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Drug exposure for PDA closure in France: a prospective, cohort-based, analysis

  • Pharmacoepidemiology and Prescription
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation.

Methods

A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was “a medically treated PDA,” defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure.

Results

The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72–0.90), paracetamol as the first-line treatment (0.32; 0.15–0.68), and pharmacological treatment before 48 h of life (0.63; 0.43–0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p < 0.0001).

Conclusion

Drug utilization patterns in infants with PDA vary among centers. Pharmacoepidemiology studies can provide new information on factors associated with PDA refractory to medical treatment.

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Acknowledgments

We thank all doctors and hospitals who accepted the principle of continuous benchmarking as a way for an improved quality of care: ABASSE Soumeth CH Mayotte, AUTRET Fanny Hôpital Privé St-Joseph Paris, BINSON Guillaume CHU Poitiers, BRAT Roselyne CHR Orléans, BOIZE Philippe CH Pontoise, CAEYMAEX Laurence CHI Créteil, CENERIC Alexandre CHU Caen, DESBRUYERES Céline CH Métropole Savoie, Di MAIO Massimo CHU Nîmes, ELGELLAB Abdellah CH Lens, ESCOURROU Guillaume CHI Montreuil, FLAMEIN Florence CHRU Lille, FLECHELLES Olivier CHU Fort-de-France, GIRARD Olivier CH St-Denis, KARAOUI Leila CH Meaux, KUGBE Yaovi CH Ouest Guyanais, LAFON Catherine CH Arras, LE BAIL DANTEC Florence CH St-Brieuc, MAZEIRAS Gaël CH Côte Basque, MOURDIE Julien CH Le Havre, MOUSSY-DURANDY Amélie CHI Poissy-St-Germain, NORBERT Karine CH Pau, PAGES Anne-Sophie CH Cotentin, RAMFUL Duksha CHU St-Denis de La Réunion, RANDRIANJAFINIMPANANA Heritiana CH Cayenne, RAZAFIMAHEFA Hasinirina CH Sud Francilien, ROSENTHAL Jean-Marc CHU Guadeloupe, and ZIAD Assaf Necker-Enfants Malades.

Funding

This study is part of a European research program FEDER number 2014–34018 (https://ec.europa.eu/regional_policy/en/funding/erdf/) about benchmark of prescription in NICU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Néonatologie, Réanimation Néonatale et Pédiatrique, CHU La Réunion, Saint Pierre, France

    Silvia Iacobelli & Francesco Bonsante

  2. Centre d’Etudes Périnatales de l’Océan Indien (CEPOI, EA7388), Université de la Réunion, Saint Pierre, France

    Silvia Iacobelli, Simon Lorrain, Béatrice Gouyon, Jean-Bernard Gouyon & Francesco Bonsante

  3. Neonatologia e TIN Universitaria DIMO Università Bari, Bari, Italy

    Silvia Gambacorta & Nicola Laforgia

Authors
  1. Silvia Iacobelli
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  2. Simon Lorrain
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  3. Béatrice Gouyon
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  4. Silvia Gambacorta
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  5. Nicola Laforgia
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  6. Jean-Bernard Gouyon
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  7. Francesco Bonsante
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Contributions

SI conceptualized the study, participated in the interpretation of the results, and wrote the paper; SL was in charge of the database quality check and formal analyses; BG contributed substantially to the conception of the study; SG participated in the redaction of the study protocol; NL critically reviewed the manuscript draft; JBG participated in the interpretation of the results and critically reviewed the manuscript. FB conceptualized and designed the study, oversaw the data analysis and interpretation, and critically reviewed and revised the manuscript drafts. All authors accept responsibility for the paper as submitted. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Silvia Iacobelli.

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Competing interests

Competing interests: Dr. Beatrice Gouyon (3rd author) was in charge of the B-PEN program (Benchmarking of Prescription in Neonatology) in the research center (CEPOI) from 2012 to 2016. Her employer was the University Hospital (CHU) of La Réunion. Then Dr. B Gouyon left the CEPOI to take the lead of a new start-up (LogipremF comp.) responsible for the development of the prescription software Logipren and its implementation in the NICUs of the B-PEN network. This change of affiliation has been contracted with the University Hospital of La Réunion, after authorization from the “Commission de Déontologie de la Fonction Publique” was obtained. Dr. B Gouyon remained closely involved in the research projects issued from the B-PEN database particularly. All other authors declare that they have no competing interests.

Ethics approval

This study was conducted in accordance with French legislation. As per French law applicable to trials involving human subjects (Jardé Act), a specific approval of an ethics committee is not required for this non-interventional study based on anonymized data of authorized collections (declaration number CNIL: DE-2015-099, DE-2017-410).

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All authors approved the final manuscript and gave consent for publication.

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Iacobelli, S., Lorrain, S., Gouyon, B. et al. Drug exposure for PDA closure in France: a prospective, cohort-based, analysis. Eur J Clin Pharmacol 76, 1765–1772 (2020). https://doi.org/10.1007/s00228-020-02974-1

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  • DOI: https://doi.org/10.1007/s00228-020-02974-1

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