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PubMed1986

Rapid karyotyping in non-lethal fetal malformations.

Pure fetal blood samples were obtained fetoscopically, at 16-36 weeks' gestation, from 118 pregnancies complicated by ultrasonographically demonstrable fetal anomalies. Cytogenetic analysis of fetal lymphocytes yielded results within two to four days. Chromosomal abnormalities were found in 12 of 37 fetuses with non-haemolytic hydrops fetalis, 8 of 12 with exomphalos, 1 of 3 with duodenal atresia, 9 of 39 with obstructive uropathy, 1 of 3 with unilateral pleural effusion, 2 of 10 with severe growth retardation and oligohydramnios, 2 of 9 with isolated hydrocephalus, and 3 of 4 with choroid plexus cysts (of the last 4, 1 also had obstructive uropathy and 1 exomphalos). 3 fetuses with gastroschisis were cytogenetically normal. The results suggest that rapid fetal karyotyping is advisable in all cases of non-lethal or potentially correctable fetal malformations detected sonographically during the second or third trimester of pregnancy.

Chromosome Aberrations↗
PubMed1999

Prospects for fetal gene therapy.

Advances in prenatal diagnosis and gene transfer technology have allowed consideration of prenatal gene therapy. A compelling argument can be made for this strategy in treating genetic diseases that are fatal in the prenatal or perinatal period. In other diseases, the fetal environment may offer unique biological advantages that favor a prenatal gene therapy strategy over treatment after birth. Although issues of safety and efficacy must be resolved before clinical application, the development of fetal gene therapy may become a new molecular therapeutic arm in the field of prenatal intervention.

Female↗
PubMed2000

Tracheal side effects of endoscopic balloon tracheal occlusion in the fetal lamb model.

OBJECTIVE: To evaluate effects of in-utero endoluminal balloon tracheal occlusion (TO) as suggested for the treatment of Congenital Diaphragmatic Hernia (CDH) on the higher airways of a fetal lamb model. STUDY DESIGN: Fetuses from time-dated pregnant ewes underwent at 94 days (term=145 days) in-utero tracheal occlusion. In study animals an endoluminal, detachable balloon was placed by tracheoscopy. For that purpose a 1.2mm fibre-optic, semi-rigid endoscope and a medically graded latex balloon were used. In group I (n=9) lambs were delivered after 2 weeks. In group II (n=8) the tracheal occlusion was released after 2 weeks, to allow in-utero recovery until term. In positive control animals (group III; n=5) the trachea was clipped at 98 days and fetuses were harvested near term by cesarean section. A total of 17 contralateral littermates in multiple pregnancies served as negative controls. After macroscopic inspection of the trachea, sections were evaluated by light microscopy. Alterations were scored with an empirical interval score for each of the different anatomical elements in the fetal trachea (epithelium, submucosa, cartilage, pars membranacea). RESULTS: For the animal experiments in group I, all balloons were found in place and according to the pulmonary response they were obstructive. Tracheas were macroscopically dilated by the plug mainly due to elongation of the pars membranacea. The total histologic score was correlated to the increase in circumference (mean increase: 3.0mm). In nearly all cases, the tracheal epithelium at the level of the plug had lost its typical folding pattern. In 44% of cases, local epithelial defects were observed and in 33% of cases there was squamous metaplasia. A chronic inflammatory response was present in over half of the cases, sometimes with giant cell reaction. In group II (the in-utero recovery group) the total score was significantly lower than in group I, with much less prominent unfolding and absence of epithelial defects. Squamous metaplastia was still present in half of the cases; whereas inflammatory responses were less frequent. In group III the trachea expanded normally after removal of the clip. The epithelium had compacted folds, and cilia were well preserved. In two animals however, intraluminal synechia were observed. Below the level of occlusion animals of groups I and II all showed areas of unfolding, but without metaplasia or epithelial defects. CONCLUSION: Tracheal obstruction by means of endoluminal plugging has been suggested as an alternative in-utero treatment for congenital diagphragmatic hernia. The balloon causes mild epithelial changes, such as unfolding, limited epithelial defects (<25% of the exposure surface) and local inflammatory changes. These changes disappear nearly completely following in-utero unplugging during the rest of gestation. Unfolding of the epithelium is also seen in the trachea under the plug.

Animals↗
PubMed2000

Endoscopic laser coagulation of placental anastomoses in 200 pregnancies with severe mid-trimester twin-to-twin transfusion syndrome.

OBJECTIVE: To investigate perinatal outcome after endoscopic laser coagulation of the placental vascular anastomoses in severe mid trimester twin-to-twin transfusion syndrome (TTTS). STUDY DESIGN: In a prospective study between January 1995 and September 1999, we performed laser therapy in 200 consecutive pregnancies with TTTS between 16 and 25 weeks of gestation. We compared outcome of the first group of 73 pregnancies whose outcome has been reported previously in a study comparing laser surgery and serial amniodrainages [Am J Obstet Gynecol 1999;180:717-24], with the following group of 127 patients. RESULTS: The overall survival rate increased from 61% (89/146) in group 1 to 68% (172/254) in group 2. The percentage of pregnancies with survival of both fetuses was 42% (31/73) in group 1 and increased to 54% (69/127) in group 2 (P=0.142). The survival rate for at least one fetus was 81% (103/127) in group 2. The median gestational age at delivery of liveborn babies was 33.7 weeks in group 1 and 34.4 weeks in group 2 with a median interval of 13 weeks between the intervention and delivery. CONCLUSION: This study of a large population of pregnancies with severe second trimester twin-to-twin transfusion syndrome confirms the improvements of outcome after laser therapy as compared to serial amniodrainages reported previously. Furthermore, it shows a trend towards an increase in survival rates with growing experience in this technique, most likely attributable to a more selective identification and efficient coagulation of the placental vascular anastomoses.

Female↗
PubMed2002

Obstetric cholestasis: outcome with active management.

OBJECTIVE: Conservative management of intrahepatic obstetric cholestasis is associated with a high stillbirth rate despite monitoring of fetal well-being with non-stress test and amniotic fluid volume assessment. Most cases of stillbirth are associated with meconium passage. We prospectively evaluated the effect of a management protocol inclusive of surveillance for presence of meconium and induction of labor at 37 weeks. STUDY DESIGN: Between January 1989 and December 1997, all women with obstetric cholestasis underwent transcervical amnioscopy after 36 weeks for assessment of amniotic fluid color, in addition to standard monitoring of fetal well-being (semi-weekly non-stress test and amniotic fluid volume determinations). Amniocentesis for fetal lung maturity and amniotic fluid color assessment was performed before 36 weeks in severe cases. Labor was induced at 37 weeks or earlier in the presence of non-reassuring fetal testing, meconium, or severe maternal symptoms unresponsive to therapy with mature fetal lungs. The obstetric outcome of the group with cholestasis was compared with that of the general obstetric population at our Institution during the study period. The rate of fetal death in the study group was compared with that of series published within the last 20 years, which used expectancy and conventional monitoring of fetal well-being. Statistical analysis utilized Fisher's exact test, Chi-square, and Student's t-test with P value <0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. RESULTS: Obstetric cholestasis was diagnosed in 206/20,815 pregnant women (1%) at a median gestational age of 34 weeks (range 20-40). Delivery was prompted by non-reassuring fetal testing in four cases (2%). Meconium passage was documented in 33 cases (16%), in 11 of which before onset of labor and in 10 before 37 weeks. The rate of meconium passage before 37 weeks (17.9 versus 2.9%, OR=7.3; 95% CI 3.3, 16.0) was significantly higher in obstetric cholestasis than in the general obstetric population, whereas the cesarean section rate was similar in the two groups (15.1 versus 16.0%, OR=0.9; 95% CI 0.6, 1.4). The fetal death rate was significantly lower in the group managed with the current strategy than in the published series of obstetric cholestasis (0/218 versus 14/888, P=0.045). CONCLUSION: In pregnancies complicated by obstetric cholestasis, a protocol inclusive of search for meconium and elective delivery at 37 weeks, in addition to standard monitoring of fetal well-being, can significantly reduce the stillbirth rate without increasing the cesarean delivery rate.

Adult↗
PubMed2003

Minimal access fetal surgery.

The development of fetal surgery has led to promising therapeutic options for a number of congenital malformations. However, preterm labor (PTL) and premature rupture of membranes continue to be ubiquitous risks for both mother and fetus. To reduce maternal morbidity and the risk of prematurity, minimal access surgical techniques were developed and are increasingly employed. Congenital diaphragmatic hernia (CDH), obstructive uropathy, twin-to-twin transfusion syndrome (TTTS), and sacrococcygeal teratoma have already been successfully treated using minimal access fetal surgical procedures. Other life-threatening diseases as well as severely disabling but not life-threatening conditions are potentially amenable to treatment. The wider application of minimal access fetal surgery depends on a continued improvement in technology and a better understanding of complications associated with fetal intervention.

Congenital Abnormalities↗
PubMed1998

Experience with fetoscopic cord ligation.

OBJECTIVE: In the case of a monochorionic multiple pregnancy with one non-viable fetus who compromises its co-twin, fetoscopic cord ligation may be performed. We describe our fetoscopic cord ligation technique and discuss the efficacy of cord ligation for salvaging the co-twin, based on available data. STUDY DESIGN: Descriptive case series of four cases and review of the cases published up to 1996. RESULTS: We performed four successful ligations. Of the 23 reported cases, which include the present series, two ligations failed. Four fetuses died in utero, and 17 were born alive at a mean of 8 weeks following the procedure. Two babies died in the perinatal period, a third after 60 days. Preterm uterine contractions do not seem to be a clinical problem. Preterm prelabour rupture of the membranes (PPROM) complicates about 40% of cases, the majority occurring prior to 32 weeks. CONCLUSION: Fetoscopic cord ligation is a feasible procedure with a 71% survival rate and a high risk for PPROM.

Adult↗
PubMed1997

Embryoscopy and early prenatal diagnosis.

Embryoscopy is a new technique that allows direct visualization of the embryo/fetus as early as the first trimester of pregnancy. A rigid fiberoptic endoscope is passed transcervically into the extracoelomic cavity and is used to identify developmental milestones and diagnose structural anomalies. Fetal blood sampling has also been performed, and using this technology, has established the feasibility of access to the human embryonic circulation. Future applications for embryoscopy include direct targeted embryonic or fetal interventions, such as gene or stem cell therapy.

Congenital Abnormalities↗
PubMed2002

[What's new in fetal medicine?].

One of the major progress in fetal medicine in recent years is the increased sensitivity of sonographic screening for foetal malformations, due to technical improvement but also to a better training of professionals. Screening for chromosomal abnormalities is no longer based on maternal age alone. Second trimester maternal serum screening (MSS) is increasingly used: thus in 1997, 376,798 MSS tests were performed in France, yielding to the prenatal diagnosis of 391 cases of Down's syndrome. First trimester sonographic nuchal translucency measurement (NTM) is an effective screening method when performed under stringent conditions. Quality control however, is more difficult to implement on a large scale for NTM than for MSS. Performing screening tests sequentially carries a danger of generating an unnecessarily high number of amniocentesis, which may be obviated by a rational calculation of an individual's risk to carry an aneuploid baby. First trimester MSS is expected to become standard practice in the next years, probably in combination with NTM. Cytogenetics underwent substantial innovations recently, due to the ever-increasing use of molecular cytogenetics. FISH techniques allow: 1) precise analysis of unexpected structural chromosomal abnormalities diagnosed by routine amniocentesis, 2) rapid screening of the most common aneuploidies by amniocentesis when a fetal structural anomaly is detected by 3rd trimester ultrasound, 3) diagnosis of micro-deletions suspected by fetal ultrasound or post-mortem. Prenatal diagnosis by maternal blood sampling and fetal cells or DNA analysis is now part of routine clinical practice in selected cases, such as fetal sexing in families affected by an X linked disease. Thus one can select those pregnancies eligible to invasive prenatal diagnosis. Pre implantation diagnosis, which has not been legal in France until 1999 is now increasingly used as an alternative to first trimester diagnosis. As for fetal therapy, a major recent breakthrough is the prenatal management of twin to twin transfusion syndrome by either amnioreduction or laser coagulation of inter-twin vascular shunts. In addition, new pathophysiologic concepts involving the renin angiotestin system could lead to further therapeutic innovations. A European randomised trial is now being completed to establish the respective indications of drainage and Laser. All this underscores that fetal medicine is no longer solely a succession of dramatic technical breakthroughs, but is entered an era of large-scale diffusion that requires evidence based evaluation.

Adult↗
PubMed1987

Techniques of chorion villus sampling.

Whilst randomized studies into the safety of chorionic villus sampling (CVS) are already under way the technique is now offered as an acceptable alternative to amniocentesis in many diagnostic centres. In counselling, the obstetrician can now quote a risk to the pregnancy of 2-4% which, even if the inevitable losses before 16 weeks are excluded, represents probably at least twice the risk of amniocentesis. The evolution of the obstetric procedures has meant that the transcervical approach to CVS has been the most popular to date but there is now increasing interest in transabdominal aspiration as it minimizes the possibility of infection. The two best known transcervical methods are aspiration with a plastic or metal cannula and biopsy with rigid forceps. The majority of aspirations have been performed using the Portex cannula technique. Using this, three centres (Milan, Chicago and Philadelphia) have had experience of over 5000 cases with a failure rate of less than 1% and a minimal fetal loss of 2.2%. However, the proportion of fetal losses may be between 4 and 7% by the time complete obstetric follow-up is available (Brambati et al, 1985). A similar technique has been used with a variety of cannulae. The experience of the first 1000 cases from San Francisco (Hogge et al, 1986) led them to conclude that CVS by this technique was acceptably safe but that continuing investigation was needed before CVS was offered routinely as an alternative to amniocentesis. The only other transcervical technique that is practical for routine use is biopsy with rigid forceps. The failure and fetal loss rates associated with this method are comparable to the aspiration technique. The pioneering work of Hahnemann and his colleague Smidt-Jensen has established transabdominal aspiration as a reliable alternative approach. Its main advantage should be to minimize the risk of infection which is inherent in all transcervical techniques. In addition, it does not need to be confined to 9-11 weeks gestation and thus offers couples the possibility of diagnosis between 12 and 14 weeks rather than waiting for amniocentesis at 16 weeks. The quality and quantity of the sample depends on the size of the needle used and the technique is said to have high patient acceptability. Nevertheless, fetal losses occur following the procedure (1.8-3.2%) and it may not always be successful (failure rate 1.9-4.2%).

Biopsy, Needle↗
PubMed2006

Fetoscopic laser therapy for twin-twin transfusion syndrome.

Twin-twin transfusion syndrome (TTTS) complicates approximately 1 in 5 of all monochorionic, diamniotic twin pregnancies. If of early onset and untreated, severe TTTS is associated with a dismal prognosis, with perinatal mortality rates exceeding 90%. The most controversial issue regarding the optimal treatment of TTTS has centered on the use of amniocentesis or laser until the first and only randomized trial on interventions for TTTS was published a couple of years ago, comparing laser to amnioreduction. That report confirmed that the laser group had a higher likelihood of the survival of at least one twin to 28 days of age and to 6 months of age. Infants in the laser group also had a lower incidence of cystic periventricular leukomalacia and were more likely to be free of neurologic complications at 6 months of age (52% vs. 31%, p = 0.003). Although not every case of TTTS is an eligible candidate for fetoscopic-guided laser therapy, it is recommended that obstetricians who have the chance to manage TTTS in their daily practice be familiar with the rationale behind this laser treatment for TTTS.

Arteriovenous Anastomosis↗
PubMed2003

Anesthesia for fetal surgery.

Fetal surgery is a rapidly growing and evolving area. Fetal surgery is based on years of animal and clinical research. In contrast, anesthesia techniques for fetal surgery are based on clinical experience. The techniques that have emerged are safe for mother and fetus. In this review, the authors describe current techniques for anesthetic management of fetal surgery patients. General anesthesia is the primary technique used for hysterotomy based surgical correction of midgestation fetuses and ex utero interpartum corrections of end-gestation fetuses. Epidural analgesia, with general anesthesia as back-up, is the primary technique used for fetoscopic cases in which anesthetic care is required. Because of the myriad of anesthetic and surgical issues these cases generate, it is essential to have good communication and cooperation between surgeons and anesthesiologists from the preoperative period to the postoperative period. This will allow development of a cohesive anesthetic and surgical plan that can be used for the safe perioperative management of the fetal surgery patient.

Anesthesia, Obstetrical↗