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Original research
Doxapram for apnoea of prematurity and neurodevelopmental outcomes at age 5–6 years
  1. Ludovic Tréluyer1,2,
  2. Elodie Zana-Taieb2,3,
  3. Pierre-Henri Jarreau1,2,
  4. Valérie Benhammou1,
  5. Pierre Kuhn4,
  6. Mathilde Letouzey5,
  7. Laetitia Marchand-Martin1,
  8. Wes Onland6,7,
  9. Véronique Pierrat1,8,
  10. Lauren Saade2,
  11. Pierre Yves Ancel1,9,
  12. Héloïse Torchin1,2
  1. 1 Sorbonne Paris-Nord, Inserm, INRAE, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, Université Paris Cité, Paris, France
  2. 2 Department of Neonatal Medicine of Port-Royal, Cochin Hospital, FHU PREMA, AP-HP Centre–Université Paris Cité, Paris, France
  3. 3 Université Paris Cité, Inserm U955, Paris, France
  4. 4 Department of Neonatal Medicine, University Hospital of Strasbourg, Strasbourg, France
  5. 5 Department of Neonatal Medicine, Poissy Saint-Germain Hospital, Poissy, France
  6. 6 Department of Neonatal Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
  7. 7 Amsterdam Reproduction and Development Research Institute, Amsterdam, The Netherlands
  8. 8 Department of Neonatology, CHI Créteil, Créteil, France
  9. 9 Clinical Research Unit, Center for Clinical Investigation P1419, Assistance Publique-Hôpitaux de Paris, Paris, France
  1. Correspondence to Dr Ludovic Tréluyer, Sorbonne Paris-Nord, Inserm, INRAE, CRESS, Obstetrical Perinatal and Pediatric Epidemiology Research Team, EPOPé, Université Paris Cité, Paris, 75010, France; ludovic.treluyer{at}inserm.fr

Abstract

Objective To assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.

Design Secondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5–6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment.

Setting Population-based cohort study.

Patients All children born before 32 weeks’ gestation alive at age 5–6 years.

Interventions Blind and standardised assessment by trained neuropsychologists and paediatricians at age 5–6 years.

Main outcome measures Neurodevelopmental outcomes at age 5–6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built.

Results The population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6–30.9) weeks. At age 5–6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63).

Conclusions In children born before 32 weeks’ gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.

  • Child Development
  • Neonatology

Data availability statement

Data are available upon reasonable request. The study protocol, the data access charter and the data access procedure can be found on the EPIPAGE-2 website (https://epipage2.inserm.fr/index.php/fr/cote-recherche/235-acces-aux-donnees-et-questionnaires). Questionnaires and data catalogues are available on https://pandora-epipage2.inserm.fr/public/.

https://doi.org/10.1136/archdischild-2023-326170

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    Data availability statement

    Data are available upon reasonable request. The study protocol, the data access charter and the data access procedure can be found on the EPIPAGE-2 website (https://epipage2.inserm.fr/index.php/fr/cote-recherche/235-acces-aux-donnees-et-questionnaires). Questionnaires and data catalogues are available on https://pandora-epipage2.inserm.fr/public/.

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    Footnotes

    • Contributors Acquisition of data—LM-M, PYA and VB. Study concept—LT, EZ-T, PYA and HT. Analysis and interpretation of data—LT, PYA and HT. Drafting of the manuscript—LT. Critical revision of the manuscript for important intellectual content—all authors. Supervision—HT and PYA. Guarantor—PYA. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

    • Funding The EPIPAGE-2 Project was funded with support from: (1) the French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer and the National Solidarity Fund for Autonomy (CNSA); (2) the National Research Agency through the French EQUIPEX programme of investments in the future (reference ANR-11-EQPX-0038 and ANR-19-COHO-001); (3) the PREMUP Foundation; (4) Fondation de France (reference 11779); (5) Fondation pour la Recherche Médicale (SPF20160936356); (6) Programme Hospitalier de Recherche Clinique Epinutri (DGOS13-040); (7) Ministère de l'Enseignement Supérieur, De La Recherche et de L'Innovation (G13129KK); and (8) Apicil Foundation (R20065KK).

    • Disclaimer The funding organisations had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.