The administration of low-dose hydrocortisone to extremely preterm infants was not associated with any adverse effects on neurodevelopmental outcomes at two years of age, according to a study in Paris.
Early low-dose hydrocortisone treatment in very preterm infants has been reported to improve survival without bronchopulmonary dysplasia (a form of chronic lung disease), but its safety with regard to neurodevelopment remains to be assessed.
Dr Olivier Baud and colleagues at the Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, Robert Debré Children’s Hospital in Paris and the Université Paris Diderot, Sorbonne Paris-Cité, Inserm U1141, analysed data from the PREMILOC trial, in which infants born between 24 0/7 weeks and 27 6/7 weeks of gestation and before 24 hours of postnatal age were randomly assigned to receive either placebo or low-dose hydrocortisone injection.
Of neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to two years of age. A total of 379 patients (93 percent) were evaluated at a median corrected age of 22 months.
The researchers found no statistically significant difference in patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group).
The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups.
"Further randomised studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants," the authors write.
Abstract
Importance: Dexamethasone to prevent bronchopulmonary dysplasia in very preterm neonates was associated with adverse neurodevelopmental events. Early low-dose hydrocortisone treatment has been reported to improve survival without bronchopulmonary dysplasia but its safety with regard to neurodevelopment remains to be assessed.
Objective: To assess whether early hydrocortisone therapy in extremely preterm infants is associated with neurodevelopmental impairment at 2 years of age.
Design, Setting, and Participants: An exploratory secondary analysis of the PREMILOC (Early Low-Dose Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia in Extremely Preterm Infants) randomized clinical trial conducted between 2008 and 2014 in 21 French neonatal intensive care units. Randomization was stratified by gestational age groups. Neurodevelopmental assessments were completed from 2010 to 2016.
Interventions: After birth, patients were randomly assigned to receive placebo or hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days).
Main Outcomes and Measures: The prespecified exploratory secondary outcome of neurodevelopmental impairment was based on a standardized neurological examination and the revised Brunet-Lézine scale (global developmental quotient score and subscores; mean norm, 100 [SD, 15]). The minimal clinically important difference on the global developmental quotient was 5 points.
Results: Of 1072 neonates screened, 523 were assigned to hydrocortisone (n = 256) or placebo (n = 267) and 406 survived to 2 years of age. A total of 379 patients (93%; 46% female) were evaluated (194 in the hydrocortisone group and 185 in the placebo group) at a median corrected age of 22 months (interquartile range, 21-23 months). The distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs 11% in the placebo group) was not statistically significantly different between groups (P = .33). The mean global developmental quotient score was not statistically significantly different between groups (91.7 in the hydrocortisone group vs 91.4 in the placebo group; between-group difference, 0.3 [95% CI, −2.7 to 3.4]; P = .83). The incidence of cerebral palsy or other major neurological impairments was not significantly different between groups.
Conclusions and Relevance: In this exploratory analysis of secondary outcomes of a randomized clinical trial of extremely preterm infants, early low-dose hydrocortisone was not associated with a statistically significant difference in neurodevelopment at 2 years of age. Further randomized studies are needed to provide definitive assessment of the neurodevelopmental safety of hydrocortisone in extremely preterm infants.
Authors
Olivier Baud, Clémence Trousson, Valérie Biran, Emilie Leroy, Damir Mohamed Corrine Alberti
[link url="https://www.sciencedaily.com/releases/2017/04/170404160134.htm"]JAMA material[/link]
[link url="http://jamanetwork.com/journals/jama/article-abstract/2614188"]JAMA abstract[/link]