Am J Perinatol 2014; 31(01): 061-068
DOI: 10.1055/s-0033-1334449
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Prophylactic Indomethacin Worsens Short-Term Respiratory Outcomes in Extremely Low-Birth-Weight Infants

Tapas Mondal
1   Division of Cardiology, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Dipayan Chaudhuri
2   Department of Health Sciences, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Brian Li
2   Department of Health Sciences, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Sandesh Shivananda
3   Division of Neonatology, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
,
Sourabh Dutta
3   Division of Neonatology, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada
› Author Affiliations
Further Information

Publication History

25 July 2012

26 December 2012

Publication Date:
01 March 2013 (online)

Abstract

Objective To compare the effects of prophylactic indomethacin versus expectant management on short-term respiratory outcomes in extremely low-birth-weight (ELBW) infants.

Methods This was a retrospective cohort study of ELBW infants with gestational age less than 28 weeks, born at a level III neonatal intensive care unit from 2004 to 2009. Patients were grouped based on whether they received prophylactic indomethacin or expectant treatment. The key outcome was the cumulative number of days of mechanical ventilation. Other outcomes were cumulative number of days supplemental oxygen and continuous positive airway pressure (CPAP) were required; duration of hospital stay; mortality; and other morbidities such as necrotizing enterocolitis and intraventricular hemorrhage. Multivariable linear regression was performed with treatment group and seven covariates, defined a priori, as predictor variables and cumulative number of days of mechanical ventilation as the outcome.

Results There were 144 infants in the prophylaxis group and 221 infants in the expectant treatment group. At baseline, the Score for Neonatal Acute Physiology–Perinatal Extension, incidence of respiratory distress syndrome, and usage of antenatal corticosteroids were significantly higher in the prophylaxis group. The cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP were significantly higher in the prophylaxis group. On multivariable linear regression, after adjusting for confounders, use of prophylactic indomethacin (unstandardized β coefficient = 12.4; 95% confidence interval [CI]: 6.6, 18.1; p < 0.001), birth weight (β =  −0.025; 95% CI: −0.05, −0.001; p = 0.043), and gestation (β =  −4.5; 95% CI: −7.24, −1.8; p = 0.001) were the independent predictors of cumulative number of days of mechanical ventilation.

Conclusion ELBW infants who received prophylactic indomethacin had significantly longer cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP. Prophylactic indomethacin is an independent predictor of cumulative number of days of mechanical ventilation.

 
  • References

  • 1 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: 674-681
  • 2 Fowlie PW, Davis PG. Prophylactic indomethacin for preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2003; 88: F464-F466
  • 3 Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26 (Suppl. 01) S14-S18 , discussion S22–S23
  • 4 Ment LR, Oh W, Ehrenkranz RA , et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 1994; 93: 543-550
  • 5 Schmidt B, Roberts RS, Fanaroff A , et al; TIPP Investigators. Indomethacin prophylaxis, patent ductus arteriosus, and the risk of bronchopulmonary dysplasia: further analyses from the Trial of Indomethacin Prophylaxis in Preterms (TIPP). J Pediatr 2006; 148: 730-734
  • 6 Schmidt B, Davis P, Moddemann D , et al; Trial of Indomethacin Prophylaxis in Preterms Investigators. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344: 1966-1972
  • 7 Ment LR, Vohr B, Allan W , et al. Outcome of children in the indomethacin intraventricular hemorrhage prevention trial. Pediatrics 2000; 105 (3 Pt 1) 485-491
  • 8 Amin SB, Handley C, Carter-Pokras O. Indomethacin use for the management of patent ductus arteriosus in preterms: a web-based survey of practice attitudes among neonatal fellowship program directors in the United States. Pediatr Cardiol 2007; 28: 193-200
  • 9 Hoellering AB, Cooke L. The management of patent ductus arteriosus in Australia and New Zealand. J Paediatr Child Health 2009; 45: 204-209
  • 10 Cordero L, Nankervis CA, Delooze D, Giannone PJ. Indomethacin prophylaxis or expectant treatment of patent ductus arteriosus in extremely low birth weight infants?. J Perinatol 2007; 27: 158-163
  • 11 Fan JL, Burgess KR, Thomas KN , et al. Influence of indomethacin on ventilatory and cerebrovascular responsiveness to CO2 and breathing stability: the influence of PCO2 gradients. Am J Physiol Regul Integr Comp Physiol 2010; 298: R1648-R1658
  • 12 Vincer M, Allen A, Evans J , et al. Early intravenous indomethacin prolongs respiratory support in very low birth weight infants. Acta Paediatr Scand 1987; 76: 894-897
  • 13 Clyman RI, Chorne N. Patent ductus arteriosus: evidence for and against treatment. J Pediatr 2007; 150: 216-219
  • 14 Fanasoff AA, Stoll BJ, Wright LL , et al. Trends in Neonatal mortality and morbidity for very low birth weight infants. Am J Obstet Gynecol 2007; e1-147
  • 15 Van OB, Van de Broek H, Van LP , et al. Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome. J Pediatr 2001; 138: 205-211
  • 16 Cifuentes RF, Olley PM, Balfe JW, Radde IC, Soldin SJ. Indomethacin and renal function in premature infants with persistent patent ductus arteriosus. J Pediatr 1979; 95: 583-587
  • 17 Lago P, Bettiol T, Salvadori S , et al. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr 2002; 161: 202-207
  • 18 Tommiska V, Heinonen K, Ikonen S , et al. A national short-term follow-up study of extremely low birth weight infants born in Finland in 1996–1997. Pediatrics 2001; 107: E2
  • 19 Tommiska V, Heinonen K, Lehtonen L , et al. No improvement in outcome of nationwide extremely low birth weight infant populations between 1996–1997 and 1999–2000. Pediatrics 2007; 119: 29-36
  • 20 Valcamonico A, Accorsi P, Sanzeni C , et al. Mid- and long-term outcome of extremely low birth weight (ELBW) infants: an analysis of prognostic factors. J Matern Fetal Neonatal Med 2007; 20: 465-471
  • 21 Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS ; Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group. Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet 2006; 367: 1913-1919
  • 22 Hayes EJ, Paul DA, Stahl GE , et al. Effect of antenatal corticosteroids on survival for neonates born at 23 weeks of gestation. Obstet Gynecol 2008; 111: 921-926
  • 23 Kumar Nair PA, Pai MG, Gazal HA, Da Costa DE, Al Khusaiby SM. Indomethacin prophylaxis for intraventricular hemorrhage in very low birth weight babies. Indian Pediatr 2004; 41: 551-558
  • 24 Hanigan WC, Kennedy G, Roemisch F, Anderson R, Cusack T, Powers W. Administration of indomethacin for the prevention of periventricular-intraventricular hemorrhage in high-risk neonates. J Pediatr 1988; 112: 941-947
  • 25 Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010; (7) CD000174