染色体微阵列分析技术应用于筛查胎儿先天性心脏病的研究进展

先天性心脏病（congenital heart disease,CHD）是一种常见的出生缺陷,是由环境和遗传因素共同引起,其中遗传因素发挥着主要作用。G显带核型检测、荧光原位杂交,及染色体微阵列分析（CMA）技术是目前常见的基因诊断技术,近年来,CMA技术已逐渐成为产前诊断胎儿CHD的一线方法。CMA的主要优点之一是它能够精确定义不平衡区域,可明确诊断微缺失或微重复综合征,同时也可检测到大量的临床意义不明的拷贝数变异。在检测产前样本中总拷贝数变异时,拷贝数变异检测具有高可靠性、准确性和再现性的特点。但在许多情况下,拷贝数变异对CHD患儿心脏发育的影响尚不清楚。该文将以染色体微阵列分析技术为重点,对其在胎儿CHD的诊断意义及预后指导作一综述。     

基因拷贝数变异与先天性心脏病的研究进展

基因拷贝数变异是指与参考基因组相比,长度在1 kb以上的DNA片段缺失、插入、重复和复杂多位点的变异.基因拷贝数变异存在于人类和其他哺乳动物基因组中,与包括先天性心脏病在内的一系列复杂遗传性疾病相关.基因拷贝数变异是目前的研究热点之一.该文就基因拷贝数变异的概念、检测方法、在先天性心脏病领域进展作一综述.     

微阵列分析技术检测脑发育迟缓患儿基因拷贝数变异

目的 分析发育迟缓患儿基因拷贝数变异(CNVs)与临床表现的相关性.方法 应用微阵列单核苷酸多态性(SNP array)分析技术对1例发育迟缓患儿及其临床表型正常的父母亲进行全基因组CNVs分析.结果 在患儿chr8p23.3p23.1区域发现7.9 Mb片段缺失,在chr8p23.1p11.23区域发现27.4 Mb片段重复;在患儿父亲chr7q31.1区域发现1.21 Mb重复,chrXp22.33区域发现99 kb缺失;患儿母亲未检测到CNVs改变.结论 SNP array技术有助于进一步明确发育迟缓患儿的遗传机制.     

MRI技术在胎儿先天性心脏病诊断中的应用

先天性心脏病是造成新生儿死亡的主要原因之一.在产前对胎儿先天性心脏病进行诊断、评估预后是目前围生医学发展的重要内容.胎儿心脏彩超对于孕中期胎儿先天性心脏病的诊断具有相对较高的灵敏度,是胎儿先天性心脏畸形诊断的金标准.胎儿心脏核磁共振技术在过去十年内发展迅速,其视野大、可重复性好等优点在某些情况下可以弥补胎儿心脏超声的不足,但其技术上的问题也局限了其在临床上的应用,目前被认为是胎儿先天性心脏病的二线诊断方法.该文就胎儿心脏核磁共振技术在胎儿先天性心脏病诊断中应用的方法、优势以及局限性进行综述.     

胰岛因子1基因2个SNP位点与儿童先天性心脏病的相关性研究

目的：探讨天津地区汉族儿童胰岛因子1（Islet1,ISL1）基因2个单核苷酸多态性（SNP）位点rs41268421、rs1017与先天性心脏病（CHD）的相关性。方法：应用聚合酶链反应（PCR）和基因测序技术对35例CHD患儿和30名除外CHD儿童的rs41268421、rs1017位点进行检测,分别比较两个SNP位点基因型频率和等位基因频率在两组的分布情况,并进行单体型分析。结果：SNP位点rs41268421存在GG、GT、TT 3种基因型,CHD组T等位基因频率及携带T等位基因的基因型（包括GT和TT）频率高于对照组（P<0.05）,携带T等位基因的儿童患CHD的危险是G等位基因的4.833倍;rs1017 位点存在AA、AT、TT 3种基因型,CHD组T等位基因频率及携带T等位基因的基因型（包括AT和TT）频率高于对照组（P<0.05）,携带T等位基因的儿童患CHD的危险是A等位基因的4.491倍;2个SNPs位点得出4种单体型,以TT型儿童发生CHD的危险性最高（OR=7.813）。结论：天津地区汉族儿童中ISL1基因单体型TT的出现很可能会增加CHD的患病风险。     

胎儿先天性心脏病和心律失常的诊断及干预

目的 研究胎儿超声心动图产前诊断先天性心脏病（简称先心病）和经胎盘治疗胎儿心律失常的价值。方法 应用国产FECG－D型胎儿心电图仪筛查,结合胎儿超声心动图检测第1胎患先心病的460例胎龄为18－40周的高危胎儿,超声仪采用ALT、Maker LX和TOSHBA SSA 40A多普勒彩色超声仪,探头频率为3．5MHz。结果 发现先心病8例,同胞一级亲属患病率为1．7％。先心病的类型：房间隔缺损（简称房缺）3例（其中1例合并胎儿水肿）,室间隔缺损（简称室缺）13例（其中1例合并神经管缺损）,完全性的房室管缺损1例,法洛四联症1例。检出23例胎儿心律失常,检出率为5．0％,以室上性心动过速（简称室上速）最多见（13例）,首选地高辛经胎盘治疗,7例有效,其中3例合并先心病或心力衰竭者加用异博定2例有效,1例因有严重的非免疫性胎儿水肿而死亡;3例窦性心运过速（简称窦速）患儿用心得安治疗有效,1例频发室性早博用普鲁卡因酰胺治疗后转复。3例妊娠晚期的室上速和2例室上性早博未用药,经阴道分娩后转复。结论 胎儿超声心动图是产前诊断胎儿心脏异常的重要手段,地高辛是经胎盘治疗胎儿快速心律失常的首选药物。     

妊娠早中期胎儿超声心动图诊断先天性心脏病的临床价值

胎儿超声心动图检查是先天性心脏病产前诊断的最有效方法.妊娠早中期胎儿超声心动图筛查先天性心脏病的敏感性及特异性均较高,有序的分段多切面检查是保证诊断准确性的关键.由产科医生、超声科医生、小儿心脏科医生参与的多学科合作可改善胎儿预后,指导孕妇对妊娠过程进行正确的决策,对胎儿进行必要、合理的干预,对降低新生儿出生缺陷具有重要意义.     

胎儿先天性心脏病介入治疗进展

既往观点认为,一旦胎儿患有左心发育不良综合征(HLHS)等严重心血管畸形,结局就只能是出生后功能性单心室循环、心脏移植或中止妊娠.到目前为止,开放性胎儿心脏外科技术尚不成熟,而通过胎儿心脏介入治疗技术可以在很大程度上阻止因先天性心脏病引起的胎儿水肿、自发性流产或胎儿死亡,促进发育不良的心室重新发育,形成生后的双心室循环,重塑右室流出道梗阻胎儿的肺血管床等,改善了胎儿严重心血管畸形的预后.这些进步在很大程度上依赖于对胎儿先天性心脏病病理生理学特点的准确判断.超声技术的发展以及其他评价手段的进步可促进目前还比较有限的胎儿先天性心脏病介入治疗进一步发展.     

胎儿先天性心脏病治疗的进展

近年来随着心脏治疗及监护技术的飞速发展,许多复杂的先天性心脏病（简称先心病）在新生儿期就可以得到有效的治疗。然而对于左心发育不良等一些严重的先天性心脏畸形,如果在胎儿期未给予相关干预措施,部分病例在出生前心脏及大血管已经出现了不可逆病变”,从而失去了根治的机会。同时,患有严重先心病的胎儿比较容易出现宫内死亡或自发性流产。因此胎儿心脏病的治疗逐渐引起人们的重视。现对近年来胎儿先心病的治疗进展综述如下。     

Fetal echocardiography in the diagnosis of congenital heart disease

Abstract Fetal echocardiography provides an opportunity to diagnose congenital heart disease as early as the midtrimester of pregnancy, allowing for proper planning of perinatal care and counselling of the parents. This paper reviews the accuracy and outcomes of fetal cardiac ultrasound studies at The Prince Charles Hospital over the past 4 years.
A total of 43 fetuses, of gestational ages 16–39 weeks, were studied. The indications for these were: previous sibling with cardiac anomaly (16 cases); abnormal heart on obstetric ultrasound scan (USS) (13 cases); abnormalities found on obstetric USS with normal appearing heart (one case); fetal bradycardia (seven cases); fetal tachycardia (four cases); irregular fetal heart beat (two cases).
At birth all fetuses assessed because of a previously affected sibling were normal. Of the 13 referred because of structural heart lesions suspected on obstetric USS, eight were abnormal, four were normal and one was terminated without autopsy. Important rhythm disturbances occurred in nine of the 11 referred because of abnormal heart rates. One false positive diagnosis of a possible coarctation was made, and in four cases an abnormality was noted on USS but the diagnosis was not completely correct. Nine of the 19 infants with abnormalities detected have died.
Fetal echocardiography is an accurate and useful method of diagnosing congenital heart disease in utero . Although the mortality of affected fetuses is high, antenatal diagnosis allows planning of medical care and offers the greatest chance of a successful outcome.     

复杂型先天性心脏病影像诊断方法的ROC评价

目的 用受试者工作特征(ROC)曲线分析法评价复杂型先天性心脏病(先心病)影像诊断方法的应用价值.方法 由三位医师双盲对28例复杂型先心病的二维超声心动图(2DE)、实时三维超声心动图(RT-3DE)、数字减影心血管造影(DSA)、磁共振成像(MRI)或多层螺旋CT资料进行观察后,对有无心内、大血管根部畸形及心外畸形等作出各自诊断,并以手术诊断为金标准,按完全正确至完全不正确5个诊断精度进行ROC分析法评价.结果 对复杂型先心病心内及大血管根部畸形诊断,RT-3DE的ROC曲线最偏左上角,曲线下面积为RT-3DE(0.96)>2DE(0.92)>MRI/CT(0.91)>DSA(0.89).Z检验示RT-3DE优于2DE(Z=2.30,双侧P=0.021 5)、MRI/CT(Z=2.80,双侧P=0.005 0)、DSA(Z=3.18,双侧P=0.001 5).而对心外畸形的诊断,DSA的ROC曲线最偏左上角,曲线下面积为DSA(0.99)>MRI/CT(0.98)>2DE(0.92).Z检验示DSA优于2DE(Z=2.67,双侧P=0.007 5),但与MRI/CT诊断结果相似(Z=1.52,双侧P=0.129 2),差异无统计学意义(P>0.05).结论 ROC评价提示对复杂型先心病心内及大血管根部畸形诊断首选超声,当要进一步明确畸形空间位置、立体形态时可加做RT-3DE;而对心外血管畸形诊断MRI、多层螺旋CT准确性高,在某种程度上可替代心血管造影.     

复杂性先天性心脏病的超声诊断

超声心动图诊断复杂性先天性心脏病应采用顺序节段分析法,按照心房、心室和大动脉等三个节段进行检测,以及分析心房-心室连接和心室-大动脉连接,才能对复杂性先心病作出全面的诊断.     

Hyperuricaemia in cyanotic congenital heart disease

This study examines the exacerbating factors of hyeruricaemia in patients with cyanotic congenital heart disease (CCHD). We studied 59 CCHD patients aged 1 month-30 years. The following variables were assessed: serum uric acid levels, red blood cell count, haemoglobin, hematocrit, partial oxygen pressure and arterial oxygen saturation. Uric acid excretion and renal function were also measured in ten patients with serum levels of uric acid greater than 8 mg/dl (hyperuricaemia group). Serum uric acid level correlated significantly with age and severity of polycythaemia. However, it did not correlate with partial oxygen pressure or arterial oxygen saturation. Uric acid excretion was measured in hyperuricaemia group. Urinary uric acid excretion (24 h) was within normal limits in infants but markedly lower in patients over 15 years of age. The aetiology of hyperuricaemia and decreased uric acid fractional excretion and clearance in infants appears to be secondary to diminished excretion of uric acid in concert with uric acid overproduction. Hyperuricaemia in adolescents and adults with CCHD, however, results mainly from age-related impairment of uric acid excretion.     

Adult congenital heart disease: Past,present and future

The diagnosis and management of congenital heart disease (CHD), the most common inborn defect, has been a tremendous success story of modern medicine. In the 1950s, survival of children born with CHD was only approximately 15%, whereas nowadays more than 90% of these children survive well into adulthood. Consequently, the prevalence of patients with CHD has shifted away from infancy and childhood towards adulthood. Adult CHD cardiology is now encompassing not only young or middle‐aged adults but also patients with CHD over 60 years old. Many adult patients are afflicted by residual haemodynamic lesions and also face additional opportunities and/or challenges such as pregnancy, acquired heart disease, non‐cardiac pathology etc., necessitating integrated care and all medical disciplines. We are faced with a “tsunami” in terms of adult CHD numbers, disease heterogeneity and complexity of work and interventions needed. We need to secure resources, welcome more people in our field, learn from “marching with our patients”, and educate better patients, public and ourselves so that every single patient with CHD, born anywhere in the world, may reach their full life potential.     

胎儿先天性心脏病产前诊断与临床意义

先天性心脏病是最常见的出生缺陷之一.孕早期先天性心脏病筛查的方法主要有颈后透明层厚度测量、静脉导管血流测量以及直接进行胎儿超声心动图检查等.孕中期绝大部分的胎儿心脏病可以直接通过胎儿超声心动图检查获得诊断,除心脏解剖结构畸形外,心律失常的诊断以及心功能的评估也是重要检查内容.加强先天性心脏病的相关基因研究,也能够为产前诊断提供可靠依据.对胎儿先天性心脏病进行筛查干预,能够帮助医生早期制定临床决策,缓解家庭负担,有明显的社会效益.     

Pathophysiologic consequences of cyanotic congenital heart disease

Cyanotic congenital heart diseases will necessarily cause many pathophysiologic changes; many of these are compensatory mechanisms designed to improve the hypoxic state and others are complications of the altered physiology or abnormal anatomy. A thorough understanding of the pathophysiologic consequences of cyanotic congenital heart disease (CCHD) will help in providing appropriate management The purpose of this paper is to present an overview of the pathophysiology of most of these consequences of CCHD (Table ) and to outline an approach to the management of these entities.