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Am J Perinatol 2018; 35(10): 972-978
DOI: 10.1055/s-0038-1632390
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Association of Antibiotic Utilization and Neurodevelopmental Outcomes among Extremely Low Gestational Age Neonates without Proven Sepsis or Necrotizing Enterocolitis

Joseph Y. Ting
1   Department of Pediatrics, University of British Columbia, Vancouver, Canada
,
Anne Synnes
1   Department of Pediatrics, University of British Columbia, Vancouver, Canada
,
Ashley Roberts
1   Department of Pediatrics, University of British Columbia, Vancouver, Canada
,
Akhil C. Deshpandey
2   Janeway Children's Health and Rehabilitation Centre, Saint John's, Newfoundland, Canada
,
Kimberly Dow
3   Department of Pediatrics, Kingston General Hospital and Queen's University, Kingston, Ontario, Canada
,
Junmin Yang
4   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
,
Kyong-Soon Lee
4   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
5   Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
,
Shoo K. Lee
4   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
5   Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
,
Prakesh S. Shah
4   Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
5   Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
,
on behalf of the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network› Author Affiliations
Funding This work was supported by the Canadian Neonatal Network (CNN) Coordinating Centre, which is based at the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. The CNN and MiCare are supported by team grant funding from the Canadian Institutes of Health Research (FRN87518 and PBN150642). Dr. Ting receives salary support from the Investigator Grant Award by the British Columbia Children's Hospital Research Institute. Dr. Shah holds an applied research chair in Reproductive and Child Health Services and Policy Research awarded by the Canadian Institutes of Health Research (APR-126340).
Further Information

Publication History

12 October 2017

12 January 2018

Publication Date:
23 February 2018 (online)

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Abstract

Objective The objective is to evaluate the association between antibiotic utilization and neurodevelopmental outcomes at 18 to 21 months' corrected age among extremely low gestational age neonates without culture-proven sepsis or necrotizing enterocolitis (NEC).

Study Design We conducted a retrospective cohort study of infants born between April 2009 and September 2011 at <29 weeks' gestation and admitted to the neonatal intensive care units contributing data to the Canadian Neonatal Network. Multivariable analysis was performed to examine the primary composite outcome of death or significant neurodevelopmental impairment (sNDI) in infants with various antibiotic utilization rates (AURs).

Result There were 1,373 infants who fulfilled our inclusion criteria. Compared with infants in the lowest AUR quartile (Q1), those in the highest quartile (Q4) had higher odds of death or sNDI (adjusted odds ratio [AOR] = 7.44; 95% confidence interval [CI]: 4.55, 12.2) and death (AOR = 39.3; 95% CI: 16.1, 95.9).

Conclusion Our results indicate an association between high AUR and a composite outcome of death or adverse neurodevelopmental outcomes at 18 to 21 months' corrected age.

Keywords

extremely low gestational age - neonate - antibiotic - neurodevelopmental outcomes

Authors' Contributions

The first draft of this manuscript was written by Joseph Y. Ting. All authors take responsibility for the reported findings and have participated in the concept and design, analysis and interpretation of data, drafting or revising, and approval of this manuscript as submitted. No honorarium, grant, or other form of payment was given to anyone to write the manuscript.


Canadian Neonatal Network Site 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, 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; 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; Victoria Bizgu, 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, MSc, LLM, NNP, 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 C. 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.