TRH AND THE PREVENTION OF CHRONIC LUNG DISEASE

产前糖皮质激素(CS)治疗可降低死亡率和发病率 小早产儿呼吸窘迫综合征(RDS)的发病率 总是很有效。在实验系统中，甲状腺的结合 激素和CS进一步加速表面活性物质的合成和释放， 肺水吸收，肺结构发育。我们 最近完成了一项多中心产前治疗试验(1986-89) 促甲状腺激素释放激素(TRH)加CS与单纯CS比较。这个 极低出生体重儿的慢性肺部疾病(CLD)发病率显著降低 (1500克以下)接受TRH+CS全面治疗的婴儿 (17.6%)与单纯接受CS组(43.9%)相比，P<0.05 0.01)。然而，研究中没有一名婴儿服用表面活性物质。 替代，现在已被证明可以降低死亡率和发病率 来自RDS，并被接受临床实践。年提出的临床试验 该应用程序将测试接受治疗的婴儿对TRH的反应 产前使用CS，产后使用表面活性物质替代(Exosurf)， 评估益处和可能的不利影响。此外, TRH+CS产前治疗减少的可能机制 将对慢性肺部疾病进行调查。五年中有一千二百个女人 有可能以较低价格生产早产儿的合作中心 将妊娠30周以上的孕妇随机分为2组。这个 治疗组予TRH+CS，对照组给予TRH+CS 安慰剂+CS。出生后，Exosurf将按以下规定使用 标准的临床标准。建议的样本量将提供90% 检测慢性阻塞性肺病风险从18%降至9%的权力 总体意向治疗组。关于亚群的补充分析 有风险(约720名极低出生体重儿在31.5周内出生 并且重量小于1500克)将具有95%的功率来检测 将慢性阻塞性肺病的风险从26%降低到15%。还将收集数据 研究CLD和指标演变中的几个因素 关于结果的。我们将测定表面活性蛋白A和B以及指示剂 支气管肺泡灌洗中的炎症反应及检测 血浆中甲状腺激素和皮质醇的浓度。肺 功能测量(包括顺应性、阻力和FRC)和 对动脉导管的研究将在#年的第一个月进行。 生活。将对研究婴儿进行长期随访。我们 出生前TRH加入CS和出生后表面活性物质的假说 更换将导致CLD的发生率降低，严重程度减轻 RDS，较短的住院时间和更好的长期结果。

Prenatal corticosteroid (CS) therapy reduces mortality and the incidence of respiratory distress syndrome (RDS) in small preterm infants but is not always effective. In experimental systems, the combination of thyroid hormone and CS further accelerates surfactant synthesis and release, resorption of lung water, and the development of lung structure. We recently completed a multicenter trial (1986-89) of prenatal treatment with thyrotropin-releasing hormone (TRH) plus CS vs CS alone. The incidence of chronic lung disease (CLD) was significantly reduced for VLBW (less than 1500 grams) infants who received full treatment with TRH + CS (17.6%) compared to the group who received only CS (43.9%, p is less than 0.01). However, none of the infants in the study received surfactant replacement, which has now been shown to reduce mortality and morbidity from RDS and is accepted clinical practice. The clinical trial proposed in this application will test the response to TRH among infants treated antenatally with CS and postnatally with surfactant replacement (Exosurf), evaluating both benefit and possible adverse effects. In addition, possible mechanisms by which antenatal treatment with TRH + CS reduces chronic lung disease will be investigated. Twelve hundred women in five cooperating centers who are at risk of delivering a preterm infant at less than 30 weeks gestation will be randomly assigned to 2 groups. The treatment group will receive TRH + CS, and the control group will receive placebo + CS. After birth, Exosurf will be administered according to standard clinical criteria. The sample size proposed will provide 90% power to detect a reduction of the risk of CLD from 18% to 9% in the overall intention-to-treat group. A supplemental analysis of the subgroup at risk (approximately 720 VLBW infants delivered at less than 31.5 weeks and weighing less than 1500 grams) will have 95% power to detect a reduction of the risk of CLD from 26% to 15%. Data will also be collected to study several factors involved in the evolution of CLD and indicators of outcome. We will assay surfactant proteins A and B and indicators of inflammatory response in bronchoalveolar lavage and determine concentrations of thyroid hormones and cortisol in plasma. Pulmonary function measurements (including compliance, resistance and FRC) and studies of the ductus arteriosus will be made over the first month of life. Long term follow-up of study infants will be performed. We hypothesize that antenatal TRH added to CS and postnatal surfactant replacement will result in lower incidence of CLD, decreased severity of RDS, shorter hospital stays and better long-term outcome.