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Am J Perinatol 2021; 38(07): 707-713
DOI: 10.1055/s-0039-3400996
Original Article

High Dose Indomethacin for Patent Ductus Arteriosus Closure Increases Neonatal Morbidity

Salome Waldvogel
1   Department of Neonatology, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland
2   Children's Hospital, Inselspital Berne, Division of Neonatology, University of Berne, Berne, Switzerland
,
Andrew Atkinson
3   Department of Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland
4   University Hospital Inselspital Berne Department of Infectious Diseases, University of Berne, Berne, Switzerland
,
Mélanie Wilbeaux
3   Department of Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland
,
Mathias Nelle
2   Children's Hospital, Inselspital Berne, Division of Neonatology, University of Berne, Berne, Switzerland
,
Markus R. Berger
2   Children's Hospital, Inselspital Berne, Division of Neonatology, University of Berne, Berne, Switzerland
,
Roland Gerull
1   Department of Neonatology, University Children's Hospital Basel UKBB, University of Basel, Basel, Switzerland
2   Children's Hospital, Inselspital Berne, Division of Neonatology, University of Berne, Berne, Switzerland
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Abstract

Objective Symptomatic patent ductus arteriosus (sPDA) is the most common heart abnormality in preterm infants. Optimal duration and dose of medical treatment is still unclear. We assessed undesired effects and closure rate of high-dose indomethacin (HDI) for pharmacological closure of sPDA.

Study Design Retrospective single center analysis of 248 preterm infants born between January 2006 and December 2015 with a birth weight <2,000 g and sPDA which was treated with indomethacin. Patients were treated with either standard dose indomethacin (SDI; n = 196) or HDI (n = 52). Undesired effects and PDA closure were compared between patients treated with SDI and HDI.

Results In univariate analysis, patients receiving HDI had a significant increase in gastrointestinal hemorrhage (32.7 vs.11.7%, p = 0.001), bronchopulmonary dysplasia (BPD) (77.8 vs. 55.1%, p = 0.003), and retinopathy of prematurity (13.5 vs. 2.6%, p = 0.004). Moreover, HDI patients needed longer mechanical ventilation (2.5 vs. 1.0 days, p = 0.01). Multivariate analyses indicated that necrotizing enterocolitis (17 vs. 7%, p = 0.01) and BPD (79 vs. 55%, p = 0.02) were more frequent in HDI patients. PDA closure rate was 79.0% with HDI versus 65.3% with SDI.

Conclusion HDI used for PDA closure is associated with an increase in necrotizing enterocolitis and BPD. Risks of HDI should be balanced against other treatment options.

Keywords

patent ductus arteriosus - preterm - indomethacin - retinopathy of prematurity - bronchopulmonary dysplasia - necrotizing enterocolitis

Note

The cantonal ethics committee waived the need for informed consent. However, the patients' representatives were informed about the use of data for research.


Supplementary Material



Publication History

Received: 06 June 2019

Accepted: 24 October 2019

Article published online:
30 December 2019

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