Association between Baseline Cortisol Serum Concentrations and the Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants
Chloe Renolleau, Artemis Toumazi, Aurélie Bourmaud, Jean-François Benoist, Didier Chevenne, Damir Mohamed, Corinne Alberti, Valérie Biran, Olivier Baud, PREMILOC Trial Study Group, Valérie Biran, Caroline Farnoux, Sophie Soudée, Laure Maury, Michèle Granier, Florence Lebail, Duksha Ramful, Sylvain Samperiz, Alain Beuchée, Karine Guimard, Fatima El Moussawi, Pascal Boileau, Florence Castela, Claire Nicaise, Renaud Vialet, Pierre Andrini, Thierry Debillon, Véronique Zupan-Simunek, Hasinirina Razafimahefa, Anne Coursol, Saïd Merbouche, Pascal Bolot, Jean-Marc Kana, Julie Guichoux, Olivier Brissaud, Gérard Thiriez, Olivier Schulze, Mickael Pomedio, Patrice Morville, Thierry Blanc, Stéphane Marret, Bernard Guillois, Cénéric Alexandre, Stéphane Le Bouëdec, Bertrand Leboucher, Umberto Simeoni, Valérie Lacroze, Pierre Kuhn, Stéphanie Litzler-Renaud, Elodie Zana-Taïeb, Pierre-Henri Jarreau, Sylvain Renolleau, Virginie Meau-Petit, Gilles Cambonie, Aline Rideau Batista-Novais, Chloe Renolleau, Artemis Toumazi, Aurélie Bourmaud, Jean-François Benoist, Didier Chevenne, Damir Mohamed, Corinne Alberti, Valérie Biran, Olivier Baud, PREMILOC Trial Study Group, Valérie Biran, Caroline Farnoux, Sophie Soudée, Laure Maury, Michèle Granier, Florence Lebail, Duksha Ramful, Sylvain Samperiz, Alain Beuchée, Karine Guimard, Fatima El Moussawi, Pascal Boileau, Florence Castela, Claire Nicaise, Renaud Vialet, Pierre Andrini, Thierry Debillon, Véronique Zupan-Simunek, Hasinirina Razafimahefa, Anne Coursol, Saïd Merbouche, Pascal Bolot, Jean-Marc Kana, Julie Guichoux, Olivier Brissaud, Gérard Thiriez, Olivier Schulze, Mickael Pomedio, Patrice Morville, Thierry Blanc, Stéphane Marret, Bernard Guillois, Cénéric Alexandre, Stéphane Le Bouëdec, Bertrand Leboucher, Umberto Simeoni, Valérie Lacroze, Pierre Kuhn, Stéphanie Litzler-Renaud, Elodie Zana-Taïeb, Pierre-Henri Jarreau, Sylvain Renolleau, Virginie Meau-Petit, Gilles Cambonie, Aline Rideau Batista-Novais
Abstract
Objective: To define nomograms of serum cortisol values before 24 hours of postnatal life for extremely preterm infants and determine whether baseline cortisol values affect the benefit/risk ratio of prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia (BPD).
Study design: We performed a predefined secondary analysis of the multicenter randomized controlled PREMILOC trial that included inborn infants delivered before 28 weeks of gestation. Nomograms of baseline serum cortisol values measured in 325 enrolled patients were determined for male and female neonates and correlated to perinatal events. BPD-free survival and severe adverse events were analyzed in placebo and hydrocortisone groups according to the cortisol z score in multivariate logistic regression models.
Results: Increased cortisol levels measured before 24 hours following birth were associated with a significantly higher chance of BPD-free survival only in placebo-treated infants (aOR [95% CI] 1.57 [1.08-2.27], P = .02) based on sex-specific nomograms for baseline cortisol levels. The cortisol z score for infants treated with prophylactic hydrocortisone predicted a risk of high-grade intraventricular hemorrhage (aOR [95% CI] 1.82 [1.06-3.15], P = .03) and spontaneous intestinal perforation (aOR [95% CI] 4.81 [1.34-17.22], P = .02).
Conclusions: We found no predictive value of baseline cortisol levels for BPD-free survival in infants born extremely preterm treated with hydrocortisone. However, high cortisol levels early after birth were associated with a greater risk of severe intraventricular hemorrhage and spontaneous intestinal perforation in infants treated with hydrocortisone and, therefore, a lower benefit/risk ratio for the treatment.
Trial registration: EudraCT 2007-002041-20, ClinicalTrial.gov: NCT00623740.
Keywords: bronchopulmonary dysplasia; cortisol; extremely preterm birth; hydrocortisone.
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Source: PubMed