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Journal of Pediatrics, The

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Gestational Age-Dependent Variations in Effects of Prophylactic Indomethacin on Brain Injury and Intestinal Injury - 22/07/21

Doi : 10.1016/j.jpeds.2021.02.073 
Mosarrat Qureshi, FRCPC 1, Prakesh S. Shah, FRCPC 2, Dalal Abdelgadir, FRCPC 1, Xiang Y. Ye, MSc 3, Jehier Afifi, MBBCh 5, Ryan Yuen, FRCPC 1, 6, Sara Calderon Crossman, MN 1, Barbara Taylor, MN 1, Khorshid Mohammad, MD 4, Bruno Piedboeuf, FRCPC 7, Khalid Aziz, FRCPC 1, ⁎
on behalf of the

Canadian Neonatal Network investigators∗

  List of additional Canadian Neonatal Network investigators available at www.jpeds.com (Appendix).
Marc Beltempo, MD 8, Jaideep Kanungo, MD 9, Joseph Ting, MD 10, Zenon Cieslak, MD 11, Rebecca Sherlock, MD 12, Ayman Abou Mehrem, MD 13, Jennifer Toye, MD, MBBS 14, Carlos Fajardo, MD 15, Zarin Kalapesi, MD 16, Jaya Bodani, MD 16, Koravangattu Sankaran, MD, MBBS 17, Lannae Strueby, MD 17, Mary Seshia, MBChB 18, Deepak Louis, MD 18, Ruben Alvaro, MD 19, Amit Mukerji, MD 20, Orlando Da Silva, MD, MSc 21, Mohammad Adie, MD 22, Kyong-Soon Lee, MD, MSc 23, Eugene Ng, MD 24, Brigitte Lemyre, MD 25, Faiza Khurshid, MD 26, Ermelinda Pelausa, MD 27, Keith Barrington, MBChB 28, Anie Lapoint, MD 28, Guillaume Ethier, NNP 28, Christine Drolet, MD 29, Martine Claveau, MSc, LLM, NNP 30, Valerie Bertelle, MD 31, Edith Masse, MD 31, Roderick Canning, MD 32, Hala Makary, MD 33, Cecil Ojah, MBBS 34, Luis Monterrosa, MD 34, Julie Emberley, MD 35, Andrzej Kajetanowicz, MD 36, Shoo K. Lee, MBBS, PhD 37
8 Associate Director, Canadian Neonatal Network and Site Investigator, Montreal Children's Hospital at McGill University Health Centre, Montréal, Québec, Canada 
9 Victoria General Hospital, Victoria, British Columbia, Canada 
10 B.C. Women's Hospital and Health Centre, Vancouver, British Columbia, Canada 
11 Royal Columbian Hospital, New Westminster, British Columbia, Canada 
12 Surrey Memorial Hospital, Surrey, British Columbia, Canada 
13 Foothills Medical Centre, Calgary, Alberta, Canada 
14 Royal Alexandra Hospital, Edmonton, Alberta, Canada 
15 Alberta Children's Hospital, Calgary, Alberta, Canada 
16 Regina General Hospital, Regina, Saskatchewan, Canada 
17 Royal University Hospital, Saskatoon, Saskatchewan, Canada 
18 Winnipeg Health Sciences Centre, Winnipeg, Manitoba, Canada 
19 St Boniface General Hospital, Winnipeg, Manitoba, Canada 
20 Hamilton Health Sciences Centre, Hamilton, Ontario, Canada 
21 London Health Sciences Centre, London, Ontario, Canada 
22 Windsor Regional Hospital, Windsor, Ontario, Canada 
23 Hospital for Sick Children, Toronto, Ontario, Canada 
24 Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada 
25 Children's Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario, Canada 
26 Kingston General Hospital, Kingston, Ontario, Canada 
27 Jewish General Hospital, Montréal, Québec, Canada 
28 Hôpital Sainte-Justine, Montréal, Québec, Canada 
29 Centre Hospitalier Universitaire de Québec, Sainte Foy, Québec, Canada 
30 Montreal Children's Hospital at McGill University Health Centre, Montréal, Québec, Canada 
31 Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada 
32 Moncton Hospital, Moncton, New Brunswick, Canada 
33 Dr Everett Chalmers Hospital, Fredericton, New Brunswick, Canada 
34 Saint John Regional Hospital, Saint John, New Brunswick, Canada 
35 Janeway Children's Health and Rehabilitation Centre, St. John's, Newfoundland, Canada 
36 Cape Breton Regional Hospital, Sydney, Nova Scotia, Canada 
37 Chairman, Canadian Neonatal Network, Mount Sinai Hospital, Toronto, Ontario, Canada 

1 Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada 
2 Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada 
3 MiCare Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada 
4 Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada 
5 Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada 
6 Discipline of Pediatrics, Memorial University of Newfoundland, St. John's, Newfoundland, Canada 
7 Department of Pediatrics, Laval University, Quebec City, Quebec, Canada 

∗Reprint requests: Khalid Aziz, FRCPC, Department of Pediatrics, Faculty of Medicine & Dentistry, University of Alberta, DTC 5027, 10240 Kingsway Ave, Edmonton, Alberta, T5H 3V9, Canada.Department of PediatricsFaculty of Medicine & DentistryUniversity of AlbertaDTC 5027, 10240 Kingsway AveEdmontonAlbertaT5H 3V9Canada

Abstract

Objective

To evaluate the impact of prophylactic indomethacin on early death (<10 days after birth) or severe neurologic injury and on early death or spontaneous intestinal perforation by completed weeks of gestational age in neonates born <29 weeks of gestation.

Study design

This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation.

Results

Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age.

Conclusions

Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

Il testo completo di questo articolo è disponibile in PDF.

Keywords : severe neurologic injury, spontaneous intestinal perforation, necrotizing enterocolitis, preterm infants

Abbreviations : CNN, ELGAN, IVH, NEC, NICU, PDA, PI, SGA, SNAPII-PE, TIPP


Mappa


 Supported by 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 the Canadian Institutes of Health Research (CIHR) (CTP 87518), the Ontario Ministry of Health and Long-Term Care, and the participating hospitals. P.S. holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research from the CIHR (APR-126340). The funding agencies 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. The authors declare no conflicts of interest.
 Portions of this study were presented at the Pediatric Academic Societies annual meeting, April 24-May 1, 2019, Baltimore, MD.


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