Fetal diaphragmatic hernia: the value of fetal echocardiography in the prediction of postnatal outcome

Summary. Nineteen pregnancies complicated by fetal congenital diaphragmatic hernia (CDH) referred for fetal echocardiography have been reviewed. Congenital heart disease was diagnosed prenatally in three fetuses; in one of these the pregnancy was terminated, the two other infants died in the neonatal period. The presence of the fetal stomach within the thorax or a hernia/heart area ratio greater than 1·7 was associated with a large diaphragmatic defect. Polyhydramnios was not associated with a poor postnatal outcome. Evidence of cardiac ventricular disproportion before 24 weeks gestation in isolated CDH was associated with 100% mortality. Development of ventricular disproportion during the third trimester was associated with a survival rate of 75%. In three fetuses, all of whom survived, no ventricular disproportion was detected during the third trimester examination.     

Congenital diaphragmatic hernia in a first-trimester ultrasound aneuploidy screening program

OBJECTIVES: To review our experience with the prenatal detection of congenital diaphragmatic hernia (CDH) in fetuses presenting for ultrasound screening of chromosomal abnormalities in the first trimester. METHODS: As part of our first-trimester ultrasound protocol, fetuses with a crown-rump length between 45 and 84 mm underwent a limited anatomical assessment in conjunction with nuchal translucency thickness measurement and nasal bone assessment. Cases of CDH diagnosed prenatally or after delivery in this population were identified. RESULTS: Among the six cases of CDH detected (prevalence of 1 in 927), the first-trimester ultrasound findings were abnormal in five fetuses (83%), including three with increased nuchal translucency only; one with increased nuchal translucency, an intrathoracic stomach, dextrocardia and a cephalocele; and one with normal nuchal translucency thickness and a small, complex intrathoracic mass later confirmed as the fetal stomach. The diagnosis of CDH was confidently made in the first trimester in one case, in the second trimester in three cases, and after birth in the remaining two cases. CONCLUSION: The diagnosis of CDH in the first trimester is difficult, especially in those cases in which the defect is small or late migration of the abdominal viscera occurs. Therefore, screening for CDH in the first trimester is unlikely to be effective.     

Bilateral diaphragmatic hernia followed by fetal ultrasonography. A report of two cases

Two cases of bilateral congenital diaphragmatic hernia (CDH) followed by fetal ultrasonography were described. Although many cases of CDH are diagnosed by fetal ultrasonography, it is difficult to diagnose bilateral CDH in utero, which is a relatively rare and fatal condition. Two fetuses were diagnosed as having left CDH associated with severe anomalies. However, a retrospective review of fetal ultrasonography indicated elevation of the liver in the right posterior chest. Both patients died shortly after surgical repair for left CDH despite the use of extracorporeal membrane oxygenation. Diagnosis of bilateral CDH by fetal ultrasonography and the evaluation of its prognosis were discussed.     

Association of deletions of the chromosomal region 15q24-ter and diaphragmatic hernia: a new case and discussion of the literature

OBJECTIVE: To provide new insights into how chromosomal aberrations affect fetal development, as well as for the counseling of parents in comparable situations, it is important to characterize and report the genotypes of fetuses with clinical anomalies. METHODS: Molecular cytogenetic analyses in a fetus with congenital diaphragmatic hernia (CDH). RESULTS: This report describes the first case of a deletion of the region q26.1-ter on chromosome 15 occurring as a de novo event associated with CDH. A detailed review of the literature provides further evidence of a functional association between deletions within the chromosomal region 15q24-ter and the development of CDH. CONCLUSIONS: The obtained data argue that detection of such a deletion in the region 15q24-ter associated with CDH likely predicts a poor prognosis. This report highlights the importance of giving special diagnostic attention to the chromosomal region 15q24-ter when prenatal ultrasound examination provides evidence of a CDH and warrants further research to identify genetic elements within the chromosomal region 15q24-ter related to the development of diaphragmatic hernia.     

胎儿先天性膈疝及其相关异常的产前诊断

目的 分析胎儿先天性膈疝与合并其他畸形及染色体异常的相关性,探讨可能影响膈疝预后的因素. 方法 总结2002年1月至2008年11月在我院产前超声诊断的胎儿膈疝病例,分析其类型、合并畸形种类、与染色体异常的关系及临床结局.采用Fisher精确概率法进行统计学分析. 结果 产前超声诊断胎儿膈疝71例,左侧62例(87.3%),右侧9例(12.7%).单纯型膈疝38例(53.5%),复合型膈疝33例(46.5%).复合型膈疝中合并的其他异常中常见的有心血管系统畸形18例(54.5%),神经系统畸形10例(30.3%),泌尿系统畸形9例(27.2%).71例膈疝病例中19例行胎儿染色体核型检查,其中12例单纯型膈疝胎儿的染色体均正常,7例复合型膈疝中4例(4/7)染色体核型异常:18-=体综合征2例,13、21-三体综合征各1例.复合型膈疝病例染色体异常的发生率高于单纯型膈疝(P=0.009).复合型膈疝病例均引产;单纯型膈疝病例中32例引产,6例继续妊娠,其中5例足月出生后接受膈疝修补术,均存活;1例出生后死亡. 结论 胎儿先天性膈疝以左侧多见,近半数合并其他异常且以心血管系统畸形为主.单纯型膈疝发生染色体异常的风险低,复合型膈疝发生染色体异常的风险高.膈疝手术对预后的影响尚不能确定.     

Advances in prenatal diagnosis and treatment of congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a common birth anomaly. Absence or presence of liver herniation and determination of lung-to-head ratio are the most accurate predictors of prognosis for fetuses with CDH. Though open fetal CDH repair has been abandoned, fetal endoscopic balloon tracheal occlusion promotes lung growth in fetuses with severe CDH. Although significant improvements in lung function have not yet been shown in humans, reversible or dynamic tracheal occlusion is promising for select fetuses with severe CDH. This article reviews advances in prenatal diagnosis of CDH, the experimental basis for tracheal occlusion, and its translation into human clinical trials.     

The role of fetal echocardiography in genetic sonography

Genetic sonography identifies between 60% and 93% of fetuses with trisomy 21. One of the reasons for the variation in sensitivity is because of the under-detection of congenital heart defects. Although congenital heart defects are present in 56% of second trimester fetuses and 44% of newborns with trisomy 21, most studies evaluating second-trimester fetuses at risk for trisomy 21 detect less than 10% of heart malformations. This review discusses an approach that allows the fetal sonographer to incorporate fetal echocardiography, based upon the examiner's level of skill and experience, when evaluating the fetus at risk for trisomy 21. The cardiovascular examination consists of three levels. In the Level I examination only noncardiac markers are evaluated for a detection rate of 60% and false-positive rate of 5.9%. The Level II examination incorporates the four-chamber view with non-cardiac markers. If the examiner can identify atrial and/or ventricular chamber disproportion, then the sensitivity is increased to 75%, with a false-positive rate of 6.4%. The Level III examination utilizes grayscale and color Doppler ultrasound to evaluate the fetal heart. If the examiner can identify ventricular septal defects, atrioventricular septal defects, pericardial effusion, tricuspid regurgitation, and chamber disproportion, then the sensitivity of genetic sonography increases to 91% with a false-positive rate of 14%. This review includes Likelihood Ratios for each of the ultrasound markers so that the examiner can compute the risk for trisomy 21 for an individual patient.     

Fetal diaphragmatic hernia and upper limb anomalies suggest Brachmann-de Lange syndrome

We describe two independent cases of Brachmann-de Lange syndrome (BDLS) in which second trimester fetal sonographic studies showed the presence of a diaphragmatic hernia and upper limb anomalies. In both cases the karyotypes were normal. Intrauterine growth restriction (IUGR) developed in the third trimester. Postnatal and postmortem physical examinations demonstrated typical physical findings associated with BDLS. The prenatal diagnosis of diaphragmatic hernia with associated anomalies should prompt consideration of an underlying genetic etiology.     

First trimester ultrasound diagnosis of congenital diaphragmatic hernia

Congenital diaphragmatic hernia is a rare structural defect, usually diagnosed in the second or third trimester of pregnancy. We present here a case of left-sided diaphragmatic hernia diagnosed at 12 weeks of gestation and a short review of published reports on first trimester diagnosis of this defect. Ultrasound diagnosis of congenital diaphragmatic hernia cases, with early herniation of the viscera in the thorax, is feasible during the first trimester. The prerequisite is the systematic examination of the fetal anatomy. Hallmarks of the diagnosis, in the first trimester as well as later in pregnancy, are the presence of the stomach, bowel or liver in the chest, and the shift of the mediastinum. Early diagnosis of this defect is essential. This will allow timely intervention and appropriate management, following extensive parental counseling.     

Congenital heart disease and fetal thoracoabdominal anomalies: associations in utero and the importance of cytogenetic analysis.

We examined the frequency with which congenital heart disease (CHD) and cytogenetic abnormalities were found associated with omphalocele, gastroschisis, duodenal atresia and posterior diaphragmatic hernias. We performed fetal echocardiograms on 80 patients with these diagnoses and found congenital heart disease in 13 of 37 with omphalocele (35%), 2 of 17 with gastroschisis (12%), 4 of 15 with duodenal atresia (27%), and 2 of 11 with posterior diaphragmatic hernia (18%). Karyotypes were obtained in 74 and were abnormal in 24 (32%). Although most fetuses with these extracardiac malformations and abnormal karyotypes had associated CHD, many did not. Normal karyotypes were found in 69% of fetuses with CHD and omphalocele, and 50% of fetuses with CHD and duodenal atresia. We conclude that CHD may be present in fetuses with extracardiac malformations whether or not the karyotype is normal and that the prenatal evaluation of fetuses with these lesions should include both karyotype and fetal echocardiography. Although karyotypes play an important role in prenatal diagnosis, they are not predictive of normal cardiac structure when normal in the abnormalities studied. Even when the karyotype is normal in the presence of these abnormalities, fetal echocardiography is indicated.     

Prenatal MRI evaluation of congenital diaphragmatic hernia

The objective of this paper is to evaluate the efficacy of various magnetic resonance imaging (MRI) sequences and the general usefulness of prenatal MRI in determining the position of the fetal liver and visualizing lung tissue in fetuses who have congenital diaphragmatic hernia (CDH). This was a retrospective review of prenatal MRI of fetuses with a confirmed diagnosis by surgery or autopsy of CDH. MRI was performed in a 1.5-Tesla magnet using fast gradient echo, half-Fourier single-shot turbo spin-echo (HASTE) and echo planar images. The presence of a chest mass, position of the stomach and liver and visualization of the lungs by MRI was noted in all fetuses. This was compared to ultrasound studies performed the same day and correlated with postnatal or autopsy studies. The fetuses were 18-36 weeks gestational age (mean 24.5 weeks). MRI diagnosed left CDH (33), right CDH (4), and bilateral CDH (1) and agreed with the postnatal diagnosis in all patients. Ultrasound (US) diagnosed left CDH (33), right CDH (2), and congenital cystic adenomatoid malformation (3). MRI changed the diagnosis in four patients. The fetal liver was easily demonstrated with MRI in all fetuses and was herniated into the chest in 25 of the 38. US diagnosed liver up in 21. Correlation with postnatal studies found MRI correctly diagnosed liver position in 37 out of 38 cases. US correctly diagnosed liver position in 32 out of 38. Both lungs could be visualized in all fetuses with MRI. MRI accurately and easily diagnoses CDH and can differentiate it from other chest masses. MRI was superior to US in demonstrating the position of the fetal liver above or below the diaphragm. MRI reliably visualized fetal lung tissue. These findings are important for counseling parents, selecting fetal surgical candidates, and estimating prognosis.     

Fetal surgery for congenital diaphragmatic hernia: the North American experience

The role for fetal surgery in treating fetuses with congenital diaphragmatic hernia (CDH) is unclear. Two decades of investigation have improved our understanding of the prenatal natural history, pathophysiology, and outcomes of these patients. During this same period, there have been advances in fetal surgery techniques including improvements in fetal monitoring, maternal-fetal anesthesia, tocolysis, and improved instrumentation to permit increased application of videoscopic approaches. Because of technical challenges, open fetal repair of CDH has been abandoned. Fetal tracheal ligation has shown promise, but a recently published prospective, randomized trial failed to show a benefit of fetoscopic tracheal ligation compared with expert postnatal treatment. Although there is evidence that postnatal outcomes for infants with this disease have improved with the adoption of gentilation ventilator management, high-frequency ventilation, and ECMO, there continues to be a subset of infants with severe CDH that die or suffer serious long-term morbidity despite advanced surgical care. The purpose of this article is to review issues related to prenatal diagnosis, patient selection, and outcomes for fetal surgery; and ultimately to assess whether there is a role for fetal surgery in treating fetuses with CDH.     

Invasive intrauterine Therapie

Some fetuses with malformations which cannot wait for therapy after birth may benefit from intra-uterine fetal therapy in order to either prevent permanent damage or to save their life. Criteria for fetal surgery are the possibility of an accurate diagnosis with exclusion of associated anomalies and reversibility of deleterious effects of the condition by a fetal intervention at specialized multidisciplinary treatment centers with a much better prognosis afterwards. Examples of intra-uterine fetal therapy are open fetal surgery for fetal myelomeningocele (MMC) repair, fetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) and fetoscopic laser coagulation in twin-twin transfusion syndrome (TTTS). The main complication of fetal surgery is the premature rupture of membranes.     

Detection of congenital heart defects throughout pregnancy; impact of first trimester ultrasound screening for cardiac abnormalities

Objective: To evaluate prospectively the efficacy to screen for congenital heart defects (CHD) during the first trimester nuchal translucency (NT) ultrasound examination by assessing the four chambers’ view of fetal heart. Methods: Pregnancies that were examined prospectively by ultrasound in the first trimester (11th–14th week), the second (19th–24th week) and third trimester were included in the study. 3774 fetuses were examined and fetal heart was assessed during the NT scan by examining the four chambers view. Detailed echocardiography was performed during the anomaly and growth scans. Diagnosis of congenital heart defects (CHD) was further confirmed by a fetal cardiologist. Results: The four chambers view was obtained in 99.52% of the cases. CHD were diagnosed in 29 fetuses (0.77%). Thirteen cases (44.8%) were detected during the 11–13 weeks’ scan, 14 cases (48.3%) during the anomaly scan, 1 CHD (3.5%) during the third trimester scan and 1 case (3.5%) postpartum. Conclusion: Assessment of the four chambers of fetal heart early in pregnancy was feasible and allowed the detection of 45% of CHD. Additional parameters of fetal cardiac anatomy during the NT scan may further improve the detection rate providing pregnancy management information early in the first trimester.     

Prevalence of fetal left ventricular hyperechogenic foci in a low risk population

Objective To ascertain the prevalence and clinical significance of small hyperechogenic foci detected in the fetal left ventricle in routine ultrasound screening of pregnant women attending our hospital.
Population and methods From April 1994 to April 1995, 1135 consecutive pregnant women examined at the obstetric ultrasound unit of our hospital were studied prospectively. A postnatal cardiologic examination was performed when signs of cardiopathy were observed at the prenatal ultrasound investigation or the neonatal examination.
Results Congenital heart disease was detected in 10/1148 infants born (0.9%); eight diagnoses were made prenatally (detection rate 80%). The prevalence of left ventricular hyperechogenic foci was 3.2% (37/1148 fetuses). In 35 cases (94.6%) the foci were no longer observed at the routine third trimester examination. Only in two cases (5.4%) did foci persist at the postnatal examination but without clinical signs of cardiopathy or karyotype anomalies. No association was observed between foci and major structural abnormalities. The foci were single in 32 cases (86.5%). Four foci (10.8%) were located at the interventricular septum, five (13.5%) bilaterally at the papillary apparatus of the mitral valve, and the others at the ventricular wall. No focus was associated with incompetence of the affected valve, whereas five (13.5%) were associated with a fetal disorder.
Conclusions The prevalence of intracardiac hyperechogenic foci in our general population considered at low risk was more than five times greater than that reported in the literature. Foci were not associated with structural heart defects or chromosomal abnormalities. Persistence during the third trimester and postnatal life was rare and without evident signs of heart disease.     

Evaluation of the development of lung hypoplasia in the premature lamb

Background The death rate from human diaphragmatic hernia (CDH) ranges from 50 to 80%, mainly due to the associated lung hypoplasia. To prevent these irreversible pathological and physical defects, the question of intrauterine surgical intervention arises. The histological changes of the lung tissue after inducement of a diaphragmatic hernia were examined. Of special interest was the time elapsing until the development of lung hypoplasia.Methods A model of intrauterine inducement of diaphragmatic hernia was established using five fetal lambs to study consecutive pulmonary hypoplasia. Inducement of a diaphragmatic hernia was undertaken between 105 and 108 days gestation. Lung tissue was examined histologically on postoperative days 8, 17, 21, 22, and 25 after inducement of the defect.Results On postoperative days 8, 17, and 21, no signs of pulmonary hypoplasia were found on histological examination. A pulmonary hypoplasia was found in two fetuses (on the 22nd and 25th postoperative day). The pathological and anatomical examination of a unilateral pulmonary hypoplasia after a short period of time shows that the artificially created diaphragmatic defect is a good model for producing a congenital diaphragmatic hernia.Discussion The severity of the pulmonary hypoplasia is related to the duration of lung compression by the herniated organs. The time elapsing until the development of lung hypoplasia is shorter than expected. Tracheal occlusion seems to be an effective strategy for treatment of the defect CDH, but the best technique for achieving occlusion, and particularly the ideal point in time to carry out Fetendo, are unknown. Further research into this congenital illness is required in order to treat it.     

Sonographic assessment of the extra-abdominal fetal small bowel in gastroschisis: a retrospective longitudinal study in relation to prenatal complications

OBJECTIVE: An explorative retrospective study following a case-series of fetuses with isolated gastroschisis, to evaluate if small-bowel dilatation may be indicative for emerging obstetric complications. The secondary aim was to establish preliminary normative curves for the external diameter and wall thickness of eventerated fetal small bowel in gastroschisis during the second and third trimester of pregnancy. METHODS AND MATERIALS: Fourteen fetuses with isolated gastroschisis were followed at a single center. Repeated ultrasound examinations for fetal surveillance with measurement of fetal small-bowel diameter and wall thickness over the course of pregnancy until delivery were performed. RESULTS: Longitudinal data analysis showed significantly increasing bowel diameter and wall thickness of eventerated small bowel with advancing gestation. Dilatation of small bowel more than 25 mm in the third trimester of pregnancy was associated with an increased risk of short-term prenatal complications as fetal distress or intrauterine fetal death (PPV 100%; 95% CI: 29.2-100%, NPV 100%; 95% CI: 71.5-100%). CONCLUSIONS: Dilatation of the extra-abdominal fetal small bowel in the third trimester may allow identifying fetuses with increased risk of fetal distress requiring closer monitoring of fetal well-being or delivery in a short interval to prevent impending fetal death.     

妊娠晚期合并膈疝一例并文献复习

目的研究妊娠合并膈疝的临床特征及治疗策略。 方法回顾分析广州医学院第三附属医院收治的1例及文献报道的25例妊娠合并膈疝患者的临床表现、诊治方法及妊娠结局。 结果26例妊娠合并膈疝患者中,23例出现膈疝临床症状的时间为晚期妊娠阶段,3例在妊娠中期;25例行影像学检查并确诊,1例根据临床症状诊断。膈肌裂口位于右膈肌2例,位于左膈肌15例,4例位于膈肌中心腱。22例患者因及时诊断、采取有效的处理措施而母子平安,1例因术后毒血症抢救无效导致母亲死亡,1例因孕妇短时间内行2次膈疝修补术而导致胎死宫内,2例因就诊时间较晚或未能及时明确诊断延误治疗而导致母婴死亡。 结论妊娠合并膈疝及时而准确的诊断和治疗需多学科合作,严密观察患者病情变化,可获得良好的妊娠结局。     

Prenatal diagnosis of congenital diaphragmatic hernia: an update

Congenital diaphragmatic hernia (CDH) has an incidence of approximately 1:4000 live births. Most frequently the diaphragmatic defect is a left and posterolateral (Bochdalek) one. Prenatal diagnosis is made at ultrasonography; the relevant sonographic features will be described in the paper. Cystic adenomatoid malformation of the lung (CAML), pulmonary sequestration, bronchogenic cysts, pulmonary hypoplasia/agenesia need to be considered in differential diagnosis. In some cases, diagnosis of CDH is not possible "in utero": in such cases, herniation of abdominal viscera into the thorax takes place presumably just at delivery through a small diaphragmatic defect. CDH may be associated with intrauterine growth retardation (IUGR), chromosomal abnormalities (3%) and/or other malformations (10-50%): such as Central Nervous System, digestive, cardiac and urogenital anomalies. Therefore, search of associated malformations and amniocentesis with analysis of fetal karyotype are mandatory, whenever a CDH is diagnosed. CDH is still at present characterised by a high mortality (reportedly, about 45%). Many prognostic factors have been correlated to postnatal outcome of CDH: some of them are valuable prenatally by ultrasonography. However, the role of sonography in the prediction of neonatal outcome is still controversial: in particular, although many ultrasonographic parameters have been proposed, prenatal evaluation of pulmonary hypoplasia (a crucial factor related to postnatal survival) has not proved to be very accurate so far. Nevertheless, it is undisputable that prenatal diagnosis itself represents a crucial prognostic factor for CDH, since it allows birth of the affected fetuses in 3d level Perinatologic Centres provided with a Neonatal Intensive Care Unit and Neonatal Surgery.     

Underlying genetic etiologies of congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses with CDH. Here, we review the aneuploidies, copy number variants (CNVs), and single genes that have been clearly associated with CDH. We suggest that array-based CNV analysis, with or without a chromosome analysis, is the optimal test for identifying chromosomal abnormalities and CNVs in fetuses with CDH. To identify causative sequence variants, whole exome sequencing (WES) is the most comprehensive strategy currently available. Whole genome sequencing (WGS) with CNV analysis has the potential to become the most efficient and effective means of identifying an underlying diagnosis but is not yet routinely available for prenatal diagnosis. We describe how to overcome and address the diagnostic and clinical uncertainty that may remain after genetic testing, and review how a molecular diagnosis may impact recurrence risk estimations, mortality rates, and the availability and outcomes of fetal therapy. We conclude that after the prenatal detection of CDH, patients should be counseled about the possible genetic causes of the CDH, and the genetic testing modalities available to them, in accordance with generally accepted guidelines for pretest counseling in the prenatal setting.