University of Oulu

Hallman, M., Treluyer, J.M., Aikio, O. and Rozé, J.-C. (2021), Early closure mechanisms of the ductus arteriosus in immature infants. Acta Paediatr, 110: 1995-2007.

Early closure mechanisms of the ductus arteriosus in immature infants

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Author: Hallman, Mikko1,2; Treluyer, Jean Marc3,4; Aikio, Outi1,2;
Organizations: 1Department of Pediatrics, Oulu University Hospital, Oulu, Finland
2PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland
3Faculté de Médecine, Université de Paris, Paris, France
4CIC-1419 Inserm, Cochin-Necker, Paris, France
5Department of Neonatology, Nantes University Hospital, Nantes, France
6Centre d'Investigation ClinIque, CIC1413, INSERM, Nantes University Hospital, Nantes, France
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.6 MB)
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Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2021-09-02


Aim: According to experimental studies, cardiopulmonary distress decreases after closure of patent ductus arteriosus. However, early closure of the ductus using ibuprofen or indomethacin has failed to increase survival without serious morbidity. We review relevant data aiming to define optimal early management strategies that promote early closure of ductus arteriosus without serious adverse effects.

Methods: Literature in English was searched selectively focusing on the potential of using acetaminophen for early closure of the ductus.

Results: Prophylactic ibuprofen or indomethacin intended to close the ductus, predisposes infants to ischaemia, bleeding and immune dysfunction. Acetaminophen appears to have a similar efficacy as indomethacin or ibuprofen, and all three dose-dependently constrict the ductus. Ibuprofen and indomethacin cause non-specific inhibition of prostaglandin synthesis, while acetaminophen predominantly inhibits prostaglandin E synthesis. Owing to low CYP450 activity in infancy, acetaminophen toxicity has been rarely evident. However, increasing the dosage increases the oxidative stress. We review prophylactic treatments that may increase the safety and efficacy of acetaminophen. These include vitamin A, cysteine and glutamine, and low-dose corticosteroid supplementation.

Conclusion: The current challenge is to define a safe perinatal management practice that promotes cardiorespiratory adaptation in immature infants, particularly the seamless closure of the ductus before significant cardiopulmonary distress develops.

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Series: Acta pædiatrica
ISSN: 0803-5253
ISSN-E: 1651-2227
ISSN-L: 0803-5253
Volume: 110
Issue: 7
Pages: 1995 - 2007
DOI: 10.1111/apa.15826
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3123 Gynaecology and paediatrics
Funding: This study was supported by Sigrid Jusélius Foundation, Finland.
Copyright information: © 2021 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.