Intrauterine Intervention Research Articles

Intrauterine Aortic Valvuloplasty in Fetuses With Critical Aortic Stenosis: Experience and Results of 24 Procedures

During early morphogenesis of the heart, an obstructive lesion can lead to a complex cardiac malformation at the end of pregnancy in both the right and left heart. Valvular aortic stenosis (AS) in the left heart of mid-gestation fetuses can progress to hypoplastic left heart syndrome (HLHS), which can result in congestive heart failure and intrauterine death. Early intracardiac intervention using valvuloplasty of the fetal aortic valve has the potential to eliminate this obstructive lesion, and rescue the left ventricle, preventing progression of critical AS to HLHS and avoiding postnatal univentricular circulation. This study was designed to assess the outcome of 24 cases of aortic valvuloplasty performed in fetuses with critical AS with respect to indications, success rate, complications, and postnatal outcome. Between 2001 and 2009, 23 fetuses diagnosed with critical valvular AS underwent aortic valvuloplasty using a transabdominal ultrasound-guided approach. The gestational ages of these fetuses ranged from 21 to 32 weeks. The procedure was repeated in 1 fetus with a failed procedure after 7 days; thus, 24 interventions were performed in 23 fetuses. Of the 24 procedures, 16 (66.7%) were technically successful; intrauterine death occurred in 1 of the 16 successful valvuloplasties. After an initial learning phase, the success rate improved during the last 5 years to 78.6% for the last 14 interventions. Of the 15 successfully treated live-born fetuses, 10 (66.7%) achieved a postnatal biventricular circulation, and 5 (33.3%) were born with a univentricular circulation. Hydrops was present in 4 fetuses as a late sign of congestive heart failure and resolved within 5 weeks of successful intrauterine intervention; all had a postnatal biventricular outcome. Of the 8 unsuccessful interventions (8/24, 33%), 1 was repeated successfully with a biventricular outcome, 2 resulted in intrauterine death, and 5 were born with HLHS. These findings show that fetal aortic valvuloplasty in selected fetuses with critical AS and evolving HLHS can be performed successfully and achieve a biventricular outcome in two-thirds of patients. Critical factors for success include careful patient selection and an experienced interventional team.

PREPARATION OF PATIENTS WITH ДИСБИОЗОМ VAGINAS TO INTRAUTERINE INTERVENTIONS

Last decade against a wide circulation of chronic infectious-inflammatory processes, number increases immmunodeficilis conditions, growth of number of diseases, sexually transmitted, the increasing value get associations of microorganisms and activation of is conditional-pathogenic microflora. At use of non-standard methods of diagnostics and treatment, at wrong treatment of diseases, the pathological conditions demanding their timely correction arise ignoring social and demographic factors. In our research for the purpose of preparation of patients with disbyosis vaginas to intrauterine interventions used a preparation from live apatogenitia sort bacteria "Bacillus" "Sporobakterin" possessing a wide spectrum of action who has allowed to lower several times frequency of relapses disbyosis in the postoperative period.

Fetal therapy: progress made and lessons learnt

Fetal therapy began more than half a century ago when Liley reported the first intraperitoneal transfusion for the treatment of fetal anaemia in Rhesus disease (Liley, 1963). This was to be replaced with intravascular transfusion, initially by fetoscopy and subsequently by ultrasound-guided cordocentesis. This is now a wellestablished therapy and one which was never subjected to rigorous evaluation. In this issue of Prenatal Diagnosis, we focus on fetal therapy, exploring how far it has developed since these early reports and discuss how new approaches might further change management, highlighting the need for rigorous evaluation of any new technology prior to clinical implementation. The widespread use of ultrasound scanning in the 1980s and the prenatal detection of fetal defects stimulated the development of a wide range of techniques for intrauterine interventions. The aim was to improve the outcome for conditions that were traditionally treated by postnatal surgery because it was thought that prenatal surgery could reduce irreversible damage to the developing organs. However, for the large part the absolute benefit in terms of improved longer term outcome for affected fetuses remains unknown. It is only in the last few decades or so that we have realised that the only way to properly assess many of these therapies is with randomised trials, which must include structured long-term follow-up to determine the true benefits and costs. A good example is the management of lower urinary tract obstruction where shunting initially seemed to improve outcome as more babies survived the neonatal period. However, most studies were small and had no control group, thus making it impossible to define any benefit resulting from the intervention and longer term follow-up was patchy and inconsistently collected (Ruano, 2011). Furthermore, because of the rarity of many of these conditions, much of this research must be multicentre and multinational, raising an issue in itself as these techniques will be concentrated in centres of excellence, thereby limiting equity of access and focussing expertise in a few centres (Ville, 2011).

Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis

Despite advances in diagnosis and management, non-immune hydrops fetalis (NIHF) has a high mortality rate. Perinatal survival depends on the underlying disorder and the gestational age at diagnosis. As prognostic information is limited, this study acquired data regarding the neurological development of perinatal survivors. We performed a retrospective chart review of 214 cases in which NIHF was diagnosed antenatally. We recorded maternal demographic characteristics and interventions and their effectiveness, as well as the short-term outcome (survival) and long-term outcome including developmental quotients. Among the affected fetuses, 91 (42.5%) survived the perinatal period. Fetuses with chylothorax, chyloascites, or meconium peritonitis, and those in whom therapy was effective, had high survival rates irrespective of the type of intrauterine intervention. The subsequent intact survival rate was 28/56 (50.0%), with intact defined as ratio of the number of infants with normal development to the number of all infants followed. In contrast to the perinatal survival rate, the intact survival rate decreased as gestational age at diagnosis advanced. These findings suggest that the long-term intact survival rate depends on the underlying cause of NIHF. Additionally, while survival was improved with intensive perinatal care during the perinatal period, aggressive perinatal intervention was not a prognostic factor for neurological outcome.

Questioning the rationale and conduct of the management of myelomeningocele study

Surgical intervention in fetal spina bifida developed from the belief that amniotic fluid damages the spinal cord in utero and low spinal pressure from failure of neural tube closure causes hindbrain herniation leading to hydrocephalus after birth for many infants with open spinal lesions. Intrauterine intervention is undergoing a randomised human trial known by the acronym MOMS. It is hoped that randomisation and long-term follow up will demonstrate whether benefits to the infant may result from closure of the vertebral defect before birth. It is argued here that the premise upon which the pathogenesis of neural injury in human spina bifida used to launch this study is mistaken. This has implications for the conduct and conclusions of the trial. It is proposed that fetal surgery improves central nervous system outcome by improving cerebrospinal fluid flow at the foramen magnum. Successful intervention results in a more normal development of both neural and skeletal components of the neuraxis. Closure of the defect is required before signs of hindbrain herniation and ventriculomegaly are evident on ultrasound imaging as these are indicators of the presence of fetal hydrocephalus.

Indications and outcomes of intrauterine surgery for fetal malformations

Although the efficacy of intrauterine intervention has been clearly demonstrated for some conditions, such as twin to twin transfusion syndrome and twin reversal arterial perfusion, it is still to be determined as treatment of congenital diaphragmatic hernia, cardiac defects, lower urinary tract obstruction and sacrococcygeal teratoma. The aim of the present study was to review literature concerning the benefits and outcomes of fetal intervention for these anomalies together with its limitations and controversies. Only one randomized clinical trial, which compared prenatal versus postnatal treatment for congenital diaphragmatic hernia, was performed. For the other anomalies, small series were described and showed that fetal surgery drastically changes the natural history of the discussed anomalies, thus it prevents the progression of a disorder that is likely to be fatal. However, controversies exist with regard to operating timing and selection criteria of fetuses that may benefit from fetal surgery. Further investigations are needed with regard to the definition of appropriate operating timing and standardization of selection criteria. Multicenter randomized trials are also necessary in order to define whether fetal surgery is associated with better outcomes as compared with postnatal treatment.

Clinical and placental characteristics in four new cases of twin anemia–polycythemia sequence

We report and analyze four new cases of spontaneous twin anemia-polycythemia sequence (TAPS) and discuss antenatal management by fetoscopic laser coagulation for this uncommon form of chronic intertwin transfusion. The clinical course and placental characteristics of four pairs of monochorionic-diamniotic (MCDA) twins with spontaneous TAPS, of which one was treated with fetoscopic laser surgery, are described. For the three cases that did not undergo intrauterine intervention, serial Doppler measurement revealed a gradual increase in the middle cerebral artery peak systolic velocity (MCA-PSV) in the donor and a concomitant decrease in the recipient. These twins were born at between 32 and 34 weeks' gestation by Cesarean section. At birth, the donor twins were severely anemic and the recipient twins were polycythemic. Placental injection studies revealed a few small arteriovenous (AV) and venoarterial anastomoses. In the fourth case, because of the high suspicion of TAPS on MCA-PSV data at 24 weeks' gestation, fetoscopic laser coagulation of three small AV anastomoses was successfully performed. No hematological abnormalities were detected at birth. TAPS is a newly described form of chronic twin-to-twin transfusion associated with chronic anemia in the donor and polycythemia in the recipient, without twin oligo-polyhydramnios sequence (TOPS). The monitoring of MCDA pregnancies should include measurement of MCA-PSV in both fetuses even in the absence of intertwin discordance in amniotic fluid volume. Early detection of TAPS could indicate fetoscopic laser coagulation of AV anastomoses.

Role of quantitative assessment in fetal echocardiography

Role of quantitative assessment in fetal echocardiography

Thoraxchirurgie bei Neugeborenen und Säuglingen mit angeborenen Fehlbildungen

Congenital malformations of the lung and diaphragm are a challenge in paediatric surgery. Depending on the malformation they show a broad spectrum of symptoms and a varying age at manifestation. Thus there are many diagnostic and therapeutic options, which require a good knowledge of the pathology. The treatment of these complex cases should lead to early referral to paediatric centres containing an interdisciplinary team with neonatologists, paediatric pulmonologists and cardiologists, ENT surgeons, anaesthesiologists, radiologists and paediatric surgeons. Some malformations are diagnosed prenatally and need intrauterine interventions. Decisive is the early diagnosis and treatment of these malformations. Nowadays the surgical therapy of neonates and infants with malformations of the lung and diaphragm is enriched by a number of endoscopic and endoluminal techniques, which are discussed critically in this article.

Therapeutic Indications of Fetoscopy: A 5-Year Institutional Experience

Prenatal ultrasound study allows the detection of fetal malformations. Intrauterine interventions are now contemplated to correct, or interfere with, the natural history of these anomalies. Minimally invasive techniques, such as the so-called "Fetendo" (fetal endoscopy), are now therapeutic possibilities. From 2002 to 2007, 205 fetoscopies were performed in our hospital's fetal surgery program. Fetoscopic interventions were carried out under epidural anesthesia, accessing the uterine cavity with a fetoscope containing a 1.2-mm telescope. Following ultrasound-guided needle puncture of the amniotic cavity, the fetoscope was inserted through a 3-mm sheath by the Seldinger technique. Visibility was maintained with an amnioinfusion system. This procedure offers access to the placental surface, umbilical cord, and fetus. Fetoscopy was used to perform laser coagulation of communicant placental vessels in 148 biamniotic monochorionic gestations with twin-to-twin transfusion syndrome (TTTS) and to occlude the umbilical cord in 32 cases of discordant monochorionic twins with a severe or lethal anomaly in one of the fetuses, and 5 cases of reversed arterial perfusion (TRAP) sequence. In addition, fetoscopy was performed in 18 cases to treat severe congenital diaphragmatic hernia by tracheal occlusion with an endotracheal balloon. Finally, in 2 cases, fetoscopic release of amniotic bands was performed to rescue extremities and the umbilical cord. The most common complications (10%) were preterm rupture of membranes, which resulted in preterm delivery. Other indications for fetoscopy, which we are currently using in experimental animal models, include low urinary tract obstruction, sacrococcygeal teratoma, and repair of myelomeningocele defects. Fetoscopy can lower the incidence of preterm labor that occurs in response to the aggression of open surgery. At present, fetoscopy is effective for treating several fetal anomalies. Preterm rupture of membranes remains the weak link of fetoscopy. Refinement of the technique and technologic advances will help this problem and allow the use of fetoscopy for other pathologies in the future.

Intrauterine Closure of the Ductus Arteriosus: Implications for the Neonatologist

Intrauterine closure of the fetal ductus arteriosus is a rare but serious condition. It can lead to congestive heart failure, fetal hydrops, and fetal death. No intrauterine intervention is currently available to treat this condition. Postnatally, it can present as pulmonary hypertension and can be associated with high mortality and morbidity. Postnatal therapies aimed at pulmonary hypertension or with medications that maintain the patency of the ductus arteriosus are variably successful. We present the neonatal course of a full-term neonate with severe pulmonary hypertension and intrauterine closure of the ductus arteriosus who survived to early infancy.

Actualización en cardiología pediátrica y cardiopatías congénitas

The fields of pediatric cardiology and congenital heart disease have experienced considerable progress in the last few years, with advances in new diagnostic and therapeutic techniques that can be applied at all stages of life from the fetus to the adult. This article reviews scientific publications in a number of areas that appeared between August 2007 and September 2008. In developed countries, congenital heart disease is becoming increasingly prevalent in nonpediatric patients, including pregnant women. Actions aimed at preventing coronary heart disease must be started early in infancy and should involve the promotion of a healthy diet and lifestyle. Recent developments in echocardiography include the introduction of three-dimensional echocardiography and of new techniques such as two-dimensional speckle tracking imaging, which can be used for both anatomical and functional investigations in patients with complex heart disease, including a univentricular heart. Progress has also occurred in fetal cardiology, with new data on prognosis and prognostic factors and developments in intrauterine interventions, though indications for these interventions have still to be established. Heart transplantation has become a routine procedure, supplemented in some cases by circulatory support devices. In catheter interventions, new devices have become available for the closure of atrial or ventricular septal defects and patent ductus arteriosus as well as for percutaneous pulmonary valve implantation. Surgery is also advancing, in some cases with hybrid techniques, particularly for the treatment of hypoplastic left heart syndrome. The article ends with a review of publications on cardiomyopathy, myocarditis and the treatment of bacterial endocarditis.

Instrumental requirements for minimal invasive fetal surgery

Minimal invasive intrauterine interventions have gained their place in fetal medicine. Interventions on the placenta, umbilical cord, fetal membranes or on the fetus require special endoscopes with their respective sheaths, cannulas and additional instruments. Instruments for fetal therapy are purpose designed for the procedure of interest and most gynaecologists are therefore not familiar with them. We review the currently available instrumentation used during operations for complicated monochorionic multiple pregnancies, congenital diaphragmatic hernia, amniotic band syndrome, urinary tract obstruction and hydrothorax.

Fetus‐supporting flexible manipulator with balloon‐type stabilizer for endoscopic intrauterine surgery

Minimally invasive endoscopic fetal surgery enables intrauterine intervention with reduced risk to the mother and fetus. A novel surgical manipulator is described for stabilizing the fetus and restraining it from floating free during endoscopic intrauterine surgery. We designed and fabricated a prototype fetus-supporting manipulator equipped with flexible joint and bending mechanisms and a soft balloon stabilizer. The flexible joint and bending mechanisms enable the stabilizer to reach the target sites within the confined space of the uterus under the guidance of an ultrasound device. The balloon stabilizer could be inserted into the uterus through a small incision. The accuracy evaluation showed that the maximum error of the bending mechanism was as small as 7 mm and the standard deviation of the joint mechanism was just 1.6 degrees. In the experiments using a fetus model, the manipulator could be well controlled with guidance from ultrasound images and its bending mechanism with the balloon stabilizer could be clearly visualized while stabilizing the fetus model. The manipulator has the potential to be used in minimally invasive intrauterine surgery, although further improvements and experiments remain to be carried out.

Is premature induced labour justified in case of fetal urinary tract dilatation?

There is a decreasing trend in the number of intrauterine interventions performed due to urinary tract dilatations of the foetus diagnosed ultrasonographically. This is due to the low efficacy of the interventions, the high rate of complications and a better knowledge of the foetal physiology. However, the demand for early corrective surgery is still present. In Hungary pre-term caesarean section is performed in many institutions in order to enable the operation of the neonate, despite the fact that the benefits of this intervention have not been established. In order to test the correctness of this practice, the authors conducted a retrospective analysis of the patients of two large case-volume paediatric institutions. In a period of 5 years, 329 neonates were followed due to intrauterine diagnosis of urinary tract dilatations (197 at the Department of Urology, Heim Pál Children's Hospital in Budapest, whereas in Miskolc 132), including 13 cases where the urological anomaly was the indication for pre-term induction of labour. Of the 13 neonates who had been delivered prematurely, none were operated before the postconceptional age of 40 weeks, and 3 subsequently required no surgical intervention. Two neonates developed life-threatening conditions that presumably could have been avoided without the premature caesarean section. The authors conclude that there are several arguments against pre-term delivery: 1. Prenatal diagnostics does not always yield as accurate information as the diagnostic procedures performed in infancy; 2. Intrauterine urinary tract dilatation often resolve spontaneously, superseding the need for both pre- and post-natal surgical interventions. 3. Scientific observations have confirmed that there is no difference between the efficacy of postnatal and pre-term interventions. Based on the above-mentioned, authors emphasize that this outdated practice can no longer be accepted, and call for good cooperation between the obstetrician, the paediatric urologist and nephrologist, to coordinate the management of the case.

The role of perinatal and intrapartum risk factors in the etiologyof cerebral palsy in term deliveries in a Turkish population

Objective. To investigate the relationship between cerebral palsy (CP) and perinatal and intrapartum risk factors and markers of birth asphyxia.Methods. This was a retrospective case–control study of 101 children with CP and 308 controls who were born at the Zeynep Kamil Hospital between 1990 and 2000. The roles of possible perinatal and intrapartum risk factors were investigated in CP development. Chi-square tests, Fisher's exact tests, Student t-tests, and regression analysis were used for statistical analysis (p < 0.05).Results. The only significant perinatal risk factor was neonatal weight of <2500 grams. The CP rate in the presence of solely intrapartum risk factors was estimated as 24.7% (n = 25). In 39.6% of cases, no risk factor could be identified. When regression analysis was performed, the following factors were significant: decreased beat-to-beat variability on electronic fetal monitoring (EFM) (p = 0.02), an Apgar score of <7 at 1 and 5 minutes (p = 0.02), and the necessity for neonatal intensive care unit admission (p < 0.0001).Conclusion. Intrapartum risk factors were significantly more frequent in the CP group (p < 0.01). An increased cesarean section rate could not prevent CP, suggesting that the hypoxic insult that causes CP might be of chronic onset. The development of diagnostic tests to detect non-reassuring fetal status in its intrauterine life and interventions at appropriate times may decrease the CP rate.

Perinatal outcome in monochorionic twin pregnancies complicated by amniotic fluid discordance without severe twin–twin transfusion syndrome

To assess the natural history and perinatal outcome in monochorionic diamniotic twin pregnancies with discordant amniotic fluid volume without signs of severe twin-twin transfusion syndrome (TTTS). This was an observational study of 84 consecutive monochorionic twin pregnancies which did not meet the criteria for severe TTTS and endoscopic laser coagulation of placental anastomoses at initial presentation. The population was subdivided into two groups. Group 1 consisted of 64 pregnancies (median gestational age, 20.1 (range, 15.6-24.7) weeks) with amniotic fluid discordance and no signs of congestive heart failure in the twin with the larger amniotic fluid volume (Twin 1) and positive end-diastolic flow in the umbilical artery of the twin with the smaller amniotic fluid volume (Twin 2). Group 2 (median gestational age, 19.1 (range, 16.0-24.4) weeks) consisted of 20 pregnancies with amniotic fluid discordance and intrauterine growth restriction (IUGR) (abdominal circumference < 5th percentile) in combination with absent or reversed end-diastolic (ARED) flow in the umbilical artery of Twin 2. After exclusion of one patient from Group 1, who opted for termination of pregnancy, nine patients in Group 1 and one in Group 2 developed severe TTTS, and laser coagulation was offered. The remaining 54 pregnancies of Group 1 were compared with the remaining 19 pregnancies of Group 2. Fetuses in Group 1 showed significantly higher survival rates (overall survival, 100/108 (92.6%) vs. 23/38 (60%), P < 0.0001; survival of both fetuses, 49/54 (90.7%) vs. 9/19 (47.4%), P = 0.0002) and median gestational age at delivery (33.6, (range, 27.6-37.8) weeks vs. 32.0 (range, 26.9-36.3) weeks, P = 0.0457). Overall, there was a significantly higher incidence of complications, defined as necessity for intrauterine intervention, fetal or neonatal death or delivery prior to 32 weeks, in Group 2 (Group 1: 30/63 (47.6%); Group 2: 16/20 (80%), P = 0.0188). Our data suggest that amniotic fluid discordance in monochorionic diamniotic twin pregnancies in combination with IUGR and umbilical artery ARED flow in one fetus represents an extremely high-risk constellation for adverse pregnancy outcome.

Foetal surgery and cleft lip and palate: current status and new perspectives

Now-a-days, high-resolution ultrasound allows an accurate and relatively early diagnosis of congenital malformations. In a limited number of such conditions foetal surgery may be lifesaving. However, premature labour has been the major drawback for open foetal surgery. Recently, improvement of video-endoscopic technology has boosted the development of operative techniques for feto-endoscopic surgery, which has been demonstrated to be less invasive than the open approach. Main clinical application of fetoscopic procedures today is the treatment of feto-foetal transfusion syndrome. Although still in development, feto-endoscopic surgery seems to offer new hope for surgical foetal therapy not only in cases of life threatening conditions. Experimental intrauterine correction of cleft lip and palate (CLP) has been lately performed using the feto-endoscopic approach. This procedure offers two major advantages: first, scarless foetal wound healing and bone healing without callus formation, which would also allow a better/normal maxillary growth, and second, significant decrease of foetal and maternal morbidity. Herein, we report the current status of experimental and clinical foetal surgery and propose possible directions for continuing research to make intrauterine procedures safer. Furthermore, we discuss current knowledge and new perspectives of experimental foetal cleft lip and palate repair, which in the future may lead to such excellent results in the operative treatment of clefts, that less or no secondary corrections and therapies, such as orthodontic, dental, logopedic, etc. would be needed. Only if these conditions can be fulfilled, will we be able to improve substantially our therapy for the human foetus with a cleft lip and palate. In spite of all efforts, however, it must be considered that it may not ever be possible to find the optimal treatment method for this or other craniofacial malformations.

Ultrasonic Biophysical Measurements in the Normal Human Fetus for Optimal Design of the Monolithic Fetal Pacemaker

Ultrasound measurements, including xiphoid-to-pericardial distance and deployment angle, were made on human fetuses as a function of gestational age for the purpose of assessing the likelihood of 3 failure modes of a monolithic fetal pacemaker, including primary positioning failure due to device length and secondary dislodgement failure due to somatic growth. The small variation of the measurements over the gestational age range relevant to device implantation for the major indications of the device (for complete heart block complicated by hydrops and for bradycardia risk after fetal surgery or intrauterine intervention) predicts a small likelihood of these failure modes.

Evaluation of the development of lung hypoplasia in the premature lamb.

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. 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. 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. 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.