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[Status of prenatal diagnosis in Switzerland].

In Swiss laboratories of Basel, Berne, Geneva, Lausanne, Locarno and Zurich 19'872 prenatal diagnosis were carried out from 1971 to 1983. The frequency of the tests carried out for the different indications and the numbers of the detected anomalies are presented. In 12'485 tests performed because of advanced maternal age (35 years and older) 241 chromosome anomalies were diagnosed with 125 trisomies 21 among them. In contrast, only 7 trisomies 21 were found in 5'225 samples from women below 35 years. Prevention of Down's syndrome was the prevalent motivation of 93 percent of the pregnant women. Approx. 42 percent of the Swiss women, 35 years and older, requested an amniocentesis in the course of the last few years. Remarkable progress was made in the ultrasound diagnosis of fetal malformations. Developments in the field of first trimester prenatal diagnosis and in the use of DNA technology for the diagnosis of monogenic defects are dealt with.

Adult↗

Techniques for in utero endoscopic surgery. A new approach for fetal intervention.

In utero open surgery can salvage many fetuses with life-threatening anomalies. This approach carries risks, especially from preterm labor induced by the hysterotomy incision. In an effort to decrease uterine injury during hysterotomy, we developed techniques for endoscopic manipulation of the fetus. We developed these methods in fetal lambs. The uterus was exposed and insufflated with CO2. As a model for in utero surgery, a simulated cleft lip was created and immediately repaired using intracorporeal suturing and knot-tying procedures. The techniques for endoscopic suture placement and knot-tying were based on microsurgical principles. We also designed and created several specialized instruments to facilitate precise work in this highly magnified surgical field. The novel techniques of endoscopic fetal surgery described here offer an alternate approach to fetal intervention. Our future goals include the application of these techniques to a nonhuman primate model and the development of percutaneous access methods.

Animals↗

Congenital diaphragmatic hernia: advances in prenatal therapy.

Congenital diaphragmatic hernia (CDH) is one of the most common causes of neonatal morbidity and mortality. The clinical spectrum of CDH ranges from minimally affected infants who do well with modern neonatal care to severely affected infants who die despite all interventions. Two decades of research have led to advances in the prenatal diagnosis of CDH and have better defined the natural history of CDH. Fetuses with CDH now can be stratified into "low" and "high" risk groups based on sonographic parameters. "Low risk" fetuses have an excellent chance of survival with postnatal therapy. Prenatal intervention is reserved for "high risk" fetuses. Ongoing research is focused on improving both prenatal and postnatal treatment of these severely affected infants.

Extracorporeal Membrane Oxygenation↗

Minimal access techniques for fetal surgery.

The impetus for the development of minimal access techniques for fetal surgery was the unusual occurrence with open hysterotomy of preterm labor, premature rupture of membranes, and the maternal complications resulting from tocolytic therapy. This strategy involves a constellation of techniques that allow surgical procedures to be performed inside the uterus without a hysterotomy. The unique requirements of this approach necessitated modifications of existing endoscopic techniques, development of novel fetoscopic instruments, and utilization of the expertise of a wide variety of specialists. Technical expertise in the field and a natural evolution of techniques have given rise to innovative repairs previously not envisioned. Severe congenital diaphragmatic hernia, diseases of monochorionic twins, and obstructive uropathy have already been successfully treated using fetoscopic surgical techniques. Fetoscopic correction of many other non-life-threatening anomalies continues to evolve. The future of fetoscopic surgical intervention depends on the continual evolution of novel techniques, the elucidation of the pathophysiology and treatment of other fetal disorders, and a better understanding of treatment of complications of intervention.

Amniotic Band Syndrome↗

Percutaneous fetoscopic patch coverage of experimental lumbosacral full-thickness skin lesions in sheep.

BACKGROUND: In order to minimize maternal trauma from open fetal surgery for prenatal coverage of fetal myelomeningoceles in humans, we assessed the feasibility of a percutaneous fetoscopic approach in sheep. METHODS: In seven ewes between 90 and 100 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was postured and a full-thickness skin lesion was created in the lumbosacral region. Then, the feasibility of covering this lesion with a patch and fetal skin by standard endoscopic suturing techniques (n = 3) or robot assistance (n = 4) was assessed. RESULTS: Percutaneous fetoscopic patch and skin coverage of the full-thickness skin lesion was achieved in six of the seven fetal sheep. Five fetuses survived gestation and were delivered healthy. CONCLUSIONS: Percutaneous fetoscopic posturing and patch coverage of lumbosacral full-thickness skin lesions can effectively and safely be achieved in sheep. This approach promises to provide a substantial reduction of maternal trauma from fetal surgery for myelomeningoceles.

Animals↗

Percutaneous fetoscopic tracheal balloon occlusion in sheep.

BACKGROUND: In order to minimize maternal trauma from current techniques for temporary fetoscopic tracheal occlusion, we tried to develop a percutaneous fetoscopic technique in sheep. METHODS: In nine ewes between 77 and 128 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was positioned and the feasibility of fetal laryngoscopy and percutaneous fetoscopic tracheal balloon occlusion was assessed. RESULTS: Percutaneous intraamniotic access, fetal positioning, oropharyngeal sheath insertion, and fetoscopic laryngoscopy were achieved in all nine fetal sheep. Following some technical modifications to the working channel of the fetoscope, percutaneous fetoscopic tracheal balloon occlusion was successfully achieved in the last seven sheep. CONCLUSION: Percutaneous fetoscopic balloon occlusion of the fetal trachea can effectively and safely be achieved in sheep. Because intraamniotic spatial relationships, fetal position, and umbilical cord length are technically less favorable in sheep, our operative techniques might be feasible in humans even if difficult intraamniotic conditions are encountered.

Animals↗

Minimal-access fetal surgery for twin-to-twin transfusion syndrome.

BACKGROUND: Laser ablation of placental vessels effectively halts severe twin-to-twin transfusion syndrome (TTTS), but fetal surgery remains a dangerous approach. The authors present the technical aspects of endoscopic fetal surgery in their initial clinical experience. METHODS: Altogether, 11 women underwent endoscopic fetal surgery for severe TTTS. Access to the recipient's sac was obtained by the Seldinger technique via minilaparotomy. A 12-Fr peel-away introducer was used as a cannula to accommodate a custom-curved 9-Fr sheath containing a 1.9-mm semirigid fiber endoscope. Laser ablation was performed on all unpaired vessels crossing the intertwin membrane using a 400- micro m neodymium: yttrium-aluminum-garnet (Nd: YAG) fiber. The cannula was removed over a gelatin sponge plug. RESULTS: The median operating time was 65 min (range, 45-105 min). No patient experienced amniotic leak postoperatively. The length of hospital stay was 2.8 +/- 1.6 days. Immediate improvement of the TTTS was noted in all but two patients. Pneumonia developed, in one mother leading to premature labor. There were no other major surgical complications. Fetal survival at 2 weeks was 73%. CONCLUSIONS: The safety and efficacy of endoscopic fetal surgery for severe TTTS can be optimized with the application of current minimal-access techniques. The superiority of this approach over less invasive means is still being evaluated through prospective studies.

Adult↗

Analysis of the stepwise clinical introduction of experimental percutaneous fetoscopic surgical techniques for upcoming minimally invasive fetal cardiac interventions.

BACKGROUND: This study assessed the feasibility and safety of surgical techniques developed in sheep for fetoscopic fetal cardiac interventions during three selected less complex procedures for noncardiac fetal conditions in humans. On the basis of this assessment, the implications for the clinical introduction of minimally invasive fetoscopic fetal cardiac interventions in the near future are discussed. METHODS: The authors performed 16 percutaneous fetoscopic procedures in 13 human fetuses at between 19 + 2 and 34 + 6 weeks of gestation, then analyzed various parameters of surgical relevance for minimally invasive fetoscopic fetal cardiac interventions. Each of the three noncardiac malformations posed typical surgical challenges that will be critical for the technical success of minimally invasive fetoscopic cardiac interventions. RESULTS: Overall technical success was achieved in 14 of the 16 procedures. Percutaneous fetoscopic surgery did not result in any untoward effects and was well tolerated by all but two pregnant women: one with bleeding complication and one with mild postoperative pulmonary edema. No fetal complications or injuries from the various percutaneous fetoscopic surgical approaches were observed. CONCLUSIONS: The author's experience with surgical techniques introduced for percutaneous fetoscopic fetal cardiac intervention in selected noncardiac fetal lesions has led them to believe the time has come for the clinical introduction of fetoscopic fetal cardiac interventions. After an adequate learning curve supervised by committees of human research, the overall outcome and quality of postnatal life for the unborn patients ultimately will determine whether fetoscopic or other fetal cardiac interventions will be better therapeutic alternatives to currently available postnatal procedures.

Female↗

Operative techniques and strategies for minimally invasive fetoscopic fetal cardiac interventions in sheep.

BACKGROUND: Recent efforts to develop procedures for fetoscopic fetal cardiac interventions have been prompted by the development of severe secondary damage to the fetal heart due to semilunar valvar obstructions and the poor outcome of therapy-refractory fetal arrhythmias. The purpose of our manuscript is to analyze and share our experience with the creation of an operative setup for these procedures in sheep. METHODS: We studied a total of 48 fetal sheep between 81 and 106 days of gestation (term, 145 days). After entering the amniotic cavity by a percutaneous approach, we performed various fetoscopic fetal cardiac procedures. We analyzed the success of percutaneous fetal access, methods of trocar support, the incidence and management of trocar dislodgement or accidental insertion into the chorioamniotic space, problems related to amniotic insufflation and trocar placement, as well as techniques for fetal posturing and uterine closure. RESULTS: Percutaneous fetal access was achieved in all sheep. The use of resterilizable trocars substantially decreased the costs of our procedures. Utilizing a percutaneous transuterine purse-string suture for trocar support helped to minimize the number of nonabsorbable T-fasteners remaining inside the uterus postoperatively. As complications such as trocar dislodgement, insertion of the trocar into the chorioamniotic space, and problems with intraamniotic insufflation and gas loss were mastered, conversion to an open operative approach was never required. A novel strategy that we devised for percutaneous fetal posturing permitted adequate fetal posturing with ease and minimal trauma to the fetal skin. CONCLUSION: As operative techniques have become more refined, the feasibility of performing fetoscopic fetal cardiac interventions in human fetuses now depends mainly on technical improvements in imaging and interventional catheters, as well as advances in pacemaker equipment.

Animals↗

Effects of amniodistention with carbon dioxide on fetal acid-base status during fetoscopic surgery in a sheep model.

BACKGROUND: Because the data from previous experiments on the fetal effects of carbon dioxide (CO2) amniodistention in endoscopic fetal surgery are conflicting, we set out to evaluate the fetal acid-base status during CO2 amniodistention, with or without maternal hyperventilation, using a sheep model for endoscopic surgery. METHODS: We assigned 26 pregnant ewes undergoing amniodistention with CO2 (4-5 mmHg intraamniotic pressure) to one of the following three groups: group I had fetal surgery + no maternal hyperventilation (n = 10); group II had fetal surgery + maternal hyperventilation (n = 10); group III had no fetal surgery + maternal hyperventilation (n = 6). Hyperventilation kept CO2 at 29-31 mmHg; in its absence, pCO2 ranged from 38 to 41. Fetal surgery consisted of fetoscopic tracheal clipping. Maternal blood pressure (mean, 98/69 mmHg) and heart rate (mean, 72 bpm) were kept at values comparable to human pregnancy. Fetal and maternal blood gas measurements were taken every 15 min during 1 h of amniodistention. RESULTS: The ranges for baseline mean fetal pCO2 (mmHg) and pH were 51-55 and 7.24-7.25, respectively, in all study groups. After 1 h of amniodistention, mean +/- SEM values of fetal pCO2 and pH were 88 +/- 3 and 7.06 +/- 0.03 in group I, 69 +/- 4 and 7.13 +/- 0.02 in group II, and 71 +/- 5 and 7.14 +/- 0.04 in group III, respectively. Therefore, maternal hyperventilation attenuated but could not prevent significant fetal hypercarbia and acidosis. Fetal surgical manipulation had no effect on these observations. CONCLUSION: CO2 amniodistention should not be considered for clinical practice until ways of preventing its effects on the fetal acid-base status can be demonstrated.

Acid-Base Equilibrium↗

Percutaneous fetal access and uterine closure for fetoscopic surgery. Lessons learned from 16 consecutive procedures in pregnant sheep.

BACKGROUND: Maternal morbidity and preterm labor from fetal surgery might be minimized by a percutaneous technique for fetal access and uterine closure. METHODS: In each of 16 ewes, we inserted three trocars percutaneously into the amniotic cavity using ultrasound and fetoscopic guidance. In six ewes, percutaneous uterine closure after the procedure was attempted. We assessed feasibility and acute complications of our technique during surgery and at autopsy. RESULTS: We achieved percutaneous fetal access in 14 ewes and closed the uterus percutaneously in all six ewes attempted. Fetal injury was related to amnioinfusion or fixation of chorioamniotic membranes. Other complications were trocar dislodgment and damage to uterine wall and chorioamniotic membranes. The latter complication was prevented using balloon-tipped trocars. CONCLUSIONS: Percutaneous intraamniotic access and uterine closure for fetoscopic surgery can be achieved reliably with little maternal and fetal morbidity in sheep. Minor modifications are desired to apply this approach in humans.

Amnion↗

Endoscopic intrauterine surgery in primates: overcoming technical obstacles.

Current protocols for fetal surgery require cesarean section and partial fetal extraction, both of which impart significant risks to the mother and fetus. Endoscopic fetal surgery is less invasive and will likely reduce some of these risks, but the technical difficulties and feasibility in a primate model have yet to be explored fully. Four pregnant baboons (95 days gestation) were anesthetized, their uteruses exposed via an abdominal incision, and blunt-tipped flanged endoscopic ports inserted. Amniotic fluid was removed, and warmed saline was infused to dilate the uterus. To evaluate instrumentation and wound closure, the tip of the snout was externalized and bilateral cleft lip-like defects made. The lips were then endoscopically repaired by suture (Endostitch, U.S. Surgical) or unique nonpenetrating clips (VCS, U.S. Surgical). The saline was then removed, amniotic fluid returned, and the ports carefully removed. After 4 weeks, the fetuses were delivered and evaluated. Eight cleft lip-like defects were successfully repaired in all four cases. Operative time averaged 83 min. No infections, amniotic leaks, or adhesions developed. Survival was 50% with two fetuses delivering within 48 hours postoperatively: one from preterm labor, the other with fetal demise from retroperitoneal hemorrhage after operative blunt abdominal trauma. We demonstrate the feasibility of endoscopic fetal surgery in primates. The use of blunt-tipped flanged ports provides a fluid tight seal and allows appropriate closure of the fetal membranes, but requires laparotomy and uterine exposure. Distension of the uterus with warmed saline affords a larger operating field, enhancing visualization and instrumentation of the fetus. Grasping the fetus through the exposed uterus gives excellent control for repair. However, such control is also needed in a percutaneous approach. Further instrumentation development is needed to accomplish similar control for the percutaneous approach.

Animals↗

Fetal therapy for obstructive uropathy: past, present.future?

Antenatal treatment of obstructive uropathy, although widely performed, remains controversial. An overview of prenatal therapy for obstructive uropathy, the limitations of the early published experience, advances of recent years, and future directions for treatment are reviewed. The clinical approach and outcomes of the Fetal Treatment Program of Hutzel Hospital and Wayne State University are presented. Patient selection for antenatal treatment is based on the existence of a significant threat of neonatal death due to pulmonary hypoplasia, pending exclusion criteria such as anatomical structural anomalies and chromosomal defects. Ultrasonography, karyotyping, and sequential urinary electrolyte analysis are essential. Current treatment involves the placement under ultrasonic guidance of a Rodeck vesicoamniotic shunt. Recent technical advances include the use of amnioinfusion for fetal visualization, temporary fetal paralysis, routine antibiotics, and more-precise catheter placement. The establishment of standardized short- and long-term outcome measures and the documentation of fetal and maternal complications are in progress. Procedural refinement, development of fetoscopic techniques and equipment, identification of urinary markers to aid patient selection, and the collection of multicenter outcome data will assist the future management of prenatally detected obstructive uropathy.

Animals↗

[Experimental endoscopic intrauterine surgery for craniofacial malformations such as the cleft lip and palate].

INDICATION FOR FETAL SURGERY: The widespread use of high-resolution ultrasound in prenatal diagnosis allows nowadays an accurate and early diagnosis of congenital malformations. Some of these can be corrected surgically. In certain cases intrauterine surgery could present functional and aesthetic advantages or be even lifesaving. Due to the extreme sensitiveness of the fetal patient and the fetal membranes, only some defined anomalies currently meet the criteria for intrauterine surgery. However, the list can change in the future since prenatal diagnosis, technical advances, and knowledge of pathophysiology improve constantly. ENDOSCOPIC INTRAUTERINE SURGERY: Additionally, the recent development of endoscopic intrauterine surgery represents a new and more careful possibility for intrauterine surgery. Endoscopic procedures could avoid the disadvantages of open intrauterine surgery and thus make fetal operations safer, in life-threatening as well as in non-life-threatening malformations such as cleft lip and palate (CLP). The main advantages of these procedures are (1) scarless wound healing and bone healing without callus formation that leave to expect normal growth of the midface and (2) lower fetal and maternal morbidity. DISCUSSION: Based on the results achieved until now, it can be stated that at present the intrauterine operation of CLP on humans cannot be recommended. The high morbidity and mortality risk for mother and fetus cannot be counterbalanced by the unsatisfactory results of a prenatal operation. CONCLUSION: In this study first results of an experimental investigation with the new endoscopic techniques are presented, whereby the possibilities for optimization and quality improvement of the intrauterine surgical procedures are analyzed in detail.

Animals↗