Randomized Trial of Antenatal Late Preterm Steroids (ALPS) - Clinical Coordinatin

描述（由申请人提供）：使用产前类固醇加速胎儿肺发育并诱导内源性表面活性物质产生可能是产科领域改善极早产儿结局的最重要进展之一。1994年美国国立卫生研究院共识会议的建议是，所有妊娠24至33周的孕妇，如果在7天内有早产风险，应考虑接受单疗程皮质类固醇产前治疗。然而，极早产儿占早产儿的比例相对较小。2005年，超过9%的分娩在34至36周之间，其中三分之一估计有某种形式的呼吸道疾病。2005年，在国家儿童健康和人类发展研究所（NICHD）研讨会上，为解决这一新出现的问题，提出了改善结果的建议之一是调查产前皮质类固醇在这一“晚期早产”人群中的使用情况。 这项研究是NICHD MFMU网络的合作成果，该网络由14个学术临床中心、一个数据协调中心和NICHD的妊娠和围产期学分支组成。拟议的研究设计是一项随机、双盲、临床试验，纳入2800名单胎妊娠妇女，这些妇女在34周0天至36周5天之间发生自发性早产或胎膜破裂，或其护理提供者计划在未来7天内分娩，不迟于36周6天。将排除妊娠期间既往使用皮质类固醇的女性以及预计在6小时内分娩的女性。在随机化之前通过标准化算法确定生育年龄。合格且同意的女性将被随机分配至两次肌内注射12 mg倍他米松的疗程，间隔24小时，或相似疗程的相同外观安慰剂。首次给药将在随机化后立即进行。将对所有女性进行随访，直至分娩后出院，对新生儿进行随访，直至出院或120日龄，以较早者为准。 复合主要结局是24小时内死产或新生儿死亡或出生后72小时内需要新生儿呼吸支持。呼吸支持定义为使用持续气道正压通气或加湿高流量鼻插管至少连续2小时，FiO2 e 0.3的氧气需求至少连续4小时，或使用机械呼吸机。ECMO的使用也包括在主要结局中。 总之，产前皮质类固醇有可能降低早产晚期出生的新生儿的呼吸道发病率，这反过来又可以转化为儿童健康的持久改善，并减轻医疗保健系统的负担。 公共卫生相关性：在过去10年中，早产率的增加部分是由于晚期早产的增加，晚期早产的定义是34至36周之间的分娩。晚期早产儿更容易出现呼吸窘迫、体温过低和黄疸等并发症，并且比足月出生的婴儿更频繁地再次入院。产前使用皮质类固醇已被证明可以改善极早产儿的肺功能，但尚未在那些可能在早产后期分娩的婴儿中进行评估。如果显示出减少呼吸支持的需要，从而降低特殊护理托儿所的入住率并改善短期结果，则公共卫生和经济影响将是相当大的。

DESCRIPTION (provided by applicant): The use of antenatal steroids to accelerate fetal lung development and induce endogenous surfactant production is perhaps one of the most important advances in the field of obstetrics to improve the outcome of the very premature neonate. The recommendation of the 1994 NIH Consensus Conference was that all pregnant women between 24 and 33 completed weeks of gestation who are at risk of preterm delivery within 7 days should be considered candidates for antenatal treatment with a single course of corticosteroids. However the very premature infant accounts for a relatively small portion of preterm birth. Over 9% of all births in 2005 were between 34 and 36 completed weeks with a third of those estimated to have some form of respiratory morbidity. In 2005, at a National Institute of Child Health and Human Development (NICHD) workshop to address this emerging issue, one of the recommendations made to improve outcomes was to investigate the use of antenatal corticosteroids in this "late preterm" population. This study is a collaborative effort of the NICHD MFMU Network, which consists of fourteen academic clinical centers, a data coordinating center, and the Pregnancy and Perinatology Branch of the NICHD. The proposed study design is a randomized, double-masked, clinical trial of 2800 women with a singleton pregnancy who are between 34 weeks 0 days and 36 weeks 5 days with spontaneous preterm labor or ruptured membranes, or whose care providers have scheduled delivery to take place in the next 7 days, and no later than 36 weeks 6 days. Women with prior corticosteroid use during pregnancy, and those whose delivery is expected within 6 hours will be excluded. Gestational age is determined by a standardized algorithm prior to randomization. Eligible and consenting women will be randomized to a course of two intramuscular injections containing 12 mg of betamethasone, 24 hours apart or to a similar course of an identically appearing placebo. The first dose will be administered immediately after randomization. All women will be followed until hospital discharge following delivery and neonates until discharge or 120 days of age, whichever is sooner. The composite primary outcome is stillbirth or neonatal death before 24 hours or the need for neonatal respiratory support within the first 72 hours of life. Respiratory support is defined as the use of continuous positive airway pressure or humidified high-flow nasal cannula for at least two continuous hours, oxygen requirement of FiO2 e 0.3 for at least four continuous hours, or mechanical ventilator use. The use of ECMO is also included in the primary outcome. In summary, antenatal corticosteroids could potentially reduce respiratory morbidity in newborn infants born in the late preterm period, which in turn could translate into a lasting improvement in the health of children, and a reduction in burden on the health care system. PUBLIC HEALTH RELEVANCE: The increase in the rate of preterm birth over the past 10 years has been driven in part by the increase in late preterm births, defined as those births occurring between 34 and 36 weeks. Late preterm infants are more likely to suffer complications such as respiratory distress, hypothermia, and jaundice and are readmitted to the hospital more frequently than infants born at term. The use of antenatal corticosteroids has been shown to improve lung function in very premature infants, but has not been evaluated in those likely to deliver in the late preterm period. If shown to reduce the need for respiratory support and thus to decrease the rate of special care nursery admissions and improve short-term outcomes, the public health and economic impact will be considerable.