Am J Perinatol 2025; 42(07): 907-914
DOI: 10.1055/a-2441-6639
Original Article

Impact of Pharmacologic Patent Ductus Arteriosus Treatment on Acute Respiratory and Oxygenation Metrics in Very Low Birth Weight Infants

Mara K. Weigner
1   Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia
,
Sherry L. Kausch
1   Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia
,
Karen D. Fairchild
1   Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia
,
1   Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, Virginia
› Author Affiliations
Funding This study was supported by a grant from U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Child Health and Human Development (grant no.: K23 HD097254).

Abstract

Objective

Hypoxemia and respiratory compromise occur in very low birth weight (VLBW, <1,500 g) infants and may be associated with shunting across patent ductus arteriosus (PDA). The impact of pharmacologic PDA treatment on acute hypoxemia and respiratory metrics is unclear. This study aimed to determine whether pharmacologic PDA treatment is associated with acute improvement in hypoxemia and respiratory metrics in VLBW infants.

Study Design

At a single center (2012–2022), all VLBW infants with echocardiographic evidence of PDA and without exclusions were classified as having received or not received pharmacologic PDA treatment (PDA-T and PDA-NT). Mean daily fraction of inspired oxygen (FIO2) and Respiratory Acuity Score (RAS, PMID 30374050) were compared at baseline (day 0) and 3 days after the start of treatment. For PDA-T infants with archived 0.5 Hz (every 2-second) oxygen saturation (SpO2) data, mean daily SpO2 and the percentage of time with severe hypoxemia (SpO2 <80%) were compared before and after treatment. Severe hypoxemia was further analyzed after stratification by clinical variables (sex, medication, gestational age, and postnatal age).

Results

We analyzed 125 VLBW infants with PDA, of whom 66 received pharmacologic PDA treatment. We analyzed a subgroup of 43 PDA-T infants with every 2-second SpO2 data available. PDA-T infants had higher baseline FiO2 and RAS and lower SpO2 than PDA-NT infants (p < 0.05). Compared to baseline, RAS decreased from a median of 258 (interquartile range [IQR]: 171, 348) to 254 (IQR: 174, 419), 3 days after the start of treatment (p = 0.012), but median FiO2 increased from 37% (IQR: 28, 46) to 40% (IQR: 29, 52; p = 0.008). SpO2 and the percent time with severe hypoxemia were unchanged.

Conclusion

In this 10-year, retrospective, single-center analysis, pharmacologic PDA treatment in VLBW infants was not associated with a major improvement in acute measures of oxygenation or level of respiratory support.

Key Points

  • Infants with pharmacologically treated PDA had worse baseline respiratory and oxygenation metrics.

  • RAS decreased but FiO2 increased 3 days after pharmacologic PDA treatment.

  • Pharmacologic PDA treatment did not acutely improve SpO2 or severe hypoxemia.



Publication History

Received: 24 June 2024

Accepted: 14 October 2024

Accepted Manuscript online:
15 October 2024

Article published online:
12 November 2024

© 2024. Thieme. All rights reserved.

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

 
  • References

  • 1 Clyman RI, Couto J, Murphy GM. Patent ductus arteriosus: are current neonatal treatment options better or worse than no treatment at all?. Semin Perinatol 2012; 36 (02) 123-129
  • 2 Benitz WE. Committee on Fetus and Newborn, American Academy of Pediatrics. Patent ductus arteriosus in preterm infants. Pediatrics 2016;137(01):
  • 3 Gillam-Krakauer M, Reese J. Diagnosis and management of patent ductus arteriosus. Neoreviews 2018; 19 (07) e394-e402
  • 4 Jain A, Shah PS. Diagnosis, evaluation, and management of patent ductus arteriosus in preterm neonates. JAMA Pediatr 2015; 169 (09) 863-872
  • 5 Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev 2020; 2 (02) CD003481
  • 6 Jasani B, Mitra S, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2022; 12: CD010061
  • 7 El-Mashad AE-R, 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
  • 8 Gupta S, Subhedar NV, Bell JL. et al; Baby-OSCAR Collaborative Group. Trial of selective early treatment of patent ductus arteriosus with ibuprofen. N Engl J Med 2024; 390 (04) 314-325
  • 9 Hundscheid T, Onland W, Kooi EMW. et al; BeNeDuctus Trial Investigators. Expectant management or early ibuprofen for patent ductus arteriosus. N Engl J Med 2023; 388 (11) 980-990
  • 10 Mitra S, Scrivens A, von Kursell AM, Disher T. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Database Syst Rev 2020; 12 (12) CD013278
  • 11 Kaluarachchi DC, Rysavy MA, Carper BA. et al. Secular trends in patent ductus arteriosus management in infants born preterm in the NICHD neonatal research network. J Pediatr 2023; 266: 113877
  • 12 Fairchild KD, Nagraj VP, Sullivan BA, Moorman JR, Lake DE. Oxygen desaturations in the early neonatal period predict development of bronchopulmonary dysplasia. Pediatr Res 2019; 85 (07) 987-993
  • 13 Walsh MC, Yao Q, Gettner P. et al; National Institute of Child Health and Human Development Neonatal Research Network. Impact of a physiologic definition on bronchopulmonary dysplasia rates. Pediatrics 2004; 114 (05) 1305-1311
  • 14 Finer NN, Bates R, Tomat P. Low flow oxygen delivery via nasal cannula to neonates. Pediatr Pulmonol 1996; 21 (01) 48-51
  • 15 Mitra S, de Boode WP, Weisz DE, Shah PS. Interventions for patent ductus arteriosus (PDA) in preterm infants: an overview of Cochrane Systematic Reviews. Cochrane Database Syst Rev 2023; 4 (04) CD013588
  • 16 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 (06) 730-734
  • 17 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 (06) 894-897
  • 18 Yaseen H, al Umran K, Ali H, Rustum M, Darwich M, al-Faraidy A. Effects of early indomethacin administration on oxygenation and surfactant requirement in low birth weight infants. J Trop Pediatr 1997; 43 (01) 42-46
  • 19 Moronta SC, Bischoff AR, Ryckman KK, Dagle JM, Giesinger RE, McNamara PJ. Clinical and echocardiography predictors of response to first-line acetaminophen treatment in preterm infants with hemodynamically significant patent ductus arteriosus. J Perinatol 2024; 44 (03) 379-387
  • 20 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
  • 21 McClure C, Jang SY, Fairchild K. Alarms, oxygen saturations, and SpO2 averaging time in the NICU. J Neonatal Perinatal Med 2016; 9 (04) 357-362
  • 22 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