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.

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General Clinical Research Centers Program (M01)
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Stanford University
Internal Medicine/Medicine
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United States
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