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PubMed1981

Prenatal diagnosis of haemoglobinopathies: A status report.

An international registry of prenatal tests for haemoglobinopathies has been kept since July, 1974. Up to March, 1981, 1856 tests had been done with fetal blood and 70 with amniotic fibroblast DNA in 21 centres. Of the tests on fetal blood 92% were for the diagnosis of thalassaemia and 8% for that of sickle disorders. Blood was sampled via fetoscopy in 67% of cases and by placental aspiration in 33%. Adequate samples were obtained in 97% of cases. With fetoscopy the proportion of red cells obtained that were of fetal origin was 92%, and with aspiration it was 57%. In the most recent year of the registry the fetal loss rate was 3.9% (of 725 cases); and the rate was 5.6% overall (5.2% by fetoscopy and 6.5% by aspiration). Affected fetuses were detected in 23% of cases at risk for thalassaemia, and in 15% at risk for sickle disorders. The error rate was 0.9% and consisted mostly of false negatives. Fibroblast DNA analyses were used to assess the risk of sickle disorders in 61 (87%) of the 70 cases studied. 24% were affected. 26% had exclusion diagnoses only. The use of prenatal tests, together with genetic screening and counselling, has considerably reduced the rate at which new homozygous thalassaemics are born in several regions of the world.

Anemia, Sickle Cell↗
PubMed1991

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↗
PubMed1982

Prenatal fetoscopic diagnosis of the Apert syndrome.

We report the prenatal diagnosis of the Apert syndrome by fetoscopy. The patient was a 22-year-old college student with this autosomal dominant form of acrocephalosyndactyly whose first pregnancy had resulted in a stillborn, affected infant. Fetoscopy at 17 weeks showed that she was carrying another affected fetus, and the pregnancy was terminated.

Acrocephalosyndactylia↗
PubMed2001

Amnion rupture sequence in a first trimester missed abortion.

We report the diagnosis of amnion rupture sequence made by sonography and fetoscopy during the first trimester of gestation in a case of missed abortion. The investigation revealed a demised fetus with the characteristics of 9 weeks of development. The early fetus had an amnion adhesion at the tip of the nose and strands of amnion wrapped around the terminal phalanges of both feet. No defects in addition to the face and limb involvement were identified. The karyotype was normal: 46,XX. In the reported case, fetoscopy allowed confirmation of the sonographic diagnosis of an amnion rupture sequence in the first trimester of gestation and consequently helped to clarify the cause of abortion in this case of early fetal demise.

Abortion, Missed↗
PubMedDate not supplied

Prenatal diagnosis of anhidrotic ectodermal dysplasia.

This paper reports on successful prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia (AED) by means of light and electron microscopy on fetal skin biopsies obtained under fetoscopy. In the present family two brothers of the proband were severely affected with the full symptomatology of AED, the pregnant female and her mother revealed minor symptoms with patches of skin lacking vellus hair. Control of lesional skin of the affected family members by electron microscopy revealed no ultrastructural abnormalities. However, all biopsies lacked skin appendages including hair follicles, sebaceous glands, and sweat glands. The lack of pilosebaceous follicles can be used as a diagnostic criterion since these structures are fully developed in normal fetuses of 20 weeks whereas the development of sweat glands does not start before week 20 to 24 of fetal life. Skin biopsies were taken from various regions of the fetus at risk via fetoscopy in week 20 and processed for light and electron microscopy. All samples revealed complete absence of all skin appendages in contrast to a total of 61 non-AED fetuses. Thus positive prenatal diagnosis of AED was made and the pregnancy was terminated. Control investigations after abortion confirmed the diagnosis.

Adult↗
PubMed1990

Fetal skin biopsy in prenatal diagnosis of some genodermatoses.

Various methods of obtaining fetal skin for prenatal diagnosis of certain autosomal-recessive congenital genodermatoses have been assessed. An attempt was made to obtain fetal skin by fetoscopy in 15 patients prior to pregnancy termination for a variety of medical reasons at 18-26 weeks. Specimens were obtained only in five cases (8 successful attempts out of 48). In twelve cases, of which five had a history of a child with junctional (Herlitz type) or dystrophic (Hallopeau-Siemens type) epidermolysis bullosa or non-bullous congenital ichthyosiform erythroderma at 16-25 weeks of pregnancy, fetal skin was obtained without fetoscopy under direct ultrasonic control. Specimens were obtained in all cases (33 successful attempts out of 39). In three cases, fetal pathology was diagnosed by the method of semi-thin and ultra-thin skin sections, and the respective pregnancies were terminated.

Biopsy↗
PubMed1988

Fetal blood sampling.

Fetal blood sampling is now performed in many centres through different approaches (fetoscopy, placentacentesis, cardiac puncture, umbilical cord needling, intrahepatic vein puncture) for prenatal diagnosis of congenital defects, management of intrauterine growth retardation and fetal therapy. One hundred and thirty-nine fetal blood samples have been performed during a 10 month period at Queen Charlotte's Maternity Hospital, London, using an individualized approach. One failure to obtain fetal blood occurred and there were four fetal losses, three of which followed an intrauterine transfusion in very severely affected fetuses. Two of these losses were associated with peculiar circumstances (see above). The procedure-related risk is nowadays more difficult to evaluate than in the past, when most fetal blood samplings were carried out in the second trimester for prenatal diagnosis. Most case studies, and ours as well, are not homogeneous and high-risk patients such as those with Rhesus disease or intrauterine growth retardation are also included. It seems, however, that transabdominal needling of the cord, at either placental or fetal insertion, is a low-risk procedure although a larger number of cases should be collected to draw definite conclusions about sampling from the intrahepatic vein. Fetoscopy also has a low risk in experienced hands, but the training period is certainly longer and the application in the second half of the pregnancy has been limited to a few cases. It is likely to be used only very little in the future. A flexible approach to fetal blood sampling allows the best choice of technique and utilizes the advantages of each technique.

Female↗
PubMed2000

Minimally invasive treatment of twin-to-twin transfusion syndrome.

Selective laser photocoagulation of communicating vessels (SLPCV) is an application of minimally invasive endoscopic fetal surgery (i.e., surgical fetoscopy) performed for severe cases of twin-to-twin transfusion syndrome (TTTS), a complication of monochorionic twin pregnancies. Advances in ultrasound and endoscopy have aided the identification and treatment of this potentially lethal or fatal condition. Surgical fetoscopy, an innovation in the field of surgery and maternal-fetal medicine, benefits patients by reducing the morbidity and mortality associated with TTTS, with minimal risks to the mother.

Amniocentesis↗
PubMed2000

Successful sealing of fetoscopic access sites with collagen plugs in the rabbit model.

OBJECTIVE: The aim of this study was to evaluate the efficacies of various plugging techniques in sealing the membrane defect created by fetoscopy in the rabbit at midgestation. STUDY DESIGN: Fetoscopy was performed in pregnant rabbits at 23 days' gestation (term, 32 days' gestation). In group 1 fetal sacs were left unclosed (positive control group, n = 24). In group 2 injection with commercially available extracellular matrix (Matrigel; BD Labware, Bedford, Mass) was performed and a myometrial suture was inserted (n = 23). In group 3 the entry site was plugged with collagen (Colgen; Inter-Phar, Paris, France) combined with a myometrial suture (n = 22). At 30 days' gestation the membrane integrity, amniotic fluid presence, and fetal lung/body weight ratios were assessed. The plugging site was examined histologically. RESULTS: The use of suture and collagen plugs (group 3) resulted in functional restoration of membrane integrity with preservation of amniotic fluid and normal fetal lung/body weight ratio at term in 82% of cases, compared with 42% in the positive control group (group 1; P <.05). Histologic examination revealed entrapment of membranes between the plug and the myometrium but no anatomic repair of the membranes. The use of suture and extracellular matrix (group 2) did not achieve better results than those seen in group 1 (positive control group). CONCLUSION: Collagen plugs achieved functional sealing of fetoscopic access sites in a rabbit model and prevented oligohydramnios and pulmonary hypoplasia.

Amnion↗
PubMed1999

Treatment of iatrogenic previable premature rupture of membranes with intra-amniotic injection of platelets and cryoprecipitate (amniopatch): preliminary experience.

OBJECTIVE: Our aim was to describe the treatment of iatrogenic previable premature rupture of membranes with the intra-amniotic injection of platelets and cryoprecipitate (amniopatch). STUDY DESIGN: Patients with iatrogenic previable premature rupture of membranes and without evidence of intra-amniotic infection underwent transabdominal intra-amniotic injection of platelets and cryoprecipitate through a 22-gauge needle. The study was approved by the Institutional Review Board of St Joseph's Hospital in Tampa, Florida, and all patients gave written informed consent. RESULTS: Seven patients with iatrogenic preterm premature rupture of membranes underwent placement of an amniopatch. Membrane sealing was verifiable in 6 of 7 patients. Three patients had iatrogenic preterm premature rupture of membranes after operative fetoscopy, 3 cases were after genetic amniocentesis, and 1 was after diagnostic fetoscopy. Three pregnancies progressed well, with restoration of the amniotic fluid volume and no further leakage. Two patients had unexplained fetal death despite successful sealing. One case of bladder outlet obstruction had no further leakage, but oligohydramnios persisted and did not allow unequivocal documentation of sealing. One patient miscarried from twin-twin transfusion, but the amniotic cavity was sealed. CONCLUSIONS: Iatrogenic preterm premature rupture of membranes can be treated effectively with an amniopatch. The technique is simple and does not require knowledge of the exact location of the defect. Unexpected fetal death from the procedure may be attributable to vasoactive effects of platelets or indigo carmine. Although the appropriate dose of platelets and cryoprecipitate needs to be established, the amniopatch may mean that iatrogenic preterm premature rupture of membranes no longer needs to be considered a devastating complication of pregnancy.

Adult↗
PubMed1997

The pregnant ewe: an animal model for fetoscopic surgery.

OBJECTIVE: To develop an animal model for fetal endoscopic surgery which could be feasible and reproducible. The aim of this work was to perform a fetoscopy without the need of a laparotomy. METHODS: Pregnant ewes underwent under general anesthesia laparoscopy with the creation of a maternal pneumoperitoneum. After localizing the placenta by transillumination, we carried out fetoscopy through a 5 mm trocar using a perfusion of Ringer's solution. RESULTS: Five video-assisted procedures have been performed. None of the cases has shown any bleeding from myometrial wounds and no suture was necessary. There was no leakage of amniotic fluid. Intrauterine space was large enough to manipulate instruments without producing any fetal damage. Sharp visualization and anatomical description of the fetus were precise without the use CO2. There were no miscarriages and postnatal examinations of the lambs were normal. CONCLUSION: Fetoscopic surgery can be performed in the pregnant sheep without any complications but preterm labor which is the main problem in human fetal surgery, is infrequent in the sheep. Our model is reproducible and simulates the surgical endoscopic procedures which will occur in a close future in the human species.

Animals↗
PubMed1979

Prenatal diagnosis of classic hemophilia.

Prenatal diagnosis of classic hemophilia (hemophilia A) in mid-trimester was achieved by means of immunoradiometric assays for factor VIII on fetal plasma and amniotic-fluid mixtures obtained by fetoscopy. Samples were analyzed from six male fetuses at risk for severe hemophilia and from nine control fetuses for which fetoscopy was carried out to attempt prenatal diagnosis of other genetic disorders. The factor VIII coagulant-antigen values for the control (non-hemophilic) samples were 17 to 94, and the factor VIII related-antigen concentrations were 50 to 155 U per deciliter. Three of the fetuses at risk for hemophilia had factor VIII values in the control range, and these infants were normal at birth. The other three fetuses had low concentrations of factor VIII coagulant antigen but normal concentrations of factor VIII related antigen. These values and the diagnoses of severe hemophilia were confirmed with blood from the abortuses.

Amniotic Fluid↗
PubMed2002

Nitrous oxide amniodistention compared with fluid amniodistention reduces operation time while inducing no changes in fetal acid-base status in a sheep model for endoscopic fetal surgery.

OBJECTIVE: Our purpose was to evaluate in a sheep model for endoscopic fetal surgery the impact of nitrous oxide-gas amniodistention compared with fluid amniodistention on duration of surgery, hemorrhagic events, and fetomaternal acid-base status. STUDY DESIGN: Pregnant ewes (n = 16) at 92 to 104 days of gestation (term, 145 days) underwent amniodistention with Hartmann's solution (group I, n = 8) or nitrous oxide (group II, n = 8) at 38 degrees C. Endoscopic tracheal clipping according to a standardized surgical protocol was performed in all animals. The duration of fetoscopy (from insertion of first cannula until removal of last one), fetal surgery (fetal skin incision to skin closure), and number of bleeding episodes was recorded. Maternal and fetal blood gas values (pH, PO2, and PCO2) were measured at baseline and every 15 minutes during the experiment. Videotapes of the operations were assessed independently and scored by a visual analog scale in terms of smoothness of the operation and control of hemorrhagic events. RESULTS: Mean duration of fetoscopy (+/-SEM) (68 +/- 16 minutes vs 92 +/- 23 minutes) and fetal surgery (19 +/- 6 minutes vs 42 +/- 18 minutes) as well as number of bleeding episodes (1.9 +/- 0.8 minutes vs 5.8 +/- 2.1 minutes) was significantly reduced in animals operated with use of nitrous oxide amniodistention. In both groups, fetal and maternal blood gases remained unchanged during the entire experiment. Visual analog scale (VAS) scores were significantly higher for procedures conducted with use of gas distention. CONCLUSION: In a lamb model for fetal surgery, gas amniodistention with use of nitrous oxide results in a quicker operation procedure with less bleeding compared with fluid amniodistention, and without adverse side effects on fetomaternal acid-base status.

Acid-Base Equilibrium↗
PubMed1981

Obstetric outcome and problems of mid-trimester fetal blood sampling for antenatal diagnosis.

Detailed follow-up is presented of 335 pregnancies in which mid-trimester fetal blood sampling was performed for the diagnosis of a haemoglobinopathy, mostly beta-thalassemia. There were three twin pregnancies. Thirty-eight fetuses were lost including four in whom a diagnosis of thalassemia major was made. Placentacentesis was particularly associated with fetal vessel trauma, exsanguination and early intrauterine fetal death, while late complications associated with fetoscopy or failed fetoscopy necessitating subsequent placentacentesis included spontaneous abortion, leakage of amniotic fluid and premature onset of labour.

Abortion, Spontaneous↗
PubMed1981

Antenatal diagnosis of homozygous beta thalassaemia in Mediterraneans in Australia.

Facilities for the antenatal diagnosis of homozygous beta thalassaemia have recently become available in Australia and in this paper, data from a series of 18 pregnancies examined at The Royal Women's Hospital, Melbourne, are analysed. Fetal blood was collected by fetoscopy and adequate samples were obtained in 16 cases (89%). In 5 pregnancies, fetal blood was shown to have a marked reduction in beta globin production (beta/alpha synthesis less than 0.030) and these pregnancies were terminated. Two pregnancies (11%) were lost in the immediate post-fetoscopy period and in a third pregnancy, neonatal death followed premature labour at 26 weeks' gestation. Seven babies were delivered normally at 36-40 weeks' gestation and cord blood studies excluded homozygous thalassaemia in all cases. The remaining pregnancy has yet to be delivered.

Australia↗
PubMed2006

Amnion cells engineering: a new perspective in fetal membrane healing after intrauterine surgery?

In this study we aimed to set up an in vitro culture of the rabbit amnion in order to support in vivo fetal membrane healing capacity following fetoscopy. Fetal membranes were collected from a mid-gestational rabbit, and cultured on collagen support material for 14 days. 34 rabbits at 22-23 days gestational age (GA) underwent fetoscopy. The entry site was randomly allocated to 4 closure technique study groups: group I, human amnion membrane (n = 23); group II, collagen foil (n = 16); group III, collagen plug (n = 19), and group IV, collagen plug with cultured amnion cells (n = 19). In all groups membrane access sites were additionally sealed with fibrin sealant, and the myometrium was closed with sutures. Fetal survival, amnion membrane integrity, and the presence of amniotic fluid were evaluated at 30 days GA. Cultures showed good survival in the collagen support material. Increased cellularity, survival and proliferations were observed. The amnion at the access site resealed in 58-64% of cases in groups II-IV, but none of the tested techniques was significantly better than the other. Histological examination indirectly revealed the anatomic repair of the membranes, since no entrapment of the membranes could be demonstrated in the myometrial wound.

Amnion↗
PubMed2000

Fetoscopic direct fetal cardiac access in sheep : An important experimental milestone along the route to human fetal cardiac intervention.

BACKGROUND: Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. METHODS AND RESULTS: In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. CONCLUSIONS: Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.

Animals↗
PubMed2005

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↗