Download PDF
Am J Perinatol
DOI: 10.1055/s-0042-1756678
Original Article

Indomethacin Prophylaxis in Preterm Infants: Changes over Time

Samantha F. Curtis
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
C. Michael Cotten
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Matthew Laughon
2   Department of Pediatrics, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina
,
Noelle Younge
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Jennifer Peterson
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
,
Reese H. Clark
3   MEDNAX, Inc., Sunrise, Florida
,
Rachel G. Greenberg 
1   Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina
4   Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina
› Author Affiliations Funding None.
› Further Information
    Permissions and Reprints

Abstract

Objective Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018.

Study Design The design of the study included cohort of 19,715 infants born between 220/7 and 266/7 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time. We evaluated the prevalence of indomethacin prophylaxis by the center and the correlation between indomethacin prophylaxis and severe intraventricular hemorrhage prevalence among 12 centers with the largest relative change in indomethacin prophylaxis prevalence.

Results In total, 16% of infants received indomethacin prophylaxis. The use of indomethacin prophylaxis did not significantly decrease between 2008 and 2018 but it significantly decreased between 2014 and 2018 (p = 0.046). Among 74 centers with ≥10 infants included, 20% increased the use of indomethacin prophylaxis, while 57% decreased the use over the study period. Of the 12 centers with the largest relative change in indomethacin prophylaxis prevalence, 50% showed an inverse correlation between indomethacin prophylaxis prevalence and severe intraventricular hemorrhage, while 50% showed a positive correlation.

Conclusion Receipt of indomethacin prophylaxis remained similar until 2014, decreased from 2014 to 2018, and varied by the center.

Key Points

  • The receipt of indomethacin prophylaxis decreased over time.

  • Center change in the use of indomethacin prophylaxis does not correlate with the center prevalence of IVH.

  • Variability in the use of indomethacin prophylaxis across centers persists.

Keywords

indomethacin - neonates - intraventricular hemorrhage - prophylaxis

Authors' Contributions

S.F.C. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. S.F.C. contributed to the conception and design of the study, the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


C.M.C. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


M.L. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


N.Y. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


J.P. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


R.H.C. contributed to the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


R.G.G. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. R.G.G. contributed to the conception and design of the study, the data interpretation, the manuscript drafting, and the critical revision of the manuscript.


Supplementary Material



Publication History

Received: 18 February 2022

Accepted: 09 August 2022

Article published online:
29 September 2022

© 2022. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Stoll BJ, Hansen NI, Bell EF. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993-2012. JAMA 2015; 314 (10) 1039-1051
    CrossrefPubMedGoogle Scholar
  • 2 Hu X, Tao C, Gan Q, Zheng J, Li H, You C. Oxidative stress in intracerebral hemorrhage: sources, mechanisms, and therapeutic targets. Oxid Med Cell Longev 2016; 2016: 3215391
    PubMedGoogle Scholar
  • 3 Pinto-Martin JA, Whitaker AH, Feldman JF, Van Rossem R, Paneth N. Relation of cranial ultrasound abnormalities in low-birthweight infants to motor or cognitive performance at ages 2, 6, and 9 years. Dev Med Child Neurol 1999; 41 (12) 826-833
    CrossrefPubMedGoogle Scholar
  • 4 Bhat R, Zayek M, Maertens P, Eyal F. A single-dose indomethacin prophylaxis for reducing perinatal brain injury in extremely low birth weight infants: a non-inferiority analysis. J Perinatol 2019; 39 (11) 1462-1471
    CrossrefPubMedGoogle Scholar
  • 5 Bhombal S, Benitz WE. Prophylactic indomethacin-is it time to reconsider?. J Pediatr 2017; 187: 8-10
    CrossrefPubMedGoogle Scholar
  • 6 Clyman RI, Saha S, Jobe A, Oh W. Indomethacin prophylaxis for preterm infants: the impact of 2 multicentered randomized controlled trials on clinical practice. J Pediatr 2007; 150 (01) 46-50.e2
    CrossrefPubMedGoogle Scholar
  • 7 Heuchan AM, Clyman RI. Managing the patent ductus arteriosus: current treatment options. Arch Dis Child Fetal Neonatal Ed 2014; 99 (05) F431-F436
    CrossrefPubMedGoogle Scholar
  • 8 Jensen EA, Dysart KC, Gantz MG. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Association between use of prophylactic indomethacin and the risk for bronchopulmonary dysplasia in extremely preterm infants. J Pediatr 2017; 186: 34-40.e2
    CrossrefPubMedGoogle Scholar
  • 9 McNally MA, Soul JS. Pharmacologic prevention and treatment of neonatal brain injury. Clin Perinatol 2019; 46 (02) 311-325
    CrossrefPubMedGoogle Scholar
  • 10 Ment LR, Oh W, Ehrenkranz RA. et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 1994; 93 (04) 543-550
    CrossrefPubMedGoogle Scholar
  • 11 Mirza H, Laptook AR, Oh W. et al; Generic Database Subcommittee of the NICHD Neonatal Research Network. Effects of indomethacin prophylaxis timing on intraventricular haemorrhage and patent ductus arteriosus in extremely low birth weight infants. Arch Dis Child Fetal Neonatal Ed 2016; 101 (05) F418-F422
    CrossrefPubMedGoogle Scholar
  • 12 Reese J, Shelton EL, Slaughter JC, McNamara PJ. Prophylactic indomethacin revisited. J Pediatr 2017; 186: 11-14.e1
    CrossrefPubMedGoogle Scholar
  • 13 AlFaleh K, Alluwaimi E, AlOsaimi A. et al. A prospective study of maternal preference for indomethacin prophylaxis versus symptomatic treatment of a patent ductus arteriosus in preterm infants. BMC Pediatr 2015; 15: 47
    CrossrefPubMedGoogle Scholar
  • 14 Bixler GM, Powers GC, Clark RH, Walker MW, Tolia VN. Changes in the diagnosis and management of patent ductus arteriosus from 2006 to 2015 in United States neonatal intensive care units. J Pediatr 2017; 189: 105-112
    CrossrefPubMedGoogle Scholar
  • 15 Jensen EA, Foglia EE, Schmidt B. Association between prophylactic indomethacin and death or bronchopulmonary dysplasia: a systematic review and meta-analysis of observational studies. Semin Perinatol 2018; 42 (04) 228-234
    CrossrefPubMedGoogle Scholar
  • 16 Schmidt B, Seshia M, Shankaran S. et al; Trial of Indomethacin Prophylaxis in Preterms Investigators. Effects of prophylactic indomethacin in extremely low-birth-weight infants with and without adequate exposure to antenatal corticosteroids. Arch Pediatr Adolesc Med 2011; 165 (07) 642-646
    CrossrefPubMedGoogle Scholar
  • 17 Jensen EA, Dysart K, Gantz MG. et al. The diagnosis of bronchopulmonary dysplasia in very preterm infants. an evidence-based approach. Am J Respir Crit Care Med 2019; 200 (06) 751-759
    CrossrefPubMedGoogle Scholar
  • 18 Kandraju H, Kanungo J, Lee KS. et al; Canadian Neonatal Network (CNN), Canadian Preterm Birth Network (CPTBN) Investigators. Association of co-exposure of antenatal steroid and prophylactic indomethacin with spontaneous intestinal perforation. J Pediatr 2021; 235: 34-41.e1
    CrossrefPubMedGoogle Scholar
  • 19 Qureshi M, Shah PS, Abdelgadir D. et al; Canadian Neonatal Network investigators. Gestational age-dependent variations in effects of prophylactic indomethacin on brain injury and intestinal injury. J Pediatr 2021; 235: 26-33.e2
    CrossrefPubMedGoogle Scholar
  • 20 Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev 2010; (07) CD000174
    PubMedGoogle Scholar
  • 21 Rysavy MA, Mehler K, Oberthür A. et al. An immature science: intensive care for infants born at ≤23 weeks of gestation. J Pediatr 2021; 233: 16-25.e1
    CrossrefPubMedGoogle Scholar
  • 22 Spitzer AR, Ellsbury DL, Handler D, Clark RH. The Pediatrix BabySteps Data Warehouse and the Pediatrix QualitySteps improvement project system–tools for “meaningful use” in continuous quality improvement. Clin Perinatol 2010; 37 (01) 49-70
    CrossrefPubMedGoogle Scholar
  • 23 Amin SB, Kamaluddeen M, Sangem M. Neurodevelopmental outcome of premature infants after exposure to antenatal indomethacin. Am J Obstet Gynecol 2008; 199 (01) 41.e1-41.e8
    CrossrefPubMedGoogle Scholar
  • 24 Afsharkhas L, Khalessi N, Karimi Panah M. Intraventricular hemorrhage in term neonates: sources, severity and outcome. Iran J Child Neurol 2015; 9 (03) 34-39
    PubMedGoogle Scholar
  • 25 Thompson EJ, Greenberg RG, Kumar K. et al. Association between furosemide exposure and patent ductus arteriosus in hospitalized infants of very low birth weight. J Pediatr 2018; 199: 231-236
    CrossrefPubMedGoogle Scholar
  • 26 Trembath A, Hornik CP, Clark R, Smith PB, Daniels J, Laughon M. Best Pharmaceuticals for Children Act—Pediatric Trials Network. Comparative effectiveness of surfactant preparations in premature infants. J Pediatr 2013; 163 (04) 955-60.e1
    CrossrefPubMedGoogle Scholar
  • 27 Romejko-Wolniewicz E, Teliga-Czajkowska J, Czajkowski K. Antenatal steroids: can we optimize the dose?. Curr Opin Obstet Gynecol 2014; 26 (02) 77-82
    CrossrefPubMedGoogle Scholar
  • 28 Olsen SJ, Mirza SA, Vonglokham P. et al. The effect of influenza vaccination on birth outcomes in a cohort of pregnant women in Lao PDR, 2014-2015. Clin Infect Dis 2016; 63 (04) 487-494
    CrossrefPubMedGoogle Scholar
  • 29 Clyman RI, Liebowitz M. Treatment and nontreatment of the patent ductus arteriosus: identifying their roles in neonatal morbidity. J Pediatr 2017; 189: 13-17
    CrossrefPubMedGoogle Scholar
  • 30 Luque MJ, Tapia JL, Villarroel L. et al; Neocosur Neonatal Network. A risk prediction model for severe intraventricular hemorrhage in very low birth weight infants and the effect of prophylactic indomethacin. J Perinatol 2014; 34 (01) 43-48
    CrossrefPubMedGoogle Scholar
  • 31 Slaughter JL, Reagan PB, Bapat RV, Newman TB, Klebanoff MA. Nonsteroidal anti-inflammatory administration and patent ductus arteriosus ligation, a survey of practice preferences at US children's hospitals. Eur J Pediatr 2016; 175 (06) 775-783
    CrossrefPubMedGoogle Scholar
  • 32 Faim DRO, Tiago JAM, Castelo RJS, Francisco ASS, Alves RR, Pires AMGS. Patent ductus arteriosus closure: experience from a tertiary referral center. Rev Paul Pediatr 2020; 39: e2020013
    CrossrefPubMedGoogle Scholar
  • 33 Goldman RD, Spierer A, Zhurkovsky A, Kwint J, Schwarcz M, Ben Simon GJ. Retinopathy of prematurity in very low birth weight infants and the potential protective role of indomethacin. Ophthalmic Surg Lasers Imaging 2010; 41 (01) 41-47
    CrossrefPubMedGoogle Scholar
  • 34 Cahill AG, Kaimal AJ, Kuller JA, Turrentine MA. American College of Obstetricians and Gynecologist SfM-FM. Use of antenatal corticosteroids at 22 weeks of gestation. ACOG. Accessed October 13, 2021 at: https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2021/09/use-of-antenatal-corticosteroids-at-22-weeks-of-gestation
    PubMedGoogle Scholar
  • 35 Arnautovic TI, Longo JL, Trail-Burns EJ, Tucker R, Keszler M, Laptook AR. Antenatal risk factors associated with spontaneous intestinal perforation in preterm infants receiving postnatal indomethacin. J Pediatr 2021; 232: 59-64.e1
    CrossrefPubMedGoogle Scholar
  • 36 de Bijl-Marcus K, Brouwer AJ, De Vries LS, Groenendaal F, Wezel-Meijler GV. Neonatal care bundles are associated with a reduction in the incidence of intraventricular haemorrhage in preterm infants: a multicentre cohort study. Arch Dis Child Fetal Neonatal Ed 2020; 105 (04) 419-424
    CrossrefPubMedGoogle Scholar
  • 37 Sauer CW, Kong JY, Vaucher YE. et al. Intubation attempts increase the risk for severe intraventricular hemorrhage in preterm infants—a retrospective cohort study. J Pediatr 2016; 177: 108-113
    CrossrefPubMedGoogle Scholar