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Incidence, origin, and character of cerebral injury in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery.

OBJECTIVE: The objective of the study was to determine the incidence, origin, and character of cerebral lesions in monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery. STUDY DESIGN: This was a prospective study of monochorionic twins with twin-to-twin transfusion syndrome treated with fetoscopic laser surgery and monochorionic twins without twin-to-twin transfusion syndrome delivered at our center between June 2002 and September 2005, using cranial ultrasonography. RESULTS: Incidence of antenatally acquired severe cerebral lesions in the twin-to-twin transfusion syndrome group was 10% (8/84) and 2% (2/108) in the non-twin-to-twin transfusion syndrome group (P = .02). Incidence of severe cerebral lesions at discharge was 14% (12/84) in the twin-to-twin transfusion syndrome group and 6% (6/108) in the non-twin-to-twin transfusion syndrome group (P = .04). Antenatal injury was responsible for severe cerebral lesions in 67% (8/12) of the twin-to-twin transfusion syndrome group. CONCLUSION: Incidence of severe cerebral lesions in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery is high and results mainly from antenatal injury.

Brain Injuries↗

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↗

Fetal lung-to-head ratio in the prediction of survival in severe left-sided diaphragmatic hernia treated by fetal endoscopic tracheal occlusion (FETO).

OBJECTIVE: The objective of the study was to investigate the value of fetal lung area to head circumference ratio in the prediction of the postnatal outcome in left-sided congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion. STUDY DESIGN: The lung area to head circumference ratio was measured before fetoscopic endoluminal tracheal occlusion in 28 fetuses with congenital diaphragmatic hernia at 25 to 29 weeks. Regression analysis was used to investigate the effect on survival of lung area to head circumference ratio, gestation at fetoscopic endoluminal tracheal occlusion, gestation at delivery, preterm amniorrhexis following fetoscopic endoluminal tracheal occlusion, and prenatal removal of the balloon. RESULTS: The median lung area to head circumference ratio prior to fetoscopic endoluminal tracheal occlusion was 0.7 (range 0.5 to 0.9). The median gestation at delivery was 34 (range 27 to 39) weeks, and there were 16 survivors (57%). Only lung area to head circumference ratio provided significant prediction of survival, which increased from 17% for lung area to head circumference ratio of 0.4 to 0.5 to 62% for lung area to head circumference ratio of 0.6 to 0.7 and 78% for lung area to head circumference ratio of 0.8 to 0.9. CONCLUSION: In congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion, postnatal survival can be predicted by the lung area to head circumference ratio measured prior to the procedure.

Balloon Occlusion↗

Foetal surgery and cleft lip and palate: current status and new perspectives.

Now-a-days, high-resolution ultrasound allows an accurate and relatively early diagnosis of congenital malformations. In a limited number of such conditions foetal surgery may be lifesaving. However, premature labour has been the major drawback for open foetal surgery. Recently, improvement of video-endoscopic technology has boosted the development of operative techniques for feto-endoscopic surgery, which has been demonstrated to be less invasive than the open approach. Main clinical application of fetoscopic procedures today is the treatment of feto-foetal transfusion syndrome. Although still in development, feto-endoscopic surgery seems to offer new hope for surgical foetal therapy not only in cases of life threatening conditions. Experimental intrauterine correction of cleft lip and palate (CLP) has been lately performed using the feto-endoscopic approach. This procedure offers two major advantages: first, scarless foetal wound healing and bone healing without callus formation, which would also allow a better/normal maxillary growth, and second, significant decrease of foetal and maternal morbidity. Herein, we report the current status of experimental and clinical foetal surgery and propose possible directions for continuing research to make intrauterine procedures safer. Furthermore, we discuss current knowledge and new perspectives of experimental foetal cleft lip and palate repair, which in the future may lead to such excellent results in the operative treatment of clefts, that less or no secondary corrections and therapies, such as orthodontic, dental, logopedic, etc. would be needed. Only if these conditions can be fulfilled, will we be able to improve substantially our therapy for the human foetus with a cleft lip and palate. In spite of all efforts, however, it must be considered that it may not ever be possible to find the optimal treatment method for this or other craniofacial malformations.

Animals↗

Abnormal embryonic development diagnosed embryoscopically in early intrauterine deaths after in vitro fertilization: a preliminary report of 23 cases.

OBJECTIVE: To provide data about the phenotypic appearance of the embryo of early failed pregnancies after IVF. DESIGN: Clinical prospective descriptive study. SETTING: Tertiary care center. PATIENT(S): Twenty-three women who had conceived by IVF and had a missed abortion before 12 weeks of gestation. INTERVENTION(S): Embryoscopic examination of the embryo before curettage. Cytogenetic analysis of the chorionic villi by standard G-banding cytogenetic techniques or by comparative genomic hybridization in combination with flow cytometry analysis. MAIN OUTCOME MEASURE(S): Embryonic phenotype and karyotype were determined. RESULT(S): Twenty-one of 23 IVF embryos showed structural defects on embryoscopic examination. Seventeen of 23 specimens had a chromosomal abnormality. The majority were numerical aberrations such as monosomy X (2 cases). Trisomies for chromosomes 18 (one case), 16 (three cases), 15 (one case), 14 (two cases), 13 (one case), 12 (one case), 11 (one case), 10 (one case), 9 (one case), 8 (one case), and 3 (one case) were observed. A structural chromosome anomaly leading to a chromosomal trisomy was observed in one case. Aneuploidy explained the grossly abnormal embryonic development documented by embryoscopy in 15 of 21 cases. CONCLUSION(S): Aneuploidy is the major factor affecting normal embryonic development in missed abortions after IVF. Further investigation is needed to elucidate mechanisms that might prevent normal embryogenesis but evade detection by the cytogenetic techniques used in the present study.

Abortion, Missed↗

[Decreased fetal movements in the third trimester: what to do?].

OBJECTIVE: To appreciate at the end of pregnancy, in a low-risk pregnant population, the interest of a screening for fetal well-being in case of decreased fetal movements. To define the most adapted screening. PATIENTS AND METHODS: Retrospective study over a complete year of the patients having consulted in the same center for decreased fetal movements and subjected to the same screening for fetal activity in hospitalization during 48 hours. This screening included a study of fetal heart rate repeated three times a day, a fetal biophysical profile scoring, an umbilical artery Doppler, a Kleihauer-Betke testing, and an amnioscopy. RESULTS: One hundred and sixty patients were identified, representing 6.1% of pregnancies followed in the center. There was no relation between the age, the parity of the patients and the probability to consult for a decrease of fetal movements. Nevertheless the antecedents of pathological pregnancy or fetal malformation were frequent. Twenty-one percent of the deliveries were induced for a global rate of 18% in the center. Twenty-eight percent of the patients had a cesarean section for a global rate of 22.8%. Five percent of fetuses were at risk for prenatal asphyxia on the data of the screening. Fetal heart rate was abnormal in 3.75% of cases, fetal biophysical profile score pathological in 3.1% of cases. Just one umbilical Doppler was highly pathological. No meconium amniotic fluid was found. Two Kleihauer-Betke tests were disturbing. At the time of delivery, 28% of fetuses presented a funicular abnormality, 4.3% a severe growth restriction, 4.3% a malformation. One child only had an anemia. There was no perinatal mortality. DISCUSSION AND CONCLUSION: Screening for fetal vitality remains necessary in case of decreased fetal movements. It has to associate the study of fetal heart rate and the fetal biophysical profile with a Kleihauer-Betke testing. In a low-risk pregnant population, the study of fetal Doppler velocimetry is not profitable. Amnioscopy presents not enough interest. It is necessary to insist with the patients on the necessity of consulting in case of decreased fetal movements even in the approach of the term.

Adolescent↗

Robot-enhanced fetoscopic surgery.

BACKGROUND: Fetoscopic surgery carries with it less maternal morbidity than open fetal surgery. Robotic surgery facilitates endoscopic surgery through tremor filtration, motion scaling, indexed movement, articulation, and improved ergonomics. The goal of the authors was to explore using a robotic surgery platform in a fetal animal model. METHODS: Using the Zeus Robotic Surgery System (Computer Motion, Santa Barbara, CA), fetoscopic surgery in pregnant sheep was performed using a variety of techniques: uterus exteriorized or totally percutaneous and with liquid or gas insufflation. Using the percutaneous technique and gas insufflation, the authors created and sutured fetal skin and fascial defects. The ewes were recovered and killed 2 weeks postoperatively, and autopsies were performed on them and their fetuses. RESULTS: In the exteriorized uterus model, instrument movement was unpredictable and fluid leaked. In the fluid environment, clouding of the visual field and difficulty in immobilizing the fetus were major difficulties. In the survival model, 4 of the 6 fetuses survived to autopsy at 2 weeks and showed good healing grossly and histologically. CONCLUSIONS: The Zeus Robotic Surgery System can be used for fetoscopic surgery in a sheep model. The percutaneous approach with a nitrous oxide environment is the most effective. Advantages of robotic surgery may be applicable in fetoscopic surgery, but further work in a primate model is required.

Animals↗

Survival of severe congenital diaphragmatic hernia has morbid consequences.

BACKGROUND/PURPOSE: Fetal tracheal occlusion (TO) was developed in an attempt to enhance prenatal lung growth and improve survival in fetuses with severe congenital diaphragmatic hernia (CDH). We conducted a randomized, controlled clinical trial in 24 fetuses with severe left CDH (liver herniated into the thorax and low lung-to-head ratio) to compare survival after endoscopic fetal TO vs standard perinatal care (control) and prospectively followed up the 16 survivors (9 control, 7 TO) to compare neurodevelopmental, respiratory, surgical, growth, and nutritional outcomes. METHODS: At 1 and 2 years old, subjects underwent evaluation consisting of medical and neurological history and physical, developmental testing, nutritional assessment, oxygen saturation and pulmonary function testing, chest radiograph, and echocardiogram. Growth and developmental measures were corrected for prematurity. Data were analyzed by Mann-Whitney rank sum test, Fisher's Exact test, and logistic and linear regression. RESULTS: Infants with TO were significantly more premature at birth (control vs TO, 37.4 +/- 1.0 vs 31.1 +/- 1.7 weeks; P < .01). Growth failure ( z score for weight <2 SDs below mean) was severe in both groups at 1 year of age (control vs TO, 56% vs 86%; P = .31). There was considerable catch-up growth by age 2 years (growth failure: control vs TO, 22% vs 33%; P = .19). There were no differences in other growth parameters. There were also no differences in neurodevelopmental outcome at 1 and 2 years. Supplemental oxygen at hospital discharge was a significant predictor of worse neurodevelopmental outcome at 1 and 2 years old (P = .05 and P = .02, respectively). Hearing loss requiring amplification has been diagnosed in 44% of the group (control vs TO, 44% vs 43%; P = 1.0). CONCLUSIONS: In this group of infants with severe CDH, there were no differences in outcome at 2 years old despite significant prematurity in the TO group. Oxygen supplementation at hospital discharge identified the most vulnerable group with respect to neurodevelopmental outcome, but all infants had significant growth failure, and hearing impairment is a substantial problem in this population. Severe CDH carries significant risk of chronic morbidity.

Female↗

Current consequences of prenatal diagnosis of congenital diaphragmatic hernia.

BACKGROUND: Today, the diagnosis of congenital diaphragmatic hernia (CDH) can readily be made in the prenatal period during screening ultrasound examination. Patients ought to be referred to rule out associated anomalies, and in isolated cases, prognosis is poor when the liver is intrathoracic and the lung-to-head ratio (LHR) is less than 1. In these patients, prenatal intervention aiming to reverse pulmonary hypoplasia can be considered. METHODS: We present our current algorithm for counselling patients presenting with CDH. Patients with a poor prognosis are offered percutaneous fetal endoluminal tracheal occlusion (FETO) with a balloon, inserted at 26 to 28 weeks. We report on the evolution of technique and results in a consecutive homogeneous case series and compare outcome in cases with similar severity managed in the postnatal period. RESULTS: Within a period of 28 months, FETO was performed between 26 and 28 weeks in 24 fetuses with severe left-sided CDH. Under general (n = 5), epidural (n = 17) or local (n = 2) anesthesia, the balloon was successfully positioned at first surgery (23/24) with a mean operation time of 20 minutes (range, 3-60 minutes). There were no serious maternal complications or direct fetal adverse effects. In the first 2 weeks after FETO, LHR increased from 0.7 to 1.7. Premature prelabour rupture of the membrane (PPROM) occurred in 16.7% and 33.3% at 28 and 32 weeks or earlier, respectively. Gestational age at delivery was 33.5 weeks. Patency of airways was restored either in the prenatal (n = 12) or perinatal period (n = 12). Early (7 days) and late (28 days) survival, and survival at discharge were 75% (18/24), 58.3% (14/24) and 50% (12/24), respectively. Half of nonsurvivors (n = 6) died of pulmonary hypoplasia and hypertension, in combination with PPROM and preterm delivery (n = 4) and balloon dislodgement (n = 2), which coincided with a short tracheal occlusion (TO) period (12 days). In the other 6, TO period was comparable to that in the 12 survivors (47 vs 42 days, respectively). In that group of 6 babies, only 2 died of pulmonary problems. Late neonatal survival (28 days) was higher with prenatal vs perinatal balloon retrieval 83.3% vs 33.3% (P = .013). In a multicentre study validating the criteria, survival till discharge in 37 comparable cases was 9% (3/32) and 13% (5/37) of parents opted for termination. CONCLUSION: Fetuses with isolated left-sided CDH, liver herniation, and LHR of less than 1 have a poor prognosis. Percutaneous FETO is minimally invasive and may improve the outcome in these highly selected cases. Airways can be restored before birth, allowing vaginal delivery and return to the referring tertiary unit and may improve survival rate. The procedure carries a risk for PPROM, although that may decrease with experience.

Decision Trees↗

Amniotic air insufflation during minimally invasive fetoscopic fetal cardiac interventions is safe for the fetal brain in sheep.

BACKGROUND: Amniotic air insufflation during experimental fetoscopic fetal cardiac interventions greatly improves the visualization of intra-amniotic contents. The purpose of this study was to assess any histologically discernible effects from this approach on the fetal brain after short-term studies and long-term survival in sheep. METHODS: Thirty pregnant ewes between 80 and 110 days of gestation underwent amniotic air insufflation during various fetoscopic fetal cardiac interventions. After 18 short-term and 12 long-term studies, the brains of the operated fetuses and-if available-their unoperated siblings were examined for hemorrhage, embolism, infarctions, inflammatory changes, and abnormal cortical maturation. RESULTS: Amniotic air insufflation during minimally invasive fetoscopic fetal cardiac interventions did not result in any histologically discernible damage to the brain in short-term and long-term studies in any but 2 sibling sheep. In the 2 affected siblings, a small area of chronic cortical frontal lobe infarction was observed after long-term survival. CONCLUSIONS: Amniotic air insufflation during minimally invasive percutaneous fetoscopic fetal cardiac interventions is safe for the fetal brain and does not compromise maternal hemodynamics in sheep. These findings encourage further investigation of the role this technique might play during fetoscopic fetal cardiac interventions in humans.

Amnion↗

Successful patching of iatrogenic rupture of the fetal membranes.

Rupture of the fetal membranes is a common, but potentially serious complication of invasive fetal procedures. Quintero described a technique to seal the fetal membrane defect by means of a bloodpatch, usually called 'amniopatch' in this application. The successful use in two consecutive patients with ruptured membranes after a fetoscopic intervention at respectively 17 and 22 weeks' gestational age is described, together with a literature review of published experience.

Adult↗

Pseudo-arterio-arterial anastomoses in twin-twin transfusion syndrome.

OBJECTIVE: It has recently been claimed that fetoscopic recognition of a haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests minimal net intertwin flow. This was based on blood from one fetus being dark and from the other bright red, the boundary between them reciprocating with the fetal heart beats. However, bright red indicates that the blood had passed through a cotyledon and been freshly oxygenated, which should be impossible in an AAA. We applied a computer model of chorionic vessels to determine a configuration that reproduced this phenomenon. METHODS: A previously published TTTS model was extended to provide placental detail in a segment containing four cotyledons of each placenta supplied by three generations of placental arteries and veins. RESULTS: Reciprocating flow is not unique to AAAs. It also occurs in the chorionic arteries of any cotyledon deprived of its venous outflow, in a similar manner to that in which reverse end-diastolic flow occurs in umbilical arteries when whole placental resistance is high. If venous return from the common chorionic vein in the recipient (draining the venous end of an AVA) is blocked as might happen after laser, there can be bidirectional flow from one umbilical artery insertion, through two cotyledons to the other insertion. We define this phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path means that its resistance cannot match the low flow resistance of a true AAA, and transmission of the contralateral pulsatile pattern is absorbed in the cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two sets of systolic peaks, one forward and one reverse, can be discerned in true AAAs but only one in PAAAs. CONCLUSIONS: We demonstrate how venous occlusion of an arterio-venous anastomosis may produce a pseudo-AAA colour equator at endoscopy. However, visual observation of reciprocating flow is not sufficient to define a vessel as a true AAA which instead requires ultrasonical identification of two systolic patterns.

Adult↗

Residual anastomoses after fetoscopic laser surgery in twin-to-twin transfusion syndrome: frequency, associated risks and outcome.

Fetoscopic laser coagulation of placental vascular anastomoses is considered to be the treatment of choice in severe twin-to-twin transfusion syndrome. The aim of fetoscopic laser surgery is to separate completely the inter-twin placental circulation. Incomplete laser coagulation may result in residual vascular anastomoses. The incidence and clinical implications of residual anastomoses in twin-to-twin transfusion syndrome treated with fetoscopic laser surgery has not yet been studied. We examined all placentas treated with fetoscopic laser surgery and delivered at our center between June 2002 and December 2005 with vascular injection using colored dyes. Presence of residual anastomoses was studied in association with adverse outcome and inter-twin hemoglobin difference at birth. Adverse outcome was defined as fetal demise, neonatal death or severe cerebral injury. The relation between residual anastomoses and placental localization (anterior or posterior uterine wall) was evaluated. A total of 52 laser-treated placentas were studied. Residual anastomoses were detected in 33% (17/52) of placentas. Adverse outcome was similar in the groups with and without residual anastomoses, 18% (6/34) and 29% (20/70), respectively (p=0.23). Large inter-twin hemoglobin differences (>5g/dL) were found in 65% (11/17) of cases with residual anastomoses and 20% (7/35) of cases without residual anastomoses (p<0.01). Anterior placental localization was not associated with a more frequent presence of residual anastomoses. In conclusion, residual anastomoses at our institution are seen in one-third of monochorionic placentas treated with fetoscopic laser surgery. Although residual anastomoses in our study were not associated with adverse outcome, they were often associated with neonatal hematological complications.

Arteriovenous Anastomosis↗

Transabdominal thin-gauge embryofetoscopy: a technique for early prenatal diagnosis and its use in the diagnosis of a case of Meckel-Gruber syndrome.

OBJECTIVE: Our aim was to develop and evaluate a transabdominal endoscopic technique to visualize the embryo or fetus with thin-gauge needles and submillimetric fiberoptic endoscopes. METHODS: Under ultrasonographic guidance, an 18- or 19-gauge thin-wall needle was introduced into the uterus of 28 patients undergoing first-trimester or early second-trimester termination of pregnancy. A 0.7 mm endoscope was threaded through the lumen of the needle after removal of the stylet. Visualization of the embryo-fetus was attempted before 14 weeks' gestation (n = 20). From 16 to 20 weeks (n = 8), the needle and endoscope were directed to the placental insertion of the umbilical cord, and a cordocentesis was performed. RESULTS: Excellent visualization of the surface anatomy of fetuses from 7 to 13 weeks was obtained in 85% of cases (17/20). A diagnosis of Meckel-Gruber syndrome was made at 11 weeks' menstrual age by visualizing postaxial polydactyly and an occipital encephalocele. Endoscopically assisted cordocentesis allowed visualization of the lumen of the umbilical vein and of the blood flow within it. CONCLUSION: Endoscopic visualization of the embryo or fetus can be performed transabdominally in the first trimester with small-delivered endoscopes. This represents a clear advantage over previous endoscopic approaches to the human pregnancy. Potential applications of this technique include a precise description of fetal anatomy and physiologic features, diagnosis of anomalies, and therapeutic fetal interventions.

Abdomen↗