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Chorioamniotic membrane separation: a potentially lethal finding.

Sonographic detection of chorioamniotic membrane separation (CMS) has been considered a benign incidental finding. We now report 6 cases of CMS identified by prenatal ultrasound; 1 in an otherwise normal pregnancy and 5 following fetal surgery. Following membrane separation, amniotic bands formed and compromised the umbilical cord in 4 cases leading to 2 fetal deaths. In the first case, CMS was detected by ultrasound at 22 weeks' gestation in an otherwise uncomplicated pregnancy. Because CMS was considered benign and umbilical cord blood flow was ample, the mother was followed by intermittent sonographic examinations. Fetal demise occurred 2 weeks later, clearly due to umbilical cord strangulation by an amniotic band. Surprised by this unexpected outcome, we reviewed our experience with CMS after hysterotomy for fetal surgery. Out of more than 40 fetal surgical cases, we have 5 cases in which CMS was recognized after hysterotomy. Three of these fetuses had umbilical cord compromise by a band of amniotic membrane leading to 1 fetal death. This experience demonstrates that membrane separation may be associated with amniotic band formation which can lead to cord strangulation and fetal compromise. Following fetal surgery, serial ultrasound evaluation and close fetal monitoring are indicated. In otherwise unremarkable pregnancies, clinician awareness of the possibility of amniotic band formation following CMS should be heightened. In either situation, knowledge of this potential life-threatening complication may identify cases in which cord compromise requires emergent delivery or fetoscopic release of the strangulating amniotic band.

Adult↗

Transhepatic ultrasound-guided cardiac catheterization in the fetal lamb: a new approach for cardiac interventions in fetuses.

BACKGROUND: Percutaneous transventricular and fetoscopic umbilical catheterization have been applied to animal and human fetuses. These methods have a high rate of failure and complications. Here, we propose an alternative route for anterograde echocardiography-guided cardiac catheterization through a transhepatic approach of the intra-abdominal vessels in the fetal lamb. METHODS AND RESULTS: After exteriorization of the uterus in 12 pregnant ewes between 118 to 122 days' gestation, a 4F sheath mounted over a 1.2-mm needle was placed into the intra-abdominal portion of the umbilical vein (n=2) and into the subdiaphragmatic portion of the inferior vena cava via a transhepatic approach (n=10) under ultrasound guidance. In the first 2 animals using a transumbilical approach, it was impossible to reach the heart through the ductus venosus. In the next 10 animals, using a conventional technique, echocardiography-guided catheterization of the 4 chambers was performed in the all fetuses, atrial or ventricular pacing in 6 fetuses, and ballooning of the pulmonary valve in 9 of 10 fetuses. Among the 10 fetuses catheterized through the transhepatic approach, 2 were euthanized immediately after the procedure to evaluate intraperitoneal bleeding (23 and 29 mL, respectively), and 3 died after the procedure (1 of major bleeding and 2 deaths related to balloon catheter manipulation). Finally, 5 were delivered vaginally after an uneventful pregnancy, and autopsy at day 5 did not show significant liver, vascular, or cardiac injury. CONCLUSIONS: Echocardiography-guided fetal cardiac catheterization through a transhepatic approach is feasible and provides an interesting alternative approach for human fetal cardiac interventions.

Animals↗

The steroid hormonal milieu of the undisturbed human fetus and mother at 16-20 weeks gestation.

The interrelations of steroid hormone levels in plasma and amniotic fluid from mothers and their undisturbed fetuses at early midgestation of human pregnancy have not been defined previously. We, therefore, studied 12 healthy mothers and their fetuses undergoing termination of pregnancy for social reasons at 16-20 weeks gestation. Fetal arterial and venous blood was obtained by direct vessel puncture through a fetoscope in the conscious sedated mothers immediately before termination of pregnancy. Simultaneously, maternal peripheral venous blood and amniotic fluid were collected. Aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone, progesterone (P), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol, cortisol (F), and cortisone were simultaneously determined by specific RIA after extraction and chromatography. Positive fetal arterio-venous differences were found for F, B, and Aldo, whereas arteriovenous differences were negative for P and 17OHP. In amniotic fluid, six of the eight corticosteroids showed significantly lower levels during fetoscopy than during routine amniocentesis, as reported previously using the same analytical methods. The present study demonstrates that the undisturbed human fetus at 16-20 weeks gestation actively secretes the most important gluco- and mineralocorticoids, F, B, and Aldo, independent of the mother. P and 17OHP were shown to be primarily derived from placental production and supplied to the fetus as a source of F and Aldo biosynthesis. The fetoscopy procedure with premedication seemed to give rise to less stress to the fetus than routine amniocentesis without sedation. Fetoscopy is, therefore, an ideal method to study feto-maternal steroid interrelations in human pregnancy.

17-alpha-Hydroxyprogesterone↗

The effect of treatment of twin-twin transfusion syndrome on the diagnosis-to-delivery interval.

UNLABELLED: No randomised controlled trials of treatment of twin-to-twin transfusion syndrome (TTTS) exist. Since severely preterm neonatal survival has increased over time, survival as an outcome measure is confounded by improvements in neonatal care. The diagnosis-to-delivery interval is a measure of success of treatment independent of improvements in neonatal care. We wished to evaluate whether treatment of TTTS is associated with a lengthening of the diagnosis-to-delivery interval. MEDLINE search was performed supplemented by careful reference review. All TTTS series were included where the following information on each patient was available: survival, fetal demise, gestational age at diagnosis and diagnosis-to-delivery interval in days. INCLUSION CRITERIA: gestational age at diagnosis < 29 weeks and diagnosis by ultrasound in the absence of maternal symptoms. Cases undergoing multiple types of treatment were excluded. Eight publications met inclusion criteria and included the following cases: controls (n = 16), amnioreduction (n = 61), septostomy (n = 12), and fetoscopic laser occlusion of chorioangiopagus vessels (n = 51). There was no difference in the diagnosis-to-delivery interval, overall survival, at least one survivor, or number of fetal deaths between the four groups. Logistic regression using at least one survivor as the dependent variable revealed a positive association with gestational age at diagnosis and with diagnosis-to-delivery interval, a negative correlation with fetal death, and no correlation with treatment group. We conclude that there is no difference in diagnosis-to-delivery interval or survival for any treatment for TTTS compared to expectant management. The lack of significance appears to be due to small sample sizes.

Data Interpretation, Statistical↗

Fetal cardiovascular response to large placental chorioangiomas.

A large placental chorioangioma is a relatively rare condition, which in 50% of all cases will lead to maternal and fetal complications. Since chorioangiomas are often associated with significant arterio-venous shunting within the placenta, several fetal hemodynamic compensatory mechanisms are initiated. Ultrasound and color Doppler flow mapping are important for the prenatal diagnosis of chorioangiomas, as an early prenatal diagnosis is crucial to minimize the risks for fetal well-being. Close surveillance of pregnancy and pregnancy termination by cesarean section at the earliest signs of fetal cardiac decompensation are indicated to reduce fetal and neonatal complications. Novel intrauterine treatment options include intravascular transfusion, fetoscopic devascularization, microcoil embolization, and intravascular injection of absolute alcohol.

Female↗

Laser for the treatment of twin to twin transfusion syndrome.

PURPOSE: To report the initial experience in our country with a new technique for twin to twin transfusion syndrome (TTTS) treatment, using laser to coagulate the placental vessels responsible for the twin transfusion during gestation. METHODS: Prospective study of eight cases diagnosed with TTTS evaluated in our service from january 2001 to june 2005. Through percutaneous introduction of a 2,0mm diameter fetoscope in the uterine cavity, placental surface vessels where directly visualized. Those identified as responsible for the transfusion were laser coagulated. The procedure combines ultrasonography and fetoscopy, in a so-called sonoendoscopic technique (FETENDO). RESULTS: Among the eight pregnancies evaluated, five cases were submitted to the procedure (10 fetuses). All fetuses survived for at least five weeks after surgery. A total of eight fetuses were born alive and five survived the neonatal period. In a 18 months follow-up after birth, all five are still alive and well and their mean age is now 10,6 months. The total survival rate was 50% and in three pregnancies, at least one fetus survived. CONCLUSIONS: Laser fetoscopy is actually the "gold-standard" treatment of TTTS. Nevertheless is a sophisticated technique that depends of proper training. Our service is the first in our country to offer this therapeutic technique. Our success rate is comparable with the international literature.

Female↗

Transvaginal fetoscopy in anterior placentas.

When the placenta is located anteriorly, fetoscopy by the abdominal route may be impracticable. An alternative route, i.e., insertion of the fetoscope through the anterior vaginal fornix, was used in 31 women in midpregancy. Twenty-six of the women had been admitted for therapeutic abortion; the remaining five, for diagnosis. The insertion of the instrument was uncomplicated in all 31 women. In three of the five diagnostic cases, the disease at risk was excluded. The three women continued their pregnancies, and two of them went on to term without complications. The third woman had intermittent leakage of amniotic fluid. At 33 weeks she was delivered of a normal infant (birthweight 2 150 g). Transvaginal fetoscopy may be considered when an anterior placenta has an extension so broad that the abdominal approach is unfeasible.

Abortion, Therapeutic↗

Fetal muscle biopsy.

Fetal muscle specimens suitable for histological and histochemical studies were obtained under fetoscopic visualization by removing a small piece of skin, thereby exposing the underlying muscle. The procedure was carried out in 7 cases prior to second-trimester abortion. Muscle specimens so obtained may become useful in the prenatal diagnosis of Duchenne muscular dystrophy.

Female↗

[Twin-twin transfusion syndrome--front line in fetal medicine].

Twin-twin transfusion develops in 10-20% of monochorionic twin pregnancies. As far as we know the underlying disturbance is an unbalanced anastomosis between the two fetuses on the placental surface. Without treatment mortality is as high as 80% if diagnosed before viability. One of this article's authors spent two months in Hamburg at the 'Allgemeine Krankenhaus', Barmbeck in Germany and describes the technique used there to coagulate these anastomoses via fetoscope. The outcome seems very promising with overall survival of 80% using this method. In the article pathogenesis and alternative treatments are also discussed.

Female↗

[Twin-twin transfusion syndrome--front line in fetal medicine].

Twin-twin transfusion develops in 10-20% of monochorionic twin pregnancies. As far as we know the underlying disturbance is an unbalanced anastomosis between the two fetuses on the placental surface. Without treatment mortality is as high as 80% if diagnosed before viability. One of this article's authors spent two months in Hamburg at the "Allgemeine Krankenhaus", Barmbeck in Germany and describes the technique used there to coagulate these anastomoses via fetoscope. The outcome seems very promising with overall survival of 80% using this method. In the article pathogenesis and alternative treatments are also discussed.

Female↗

[Expression of cytokeratins during embryogenesis and in pathologic epithelia].

Epithelial cell intermediate filaments, or cytokeratins, are excellent markers for cell differentiation. During embryogenesis, cytokeratins specific of a stage of differentiation step always become detectable before corresponding morphologic changes: for instance, cytokeratins 5 and 14 are found around the eight week, shortly before stratification of the epithelium occurs, and cytokeratins 1 and 10 are produced before morphologic evidence of keratinization becomes detectable. Among potential diagnostic applications, analysis of cytokeratin patterns of epidermal cells desquamated in the amniotic fluid may provide earlier and less invasive diagnosis than fetoscopic biopsies. Similarly, a review of cytokeratins expressed in a variety of epithelial diseases (involving the epidermis, digestive tract, respiratory tract, urogenital tract, or breast) demonstrated persistence of the original tissue pattern in some instances (this was the case for the majority of simple epithelia) but not in others (complex epithelia). This suggests that cytokeratins may prove valuable as markers for specific tumor stages or types and may provide earlier information than morphologic studies.

Breast Neoplasms↗

[The Harlequin Baby syndrome. A new case].

The Harlequin baby syndrome is a rare but lethal ichtyosis. We report a new case of a primiparous woman of 28 years of age who had a pregnancy that progressed normally with the delivery of a child of 2,450 grams whose Apgar was 9 at one minute and 10 at three minutes, but who died after living just 24 hours. The reason for this work is to try to analyse the features that are known about possible treatment and antenatal diagnosis of the Harlequin baby syndrome. It has been suggested that vitamin A supplements should be given for several years because the skin state may be improved. On the other hand morbidity is likely to remain serious particularly from the point of view of growth and psychomotor development. Antenatal diagnosis using skin biopsy can be obtained after 23 weeks of amenorrhoea using a fetoscope; it shows the 25% of cases recur. At present the only treatment if a recurrence does occur is to terminate the pregnancy.

Abortion, Therapeutic↗

Endoscopic fetal surgery by excimer laser. An experimental study in premature lambs.

Fetal malformations are detected early in pregnancy by means of ultrasound challenging fetal therapy. While open fetal surgery has been preformed during preliminary clinical trials we evaluated fetoscopic therapy avoiding laparotomy and uterotomy. We used a laser fibre (900 mu) which was introduced into the uterus by an endoscope. During animal experiments in five fetal lambs with a gestational age of 120-122 days we used an excimer laser (Technolas, x) with a wave-length of 308 nm. Laser incisions were compared with the conventional cutting technique using a scapel. During histological evaluation the tissue effect was morphometricly analysed. The zone of devitalisation was characterized by pycnosis of the nuclei and in a change of cytoplasma volume. The excimer laser incisions using a frequency of 40 HZ had a mean zone of devitalisation of 50.3 +/- 4.5 mu. Using the excimer laser with a frequency of 10 HZ we found a tissue alteration of only 11.2 +/- 3.4 mu. The incisions by scapel showed a extended traumatisation with a mean tissue effect of 153.2 +/- 16.3 mu. From these results we conclude, that endoscopic surgery may be come a usefull additional tool for fetal therapy.

Animals↗

Relationship of fetal hemoglobin and oxygen content to lactate concentration in Rh isoimmunized pregnancies.

Fetal blood samples were obtained fetoscopically from 32 Rh isoimmunized pregnancies at 18-32 weeks' gestation, and the hemoglobin concentration, plasma lactate concentration, and oxygen content were measured. When the hemoglobin concentration was more than 8 g/dL, the umbilical arterial and venous lactate concentrations were equal. Abnormal elevations of lactate were found in the umbilical artery at hemoglobin concentrations below 8 g/dL (oxygen content 2 mmol/L) and in the umbilical vein at hemoglobin concentrations below 4 g/dL (oxygen content 2 mmol/L); the arterial lactate values were higher than the venous. These results show that lactate is produced by the human fetus stressed by anemic hypoxia and suggest that compensatory cardiovascular mechanisms are unable to maintain adequate oxygenation to all tissues when the umbilical venous oxygen content falls below 2 mmol/L.

Anemia↗

Drugs in feto maternal medicine.

The study of drug distribution in pregnancy was limited by ethical, technical and medico-legal considerations as samples of body fluids could only be taken at delivery. In recent times fetal blood samples have been taken with the fetoscope and will provide a new tool to monitor fetal concentrations and metabolic pathways. The advanced technology of ultrasound allows non invasive study of the fetal circulation and early experience of sympathomimetic drugs administered to the mother will be discussed. Auto immune disorders carry high perinatal wastage. New drugs have made reproductive life possible and when used prudently can improve maternal state and increase fetal salvage. The author has personally managed nearly 52 cases of systemic lupus erythematosus and 16 cases of idiopathic thrombocytopenic purpura. The use of steroids and low dosage aspirin therapy with elevated lupus anticoagulant levels will be described. Two cases of early hydrops in the fetus owing to heart failure due to supraventricular tachycardia were treated with digoxin given to the mother. The potential of therapeutic agents in fetal medicine will be discussed as it recognises the fetus as a patient and provides effective intra uterine therapy.

Animals↗

Survival and short-term morbidity of the premature neonate.

Obstetric decisions regarding premature (23 to 32 weeks' gestation) infants must be based on gestational age. However, most reports of the survival of premature infants are based on birth weight. The present report relates the perinatal survival and morbidity of 105 newborns to the obstetric gestational dating criteria between 23 and 32 weeks' gestation. Gestational age was determined from at least four obstetric criteria including the first day of the last menstrual period, early pelvic examination, the earliest auscultation of fetal heart tones with a fetoscope, fundal height measurements in centimeters between 20 and 30 weeks' gestation, and sonographic gestational age measurements. At 23 to 26 weeks' gestational age, nine (39%) of 23 neonates survived. Five of nine survivors had moderate to severe intracranial hemorrhage, three had moderate to severe bronchopulmonary dysplasia, and three had moderate to severe retrolental fibroplasia. At 27 to 29 weeks' gestational age, 25 (93%) of 27 neonates survived. Of the 25 survivors, three had moderate to severe intracranial hemorrhage, one had moderate to severe bronchopulmonary dysplasia, and one had severe retrolental fibroplasia. At 30 to 32 weeks' gestational age, 52 (95%) of 55 neonates survived. Three of the 52 (6%) survivors had serious neonatal morbidity consisting of moderate to severe intracranial hemorrhage (three neonates) and moderate to severe bronchopulmonary dysplasia (one neonate). Thus, ten of 34 (29%) survivors between gestational ages of 24 to 29 weeks had a serious morbidity versus only three of 52 (6%) survivors between 30 to 32 weeks' gestation (P less than .01).

Bronchopulmonary Dysplasia↗

Prenatal diagnosis of classic hemophilia (hemophilia A) by immunoradiometric assays.

During the period from 1978 to 1983, 92 pregnancies have been evaluated by fetoscopy for the prenatal diagnosis of hemophilia A. Satisfactory fetal plasma samples were obtained in 80 instances and the diagnosis--or exclusion--of hemophilia was made by immunoradiometric assay of the factor VIII coagulant protein (VIII:CAg). The accuracy of the diagnosis established by fetoscopy has been verified after delivery or termination, and there have been no misdiagnoses resulting from laboratory error. Additional evidence for the accuracy of the analysis was the observation that the frequency of hemophilia in pregnancies of obligate carriers of the hemophilia gene, and of women whose plasma assays were indicative of the carrier state, was 29 of 59 fetuses at risk. In one case of cross-reacting material-positive hemophilia, samples obtained at fetoscopy and from the newborn infant had normal VIII:CAg levels but the infant had decreased factor VIII procoagulant activity. There were five fetal deaths resulting from fetoscopy in 55 pregnancies not intentionally terminated. Although only a small percentage of pregnant hemophilia carriers in the United States have elected to undergo fetoscopy for prenatal diagnosis, this procedure has allowed a number of pregnancies to go to term with delivery of normal males in families that were not willing to accept the risk of a hemophilic child. In eight instances, fetoscopic evaluation was sought for two successive pregnancies.

Antigens↗

Masking of fetal supraventricular tachycardia by electronic monitoring artefact.

In a fetus of 42 weeks' gestation electronic monitoring demonstrated a heart rate of 120 beats/min that lacked the normal variability. Auscultation with a fetoscope revealed the true rate to be 240 beats/min. When used in the external Doppler mode the fetal monitor had a 250-ms refractory period after the recognition of a fetal cardiac event. This precluded recognition of the next beat and produced the artefactual halving of the heart rate. With the increasing reliance upon electronic fetal monitoring, those practising obstetrics should be aware of the possibility of artefacts and ensure that they can recognize truly representative information about the fetus.

Adult↗