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The Short-Term Outcome of a Large Cohort of Very Preterm Infants Treated with Poractant Alfa (Curosurf®) for Respiratory Distress Syndrome

A Postmarketing Phase IV Study

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Abstract

Objectives

To determine the effect of a porcine-derived lung surfactant, poractant alfa (Curosurf®), on the respiratory outcome of very preterm infants with established neonatal respiratory distress syndrome (RDS), and to identify risk factors for severe bronchopulmonary dysplasia (BPD) in this population.

Design

A multicenter prospective longitudinal cohort study of 924 very preterm infants with RDS, born between 23 and 32 weeks gestation, and treated with at least one dose of poractant alfa during the first 48 hours of life.

Results

The median gestational age and the mean birthweight were 29 weeks and 1210g, respectively; babies born at <28 weeks accounted for 27.1% of the cohort. Infants were treated with poractant alfa 7.9 hours after birth on average. Approximatively 32% of them required at least one additional dose. The mortality rate was 23.5%. The rates of survival without BPD at 28 days postnatal age and 36 weeks postmenstrual age were 38.9% and 54.0%, respectively. In the univariate analysis, factors associated with a higher risk of BPD at 36 weeks postmenstrual age (severe BPD) were low gestational age, low birthweight, poor response to the first dose, and the presence of pneumothorax, interstitial emphysema, pulmonary hemorrhage, patent ductus arteriosus requiring treatment, acquired pulmonary infection, or necrotizing enterocolitis. In the multivariate analysis, significant risk factors for severe BPD were low gestational age, low birthweight, and the presence of interstitial emphysema, pulmonary infection, or necrotizing enterocolitis.

Conclusion

The rate of RDS-related complications in this high-risk cohort was comparable to the rates observed in the pivotal trials. In very premature infants treated with poractant alfa for established RDS, early barotrauma and postnatal local and/or systemic inflammation are strongly associated with the subsequent development of severe BPD.

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Notes

  1. The use of tradenames is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Serono France carried out the logistics of the study (project GF 6363). The monitoring and database management were performed by a contract research organization, Biologie Industrie. In particular, the authors wish to thank E. Ecosse for the database analysis, I. Thiriet and T. Delmas, Serono, France, for their helpful discussion, and the attending neonatologists in the contributing units, listed as follow: P. Andrini, centre Hospitalier de Grenoble, région Rhône-Alpes; N. Ayass, centre Hospitalier d’Orléans, région Centre; M. Benoit, centre Hospitalier de Mulhouse, région Alsace; T. Blanc, centre Hospitalier de Rouen, région Haute Normandie; M.C. Bloom, centre Hospitalier de Toulouse, région Midi-Pyrénées; J.M. Bonardi, centre Hospitalier du Mans, région Centre; M.C. Bouchez, centre Hospitalier de Valenciennes, région Nord-Pas de Calais; C. Bouderlique, centre Hospitalier d’Angers, région Pays de Loire; J. Bourgeois, centre Hospitalier de Lyon, région Rhône-Alpes; O. Claris, centre Hospitalier de Lyon, région Rhône Alpes; C. Daleyrac, centre Hospitalier de Rennes, région Bretagne; C. Danan, centre Hospitalier de Créteil, région Ile de France; G. Dassieu, centre Hospitalier de Créteil, région Ile de France; D. Daoud, centre Hospitalier de Montreuil, région Ile de France; B. Delaporte, centre Hospitalier du Havre, région Haute Normandie; J.L. Demarquez, centre Hospitalier de Bordeaux, région Aquitaine; P. Ensel, centre Hospitalier de Rouen, région Basse Normandie; L. Egreteau, centre Hospitalier de Reims, région Champagne; M. Farhat, centre Hospitalier Port-Royal, Paris, région Ile de France; J.F. Feron, centre Hospitalier d’Orléans, région Centre; J.B. Gouyon, centre Hospitalier de Dijon, région Bourgogne; M.J. Guillemin, centre Hospitalier de Caen, région Basse Normandie; B. Guillois, centre Hospitalier de Caen, région Basse Normandie; M. Jugie, centre Hospitalier Necker-Enfants Malades, Paris, région Ile de France; C. Kassis, Institut de puériculture, Paris, région Ile de France; V. Lacroze, centre Hospitalier de Marseille, région Provence Alpes Côte d’Azur; P. Lagier, centre Hospitalier de Marseille, région PACA; J. Laugier, centre Hospitalier de Tours, région Centre; R. Lenclen, centre Hospitalier de Poissy, région Ile de France; J. Messer, centre Hospitalier de Strasbourg, région Alsace; M. Mokhtari, centre Hospitalier de St Vincent de Paul, Paris, région Ile de France; P. Morville, centre Hospitalier de Reims, région Champagne; D. Oriot, centre Hospitalier de Poitiers, région Poitou-Charentes; J.Y. Pauchard, centre Hospitalier de Besançon, région Franche-Comté; P. Pladys, centre Hospitalier de Rennes, région Bretagne; G. Putet, centre Hospitalier de Lyon, région Rhône-Alpes; P. Rambaud, centre Hospitalier de Toulouse, région Midi-Pyrénées; J.M. Retbi, centre Hospitalier de Saint-Denis, région Ile de France; C. Savagner, centre Hospitalier d’Angers, région Pays de Loire; J. Sizun, centre Hospitalier de Brest, région Bretagne; V. Tessier, centre Hospitalier de Tours, région Centre; G. Thiriez, centre Hospitalier de Besançon, région Franche Comté; D. Unal, centre Hospitalier de Marseille, région PACA; H. Walti, centre Hospitalier de Port Royal, région Ile de France; C. Zaoui, centre Hospitalier de Valenciennes, région Nord-Pas de Calais.

The study was funded by Serono Laboratories, France. As members of both the Scientific Advisory Board and the Steering and Writing Committee, Géraldine Lamboley-Gilmert and Thierry Lacaze-Masmonteil did receive an honorarium. These authors did not receive, either directly or indirectly, any other payments from Serono Laboratories, such as grants, funding for ongoing reserch, or compensation. These authors do not have any equity in Serono Laboratories, nor do they have a proprietary interest in any product mentioned in this study, or any incentive that could affect the outcome of the study. The monitoring and database management were done by an independent contract research organization (Biologie Industrie).

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Correspondence to Thierry Lacaze-Masmonteil.

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Lamboley-Gilmert, G., Lacaze-Masmonteil, T. The Short-Term Outcome of a Large Cohort of Very Preterm Infants Treated with Poractant Alfa (Curosurf®) for Respiratory Distress Syndrome. Pediatr-Drugs 5, 639–645 (2003). https://doi.org/10.2165/00148581-200305090-00006

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