In utero therapy for fetal thoracic abnormalities

Fetal thoracic lung anomalies are rare. The specific diagnosis can be made by utilizing ultrasound, magnetic resonance imaging (MRI), and Doppler studies. Perinatal surveillance is required for large lesions and mediastinal shift regardless of the pathological diagnosis. These can cause physiological changes in the cardiovascular system with resulting hydrops. In utero therapies are variable but with no large randomized trials to compare risks and benefits. In most cases of fetal lung lesions, continued observation with postnatal therapy is the outcome. When fetal hydrops is present or impending, in utero fetal therapy is required to try to reverse that pathological course associated with fetal or neonatal death. Maternal morbidity is increased with the development of MIRROR syndrome following the presence of long-standing fetal hydrops and possible surgical procedures.     

Prenatal evaluation for fetal surgery

The selection of fetuses that may benefit with in utero surgery is being developed. Noninvasive and invasive prenatal diagnosis techniques are utilized to try and gain as much knowledge about the fetus so that the appropriate counseling of parents can be undertaken. The most common invasive techniques are amniocentesis and chorionic villus sampling for fetal karyotyping and genetic diagnosis. Noninvasive techniques include ultrasound (2D and 3D), fetal echocardiography and magnetic resonance imaging. Additional techniques such as specific Doppler evaluation of vascular components, new techniques to look at fetal electrocardiograms and the use of computer tomography are also considered. The most common conditions for which in utero fetal surgery is also being considered are twin to twin transfusion syndrome, myelomeningocele, sacrococcygeal teratoma, cystic adenomatoid malformation of the lung with fetal hydrops and other monochorionic twin abnormalities (severe discordant birth defects or twin reversal arterial perfusion sequences). Ongoing evaluation of the sensitivity, specificity, positive and negative predicted values of these evaluation tools is required so that appropriate selection of fetuses for the surgery can be made.     

Successful treatment of primary fetal hydrothorax with a double basket catheter

Fetal pleural effusions can sometimes be detected before birth with ultrasonography. Intervention may be warranted when there is a condition that results in hydroplastic lung and/or fetal hydrops. A 22-week-old fetus with a severe pleural effusion and hydrops was successfully treated by long-term pleural drainage with a double basket catheter from 22 to 39 weeks of gestation.     

Estimation of fetal lung volume using enhanced 3-dimensional ultrasound: a new method and first result

Objective To measure fetal lung volume using a computer based, enhanced, 3-dimensional ultrasound imaging system.
Design An observational study.
Setting The Fetal Medicine Unit at Guys Hospital, London.
Participants Twenty healthy women with a singleton pregnancy between 24 and 36 weeks of gestation were scanned on one occasion during pregnancy using an ultrasound based 3-dimensional imaging system. All delivered at term with weights above the 10th centile for gestation.
Results Total lung volume increased exponentially with gestational age. Right lung volume measured consistently greater than left lung volume.
Conclusions The use of this new enhanced 3-dimensional imaging system allows for estimations of fetal lung volume. Preliminary data confirm that fetal lung volume, measured by a computerised 3-dimensional ultrasound imaging system increased exponentially with gestational age. The use of this system has obvious application in the further study of lung growth in utero and possible clinical application in disease states where fetal lung growth may be impaired.     

Non-invasive diagnosis and follow-up of fetal anemia

Fetal anemia is a life-threatening condition caused by different illnesses. The only technique to assess the actual degree of fetal anemia, and thus the need for transfusion, is cordocentesis. However, ultrasound examination may be useful to detect fetal anemia, to follow known at-risk fetuses and to avoid invasive procedures. We have analyzed data collected from case reports, retrospective and prospective studies about ultrasound detection of fetal anemia. The detection of a single morphological sign of fetal anemia could help to diagnose fetal anemia, but it is not helpful in predicting the severity of the anemia or in monitoring an isoimmunized fetus, because of the large proportion of false-negative results in the presence of severe anemia. The degree of anemia is not the only determining factor in hemodynamic changes. The absence of fetal hydrops does not mean that the hemoglobin level is above 5g/dl. Signs of cardiac decompensation and cardiomegaly seem to be immediate pre-hydropic changes. Angle-dependent Doppler measurements seem to be a better tool for avoiding invasive procedures. All cases of severe anemia were correctly diagnosed by means of the deceleration angle of the splenic artery. Fetuses with splenic artery peak systolic velocity below the mean for gestational age were not at risk for any degree of anemia. Therefore, it is a useful means of monitoring the rhesus-isoimmunized fetuses. Middle cerebral artery peak systolic velocity was a good predictor of severe anemia with or without the presence of hydrops fetalis. Any of these ultrasound measurements requires a certain degree of training and expertise that may not be available outside of referral centers. The ideal combination of morphologic findings and the choice of fetal vessels for Doppler velocimetry assessment remain to be determined.

At present, the ultrasound technique cannot completely replace cordocentesis and amniotic fluid bilirubin measurement. The greatest benefit of these techniques lies in patients with severe disease before 27 weeks of gestation, where amniotic fluid bilirubin levels may not be reliable. It could also help when the cause of fetal hydrops is unknown. Further prospective studies are required to discover an ideal ultrasound protocol for monitoring at-risk fetuses.     

Pericardial teratoma complicated by hydrops: successful fetal therapy by thoracoamniotic shunting

Pericardial teratoma is a potentially curable lesion that may become life threatening when it induces mediastinal compression and fetal hydrops. So far, cases with fetal hydrops have been managed by elective delivery or pericardial needle decompression. We report a case in which pericardial teratoma resulted in fetal hydrops. Following transpleural needling of the fetal pericardium at 29 weeks and 6 days, pericardial effusion decreased but hydrops persisted, while major unilateral pleural effusion appeared. A thoracoamniotic shunt was placed at 30 weeks and 5 days. Hydrops resolved, although incompletely. The baby was delivered at 32 weeks and was operated upon on day 3. This observation suggests that fetal hydrops associated with pericardial teratoma may improve following thoracoamniotic shunting. Fetal therapy may limit the risks of respiratory distress arising from the combined effect of airways compression and lung immaturity.     

Prenatal treatment of fetal hydrops associated with the hypertelorism-dysphagia syndrome (Opitz-G syndrome)

Non-immunological fetal hydrops diagnosed prenatally presents a difficult diagnostic and therapeutic problem. In the case presented, fetal hydrops was recognized at 19 weeks gestation and no specific cause was found prenatally in spite of extensive investigations. The fetal hydrops was treated in utero by thoracocentesis and an intravenous infusion of albumin carried out at fetoscopy. After birth the infant was recognized to have the hypertelorism-dysphagia syndrome (or Opitz-G syndrome, McK no. 30710). This autosomal dominant syndrome consists of hypertelorism, laryngeal abnormalities, swallowing difficulties, hyprospadias and an imperforate anus. Fetal hydrops has been reported on one previous occasion in this syndrome. The intrauterine treatment given in this case may have been successful in reducing the neonatal complications of the Opitz-G syndrome.     

Prenatal diagnosis of fetal tumors by ultrasonography

Fetal tumors lead to serious illness or even death in the fetal or neonatal period. Problems vary from severe hydrops to underdevelopment of fetal organs. In some instances a tumor may cause mechanical obstruction during the birth process. Polyhydramnios frequently develops. Adequate prenatal diagnosis is of utmost importance. Timely detection of the fetal tumor prevents traumatic birth and postnatal care and treatment can be scheduled. This report is a review of the relevant recent literature and the tumors detected in our ultrasound unit between 1982 and 1988. The ultrasonographic appearance, clinical course, and differential diagnosis of the tumors are discussed.     

Fetal diagnosis and fetal surgery

Accurate fetal diagnosis became possible by the steadily increasingly complex techniques of amniocentesis, ultrasound, and ultrasound-guided fetal blood sampling and chorion villous sampling. A high degree of diagnostic accuracy for a wide variety of structural and metabolic anomalies is required. The field of fetal diagnosis has been extended to the point that a journal dedicated to this subject alone is a viable proposition. It is becoming apparent, however, that lesions that were well known and well understood when recognized in neonatal life appear in general to have a worse prognosis if the lesion is diagnosed in utero. Fetal surgery began with attempts to perform in utero transfusions for babies with erythroblastosis fetalis. For a while, there was competition between open surgical procedures and the percutaneous placement of blood through catheters introduced into the fetal peritoneal cavity from outside the mother's abdomen. For fetal transfusion, closed techniques proved far safer and just as efficacious. There has been a worldwide interest in shunting of hydrocephalus and obstructive uropathy. The results of shunting hydrocephalus have been disappointing, with most of the patients surviving, but most of the survivors being severely handicapped. The results of shunting obstructive uropathy were that only about 50 per cent of the babies survived, but it appeared that those that did survive did well. Other lesions that have been shunted have been hydrothoraces or fetal ascites. A limited number of open procedures have been carried out in the last few years in San Francisco, and it may well be that diaphragmatic hernia (in appropriately selected patients) will be a lesion that can be corrected by in utero surgery. The future of this field is exciting, but before this form of treatment becomes routine, the ethical implications of the possibility of fetal surgery must be defined much more clearly than is currently the case.     

A surprising case of sustained antenatal fetal bradycardia

Persistent fetal bradycardia noted in the antenatal period can occur secondary to maternal conditions, fetal cardiac structural defects, or from congenital heart block. Fetal bradycardia can be mistaken for maternal pulse and should be confirmed with ultrasound whenever possible. Prompt evaluation of the fetus with bradycardia can lead to early interventions designed to prevent cardiac damage and/or hydrops.     

Management of fetal airway obstruction

Fetal airway obstruction can make it difficult if not impossible to secure the airway at birth, before hypoxia, brain injury, or death results. Fetal airway obstruction can result from an intrinsic defect in the airway, such as the congenital high airway obstruction syndrome or extrinsic compression of the airway caused by a cervical mass, most commonly a cervical teratoma or lymphangioma. As fetuses with fetal airway obstruction reach viability, they should be monitored closely for the development or progression of hydrops in intrinsic obstruction cases or polyhydramnios in extrinsic obstruction cases. The fetus should be delivered by using the ex utero intrapartum treatment procedure, with maintenance of uteroplacental circulation and gas exchange. This approach provides time to perform procedures such as direct laryngoscopy, bronchoscopy, or tracheostomy to secure the fetal airway, thereby converting an emergent airway crisis into a controlled situation.     

Outcome of fetal cystic hygroma and experience of intrauterine treatment

OBJECTIVE: To review our cases of fetal cystic hygroma and to examine the prognostic factors with the goal of establishing criteria for the intrauterine treatment for cystic hygroma. PATIENTS AND METHODS: Thirty-one cases of fetal cystic hygroma were managed by us from January 1988 to December 1997, and 21 cases were available for analysis. Three prognostic factors, namely chromosomal abnormality, structural anomaly and hydrops fetalis, were evaluated. We treated 2 cases of cystic hygroma associated with hydrops fetalis in utero using OK-432 injection under ultrasound guidance. RESULTS: The fetuses without any of the prognostic factors listed above showed a good prognosis throughout the fetal and neonatal periods. However, in this group, 2 infants with large tumors died of hemorrhage from the tumor at 6 months and 3 years of age, respectively. Cases with hydrops fetalis without chromosomal abnormalities or structural anomalies (5 cases) resulted in either intrauterine fetal death (IUFD, 2 cases) or early perinatal neonatal death (early PND, 3 cases). The cause of early PND was circulatory failure. Most of the hydrops cases with either a chromosomal abnormality or structural anomaly resulted in IUFD before 22 weeks of gestation. The size of the cyst decreased in 1 of 2 cases treated in utero. CONCLUSIONS: The fetal cases of cystic hygroma showing hydrops fetalis without chromosomal abnormalities or structural anomalies are considered to be possible candidates for intrauterine therapy. Those with very large cystic hygroma without any of the three prognostic factors are also thought to be candidates for fetal treatment. Based on our clinical experience, sclerotherapy using OK-432 is considered to be a treatment option in selected cases with fetal cystic hygroma.     

Requirements for fetal surgery: the diaphragmatic hernia model

Fetal surgery for congenital diaphragmatic hernia and other fetal conditions can only be considered if (1) the morbidity of antenatal intervention is acceptable, (2) the diagnosis of the condition can be made accurately, (3) the condition can be differentiated from other, non-surgical anomalies. In addition, (4) the natural evolution of the disease, if left untreated, should be predictable, and the condition should be lethal or severely debilitating, (5) there should not exist adequate postnatal treatment, and (6) the proposed in utero operation should be technically feasible. Open fetal surgery has proven too invasive to be justified for the treatment of diaphragmatic hernia, and progress in postnatal therapy (including ECMO) has dramatically improved the neonatal outcome in all but a severe subgroup of patients. Recently, advances in endoscopic fetal surgery (which appears to be less stressful for the fetus and the gravid uterus) and a new approach to accelerate fetal lung growth and maturation have renewed the feasibility of in utero intervention for diaphragmatic hernia.     

Spontaneous rupture of fetal sacrococcygeal teratoma

With recent advances in technology, fetal sacrococcygeal teratoma is being diagnosed increasingly during the early prenatal period by ultrasound examination. In addition, early detection of tumor related complications such as polyhydramnios, congestive heart failure, hydrops, hemorrhage, urinary tract or bowel obstruction can be followed closely in utero. Active prenatal management can improve fetal perinatal outcome by allowing planned delivery for neonatal surgery [Chisholm, C.A. et al.: Am J Perinatol 1999;16:47-50] or in some cases, fetal intervention. Additionally, families can be counseled appropriately regarding the range of outcomes. We report a case of fetal sacrococcygeal teratoma Type I diagnosed at 20 weeks with a prominent vessel supplying the tumor mass. At 23 weeks, there was a sudden appearance of an additional lobular mass, consistent with intrauterine spontaneous ruptured of a sacrococcygeal teratoma mass.     

Intrauterine therapy with cytomegalovirus hyperimmunoglobulin for a fetus congenitally infected with cytomegalovirus

Reported herein is a case of hydrops fetalis in which the cord blood expressed cytomegalovirus (CMV) antigen. Fetal ascites was removed from an infected fetus with hydrops in utero and 2.5 g CMV hyperimmunoglobulin was administered into the fetal abdominal cavity at 28 weeks gestation. After immunoglobulin administration, fetal ascites vanished, preload index of the inferior vena cava decreased and platelet count of the infant increased. However, despite intrauterine therapy and intensive neonatal care, the infant died soon after birth. The expression of CMV antigen in the nucleus of polymorphonuclear leukocytes in fetal cord blood indicated that the fetal hydrops was caused by CMV infection. When symptomatic CMV infection of a fetus is suspected from serological and ultrasound findings, further examinations should be performed for the diagnosis. Intrauterine immunoglobulin therapy could be one of the therapeutic options for the affected fetus.     

Fetal supraventricular tachycardia refractory to digoxin cardioversion. A case report

Fetal cardiac arrhythmias are being diagnosed with increased frequency through ultrasonography and electronic fetal heart rate monitoring. Although many of them are benign, some, particularly supraventricular fetal tachycardia, have been associated with a poor outcome. Fetal hydrops and other evidence of fetal cardiac failure resulting from the elevated heart rate have been reported on. Although several modes of treatment have been described, the mainstay of cardioversion in utero continues to be digoxin. This case report demonstrates the need for prompt delivery when in utero cardioversion fails.     

Long-term outcome in fetal hydrops from parvovirus B19 infection.

Parvovirus B19 infection in the fetus is associated with anemia and hydrops and can result in fetal death. Fetal transfusion has been used in an attempt to improve outcome; however, it is associated with its own perinatal morbidity. We report two cases of fetal parvovirus B19 infection that were confirmed by polymerase chain reaction for parvovirus B19 deoxyribonucleic acid in umbilical cord blood. Ultrasonographic signs of compromise were observed at 30 and 24 weeks of gestation. Both fetuses were hydropic and one fetus was also anemic. Serial sonograms demonstrated that the hydrops resolved spontaneously over 3 to 5 weeks after diagnosis. One infant was delivered at 32 weeks of gestation as a result of idiopathic preterm labor. The other infant was delivered at term. Both infants appeared relatively normal at birth and have developed normally in the first year of life. Thus fetal hydrops in association with parvovirus B19 infection does not always lead to poor long-term outcome. A conservative approach without in utero therapy may be appropriate for the management of some of these fetuses.     

Early prenatal management of a fetal ventricular tachycardia treated in utero by amiodarone with long term follow-up

Fetal cardiac arrhythmias are one of the causes of intra-uterine congestive heart failure and non-immune hydrops fetalis leading to fetal death. As ventricular tachycardia (VT) is rarely diagnosed in utero, it leads to emergency deliveries. We report a prenatal diagnosis of fetal tachycardia at 20 weeks of gestation associated with non-immune hydrops fetalis. The tachycardia seemed to be supraventricular and was initially treated by digoxin and sotalol. The hydrops increased and sotalol was stopped in order to give the mother a high dose of amiodarone by mouth over a long period. Although the tachycardia, which the ECG recorded at birth revealed to be of ventricular origin, persisted but at a lower rate, the new treatment proved successful. The child is three years old now and health, though with persistent VT. In conclusion, fetal tachycardia with similar ventricular and atrial rates can be a VT and the drug of choice in this case seems to be amiodarone.     

146例非免疫性水肿胎儿的产前染色体分析

目的:分析非免疫性水肿胎儿的产前诊断结果,明确其染色体异常的类型。方法:选取146例非免疫性水肿胎儿,通过经腹绒毛取样、羊膜腔穿刺、脐静脉穿刺及流产后取胎儿组织送检的方法进行胎儿染色体核型及低覆盖度大规模平行测序技术(CNV-seq)的分析。结果:146例胎儿的染色体异常发生率为48.6%(71/146),其中性染色体异常29例,21-三体19例,18三体13例,13-三体3例,其他染色体异常1例,致病性拷贝数变异6例。染色体异常检出率随着孕周的增加而降低,<14孕周、14~27孕周、≥28孕周孕妇的染色体异常检出率分别为68.4%(39/57)、40.8%(31/76)和7.7%(1/13)。水肿胎儿最常合并的超声结构异常依次为NT/NF增厚、颈部水囊瘤及心脏异常,其染色体异常检出率分别为59.5%、59.2%及51.9%。结论:染色体异常是胎儿水肿的常见病因,特别是早中孕期出现水肿的胎儿,检出率较高。对于水肿胎儿的产前诊断,除了常规的核型以外,需重视拷贝数变异的检测。     

Advancing fetal therapy in the United Kingdom

Fetal therapy is a rapidly advancing sub-specialty, encompassing direct fetal treatment or the administration of substances to the mother to achieve fetal benefit. The goal of all fetal therapies is to improve the prognosis for a condition where there is evidence of pathology developing in utero. In this article we briefly examine all major types of fetal therapy and their current evidence.