Neonatal Intensive Care Unit, Assistance Publique-Hôpitaux de Paris, CHU Robert Debré, University Paris Diderot, Sorbone Paris Cité, Paris, France.
Unit of Clinical Epidemiology, Assistance Publique-Hôpitaux de Paris, CHU Robert Debré, University Paris Diderot, Sorbonne Paris-Cité, Inserm U1123 and CIC-EC 1426, Paris, France.
J Pediatr. 2021 Jul;234:65-70.e3. doi: 10.1016/j.jpeds.2020.12.057. Epub 2020 Dec 24.
To define nomograms of serum cortisol values before 24 hours of postnatal life for extremely preterm infants and determine whether baseline cortisol values affect the benefit/risk ratio of prophylactic hydrocortisone to improve survival without bronchopulmonary dysplasia (BPD).
We performed a predefined secondary analysis of the multicenter randomized controlled PREMILOC trial that included inborn infants delivered before 28 weeks of gestation. Nomograms of baseline serum cortisol values measured in 325 enrolled patients were determined for male and female neonates and correlated to perinatal events. BPD-free survival and severe adverse events were analyzed in placebo and hydrocortisone groups according to the cortisol z score in multivariate logistic regression models.
Increased cortisol levels measured before 24 hours following birth were associated with a significantly higher chance of BPD-free survival only in placebo-treated infants (aOR [95% CI] 1.57 [1.08-2.27], P = .02) based on sex-specific nomograms for baseline cortisol levels. The cortisol z score for infants treated with prophylactic hydrocortisone predicted a risk of high-grade intraventricular hemorrhage (aOR [95% CI] 1.82 [1.06-3.15], P = .03) and spontaneous intestinal perforation (aOR [95% CI] 4.81 [1.34-17.22], P = .02).
We found no predictive value of baseline cortisol levels for BPD-free survival in infants born extremely preterm treated with hydrocortisone. However, high cortisol levels early after birth were associated with a greater risk of severe intraventricular hemorrhage and spontaneous intestinal perforation in infants treated with hydrocortisone and, therefore, a lower benefit/risk ratio for the treatment.
EudraCT 2007-002041-20, ClinicalTrial.gov: NCT00623740.
为极早产儿建立出生后 24 小时内血清皮质醇值的列线图，并确定基础皮质醇值是否影响预防性氢化可的松改善无支气管肺发育不良（BPD）生存率的获益/风险比。
我们对多中心随机对照 PREMILOC 试验进行了预设的二次分析，该试验纳入了 28 周前分娩的宫内婴儿。对 325 名入组患者的基础血清皮质醇值进行了列线图分析，以确定男婴和女婴的基础皮质醇值，并与围产期事件相关联。根据皮质醇 z 评分，在多变量逻辑回归模型中分析了安慰剂和氢化可的松组的无 BPD 生存率和严重不良事件。
出生后 24 小时内皮质醇水平升高仅与安慰剂治疗婴儿的无 BPD 生存率显著相关（aOR[95%CI]1.57[1.08-2.27]，P=0.02），基于基础皮质醇水平的性别特异性列线图。接受预防性氢化可的松治疗的婴儿的皮质醇 z 评分预测了高级别颅内出血的风险（aOR[95%CI]1.82[1.06-3.15]，P=0.03）和自发性肠穿孔（aOR[95%CI]4.81[1.34-17.22]，P=0.02）。
我们发现，接受氢化可的松治疗的极早产儿出生后基础皮质醇水平对无 BPD 生存率无预测价值。然而，出生后早期皮质醇水平升高与接受氢化可的松治疗的婴儿发生严重颅内出血和自发性肠穿孔的风险增加相关，因此治疗的获益/风险比降低。
EudraCT 2007-002041-20，ClinicalTrials.gov：NCT00623740。
