STUDY OF DEXAMETHASONE IN NEONATAL LUPUS CHB

描述(取自申请表)： 新生儿狼疮目前被认为是被动获得性狼疮的一种模型 自身免疫--母亲的免疫异常(可能有全身性 红斑狼疮、干燥综合征或完全无症状)导致 抗SSA/Ro-SSB/La核糖核蛋白抗体的制备 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 房室传导阻滞，最常见的是三度房室传导阻滞和心肌炎。这个 死亡率接近20%，大多数儿童需要终生调步。 这一应用集中在诊断先天性心脏病的临床方法上 心脏传导阻滞(CHB)[介入性研究]和寻找早期 超声心动图损伤标志物[观察性研究]。在具体目标1中，a 随机、双盲、安慰剂对照试验将检查 每日口服地塞米松(4 Mg)对慢性乙型肝炎预后的影响。其基本原理在于 认为慢性乙肝是炎症过程的结果的假说 由母体抗Ro/La抗体决定。母亲，无论疾病活动如何 但每天需要不到10毫克的泼尼松，在30周前确定 怀孕时要怀的是患有慢性乙肝的胎儿，将随机接受 地塞米松或安慰剂(每臂50名患者)，至少6周。 主要观察指标包括新生儿心室率和射血。 出生时的残留率，以及是否有异常体液收集 根据分娩前最后一次胎儿超声心动图进行评估。次要结果 衡量标准包括出生时的阻塞程度、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 房室结功能障碍和/或最早的无创性超声心动图标志物 心肌损伤。目前尚不清楚房室结损伤是否 经过几个阶段的进展，最终结果是结节和 不可逆三级封堵。已经有人提出，全球炎症 工作心肌和周围心包可先于或伴随 房室结损伤。100名孕妇被认为是患糖尿病的高危人群 一名患有慢性乙型肝炎的儿童，根据先前记录的Ro/La抗体的存在而定义 到怀孕(无论他们是否有过前一个孩子 新生儿狼疮)，之后将从16周开始每周进行超声心动图检查 妊娠，特别注意机械性PR间期的延长 和/或发展为心肌功能障碍。胎儿发育的母亲 然后将第一、第二或第三度块随机接收 地塞米松或安慰剂作为特定目标的一部分1.这一点的重要性 第二个目标是双重的：首先，它将识别亚临床 作为晚期AV，组织损伤的发生率超过明显的损伤表现 解离；第二，它将提供最好的可逆性 阻断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.