Lorek Miłosz, Stradomska Teresa Joanna, Siejka Anna, Fuchs Janusz, Januś Dominika, Gawlik-Starzyk Aneta
Department of Neonatal and Pediatric Intensive Care, John Paul II Center for Child and Family Health, Sosnowiec, Poland.
Department of Pediatrics and Pediatric Endocrinology, Medical University of Silesia, Katowice, Poland.
Front Endocrinol (Lausanne). 2025 May 16;16:1569355. doi: 10.3389/fendo.2025.1569355. eCollection 2025.
Adrenal steroidogenesis plays a pivotal role in neonatal adaptation, and advanced steroid profiling offers novel insights into disease risks and personalized management strategies. This study aimed to identify adrenal steroid metabolomic clusters in neonates and to correlate them with clinical outcomes.
In a prospective observational design (June 2021-July 2022), 50 neonates (12 early preterm, 18 late preterm, and 20 full-term) admitted with respiratory distress underwent continuous 24-hour urine collection via an urinary catheter. Steroid profiles were analyzed by gas chromatography-mass spectrometry. K-means clustering was employed to classify the metabolomic data, which were subsequently correlated with mortality, bronchopulmonary dysplasia (BPD), small for gestational age (SGA), and intraventricular hemorrhage (IVH).
K-means analysis delineated three distinct metabolic clusters. Cluster 1 displayed a profoundly suppressed steroidogenesis (low C19 and C21 excretion, diminished 3β-hydroxysteroid dehydrogenase and 5α-reductase activities), correlating with an increased incidence of BPD, high mortality risk scores, and significant rates of SGA/intrauterine growth restriction. Cluster 2 exhibited adrenal hyperactivation with elevated cortisol/cortisone derivatives, moderately increased C19/C21 metabolites, and partial 3β-HSD deficits, associated with a heightened risk of IVH and mortality. Cluster 3 showed robust steroidogenesis (high C19/C21 excretion and high 3β-HSD/5α-reductase activities), accompanied by the lowest mortality rates and absence of BPD or SGA/IUGR.
Suppressed steroidogenesis increased BPD, SGA, and mortality, while excessive cortisol output in Cluster 2 was associated with a higher risk of IVH. Robust steroidogenesis supported favorable outcomes, highlighting the potential for metabolome-guided interventions.
肾上腺类固醇生成在新生儿适应过程中起关键作用，先进的类固醇谱分析为疾病风险和个性化管理策略提供了新的见解。本研究旨在识别新生儿肾上腺类固醇代谢组学集群，并将其与临床结局相关联。
在一项前瞻性观察性设计（2021年6月至2022年7月）中，50例因呼吸窘迫入院的新生儿（12例极早早产儿、18例晚期早产儿和20例足月儿）通过尿管进行连续24小时尿液收集。通过气相色谱-质谱法分析类固醇谱。采用K均值聚类对代谢组学数据进行分类，随后将其与死亡率、支气管肺发育不良（BPD）、小于胎龄儿（SGA）和脑室内出血（IVH）相关联。
K均值分析确定了三个不同的代谢集群。集群1显示类固醇生成受到严重抑制（C19和C21排泄量低，3β-羟基类固醇脱氢酶和5α-还原酶活性降低），与BPD发病率增加、高死亡风险评分以及SGA/宫内生长受限的显著发生率相关。集群2表现为肾上腺过度激活，皮质醇/可的松衍生物升高，C19/C21代谢产物适度增加，3β-HSD部分缺乏，与IVH和死亡风险增加相关。集群3显示强大的类固醇生成（高C19/C21排泄量和高3β-HSD/5α-还原酶活性），死亡率最低，且无BPD或SGA/IUGR。
类固醇生成受抑制会增加BPD、SGA和死亡率，而集群2中皮质醇输出过多与IVH风险较高相关。强大的类固醇生成支持良好的结局，突出了代谢组学指导干预的潜力。
