STUDY OF DEXAMETHASONE IN NEONATAL LUPUS CHB

描述（取自应用程序）： 新生儿狼疮目前被认为是一种被动获得性 自身免疫性，即母亲的免疫异常（可能具有全身性 红斑狼疮、干燥综合征或完全无症状）导致 SSA/Ro-SSB/La核糖核蛋白抗体的产生， 穿过胎盘可能会伤害发育中的胎儿最严重的 表现为心脏损伤，包括不同程度的 房室（AV）传导阻滞，最常见的是三度和心肌炎。的 死亡率接近20%，大多数儿童需要终身起搏。 这种应用程序的重点是临床方法，以诊断先天性 心脏传导阻滞（CHB）[干预性研究]和寻找早期 超声心动图损伤标记物[观察性研究]。在具体目标1中， 随机双盲安慰剂对照试验将检查 每日口服地塞米松（4 mg）对CHB结局的影响。理由是 假设CHB是炎症过程介导的结果， 母亲抗Ro/La抗体。母亲，无论疾病活动如何 但需要少于10 mg泼尼松/天，在30周前确定 妊娠期携带CHB胎儿，将随机接受 地塞米松或安慰剂（每组50例患者）治疗至少6周。 主要结果指标包括新生儿心室率和射血率 出生时的分数，以及是否存在异常液体收集， 在分娩前的最后一次胎儿超声心动图上评估。次要结局 测量包括出生时的阻滞程度，胎龄，出生体重， 和心胸比率在具体目标2中，我们将尝试确定 房室结功能障碍的最早非侵入性超声心动图标志物和/或 心肌损伤目前尚不清楚房室结损伤是否 通过阶段进展，最终结果是淋巴结纤维化， 不可逆性三度传导阻滞有人提出，全球炎症 工作心肌和周围心包的损伤可能先于或伴随 房室结损伤。100名孕妇被认为有高风险， 患有CHB的儿童，定义为既往记录的Ro/La抗体存在 怀孕（不管他们是否有过以前的孩子， 新生儿狼疮），从16周开始每周进行超声心动图检查。 妊娠，特别注意机械PR间期的延长 和/或心肌功能障碍的发展。胎儿发育的母亲 然后将1度、2度或3度阻滞随机分配至接受 地塞米松或安慰剂作为特定目标1的一部分。这一点的重要性 第二个目标是双重的：首先，它将确定是否亚临床 组织损伤发生率超过明显损伤，表现为晚期AV 解离;第二，它将提供可逆性的最佳机会， 块给出早期病变的识别。

DESCRIPTION (Taken from the application): Neonatal lupus is currently considered a model of passively acquired autoimmunity whereby immune abnormalities in the mother (who may have systemic lupus erythematosus, Sjogrens syndrome, or be entirely asymptomatic) lead to the production of antibodies to the SSA/Ro-SSB/La ribonucleoproteins which cross the placenta and presumably injure the developing fetus. The most serious manifestation is cardiac injury which includes varying degrees of atrioventricular (AV) block, most often third degree, and myocarditis. The mortality approaches 20% and the majority of children require lifelong pacing. This application focuses both on the clinical approach to diagnosed congenital heart block (CHB) [interventional study] and the search for an early echocardiographic marker of injury [observational study]. In Specific Aim 1, a randomized double-blind placebo-controlled trial will examine the effect of daily oral dexamethasone (4 mg) on the outcome of CHB. The rationale rests on the hypothesis that CHB is the consequence of an inflammatory process mediated by maternal anti-Ro/La antibodies. Mothers, irrespective of disease activity but requiring less than 10 mg prednisone/day, identified before 30 weeks of gestation to be carrying a fetus with CHB, will be randomized to receive dexamethasone or placebo (50 patients per arm) for a minimum of 6 weeks. Primary outcome measures include neonatal ventricular rate and ejection fraction at birth, and presence or absence of abnormal fluid collection as assessed on the final fetal echocardiogram before delivery. Secondary outcome measures include the degree of block at birth, gestational age, birth weight, and cardiothoracic ratio. In Specific Aim 2, we will attempt to identify the earliest noninvasive echocardiographic marker of AV nodal dysfunction and/or myocardial injury. At present it is not known whether injury to the AV node progresses through stages with the final outcome being fibrosis of the node and irreversible third degree block. It has been proposed that global inflammation of the working myocardium and surrounding pericardium may precede or accompany AV nodal injury. One hundred pregnant women considered at high risk for having a child with CHB, as defined by presence of Ro/La antibodies documented prior to pregnancy (regardless of whether or not they have had a previous child with neonatal lupus), will be followed by weekly echocardiograms from 16 weeks of gestation, with special attention to prolongation of the mechanical PR interval and/or development of myocardial dysfunction. Mothers whose fetuses develop 1st, 2nd or 3rd degree block will then be randomized to receive either dexamethasone or placebo as part of Specific Aim 1. The importance of this second aim is twofold: first, it will identify whether the subclinical incidence of tissue injury exceeds overt injury manifest as advanced AV dissociation; and second, it will provide the best chance for reversibility of block given identification of early lesions.