TY - JOUR
T1 - Identifying effect modifiers of systemic hydrocortisone treatment initiated 7-14 days after birth in ventilated very preterm infants on long-term outcome
T2 - Secondary analysis of a randomised controlled trial
AU - Halbmeijer, Nienke Marjolein
AU - Sonnaert, Michel
AU - Swarte, Renate M.
AU - Koopman-Esseboom, Corine
AU - van Stuijvenberg, Margriet
AU - Mulder-de Tollenaer, Susanne
AU - Tan, Ratna N. G. B.
AU - Mohns, Thilo
AU - Bruneel, Els
AU - Steiner, Katerina
AU - Kramer, Boris W.
AU - Debeer, Anne
AU - van Weissenbruch, Mirjam M.
AU - Marechal, Yoann
AU - Blom, Henry
AU - Plaskie, Katleen
AU - Offringa, Martin
AU - Merkus, Maruschka P.
AU - Onland, Wes
AU - Leemhuis, Aleid G.
AU - van Kaam, Anton H.
N1 - Funding Information: The SToP-BPD Study was funded by a project grant from the Netherlands Organization for Health Research and Development (ZonMW) Priority Medicines for Children (no. 11-32010-02). Publisher Copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - Objective: To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA). Design: Secondary analysis of a randomised placebo-controlled trial. Setting: Dutch and Belgian neonatal intensive care units. Patients: Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life. Intervention: Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). Main outcome measures: The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots. Results: The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups. Conclusion: This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.
AB - Objective: To explore clinical effect modifiers of systemic hydrocortisone in ventilated very preterm infants for survival and neurodevelopmental outcome at 2 years' corrected age (CA). Design: Secondary analysis of a randomised placebo-controlled trial. Setting: Dutch and Belgian neonatal intensive care units. Patients: Infants born <30 weeks' gestational age (GA), ventilator-dependent in the second week of postnatal life. Intervention: Infants were randomly assigned to systemic hydrocortisone (cumulative dose 72.5 mg/kg; n=182) or placebo (n=190). Main outcome measures: The composite of death or neurodevelopmental impairment (NDI) at 2 years' CA and its components. Candidate effect modifiers (GA, small for GA, respiratory index, sex, multiple births, risk of moderate/severe bronchopulmonary dysplasia or death) were analysed using regression models with interaction terms and subpopulation treatment effect pattern plots. Results: The composite outcome was available in 356 (96.0%) of 371 patients (one consent withdrawn). For this outcome, treatment effect heterogeneity was seen across GA subgroups (<27 weeks: hydrocortisone (n=141) vs placebo (n=156), 54.6% vs 66.2%; OR 0.61 (95% CI 0.38 to 0.98); ≥27 weeks: hydrocortisone (n=30) vs placebo (n=31), 66.7% vs 45.2%; OR 2.43 (95% CI 0.86 to 6.85); p=0.02 for interaction). This effect was also found for the component death (<27 weeks: 20.1% vs 32.1%; OR 0.53 (95% CI 0.32 to 0.90); ≥27 weeks: 28.1% vs 16.1%; OR 2.04 (95% CI 0.60 to 6.95); p=0.049 for interaction) but not for the component NDI. No differential treatment effects were observed across other subgroups. Conclusion: This secondary analysis suggests that in infants <27 weeks' GA, systemic hydrocortisone may improve the outcome death or NDI, mainly driven by its component death. There was insufficient evidence for other selected candidate effect modifiers.
KW - Infant Development
KW - Neonatology
KW - Respiratory Medicine
UR - http://www.scopus.com/inward/record.url?scp=85173470872&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/archdischild-2023-325558
DO - https://doi.org/10.1136/archdischild-2023-325558
M3 - Article
C2 - 37722765
SN - 1359-2998
JO - Archives of Disease in Childhood: Fetal and Neonatal Edition
JF - Archives of Disease in Childhood: Fetal and Neonatal Edition
M1 - fetalneonatal-2023-325558
ER -