Am J Perinatol 2024; 41(S 01): e1759-e1768
DOI: 10.1055/s-0043-1768962
Original Article

Patent Ductus Arteriosus Response to Treatment by Course and Associations with Perinatal and Clinical Factors

1   Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
,
Amy E. Wahlquist
2   Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina
3   Department of Biostatistics and Epidemiology, Center for Rural Health Research, East Tennessee State University, Johnson City, Tennessee
,
Ekta U. Patel
4   Department of Pediatrics (Neonatology), Children's Mercy Hospital, Kansas City, Missouri
,
Anthony M. Hlavacek
1   Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
,
Rita M. Ryan
1   Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
5   Department of Pediatrics (Neonatology), Case Western Reserve University, Rainbow Babies and Children's Hospital, Cleveland, Ohio
,
Heidi J. Steflik
1   Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina
› Institutsangaben
Funding None

Abstract

Objective The objective of this study is to examine patent ductus arteriosus (PDA) response by treatment course and investigate associations with postmenstrual age (PMA), chronological age (CA), gestational age (GA), antenatal steroid exposure (ANS), birthweight (BW), weight at treatment initiation (WT), and PDA/left pulmonary artery (LPA) ratio.

Study Design This is a single-center retrospective cohort study of preterm infants less than 37 weeks' GA born January 1, 2016 to December 31, 2018 who received acetaminophen and/or indomethacin for PDA treatment. Cox proportional hazards regression models were used to determine whether factors of interest were associated with PDA response to medical treatment.

Results In total, 289 treatment courses were administered to 132 infants. Thirty-one (23%) infants experienced treatment-associated PDA closure. Ninety-four (71%) infants had evidence of PDA constriction following any treatment course. Ultimately, 84 (64%) infants experienced definitive PDA closure. For each 7-day increase in CA at the time of treatment initiation, the PDA was 59% less likely to close (p = 0.04) and 42% less likely to respond (i.e., constrict or close) to treatment (p < 0.01). PDA/LPA ratio was associated with treatment-associated PDA closure (p = 0.01). For every 0.1 increase in the PDA/LPA ratio, the PDA was 19% less likely to close in response to treatment.

Conclusion In this cohort, PDA closure is independent of PMA, GA, ANS, BW, and WT; however, CA at treatment initiation predicted both treatment-associated PDA closure and PDA response (i.e., constriction or closure), and PDA/LPA ratio was associated with treatment-associated closure. Most infants experienced PDA constriction rather than closure, despite receiving up to four treatment courses.

Key Points

  • Detailed PDA responses for up to four treatment courses provide a novel perspective.

  • Chronological age at the start of treatment predicted treatment-associated PDA closure and response.

  • For each 7-day increase in chronological age, the PDA was 59% less likely to close.

Authors' Contributions

A.D.R., H.J.S., A.E.W., and R.M.R. were responsible for the study concept and design. A.D.R. and E.U.P. were responsible for acquisition of the data. A.E.W. was responsible for the statistical analysis. A.D.R. and H.J.S. were responsible for drafting of the manuscript. A.E.W., E.U.P., A.M.H., R.M.R., and H.J.S. were responsible for the interpretation of data and critical revision of the manuscript. All authors have reviewed and approved the final manuscript.




Publikationsverlauf

Eingereicht: 14. November 2022

Angenommen: 06. April 2023

Artikel online veröffentlicht:
18. Mai 2023

© 2023. Thieme. All rights reserved.

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

 
  • References

  • 1 Härkin P, Marttila R, Pokka T, Saarela T, Hallman M. Morbidities associated with patent ductus arteriosus in preterm infants. Nationwide cohort study. J Matern Fetal Neonatal Med 2018; 31 (19) 2576-2583
  • 2 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
  • 3 Benitz WE. Treatment of persistent patent ductus arteriosus in preterm infants: time to accept the null hypothesis?. J Perinatol 2010; 30 (04) 241-252
  • 4 Clyman RI, Liebowitz M, Kaempf J. et al; PDA-TOLERATE (PDA: TO LEave it alone or Respond And Treat Early) Trial Investigators. PDA-TOLERATE trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr 2019; 205: 41-48.e6
  • 5 Attridge JT, Clark R, Walker MW, Gordon PV. New insights into spontaneous intestinal perforation using a national data set: (1) SIP is associated with early indomethacin exposure. J Perinatol 2006; 26 (02) 93-99
  • 6 Vieux R, Desandes R, Boubred F. et al. Ibuprofen in very preterm infants impairs renal function for the first month of life. Pediatr Nephrol 2010; 25 (02) 267-274
  • 7 Semberova J, Sirc J, Miletin J. et al. Spontaneous closure of patent ductus arteriosus in infants ≤1500  g. Pediatrics 2017; 140 (02) e20164258
  • 8 Benitz WE. Patent ductus arteriosus: to treat or not to treat?. Arch Dis Child Fetal Neonatal Ed 2012; 97 (02) F80-F82
  • 9 Heuchan AM, Clyman RI. Managing the patent ductus arteriosus: current treatment options. Arch Dis Child Fetal Neonatal Ed 2014; 99 (05) F431-F436
  • 10 Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One 2013; 8 (11) e77888
  • 11 El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017; 176 (02) 233-240
  • 12 Oncel MY, Yurttutan S, Erdeve O. et al. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr 2014; 164 (03) 510-4.e1
  • 13 Mitra S, Florez ID, Tamayo ME. et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA 2018; 319 (12) 1221-1238
  • 14 Elhoff JJ, Ebeling M, Hulsey TC, Atz AM. Potential unintended consequences of a conservative management strategy for patent ductus arteriosus. Congenit Heart Dis 2016; 11 (01) 52-57
  • 15 Van Overmeire B, Van de Broek H, Van Laer P, Weyler J, Vanhaesebrouck P. Early versus late indomethacin treatment for patent ductus arteriosus in premature infants with respiratory distress syndrome. J Pediatr 2001; 138 (02) 205-211
  • 16 Kluckow M, Carlisle H, Broom M. et al. A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus. J Perinatol 2019; 39 (01) 102-107
  • 17 Liebowitz M, Kaempf J, Erdeve O. et al. Comparative effectiveness of drugs used to constrict the patent ductus arteriosus: a secondary analysis of the PDA-TOLERATE trial (NCT01958320). J Perinatol 2019; 39 (05) 599-607
  • 18 Narayanan M, Cooper B, Weiss H, Clyman RI. Prophylactic indomethacin: factors determining permanent ductus arteriosus closure. J Pediatr 2000; 136 (03) 330-337
  • 19 Ahamed MF, Verma P, Lee S. et al. Predictors of successful closure of patent ductus arteriosus with indomethacin. J Perinatol 2015; 35 (09) 729-734
  • 20 Chorne N, Jegatheesan P, Lin E, Shi R, Clyman RI. Risk factors for persistent ductus arteriosus patency during indomethacin treatment. J Pediatr 2007; 151 (06) 629-634
  • 21 Yang CZ, Lee J. Factors affecting successful closure of hemodynamically significant patent ductus arteriosus with indomethacin in extremely low birth weight infants. World J Pediatr 2008; 4 (02) 91-96
  • 22 Cuschieri S. The STROBE guidelines. Saudi J Anaesth 2019; 13 (Suppl. 01) S31-S34
  • 23 Laughon M, Bose C, Clark R. Treatment strategies to prevent or close a patent ductus arteriosus in preterm infants and outcomes. J Perinatol 2007; 27 (03) 164-170
  • 24 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
  • 25 Roofthooft DW, van Beynum IM, de Klerk JC. et al. Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure. Eur J Pediatr 2015; 174 (11) 1433-1440
  • 26 McCarthy JS, Zies LG, Gelband H. Age-dependent closure of the patent ductus arteriosus by indomethacin. Pediatrics 1978; 62 (05) 706-712
  • 27 Kaur S, Stritzke A, Soraisham AS. Does postmenstrual age affect medical patent ductus arteriosus treatment success in preterm infants?. Am J Perinatol 2019; 36 (14) 1504-1509
  • 28 Vaidya R, Knee A, Paris Y, Singh R. Predictors of successful patent ductus arteriosus closure with acetaminophen in preterm infants. J Perinatol 2021; 41 (05) 998-1006
  • 29 Kluckow M, Evans N. Early echocardiographic prediction of symptomatic patent ductus arteriosus in preterm infants undergoing mechanical ventilation. J Pediatr 1995; 127 (05) 774-779
  • 30 Schena F, Francescato G, Cappelleri A. et al. Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia. J Pediatr 2015; 166 (06) 1488-1492
  • 31 Sellmer A, Bjerre JV, Schmidt MR. et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed 2013; 98 (06) F505-F510