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Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial, a double-blind randomized placebo-controlled trial. Setting: 24 congenital heart centers. Patients: Infants (&lt;\u20091\u00a0year old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons\u2013European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD). Interventions: Methylprednisolone (30\u00a0mg\/kg) versus placebo administered into cardiopulmonary bypass pump-priming fluid. Measurements and Main Results: Outcomes included death, heart transplantation, mechanical circulatory support, reinterventions, and hospital length of stay. Ranked composite outcome (death, transplant, or one of 13 major complications) was compared between placebo and methylprednisolone for each subgroup using the win ratio. Methylprednisolone did not reduce odds of death, transplant, or mechanical circulatory support for any subgroup. Those receiving methylprednisolone had fewer catheterization or surgical reinterventions after STAT Category 1\u20133 operations [OR 0.50 (0.29\u20130.86)]; and fewer reoperations for bleeding among patients undergoing STAT Category 1-3 operations [OR 0.28 (0.09\u20130.87)], term infants [OR 0.30 (0.12\u20130.76)], and those without CSD [OR 0.22 (0.07\u20130.68)]. Length of stay was no different between methylprednisolone versus placebo. Those without chromosomal or syndromic diagnosis demonstrated a favorable association for methylprednisolone [win ratio 1.28 (1.01\u20131.61)] for the composite outcome. Conclusion: Exploratory subpopulation analyses, although underpowered, suggest that methylprednisolone is not associated with significant harm and may benefit certain subpopulations<\/jats:p>","DOI":"10.1007\/s00246-025-03875-9","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T07:16:43Z","timestamp":1746170203000},"page":"1026-1034","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Reexploring the STRESS Trial: Subgroup Postoperative Outcomes Following Methylprednisolone for Infant Heart Surgery"],"prefix":"10.1007","volume":"47","author":[{"given":"Sudeep D.","family":"Sunthankar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey P.","family":"Jacobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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