Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic IndomethacinFunding Organizational support for the CNN was provided by the Maternal-Infant Care Research Centre (MiCare) at Mount Sinai Hospital in Toronto, Ontario, Canada. MiCare is supported by a team grant from the Canadian Institutes of Health Research (CIHR, FRN87518) and in-kind support from Mount Sinai Hospital. The Canadian Neonatal Network is supported by a CIHR Preterm Birth Network Team Grant (PBN150642). Dr Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the CIHR (APR-126340).
22 September 2017
18 October 2017
28 November 2017 (eFirst)
Objective To identify clinical factors those predict the need for patent ductus arteriosus (PDA) treatment in preterm neonates who had received prophylactic indomethacin.
Patients and Methods Preterm neonates with <28 weeks' gestational age admitted to level III neonatal intensive care units (NICUs) in Canada between 2010 and 2015 and who had received prophylactic indomethacin were included. Primary outcome was surgical ligation of PDA, while secondary outcomes were any PDA treatment and common neonatal morbidities.
Results Of the 7,024 eligible neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84 neonates (10%) required surgical ligation while 367 neonates (44%) received medical or surgical treatment for PDA. Logistic regression analyses identified gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58–0.87) and outborn status (OR: 2.07, 95% CI: 1.09–3.93) as predictors for surgical ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37–0.89), rupture of membranes (ROM) ≥24 hours (OR: 0.68, 95% CI: 0.48–0.96), and surfactant treatment (OR: 1.70, 95% CI: 1.09–2.66) were predictors for medical or surgical treatment of PDA.
Conclusion In extremely preterm neonates who had received prophylactic indomethacin, gestational age and outborn status were predictors for surgical ligation of PDA, while maternal hypertension, ROM ≥24 hours, and surfactant treatment were associated with the medical or surgical treatment of PDA.
Keywordspreterm neonate - PDA treatment - prophylactic indomethacin - predictors - surgical ligation
List of 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 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.
- 1 Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010; (07) CD000174
- 2 Hamrick SE, Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics 2010; 125 (05) 1020-1030
- 3 Weiss H, Cooper B, Brook M, Schlueter M, Clyman R. Factors determining reopening of the ductus arteriosus after successful clinical closure with indomethacin. J Pediatr 1995; 127 (03) 466-471
- 4 Gittenberger-de Groot AC, van Ertbruggen I, Moulaert AJ, Harinck E. The ductus arteriosus in the preterm infant: histologic and clinical observations. J Pediatr 1980; 96 (01) 88-93
- 5 Narayanan M, Cooper B, Weiss H, Clyman RI. Prophylactic indomethacin: factors determining permanent ductus arteriosus closure. J Pediatr 2000; 136 (03) 330-337
- 6 Shah PS, Seidlitz W, Chan P, Yeh S, Musrap N, Lee SK. ; data abstractors of the Canadian Neonatal Network. Internal audit of the Canadian Neonatal Network Data Collection System. Am J Perinatol 2017; 34 (12) 1241-1249
- 7 Kramer MS, Platt RW, Wen SW. , et al; Fetal/Infant Health Study Group of the Canadian Perinatal Surveillance System. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics 2001; 108 (02) E35
- 8 Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82 (04) 527-532
- 9 International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123 (07) 991-999
- 10 Bell MJ, Ternberg JL, Feigin RD. , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187 (01) 1-7
- 11 Clyman RI, Chan CY, Mauray F. , et al. Permanent anatomic closure of the ductus arteriosus in newborn baboons: the roles of postnatal constriction, hypoxia, and gestation. Pediatr Res 1999; 45 (01) 19-29
- 12 Yu VY. Patent ductus arteriosus in the preterm infant. Early Hum Dev 1993; 35 (01) 1-14
- 13 Koch J, Hensley G, Roy L, Brown S, Ramaciotti C, Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006; 117 (04) 1113-1121
- 14 Boland RA, Davis PG, Dawson JA, Doyle LW. Outcomes of infants born at 22-27 weeks' gestation in Victoria according to outborn/inborn birth status. Arch Dis Child Fetal Neonatal Ed 2017; 102 (02) F153-F161
- 15 Mahoney K, Bajuk B, Oei J, Lui K, Abdel-Latif ME, Network N. ; NICUS Network. Risk of neurodevelopmental impairment for outborn extremely preterm infants in an Australian regional network. J Matern Fetal Neonatal Med 2017; 30 (01) 96-102
- 16 Jacob J, Gluck L, DiSessa T. , et al. The contribution of PDA in the neonate with severe RDS. J Pediatr 1980; 96 (01) 79-87
- 17 Brown S, Liu X, Ramaekers F, Rosenfiled C. Differential maturation in ductus arteriosus and umbilical artery smooth muscle during ovine development. Pediatr Res 2002; 51: 34A
- 18 Noori S, McCoy M, Friedlich P. , et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics 2009; 123 (01) e138-e144
- 19 Marshall DD, Kotelchuck M, Young TE, Bose CL, Kruyer L, O'Shea TM. ; North Carolina Neonatologists Association. Risk factors for chronic lung disease in the surfactant era: a North Carolina population-based study of very low birth weight infants. Pediatrics 1999; 104 (06) 1345-1350
- 20 Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A. ; Trial of Indomethacin Prophylaxis in Preterms Investigators. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the Trial of Indomethacin Prophylaxis in Preterms. J Pediatr 2007; 150 (03) 229-234
- 21 Madan JC, Kendrick D, Hagadorn JI, Frantz III ID. ; National Institute of Child Health and Human Development Neonatal Research Network. Patent ductus arteriosus therapy: impact on neonatal and 18-month outcome. Pediatrics 2009; 123 (02) 674-681
- 22 Bourgoin L, Cipierre C, Hauet Q. , et al. Neurodevelopmental outcome at 2 years of age according to patent ductus arteriosus management in very preterm infants. Neonatology 2016; 109 (02) 139-146