PRENATAL CORTICOSTEROIDS IN INFANTS WITH CONGENITAL DIAPHRAGMATIC HERNIA

先天性膈疝婴儿的产前皮质类固醇

• 批准号: 7375230
• 负责人: KRISA Page VAN MEURS
• 金额: $ 0.8万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7375230
• 关键词: PRENATAL; CORTICOSTEROIDS; INFANTS; CONGENITAL; DIAPHRAGMATIC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Congenital diaphragmatic hernia (CDH) occurs in approximately one out of every 2500 live births and has a mortality of 30-70% when diagnosed prenatally. Despite the aggressive support used to maintain adequate gas exchange in infants with CDH who present with early-onset severe respiratory failure, there is still a high failure rate with conventional management. There appears to be ample evidence that the lungs of animals and human infants with CDH show evidence of surfactant-deficient lung disease. With the increased use of prenatal ultrasound to evaluate fetal well being and establish appropriate gestational age, an increasing proportion of infants with CDH are diagnosed before delivery. Antenatal maternal steroids have been shown to be clearly beneficial for premature fetuses, by improving lung maturation and accelerating lung production of surfactant, thereby improving neonatal outcome. Such treatment appears to require at least 24 hours to produce an improvement in lung function, consistent with the time required for protein synthesis or enzyme induction. In the nitrogen rat model of CDH, there is now evidence that antenatal steroids reverse many of the histological and biochemical indices of immaturity. Improvements in oxygenation and lung compliance have also been shown with antenatal steroids in this model. While post-natal treatment with surfactant appears logical from these observations, in fact there is only anecdotal support for its use in infants with CDH, none of which has been the result of prospective randomized trials. Steroids are not widely administered after the thirty-fourth week of pregnancy since the normal lung is sufficiently mature at that time. In view of the previously described observations of fetal lung immaturity in CDH and the positive effects noted in fetal models of CDH, we propose a prospective, multicenter study to evaluate the effect of maternally administered corticosteroids to fetuses with diagnosed CDH. Hypothesis: The hypothesis of this study is that the administration of antenatal steroids to women carrying fetuses with proven CDH will significantly reduce the mortality for such fetuses compared to untreated fetuses with diagnosed CDH. Specific Aims: 1. To determine if prenatal steroids improve survival in CDH. 2. To determine if prenatal steroids improve lung function in infants with CDH. 3. To determine valid prenatal predictors of outcome for infants with CDH. Study Design: All mothers with fetuses diagnosed with CDH antenatally will be enrolled and asked to participate in the study. Following informed consent, mothers will be randomized to receive Betamethasone 12.5 mg or placebo beginning at 34 weeks gestation when 2 doses will be given 24 hours apart. An additional single dose of Betamethasone or saline placebo will be given at 35 weeks gestation and again at 36 weeks gestation. A total of 284 patients from 28 perinatal centers will be enrolled in the study.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。先天性腹股沟疝（CDH）发生在大约每2500个活产婴儿中有一个，产前诊断时死亡率为30-70%。尽管积极的支持，以维持足够的气体交换婴儿与CDH谁提出了早发性严重呼吸衰竭，仍然有一个高失败率与传统的管理。似乎有充分的证据表明，患有CDH的动物和人类婴儿的肺显示出表面活性剂缺乏性肺病的证据。随着产前超声用于评估胎儿健康状况和确定合适胎龄的应用越来越多，越来越多的CDH婴儿在分娩前被诊断出来。母体母体类固醇已被证明对早产儿明显有益，通过改善肺成熟和加速肺表面活性物质的产生，从而改善新生儿结局。这种治疗似乎需要至少24小时才能改善肺功能，这与蛋白质合成或酶诱导所需的时间一致。在CDH的氮大鼠模型中，现在有证据表明，产前类固醇逆转了许多不成熟的组织学和生化指标。在该模型中，产前类固醇也显示出氧合和肺顺应性的改善。虽然从这些观察结果来看，产后表面活性剂治疗似乎是合理的，但事实上，只有轶事支持其在CDH婴儿中的使用，其中没有一个是前瞻性随机试验的结果。类固醇在怀孕34周后不被广泛使用，因为正常的肺在那个时候已经足够成熟。鉴于先前描述的CDH胎儿肺不成熟的观察结果和CDH胎儿模型中观察到的积极作用，我们提出了一项前瞻性、多中心研究，以评估母体给予皮质类固醇对诊断为CDH的胎儿的影响。 假设：本研究的假设是，与未经治疗的确诊为CDH的胎儿相比，对患有确诊为CDH的胎儿的妇女产前给予类固醇将显著降低此类胎儿的死亡率。 具体目标： 1.以确定是否产前类固醇改善CDH的生存。 2.确定产前类固醇是否能改善先天性心脏病患儿的肺功能。 3.确定先天性髋关节脱位婴儿结局的有效产前预测因子。 研究设计：所有产前诊断为CDH胎儿的母亲都将入组并被要求参加本研究。在获得知情同意后，母亲将从妊娠34周开始随机接受倍他米松12.5 mg或安慰剂，两次给药间隔24小时。在妊娠35周和36周时分别给予额外的单剂量倍他米松或生理盐水安慰剂。来自28个围产期中心的共284名患者将入组本研究。