Prenatal diagnosis, prediction of outcome and in utero therapy of isolated congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) can be associated with genetic or structural anomalies with poor prognosis. In isolated cases, survival is dependent on the degree of lung hypoplasia and liver position. Cases should be referred in utero to tertiary care centers familiar with this condition both for prediction of outcome as well as timed delivery. The best validated prognostic indicator is the lung area to head circumference ratio. Ultrasound is used to measure the lung area of the index case, which is then expressed as a proportion of what is expected normally (observed/expected LHR). When O/E LHR is < 25% survival chances are < 15%. Prenatal intervention, aiming to stimulate lung growth, can be achieved by temporary fetal endoscopic tracheal occlusion (FETO). A balloon is percutaneously inserted into the trachea at 26-28 weeks, and reversal of occlusion is planned at 34 weeks. Growing experience has demonstrated the feasibility and safety of the technique with a survival rate of about 50%. The lung response to, and outcome after FETO, is dependent on pre-existing lung size as well gestational age at birth. Early data show that FETO does not increase morbidity in survivors, when compared to historical controls. Several trials are currently under design.     

In utero diagnosis of trichothiodystrophy by endoscopically-guided fetal eyebrow biopsy

OBJECTIVE: To describe the prenatal diagnosis of trichothiodystrophy (TTD) through endoscopically-guided fetal eyebrow biopsy. MATERIALS AND METHODS: A 32-year-old patient, gravida 4, para 3, with a history of 2 previous infants affected with TTD was referred at 17(5)/(7) weeks for fetal hair biopsy. DNA repair studies had been normal in the previous children. Four 1-mm biopsies were obtained from the external aspect of the fetal eyebrows under direct endoscopic guidance. Fetal hair samples were assessed with polarized microscopy, electron microscopy, hematoxylin and eosin staining, and were also sent for analysis of sulfur content (cystine levels). RESULTS: The fetal eyebrows were the only adequate source of hair in the early second trimester. The biopsy samples yielded adequate material for all tests. Polarized microscopy showed characteristic banding patterns, but trichoschisis was not apparent. Cystine levels (19 micromol/l) in the biopsy sample were significantly lower than an age-matched (fresh spontaneous abortion) control (368 micromol/l). CONCLUSION: Prenatal diagnosis of TTD is possible in the second trimester through endoscopically-guided eyebrow biopsy. An adequate amount of hair is present in the eyebrows by then, and the disease is already manifest. Analysis of sulfur content of the hair samples is preferred over polarized or electron microscopy, as many classic microscopic findings of TTD may not be present in the early second trimester.     

Prenatal diagnosis of congenital toxoplasmosis

Ninety-three pregnant women with Toxoplasma gondii seroconversion during pregnancy underwent prenatal diagnosis of fetal toxoplasmosis. The following tests were used: (1). amniocentesis for mouse inoculation (93 subjects), (2). amplification of T. gondii DNA by polymerase chain reaction (PCR) (79 subjects), and (3). cordocentesis for the detection of T. gondii-specific IgM antibodies (13 subjects). All patients had serial ultrasonographic scans to detect those fetuses with abnormalities that could be associated with congenital toxoplasmosis. Eighteen pregnancies (19.4%) had evidence of vertical transmission. A total of 11/18 (61.1%) had positive amniotic mouse inoculation test, while 10/12 (83.3%) had positive PCR results. The combination of both tests allowed the prenatal diagnosis in 17/18 infected fetuses (94.4%). All patients who underwent cordocentesis for the detection of T. gondii-specific IgM antibodies had negative results. However, in two of the above cases fetal toxoplasmosis was detected by amniotic fluid studies. In five of the infected fetuses there were abnormal ultrasonographic findings. All pregnancies with evidence of vertical transmission were terminated, whereas the remaining pregnancies proceeded normally to term. The present data showed that amniotic fluid studies, preferably PCR amplification of T. gondii DNA, are the best diagnostic tools for the detection of vertical transmission in pregnancies with seroconversion during pregnancy.     

Prenatal diagnosis of pelvic kidney

A 30-year-old woman had serial ultrasound scans from 28 weeks' gestation which revealed the presence of a cystic area in the fetal pelvis. The 'cyst' remained unchanged until delivery at 41 weeks. Fetal growth and amniotic fluid volume were normal throughout. A pelvic kidney was confirmed at birth. The differential diagnosis and antenatal management of this 'cyst' are discussed.     

Prenatal diagnosis of congenital cytomegalovirus infection

OBJECTIVE: To assess prospectively the diagnostic reliability and prognostic significance of prenatal diagnosis of cytomegalovirus (CMV) infection. METHODS: One hundred ten pregnant women (four with twin pregnancies) with a risk of congenital CMV infection were investigated. Prenatal diagnosis was carried out by amniocentesis and fetal blood sampling (n = 75) or amniocentesis alone (n = 35). Serial ultrasonographic examinations were performed from time of referral until pregnancy end. All infected neonates were given long-term follow-up. Autopsy was performed in all cases of termination of pregnancy. RESULTS: Nearly 23% (26 of 114) of fetuses were infected and prenatal diagnosis was positive in 20 cases. Sensitivity of prenatal diagnosis was 77% and specificity 100%. In eight cases, parents requested termination of pregnancy on the basis of abnormal ultrasonographic findings and/or biologic abnormalities in fetal blood. In 12 cases, parents decided to proceed with the pregnancy. In this group, one intrauterine and one neonatal death were observed. In one case, prenatal diagnosis revealed an abnormal cerebral sonography and the infant had bilateral hearing loss at birth. In 15 cases (nine positive and six false-negative prenatal diagnoses), no apparent lesion was present at birth, nor did it develop during the follow-up period (mean 31 months). In 88 (77.2%) of 114 infants, no evidence of vertical transmission was found during the pre- or postnatal period. CONCLUSION: Prenatal diagnosis provides the optimal means for both diagnosing fetal infection (amniocentesis) and identifying fetuses at risk of severe sequelae (ultrasound examination, fetal blood sampling), thus allowing proper counseling.     

Prenatal diagnosis of carbamoyl-phosphate synthetase deficiency by fetal liver biopsy

In a pregnancy at risk for carbamoyl-phosphate synthetase (CPS) deficiency, prenatal diagnosis was attempted by fetal liver biopsy, performed at 18 weeks of gestation. CPS activity was absent and the diagnosis was confirmed after termination of the pregnancy. The technique employed for fetal liver biopsy is described together with an evaluation of its possible role in prenatal diagnosis.     

Prenatal diagnosis and early in utero management of fetal dyshormonogenetic goiter

We present a case of a fetal dyshormonogenetic goiter diagnosed by ultrasound examination at 24 weeks of gestation, in a woman with no past history of thyroid disease or goitrogen treatment and with normal thyroid tests, including absence of auto-antibodies. In this situation, fetal goiter may only be associated with fetal hypothyroidism, therefore cord blood sampling was not performed but early treatment was initiated. Amniotic fluid instillation of thyroid hormone led to a rapid decrease in amniotic fluid volume and a clear reduction in thyroid goiter. However, fetal thyroid volume did not totally normalise, and cord blood analysis at birth showed elevated fetal TSH level. As prenatal treatment of fetal hypothyroidism remains controversial in euthyroid mothers, the main objective is to prevent obstetrical complications of large goiters. Therefore, in some selected cases with no maternal history of thyroid disease and normal thyroid function tests, cordocentesis is not necessary to confirm fetal thyroid status or to adjust fetal treatment.     

Prenatal diagnosis of congenital malformations in 500 pregnancies

The organization, techniques used and diagnostic findings of 500 prenatal diagnoses are reported in detail. In 15 cases the pregnancy was terminated because of abnormal laboratory findings. Follow-up of the remaining pregnancies revealed a perinatal mortality of 1.7%, and the risk of an abortion induced by amniocentesis, performed in the 15–16th wk, to be 1–2%. Serious counseling problems arose in 2 cases with trisomy X, in 2 instances of a balanced chromosome translocation and in 1 case of a de novo translocation.     

Prenatal diagnosis of congenital diaphragmatic eventration by magnetic resonance imaging

Diaphragmatic eventration is a rare abnormality, which has the similar ultrasonographic features to congenital diaphragmatic hernia. Therefore, these two diseases are difficult to differentiate from each other prenatally. We present here a case in which the presence of congenital diaphragmatic eventration was strongly suggested by magnetic resonance imaging (MRI) and ultrasonography. A 26-year-old pregnancy woman, gravida 0, para 0, week 35, was admitted to our hospital with an ultrasonographic abnormality of the fetal thorax. MRI and ultrasonography showed interesting features which strongly suggested the presence of congenital diaphragmatic eventration and helped to differentiate it from congenital diaphragmatic hernia.     

Prenatal diagnosis of symptomatic congenital cytomegalovirus infection

OBJECTIVE: The aim of this study was to evaluate whether the amniotic viral load of mothers with primary cytomegalovirus infection correlate with fetal or neonatal outcomes. STUDY DESIGN: Sixty-eight of 138 pregnant women with primary infection defined by immunoglobulin G seroconversion or the presence of immunoglobulin M with low immunoglobulin G avidity accepted amniocentesis. Polymerase chain reaction and quantitative polymerase chain reaction were used to detect amniotic fluid cytomegalovirus. Cytomegalovirus infection in neonates was determined by means of urinary viral isolation during the first week after birth or the histologic examination of tissue from aborted fetuses. RESULTS: Cytomegalovirus infection was found in 16 fetuses and neonates (23%), 5 of whom had symptoms. Quantitative polymerase chain reaction showed that the presence of >/=10(3) genome equivalents predicted mother-child infection with 100% probability; >/=10(5) genome equivalents predicted the development of a symptomatic infection. CONCLUSION: Fewer than expected cytomegalovirus-infected fetuses are at risk for development of cytomegaloviral disease, and this fact may be useful in counseling pregnant women with primary cytomegalovirus infection.     

Prenatal diagnosis of Fukuyama congenital muscular dystrophy

Fukuyama congenital muscular dystrophy (FCMD) is characterized by infantile hypotonia, symmetrical generalized muscle weakness, and neuronal migration disturbances that result in changes consistent with cobblestone lissencephaly with cerebral and cerebellar cortical dysplasia. FCMD is recognized as an autosomal recessive genetic defect. Genetic counselling is recommended for parents at risk of having a child with FCMD. Given the high risk and overwhelming prospect of having another child with this incurable devastating condition leads many couples to consider prenatal diagnosis. In Japanese families, haplotype analysis using microsatellite markers is available. In non-Japanese families, DNA sequence analysis is available. Both disease-causing alleles of an affected family member must be identified before prenatal testing can be performed.     

Prenatal diagnosis of Milroy's primary congenital lymphedema

Milroy's primary congenital lymphedema (PCL) (hereditary lymphedema type I, Milroy disease) is present at birth, and mostly affects the dorsal aspects of feet. It is mostly a life-long condition but does not affect longevity. Complications are rare except for chronic discomfort and warmness of affected areas. PCL is an autosomal dominant disease with incomplete penetrance due to a mutation in the gene locus encoding for VEGFR3 with resultant dysgenesis of microlymphatic vessels. We report on two fetuses where ultrasonographic examination at 15 weeks of gestation showed significant edema of the dorsal aspects of both feet with no evidence of other major malformations. Whereas in one fetus the edema resolved completely, it persisted in the second fetus and proved after birth to be of lymphedematous nature. To the best of our knowledge, this is the first report of early prenatal diagnosis of primary congenital lymphedema via fetal ultrasonographic examination and of spontaneous resolution of lymphedema during fetal life.     

Prenatal sonographic diagnosis of congenital hiatal hernia

OBJECTIVES: To report a rare case of congenital hiatal hernia illustrating the importance of its prenatal diagnosis as well as to discuss the prenatal sonographic criteria. CASE REPORT: A case of congenital hiatal hernia was diagnosed by ultrasound at 33 weeks of gestation. After a normal second-trimester morphologic ultrasound examination, a hypoechogenic mass was detected in the posterior mediastinum juxtaposed to the vertebral body and seemed to be in continuity with the intra-abdominal stomach bubble. Congenital hiatal hernia was suspected mainly because of the dynamic position of the stomach during the examination, without mediastinal shift, and normal appearance of the diaphragm on parasagittal sections of the thorax. Postnatal management was planned with no urgency and surgery was successfully performed, confirming the diagnosis. CONCLUSION: This rare case illustrates the importance of prenatal diagnosis of congenital hiatal hernia for prenatal counseling and postnatal management. The ultrasound criterion for prenatal diagnosis is the presence of a herniated stomach in the posterior mediastinum, sometimes having a dynamic position during examination, with no mediastinal shift associated with normal diaphragm appearance on parasagittal sections of the thorax.     

先天性心脏畸形的产前诊断及临床分析

目的探讨先天性心脏畸形的产前诊断及临床意义。方法本研究应用Yagel5个心脏横面和心脏长轴切面进行胎儿心脏扫描，并有效多普勒血流技术、彩色血流、M型超声等超声仪器各项功能技术，对2002至2004年982例先天心脏畸形高危患者进行胎儿心脏全方位检查，并对引产胎儿进行尸体解剖核对产前诊断的正确性，并进行胎儿染色体分析；对产前诊断未发现明显异常的胎儿进行临床随访，胎儿出生后进行新生儿或要儿心脏超声检查，判定产前诊断的正确性。结果（1）982例先天心脏畸形高危患者中，检查发现胎儿心脏结构异常为46例（4．7％）。其中应用单纯四腔心即能诊断的先天性胎儿心脏结构异常为32例，其余14例需同时结合其他心脏检测平面诊断。（2）41例引产胎儿中，32例进行尸体解剖，病理结果与产前超声检查符合率为93．8％（30／32），其中1例患者病理诊断为永存动脉干畸形，产前诊断为法洛四联症；另1例为右心室双流出道畸形，产前诊断为大动脉转位。（3）46例患者中，32例进行胎儿染色体检测，合并染色体异常8例（25．0％）。（4）5例为产前诊断右心系统略大胎儿，分娩后新生儿或要儿心脏超声检查，结果与产前基本相同，表现为单纯右心系统略大，但新生儿和要儿无任何临床症状。（5）936例产前诊断为正常胎儿心脏患者，新生儿或要儿心脏超声检查发现室间隔缺损1例，动脉导管未闭2例，房间隔缺损1例。结论（1）应用本研究方法，以先天心脏畸形高危患者为筛查对象，产前诊断先天性心脏畸形阳性率为4．7％，产前诊断与尸体解剖符合率为93．8％。（2）应用本研究方法可使高危人群产前诊断胎儿先天性心脏畸形的敏感性达92．0％，特异性达99．6％。（3）单纯左右心比例轻中度失调胎儿可能有较好的临床预后。     

Prenatal diagnosis of congenital lobar fluid overload

Prenatal congenital lobar fluid overload (CLFO), which was first described by Ramsay and Byron, is identical to postnatal congenital lobar overinflation. It is characterized by progressive lobar overexpansion that compresses the other adjacent lung lobes. The underlying cause can be an intrinsic cartilaginous abnormality or an extrinsic airway compression. It may be associated with cardiovascular anomalies in 12%–14% of cases and affects males more frequently than females. Most cases are diagnosed postnatally, but early antenatal diagnosis and sequential follow-up are attempted for early treatment, if clinically indicated. This article provided a thorough review of CLFO, including prenatal diagnosis and differential diagnoses, as well as comprehensive illustrations of the perinatal imaging findings of CLFO. Prenatal diagnosis of fetal lung lesions should include CLFO in the differential diagnosis and prompt investigation for associated anomalies.