Prognosis following prenatal diagnosis of heart malformations

Our objective was to document the prognosis of cases with fetal heart malformations (FHM). Forty-two fetuses assessed both in a regional fetal medicine and paediatric cardiology unit were classified prenatally into isolated FHM or those associated with extra-cardiac structural or karyotypic anomalies (ECA) and this classification was not changed subsequently (analogous to an intention to treat analysis). The end points studied included chromosomal abnormality, pregnancy outcome and follow-up at one year of age.FHM were isolated in 16 (38%) and associated with ECA in 26 (62%) of cases. The karyotypic abnormality rate was 8/42 (19%) overall and 8/26 (31%) in ECA cases. The pregnancy outcome included termination of pregnancy in 19 (45%), intrauterine death of two (5%) and live birth in 21 (50%). 12/16 (75%) of isolated FHM cases were live born compared with 9/26 (35%) of ECA cases (P<0.03). Of the isolated FHM live born babies, 8/12 (67%) were alive at the end of the first year and seven of these were growing normally and did not require cardiac medication. However, a considerable proportion of their first year was spent in hospital (median 8%, interquartile range 5–10). Only one of nine ECA live born cases was alive but with poor growth and dependence on cardiac drugs at one year.These data confirm previous findings in prenatal diagnosis series that the prognosis for FHM is worse than that reported in studies of congenital heart disease at birth and is strongly dependent upon the presence of ECA. In their absence, outcome is better than previously published. Counselling must take place only after full fetal medicine assessment and should be based upon prenatal data.     

先天性心脏病产前早期诊断

桂永浩教授:围产医学把胎儿作为一个新生命的开始,世界上不再以人口的死亡率,或者寿命作为唯一的判断指标,而是以孕产的死亡率或围产的死亡率来衡量一个地区发展的水平。人类要进一步提高人口素质,做到优生优育,围产医学及围产保健是很关键的手段之一。归纳起来就是:生命的准备,生命的保护,生命的质量。围产医学关注的是生命的准备,始自生命形成的最初阶段,其目的不仅是确保新生命的正常诞生,新生儿和婴幼儿的生存。还必须认识到,生命准备阶段所形成的将是伴随终身的、健康的基础及发育的潜能。针对生命的准备、保健策略和措施应该包括通过…     

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.     

Issues related to prenatal diagnosis of congenital heart disease

Enhanced technology and professional expertise are making the diagnosis of congenital heart disease possible with increasing frequency during the prenatal period. This article describes the process of prenatal diagnosis of congenital heart disease and the many personal issues families face when they receive news of this condition. Ethical and legal considerations of prenatal diagnosis are reviewed. Brief vignettes describe what families experience when they receive the diagnosis. The role of the nurse in educating parents, assisting them in sorting out options for treatment, and providing ongoing care and support is discussed, and implications for nurses in obstetric, neonatal, and pediatric settings are reviewed. Finally, the need for further research on this topic is explored.     

胎儿先天性心脏病产前诊断与生后治疗一体化模式的探讨

目的 探讨胎儿先天性心脏病产前诊断与生后治疗一体化模式.方法 2006年8月至2010 年5月共有46位孕妇在我院产前诊断出胎儿先心病并选择继续妊娠.在我院产科自然分娩或剖腹产,胎儿出生后24 h内复查心脏超声,连续监测经皮血氧饱和度,由小儿心内科、小儿心外科、新生儿科联合制定治疗和随访方案.结果 孕妇剖腹产36例,自然分娩10例;共分娩活产新生儿47例,男40例,女7例;平均胎龄(38.0±1.4)孕周,平均体重(3.00±0.44) kg;产前和生后主要心脏畸形诊断相符.10例动脉导管依赖型复杂先心病患儿新生儿期静脉滴注前列腺素E.23例接受外科手术治疗,其中15例于新生儿期手术.7例行内科介入治疗,4例经皮肺动脉瓣成形术,3例行房间隔或室间隔缺损封堵术.16例随访患儿中2例室间隔缺损自然愈合,7例房间隔缺损和5例室间隔缺损等待择期治疗,2例随访丢失.30例已治疗的患儿中21例心脏结构恢复正常,7例心脏瓣膜存在轻微改变,术后死亡2例(病死率6.7％).结论 产前诊断与生后治疗一体化模式符合先天性心脏病诊治的发展趋势,需要多科室合作,才能及早发现胎儿心脏畸形,预测胎儿出生后的变化,消除复杂先心病出生后的急危重状态,提高生后治疗的成功率.     

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目的探讨羊膜腔穿刺结合基因序列和染色体核型分析在严重联合免疫缺陷(SCID)高危儿产前诊断中的意义。方法 2008-2010年重庆医科大学附属儿童医院基因诊断明确的7例SCID患儿,其中6例X连锁SCID、1例Omenn综合征。追问病史,建立7个SCID家系图谱,确诊20个异常基因携带者。对其中7个携带异常基因的高危孕妇于孕18～20周经羊膜腔穿刺抽取羊水,部分羊水经离心后,提取羊水细胞DNA,经PCR扩增IL-2RG或RAG1基因,扩增PCR产物进行双向序列重复测定。此外对羊水中胎儿脱落细胞进行培养,采用原位制片、G带染色技术进行染色体核型分析。产后采集高危儿外周血重新进行基因分析,并进行免疫功能评估。结果全部病例穿刺均成功,羊水细胞培养成功率100%。基因和染色体核型分析结果显示,3例为正常男性胎儿,2例为正常女性胎儿,2例为男性缺陷胎儿。2例男性缺陷胎儿均为IL-2RG基因突变。除2例缺陷胎儿行人工流产术外,5例SCID高危儿均顺利出生,产后基因分析结果均正常,与产前结果相同。随访免疫功能均正常。结论羊膜腔穿刺结合基因和染色体核型分析在SCID的产前诊断中是一项成熟有效的操作技术。     

超声心动图对胎儿先天性心脏病产前诊断价值的Meta分析

目的探讨超声心动图用于胎儿先天性心脏病（CHD）的产前诊断价值。方法检索Cochrane 图书馆、PubMed、OVID、Springer数据库、中国期刊全文网、万方数据库和中国生物医学文献数据库（从1990年1月至2009年1月）中的文献,按照诊断试验的严格纳入标准筛选文献,提取纳入文献的特征信息。采用Meta-DiSc 1.4软件进行Meta分析,检验异质性,并根据异质性结果选择相应的效应模型。对所有文献予以加权定量合并,计算敏感度和特异度及其95%CI。绘制汇总受试者工作特征（SROC）曲线,并计算曲线下面积（AUC）,最后进行敏感度分析。结果共纳入文献18篇,检查胎儿77 939例。7篇文献采用基本心脏超声检查（BCEE）筛查胎儿CHD,研究间具异质性,采用随机效应模型,汇总敏感度、特异度和SROC AUC分别为41.7%、99.9%和0.9787。12篇文献采用扩展心脏超声检查（ECEE）筛查胎儿CHD,研究间具异质性,采用随机效应模型,汇总敏感度、特异度和SROC AUC分别为66.9%, 99.9%和0.9956。ECEE的敏感度显著高于BCEE（χ2=63.93,P<0.05）。对BCEE和ECEE筛查胎儿CHD的文献进行分层和敏感度分析,两种检查方法在妊娠中至晚期筛查胎儿CHD的敏感度均高于妊娠中期（χ2分别为5.47和39.37, P均<0.05）;ECEE筛查存在CHD低危因素孕妇的胎儿CHD的敏感度低于所有孕妇和存在CHD高危因素孕妇胎儿的敏感度, 差异有统计学意义（χ2分别为81.82和156.58,P均<0.05）;ECEE筛查所有孕妇与存在CHD高危因素孕妇的胎儿CHD的敏感度差异无统计学意义（χ2=1.67,P>0.05）。结论超声心动图对胎儿CHD的诊断敏感度较高,适用于早期筛查胎儿CHD,但仍需进一步前瞻性、多中心的研究对胎儿筛查人群和超声切面的选择等方面进行卫生经济学评估,探讨适合中国国情的胎儿CHD的最优化超声筛查操作规范。     

Progression of congenital heart disease in the prenatal period

BACKGROUND: Prenatal echocardiography has shown evidence of prenatal development of congenital heart disease. Prenatal cardiac anatomy, chamber size and function change during gestation, so that the appearance of cardiac structure in abnormal hearts may be different from that which is usually seen postnatally. METHODS: Published prenatal echocardiographic studies were reviewed and in utero development of congenital heart disease from midtrimester to the early postnatal period is discussed. RESULTS: The growth of the great vessels and ventricles is reduced in fetuses with ventricular outflow obstruction. Valve regurgitation may progress. The foramen ovale and ductus arteriosus have been reported to become restrictive in utero in several settings. Pulmonary vascular obstructive changes may progress prenatally. Fetal arrhythmia (both bradycardia and tachycardia) may develop in utero. Development of congestive heart failure is a very important issue during follow up of fetuses with significant cardiac or extracardiac problems. Some may progress to fetal hydrops and prognosis of the affected fetuses is usually very poor. CONCLUSIONS: Correct knowledge of possible development is important for accurate prenatal diagnosis. Information on prenatal progression of the cardiac anomaly is also important to make plans for follow up and perinatal management, to predict outcomes and to counsel family. Furthermore, the benefits of prenatal treatment instead of postnatal treatment should be assessed by the accurate prediction of the progression of the cardiac problem in utero. Further extensive studies using a large number of cases is required to predict progression accurately. In addition, further studies for elucidating the mechanisms of progression is important to provide better outcomes for fetuses with various congenital heart diseases.     

Pre-natal counselling--helping couples make decisions following the diagnosis of severe heart disease

The prenatal diagnosis of a major cardiac abnormality tends to precipitate a crisis for the affected parents. In a setting of grief and emotional distress, there is the challenge to provide meaningful information of the abnormality, its need for intervention and likely outcome, so as to enable the parents, if allowed the option, to come to a fully informed decision as to whether to continue with the pregnancy. This discussion paper reviews the difficulties encountered in counselling affected parents being mindful of the psychological constraints prevalent at the time. While an accurate and detailed diagnosis is important for the professionals, the information required by the parents needs to be simple and focussed on the questions raised by them as they relate to quality of life issues to be experienced by their yet unborn infant/child growing into an adult.     

A novel L1CAM mutation in a fetus detected by prenatal diagnosis

X-linked hydrocephalus is due to mutations in the L1 neuronal cell adhesion molecule (L1CAM) gene. L1 protein plays a key role in neurite outgrowth, axonal guidance, and pathfinding during the development of the nervous system. We report on a familial case diagnosed by prenatal ultrasonographic examination, with cerebellar hypoplasia, agenesis of the corpus callosum, and the bilateral overlapping of the second and third fingers of the hand. Sequencing of the L1CAM gene showed a novel missense mutation in exon 14: transition of a guanine to cytosine at position 1777 (c.1777G>C), which led to an amino acid change of alanine to proline at position 593 (Ala593Pro) in the sixth immunoglobulin domain of the L1 protein. The L1CAM mutation testing should be considered in fetuses with ultrasonographic signs of hydrocephalus and a positive family history compatible with X-linked inheritance. We agree with previous reports that suggest also considering limb abnormalities other than adducted thumbs in addition to classical neurological disgenesis, as characteristic for L1-disease.     

Treatment and outcome of serious structural congenital heart disease

Serious structural congenital heart disease usually presents to the neonatal paediatrician, although increasingly these conditions are being diagnosed before birth. It is, therefore, important that those dealing with these fetuses and infants have some knowledge of their natural and modified history. The vast majority of lesions can either be corrected or given symptomatic palliation and this review discusses treatment options and provides up-to-date outcome information to enable fetal and neonatal staff to anticipate and to complement information given to families by paediatric cardiologists.     

Reasons for trisomy 13 or 18 births despite the availability of prenatal diagnosis and pregnancy termination

BACKGROUND: Few studies have evaluated the reasons why lethal chromosomal anomalies continue to occur despite the importance of this question for maximizing perinatal care. AIMS: To determine why trisomy 13 or 18 births continue to occur in Alaska. STUDY DESIGN: Case series involving review of maternal and infant medical records. SUBJECTS: All 28 known infants and fetuses that died with trisomy 13 or 18 during 1992-2001 and their mothers. OUTCOME MEASURES: The proportion of mothers that declined or received a variety of routine prenatal tests, the results of prenatal testing, and the impact of testing on decisions related to pregnancy. RESULTS: Seventeen women declined pregnancy termination or amniocentesis, 10 had no prenatal risk factors and were not offered these procedures, and one woman had an amniocentesis but was not offered pregnancy termination. Twenty-six women had >/=1 prenatal ultrasounds; for 17 women, these were interpreted as normal throughout pregnancy (n=11) or until after 30 weeks gestation (n=6) despite substantial fetal malformations. Fourteen of 15 women with an abnormal ultrasound had an amniocentesis compared to one of eight women whose only risk factor was advanced maternal age. CONCLUSIONS: Most trisomy 13 or 18 deliveries occurred to women who declined amniocentesis or pregnancy termination. Failure to identify abnormalities on prenatal ultrasound may have contributed to the decision not to have these procedures.     

3 例Menkes病患儿的临床与ATP7A基因分析及1例产前诊断研究

Menkes 病是一种罕见的X 连锁隐性遗传病,由于ATP7A 基因突变导致铜吸收障碍,铜相关酶功能缺陷,引起多系统功能障碍。该文拟通过对3 例Menkes 病患儿的临床经过和ATP7A 基因突变分析对该症进行研究,并对1 例再孕母亲进行产前诊断研究。3 例男婴于8~9 个月时来院就诊,均为婴儿期起病,主要表现为抽搐和智力运动落后,抗癫癎治疗无效,面色苍白,毛发稀疏、卷曲,小头,MRI 扫描显示脑萎缩、白质异常、基底节损害和脑血管形态改变,血浆铜蓝蛋白均显著降低,分别为70.2、73.5、81.0 mg/L（参考值210~530 mg/L）,符合经典型Menkes 病临床表型。例1 和2 的ATP7A 基因存在c.3914A>G（p. D1305G）突变,例3 为c.3265G>T（p.G1089X）突变,均为新生突变。c.3914A>G（p. D1305G）为已知突变,c.3265G>T（p.G1089X）为新突变,均为我国首次报道。例1 患儿的母亲再孕,于妊娠20 周时抽取羊水细胞,通过胎儿ATP7A 基因突变分析,进行产前诊断。羊水细胞ATP7A 基因未见c.3914A>G,提示胎儿未患与先证者相同的疾病。胎儿出生后发育正常。