Effect of Systemic Hydrocortisone Initiated 7 to 14 Days After Birth in Ventilated Preterm Infants on Mortality and Neurodevelopment at 2 Years’ Corrected Age
Authors: Nienke M. Halbmeijer, Wes Onland, Filip Cools, Renate Swarte, Marja van der Heide-Jalving, Maruschka P. Merkus, Anton H. van Kaam, Peter H. Dijk, Susanne Mulder-de Tollenaer, Ratna Tan, Thilo Mohns, Els Bruneel, Arno F. van Heijst, Boris W. Kramer, Anne Debeer, Mirjam van Weissenbruch, Yoann Marechal, Henry Blom, Katleen Plaskie, Martin Offringa, Aleid G. van Wassenaer-Leemhuis, Debbie H. Nuytemans, Moniek van de Loo, Ingrid van Limberghen, Andre Kroon, Nienke Rietema, Annette van der Kaa, Patricia Kalkman, Karin Rademaker, Corine Koopman-Esseboom, Ingrid C. van Haastert, Ellen de Kort, Marieke Vervoorn, Eric Cavatorta, Anne Rassart, An Eerdekens, Isabelle Hermans, Julie Messiaen, Margriet Stuijvenberg, René Matthijsse, Willem de Boode, Wendy Jansen, Hendrik Niemarkt, Ilse van Hattum, Astrid Giezen, Henrica L. van Straaten, Arjan B. te Pas, Romy Berkhout, Claire Theyskens, Inge Zonnenberg, Elke Dierckx
Journal: JAMA (2021)

A randomized, double-blind, placebo-controlled trial investigating the efficacy and safety of systemic hydrocortisone treatment initiated 7 to 14 days after birth in ventilatordependent, very preterm infants found no significant difference in the composite primary outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. 1 However, a preplanned exploratory analysis found a reduced risk of death at 36 weeks' postmenstrual age in favor of hydrocortisone.We examined the prespecified follow-up of death and neurodevelopmental impairment (NDI) at 2 years' corrected age. Methods |The STOP-BPD study was performed in 16 neonatal intensive care units in the Netherlands and Belgium (enrollment November 15, 2011, to December 23, 2016; final follow-up June 27, 2019).Infants born at a gestational age less than 30 weeks and/or with a birth weight less than 1250 g and ventilator dependent between days 7 and 14 were randomly assigned to a 22-day course of systemic hydrocortisone (cumulative dose, 72.5 mg/kg) or placebo.The human research ethics committees approved the protocol and written parental informed consent was obtained. 1 The key outcome at 2 years' corrected age was a composite of death or NDI, with NDI defined as presence of 1 or more of the following: cognitive and/or motor composite score less than 85 on the Bayley Scales of Infant and Toddler Development Third Edition, Dutch version; cerebral palsy greater than level II in the Gross Motor Function Classification System; or hearing or visual impairment.Crude absolute risk differences (RDs) and odds ratios (ORs) with 95% CIs were calculated for the long-term outcome and its individual components for all infants as randomized.A logistic regression and generalized linear model were used to estimate, respectively, the OR and RD for the composite outcome adjusted for stratification factors (center, gestational age).Potential confounding was examined using multivariable logistic regression models with the preselected risk factors of gestational age and small for gestational age for the composite outcome, supplemented with parental education and multilingual environment for the NDI component, and with respiratory index (product of mean airway pressure and the fraction of inspired oxygen), sex, and multiple birth for the death component.Missing data of the key long-term outcome were not imputed because there was sufficient information to classify this outcome in more than 95% of the participants.