windsor Regional Hospital, Windsor, Ontario, Canada
    5. 5 Department of Pediatrics, McGill University, Toronto, Ontario, Canada
    6. 6 Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
    7. 7 Department of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada
    8. 8 Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
    9. 9 Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
    1. Correspondence to Dr Prakesh S Shah, Department of Paediatrics, Mount Sinai Hospital, University Ave, Toronto, ON M5G 1X5, Canada; pshah{at}


    Objective To examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks’ gestation.

    Design A retrospective cohort study.

    Setting Data collected by the Canadian Neonatal Network.

    Patients Neonates born at <29 weeks’ gestation between January 2007 and December 2016.

    Main outcome measures We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities.

    Results Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25–28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was −0.043 (95% CI −0.071 to −0.015) and for girls was −0.012 (95% CI −0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes.

    Conclusion The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

    • neonatology
    • evidence based medicine
    • epidemiology

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    • Contributors All authors approved the manuscript for publication and are accountable for the data contained therein. JG conceptualised and designed the study, drafted the initial manuscript and reviewed and revised the manuscript. EWY conducted the initial analyses and reviewed and revised the manuscript. RA, CN, SKL and MC acted as representation for the Canadian Neonatal Network, reviewed the initial study proposal and research ethics application, contributed to the acquisition and interpretation of data and reviewed and revised the manuscript. PSS conceptualised and designed the study, reviewed the initial study proposal and research ethics application, contributed to the acquisition, analysis and interpretation of data and reviewed and critically revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

    • Funding Although no specific funding has been received for this study, organisational support for the Canadian Neonatal Network was provided by the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by Canadian Institutes of Health Research (CIHR) Team Grant (CTP 87518), the Ontario Ministry of Health and individual participating centres. Dr Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the CIHR (APR-126340).

    • Disclaimer The funding agencies had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.

    • Competing interests None declared.

    • Ethics approval Data collection and transmission was approved by the research ethics board at Mount Sinai Hospital (#09–0278-D), the Executive Committee of the CNN and either the research ethics board or hospital quality improvement committees at each site.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Collaborators Canadian Neonatal Network (CNN) Investigators: Prakesh S Shah, MD, MSc (Director, Canadian Neonatal Network and site investigator), Mount Sinai Hospital, Toronto, Ontario; Jaideep Kanungo, MD, Victoria General Hospital, Victoria, British Columbia; Joseph Ting, MD, B.C. 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; 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, and Anie Lapoint, MD, 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, and Marc Beltempo, MD, Montreal Children’s Hospital at 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; 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.

    • Patient consent for publication Not required.