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Amniotic band syndrome in fetal lambs. I: Fetoscopic release and morphometric outcome.

A fetal lamb model of amniotic band syndrome (ABS) was developed to study the pathophysiology of banded extremities and evaluate the possibility of in utero treatment with the potential for functional recovery. Eight fetal lambs underwent banding of their extremities with umbilical tape at 100 days' gestation. Two lambs aborted after the open fetal surgery. The limbs of two unoperated newborn lambs served as controls in addition to five sham-operated control limbs that had no bands applied. Nine limbs were banded without reducing blood flow assessed by laser doppler (group 1), and 6 limbs were similarly banded and released fetoscopically at 125 days' gestation. Four limbs were banded, with a mean reduction in blood flow to the limb of 18.7% (group 2) by laser doppler flowmeter. Shortly after birth the lambs were killed, and segmental limb length, circumference, joint range of motion, and histology were evaluated. At birth, banded limbs showed marked brawny edema and absence of wool distal to the band. Segmental limb measurements showed shorter distal forelimbs in banded limbs compared with controls (10.97 +/- 0.59 versus 12.98 +/- 0.69, P < .05). Banded limbs were associated with progressive increase in hoof circumference (P < .03) and a decrease in joint range of motion (P < .003). In sharp contrast, there were no differences between fetoscopically released limbs and control limbs in any of the parameters measured. Histology of banded extremities showed edema, venous and lymphatic congestion, and fibrosis compared with controls. This model of ABS in fetal lambs is simple, reproducible, and replicates all the clinical features of extremity ABS.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Band Syndrome↗

Circulating cell-free fetal messenger RNA levels after fetoscopic interventions of complicated pregnancies.

OBJECTIVE: The aim of this study was to examine fetal gene expression in maternal plasma after fetoscopic intervention for twin-twin transfusion syndrome or congenital diaphragmatic hernia. STUDY DESIGN: Twelve women with pregnancies that were complicated by twin-twin transfusion syndrome and 10 women carrying fetuses with congenital diaphragmatic hernia were sampled before and sequentially after treatment. Levels of glyceraldehyde-3-phosphate dehydrogenase, human placental lactogen, and gamma globin messenger RNA were measured by real-time reverse transcriptase polymerase chain reaction amplification. RESULTS: At all time points, glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels were higher in the congenital diaphragmatic hernia cases than in the twin-twin transfusion syndrome cases (P < .05), but during the immediate postoperative observation period, there were no significant changes in glyceraldehyde-3-phosphate dehydrogenase, human placental lactogen, or gamma globin messenger RNA levels in individual patients or patients who were grouped by procedure. CONCLUSION: Fetoscopic intervention of complicated pregnancies does not affect circulating fetal messenger RNA levels, which is in contrast to earlier observations that circulating fetal DNA levels increase after laser ablation for twin-twin transfusion syndrome. Plasma glyceraldehyde-3-phosphate dehydrogenase messenger RNA levels could be a potential novel biomarker for fetal trauma.

Female↗

Troubles with twins: fetoscopic therapy.

Monochorionic twin gestations present challenges in perinatal management not seen in dichorionic twins or singleton pregnancies. Monochorionic twin gestations may be complicated by (1) a monoamniotic presentation, (2) a structurally anomalous cotwin, (3) twin reversed arterial perfusion sequence, (4) and the twin-twin transfusion syndrome. Each of these conditions is associated with increased morbidity and mortality rates. Although a variety of therapeutic interventions are available, fetoscopic surgery is a promising new approach to these conditions. Advances in microinstrumentation have allowed for the wider application of fetoscopy for a variety of prenatally diagnosed conditions, including "troubles with twins." This article examines the natural history, pathophysiology, diagnosis, and indications for fetoscopic surgery in complicated monochorionic twin gestations.

Chorion↗

Placental vascular anastomoses visualized during fetoscopic laser surgery in severe mid-trimester twin-twin transfusion syndrome.

The aim of this study was to describe the type and number of placental vascular anastomoses identified during fetoscopic laser coagulation in severe mid-trimester twin-twin transfusion syndrome (TTS). In 126 patients with severe TTS, undergoing fetoscopic laser coagulation between 16 and 25 weeks of gestation, the different types of placental anastomoses [arterio-venous (AV), arterio-arterial (AA) and veno-venous (VV)] were counted. In cases of AV anastomoses their direction was identified and four groups were defined: in group 1 there were only anastomoses shunting from donor to recipient. Group 2 consisted of placentae with more anastomoses shunting from donor to recipient than in the opposite direction, group 3 showed an equal number in both directions and in group 4 there were more anastomoses shunting from recipient to donor than in the opposite direction. In 9 cases (7 per cent) the anastomoses could not be clearly identified due to impaired visualization, leaving 117 cases for analysis. The median number of anastomoses found was 5 with a range from 1-14. In all cases AV anastomoses from donor to recipient were present, 36 cases (31 per cent) had also AA anastomoses and 14 cases (12 per cent) showed VV anastomoses. Regarding the direction of AV anastomoses, the results were as follows: there were 35 cases (30 per cent) in group 1, 52 cases (44 per cent) in group 2, 14 cases (12 per cent) in group 3 and 16 cases (14 per cent) in group 4. In 54 (46 per cent) placentae there was at least one thin anastomosis whose type was unclassifiable. There were no placentae showing AV anastomoses only from the recipient to the donor fetus. This study demonstrates that AV anastomoses are the prerequisite for the development of TTS in monochorionic placentae. The majority (74 per cent) of cases showed a higher number of AV anastomoses from donor to recipient than in the opposite direction. In approximately one third of placentae there are also AA anastomoses and the overall number of anastomoses seen and coagulated during fetoscopy is higher than reported in postnatal studies.

Arterio-Arterial Fistula↗

Magnetic resonance imaging of the feto-placentar unit after fetoscopic laser coagulation for twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is a severe complication in monochorionic twin pregnancies that results from a hemodynamical imbalance of placentar vascular anstomoses that connect the circulation of both fetuses. In TTTS, a poly/oligohydramnios sequence with high fetal morbidity and mortality rates occurs. Fetoscopic laser coagulation of the placentar anastomoses can limit or prevent fetal injury. The purpose of this report is to present and discuss fetal magnetic resonance imaging as a postoperative imaging tool after fetoscopic laser coagulation.

Adult↗

Anesthesia for fetoscopic fetal surgery: twin reverse arterial perfusion sequence and twin-twin transfusions syndrome.

IMPLICATIONS: Twin reversed arterial perfusion sequence and twin-twin transfusion syndrome can be managed by fetoscopic fetal surgery. It is important to consider the fetal, uteroplacental, and maternal issues when choosing an anesthetic technique. We report on three patients with differing anesthetic issues using fetoscopic surgery for umbilical cord coagulation.

Adult↗

Stage-related outcome in twin-twin transfusion syndrome treated by fetoscopic laser coagulation.

OBJECTIVE: To assess perinatal outcome in monochorionic twin pregnancies according to different stages of severe mid-trimester twin-twin transfusion syndrome managed by fetoscopic laser coagulation of the placental vascular anastomoses. METHODS: In a prospective study fetoscopic laser therapy was performed in 200 consecutive pregnancies with severe mid-trimester twin-twin transfusion syndrome at a median gestational age of 20.7 weeks (range 15.9-25.3 weeks). Outcome data were analyzed for the whole group and separately for each stage according to the Quintero staging system. RESULTS: The overall survival rate was 71.5% (286/400), with survival of both twins in 59.5% (119/200) and survival of at least one of the twins in 83.5% (167/200). The median gestational age at delivery of liveborn neonates was 34.3 weeks (range 23.1-40.4 weeks). There was a significant trend toward reduced survival rates with increasing stage (P=.038). The percentage of pregnancies with survival of both fetuses was 75.9% (22/29) for stage I, 60.5% (49/81) for stage II, 53.8% (43/80) for stage III, and 50% (5/10) for stage IV. At least one of the twins survived in 93.1% (27/29) at stage I, 82.7% (67/81) at stage II, 82.5% (66/80) at stage III, and 70% (7/10) at stage IV. The overall survival rate for donor fetuses was 70.5% (141/200) and for recipient fetuses, 72.5% (145/200). CONCLUSION: These data show that laser therapy is an effective therapeutic option for all stages of severe twin-twin transfusion syndrome and provide information to counsel patients according to the stage of the syndrome.

Arteriovenous Anastomosis↗

Percutaneous fetoscopic patch coverage of spina bifida aperta in the human--early clinical experience and potential.

OBJECTIVE: The current operative approach for fetal repair of spina bifida aperta requires maternal laparotomy and hysterotomy. Following technical feasibility studies in sheep, we performed percutaneous fetoscopic patch coverage of this lesion in 3 human fetuses between 23 + 4 and 25 + 3 weeks of gestation. METHODS AND RESULTS: Whereas the patch detached in the first case 3 weeks after the procedure, it covered the exposed neural tissue in the 2 other fetuses beyond their delivery. Two of the three children survived, but 1 unexpectedly died from a ventilation problem in its 3rd week of life. In 1 of the 2 survivors, ventriculoperitoneal shunt insertion was delayed. CONCLUSIONS: Percutaneous fetoscopic patch coverage of spina bifida aperta is feasible in human fetuses and offers a substantial reduction of maternal trauma compared to open fetal repair. Further clinical experience is now required before the efficacy of the new approach to protect the exposed neural tissue from mechanical and chemical damage and to improve hindbrain herniation can be evaluated.

Aborted Fetus↗

Transient chorioamniotic membrane separation after fetoscope guide laser therapy for twin-twin transfusion syndrome: a case report.

Chorioamniotic membrane separation (CMS) means that the close attachment of amniotic and chorionic membranes is disrupted, usually following the traumatic entry into the amniotic cavity including fetal therapy. We report a case of twin-twin transfusion syndrome receiving fetoscopic guide laser therapy at gestational age of 19 weeks with partial CMS detected at the fifth week (gestational age of 24 weeks) after surgery and resealed 1 week later. There was no more CMS noted till delivery at gestational age of 34 weeks 6 days. CMS after fetoscope surgery may reseal spontaneously.

Adult↗

Treating previable twin-twin transfusion syndrome with fetoscopic laser surgery: outcomes following the learning curve.

AIMS: We have performed fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) in previable pregnancies affected by twin-twin transfusion syndrome (TTTS) since 1988. Treatment outcomes obtained after the procedure's learning curve are presented and compared to those from other centers performing FLOC or other treatment methods. METHODS: A total of 100 cases of FLOC have been performed at our centers. The later 67 TTTS patients had a mean gestational age of 21.1 +/- 1.7 weeks (range 18-24.5) with a mean fundal height of 33.1 +/- 4.9 cm (range 27-44) when treated. Eighteen (27%) had failed another treatment method before FLOC. RESULTS: All 67 cases have delivered with 82% (55/67) having at least one surviving twin and 93/134 (69%) of the twins surviving overall. Thirty-eight have surviving twins, 17 have one survivor (5 neonatal and 12 fetal deaths), and 12 have none. The mean duration of pregnancy following FLOC was 9.9 +/- 5.5 weeks (range 1.0-19). Only 4 of 93 (4.3%) survivors have significant handicaps at a mean follow-up of 14.3 +/- 10.1 months (range 1.0-34). CONCLUSION: Fetoscopic laser occlusion of chorioangiopagous vessels within the vascular equator limits the duration of fetal pathophysiology in TTTS and results in neonatal outcomes superior to the modified procedure and other treatment methods.

Diseases in Twins↗

Fetoscopic neodymium:YAG laser occlusion of placental vessels in severe twin-twin transfusion syndrome.

Most pregnancies with severe twin-twin transfusion syndrome before 27 weeks' gestation result in perinatal death. Previous attempts at therapy have been generally unsatisfactory and rarely successful. We have developed a technique for intrauterine ablation of the vascular communications between the fetoplacental circulations with a fetoscopically directed neodymium:YAG laser. The operation was performed on three women at risk for pregnancy loss from acute hydramnios at 18.5, 22, and 22.5 weeks' gestation. The first two procedures were uneventful, but the third was complicated by a placental vessel perforation. The first two patients delivered at 27 and 34 weeks after premature rupture of membranes and spontaneous labor, whereas the third woman developed severe preeclampsia at 29 weeks which necessitated delivery. Four of the six infants survived. Clinical and ultrasonographic evidence, as well as pathologic examination of the placentas, suggested that stabilization or resolution of the syndrome was due to photocoagulation of the vascular communications. This initial experience suggests that fetoscopic laser occlusion of placental vessels is feasible and superior to previous therapies because it treats the underlying pathophysiology directly.

Adult↗

[Prenatal diagnosis of Duchenne muscular dystrophy by fetoscopic muscle biopsy. Report of a case].

A needle muscle biopsy through a fetoscope for the antenatal diagnosis of Duchenne muscular dystrophy (DMD) was reported the mother was a carrier of 30 years old with a family history of Duchenne muscular dystrophy. Her brother died of DMD and her son had suffering from DMD. At 17 weeks of her second gestation, an amniotic puncture was performed. The cellular chromosome was found to be a male fetus (46,xy). At 20 weeks of her gestation, a needle muscle biopsy of the male fetus was performed under fetoscopy and turned out to be Duchenne muscular dystrophy. At 23 weeks, a male fetus was born with induced labor. The pre and postnatal muscles were examined under the light and electron--microscopes. The large hyaline round fibres were positive for calcium. There was evidence of a break down of the basement membranes, appearance of A and I bands and fragmentation of Z bands. Myofibrils were replaced by thin filaments. The diagnosis of Duchenne muscular dystrophy was established on the basic of these findings. This was considered the first case of antenatal fetal Duchenne muscular dystrophy diagnosed with the aid of fetoscope and needle muscle biopsy.

Abortion, Induced↗

Ex vivo testing of a temperature- and pressure-controlled amnio-irrigator for fetoscopic surgery.

BACKGROUND: Currently, amnioinfusion fluids used in operative fetoscopy usually are preheated to body temperature. As the complexity of procedures increases, purposed designed devices should be designed that allow control of pressure and temperature during amnioinfusion or amnioexchange. In the current study, a prototype amnio-irrigator and fluid heater were evaluated. METHODS: The medical fluid heater heats fluid by conduction up to 37 degrees C. The maximum irrigation pressure and flow rates can be preset. Actual irrigation pressure (0 to 30 mm Hg) and flow rate (0 to 300 mL/min) can be read on the front panel. A series of ex vivo experiments were set up to determine the relationship between the flow rate (FR) and lumen of the instruments as well as the maximum flow rate (MFR) with and without the pressure control. Further, the relationship between FR and the irrigation pressure (IP) was determined. In an artificial pseudoamniotic sac the relationship between FR and change in temperature was measured, with and without the use of the medical fluid heater. RESULTS: When the IP was limited to 24 mm Hg, FR and pressure were correlated (r = 0.34; P <.001). The larger the functional lumen of the fetoscopic instrumentation, the higher the flow (r = 0.43; P <.001) and the lower the increase in IP (r = -0.47; P <.001). A quadratic relation between flow and temperature was observed both for preheated fluid as when using the fluid heater (r(2) = 0.71 and r(2) = 0.88; P <.001). However, at low flow rates, a thermal decrease of over 3 degrees C was observed when the fluid heater was not used. CONCLUSIONS: The current study quantifies an expected relationship between the diameter of the irrigation channel and achievable flow rates. It also shows that a medical fluid heater is needed when strict control of temperature would be desired.

Equipment Design↗

[Development of a fetoscope and its clinical application].

One of the major goals in modern obstetrics is to provide more detailed informations of prenatal fetal physiology. Since 1972, more than 200 amniocentesis were performed in our hospital and the importance of prenatal genetic diagnosis has been recognized. But amniocentesis has the limitations which are 1) the lack of expression of many single gene hereditary disorders in amniotic fluid and its cells, 2) the large percentage (90%) of nonviable fetal cells in any given sample, 3) the length of time required to culture fetal cells. Accordingly the necessity of development of other methods to obtain further direct data on the fetus from the uterine cavity has been indicated. Among gynecological endoscopies, fetoscopy which is direct visualization of the fetus by introduction of an endoscope into the amniotic cavity is expected to obtain direct information from the uterine environment in pregnant women. By our newly developed fetoscope, we investigated clinical indications and contraindications of fetoscopy as well as future possibilities of this endoscope. Our present study indicates that further developments and future benefits of fetoscopy entirely depend on the progress of laboratory techniques which can provide more accurate data through specimens obtained fetoscopy.

Adult↗

Transcervical fetoscopic diagnosis of structural defects in four first-trimester monochorionic twin intrauterine deaths.

OBJECTIVE: While chromosomal abnormalities are often the cause of early failed pregnancies, other mechanisms could be involved in monochorionic twin intrauterine deaths, that might be screened for careful morphological analysis. METHODS: Transcervical fetoscopy prior to instrumental evacuation of the uterus was performed in four first-trimester monochorionic twin intrauterine deaths. RESULTS: We present fetoscopic and cytogenetic findings in four cases of monochorionic twin intrauterine deaths. In the first, generalized abnormal embryonic development observed in both twins was a manifestation of trisomy 20. The second (thoracophagus) and third (acardius) pair of twins had anomalies peculiar to multiple gestations. The fourth pair of twins was remarkable because of the concordance for the observed limb-reduction defects. CONCLUSION: Malformations of first-trimester monochorionic twin intrauterine deaths might cover a wide spectrum of etiologies from abnormal chromosomes and single gene defects to rare duplication anomalies. Their detection by careful morphological analysis and the identification of a specific mechanism provides valuable information for genetic counseling and prenatal investigation in a future pregnancy.

Abnormalities, Multiple↗

Fetoscopic tracheal occlusion (FETO) for severe congenital diaphragmatic hernia: evolution of a technique and preliminary results.

BACKGROUND: Congenital diaphragmatic hernia (CDH) with liver herniation and a lung area to head circumference ratio (LHR) < 1 [corrected] is associated with a high rate of neonatal death due to pulmonary hypoplasia. METHODS: We report the development of a minimally invasive and reversible fetoscopic tracheal occlusion (FETO) with a balloon, carried out in 21 consecutive fetuses with severe CDH. RESULTS: Endotracheal placement of the balloon was successfully performed in all 21 cases and the mean duration of the operation was 20 (range, 5-54) min. The median gestation at FETO was 26 (range, 25-33) weeks. There were no maternal complications such as hemorrhage, placental abruption or pulmonary edema. In 11 (52.4%) patients there was postoperative prelabor amniorrhexis, which occurred within 2 weeks in five patients and after 2 weeks in six patients. Ultrasound scans after FETO demonstrated an increase in the echogenicity of the lungs within 48 h and improvement in the LHR from a median 0.7 (range, 0.4-0.9) before FETO to 1.8 (range, 1.1-2.9) within 2 weeks following surgery. The median gestation at delivery was 34 (range, 27-38) weeks and in 17 (77.3%) patients delivery occurred after 32 weeks. Nine babies died in the neonatal period due to complications from pulmonary hypoplasia. Surgical repair of the diaphragmatic hernia was carried out in 12 babies and in all but one the defect was extensive and required the insertion of a patch. Ten of these babies survived, and at the time of writing were aged 6-25 (median, 18) months and were developing normally. Survival was 30% in the first group of 10 fetuses and 63.6% in the second group of 11 fetuses. The total number of cases was too small for definite conclusions to be drawn as to the causes of this apparent improvement in survival. Nevertheless, improved survival coincided with a shift in the timing of FETO from the third to the second trimester, the administration of epidural rather than general anesthesia, reduced incidence of postoperative amniorrhexis and a change in the policy on the timing of removal of the balloon from the intrapartum to the prenatal period. During the same period of study there were 17 cases examined in the participating centers that met the criteria for FETO but which declined prenatal therapy. In all cases there was isolated left-sided CDH with liver in the thorax and LHR of 0.4-0.9 (mean, 0.7). In five cases the parents elected to terminate the pregnancy. In the 12 cases with expectant management all babies were liveborn but 11 died in the neonatal period due to pulmonary hypoplasia and only one (8.3%) survived. CONCLUSION: Severe CDH can be successfully treated with FETO, which is minimally invasive and may improve postnatal survival.

Balloon Occlusion↗

Cervical length as a prognostic factor for preterm delivery in twin-to-twin transfusion syndrome treated by fetoscopic laser coagulation of chorionic plate anastomoses.

OBJECTIVE: To evaluate the risk of spontaneous preterm delivery in relation to cervical length in severe cases of twin-to-twin transfusion syndrome (TTTS) diagnosed before 26 weeks of gestation and treated by laser coagulation of the intertwin placental anastomoses. METHODS: This was an observational study of cases of severe TTTS diagnosed before 26 weeks of gestation and treated by fetoscopic laser coagulation between January 2002 and December 2003 in three centers. Laser was the first-line treatment in all cases. Elective preterm deliveries before 34 weeks' for maternal or fetal indications, including intrauterine death of both fetuses, were excluded. Transvaginal sonographic measurement of cervical length prior to laser treatment and other risk factors of preterm delivery were evaluated by univariate and logistic regression analysis. RESULTS: Among the 137 women included, the mean cervical length was 32 and 38 mm in women delivering before and at or after 34 weeks, respectively (P < 0.001). For a cervical length of < 30 mm, the risk of delivery before 34 weeks was 74%. Severity of the disease, deepest vertical pool of amniotic fluid and amniotic fluid volume drained after the procedure were not associated with preterm delivery. Logistic regression analysis identified three independent factors to predict preterm delivery: short cervical length (increased risk), parity (increased risk) and intrauterine death of one twin (decreased risk). CONCLUSION: In TTTS treated by laser, without indications for elective preterm birth, cervical length before treatment is significantly associated with gestational age at delivery, and this is independent of parity, intrauterine death of one fetus and other risk factors.

Adult↗

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↗