You do not have subscription access to articles in this section. Learn more about access.

  JoVE Biology

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Neuroscience

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Immunology and Infection

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Medicine

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Bioengineering

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Engineering

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Chemistry

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Behavior

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Environment

You do not have subscription access to articles in this section. Learn more about access.

  JoVE Developmental Biology


JoVE Science Education

General Laboratory Techniques

You do not have subscription access to videos in this collection. Learn more about access.

Basic Methods in Cellular and Molecular Biology

You do not have subscription access to videos in this collection. Learn more about access.

Essentials of Biology 1

You do not have subscription access to videos in this collection. Learn more about access.

Essentials of Biology 2

You do not have subscription access to videos in this collection. Learn more about access.

Essentials of

You do not have subscription access to videos in this collection. Learn more about access.

Essentials of Developmental Biology

You do not have subscription access to videos in this collection. Learn more about access.

Essentials of Behavioral Science

You do not have subscription access to videos in this collection. Learn more about access.

In JoVE (2)

Other Publications (170)

Articles by Jan Deprest in JoVE

 JoVE Medicine

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

1Molecular Virology and Gene Therapy, KU Leuven, 2Department of Woman and Child, KU Leuven, 3Neurobiology and Gene Therapy, KU Leuven, 4Division of Nuclear Medicine, KU Leuven, 5Biomedical NMR Unit/ MoSAIC, KU Leuven

JoVE 4219

We developed a novel surgical approach for intratracheal administration of bioactive agents into the mouse fetus. The delivery route is more efficient in targeting the fetal mouse lungs than the commonly used intra-amniotic injection. This procedure has to date not been described in a mouse model.

 JoVE Medicine

Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

1Division Woman and Child, Department Women, University Hospitals Leuven, 2The Ritchie Centre, Monash Institute of Medical Research, Department of Obstetrics and Gynaecology, Monash University, Victoria, Australia, 3Department of Cardiovascular Sciences, Katholieke Universiteit Leuven, 4Fetal and Perinatal Medicine Research Group, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), 5Maternal-Fetal Medicine Department, ICGON, Hospital Clínic, Universitat de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)

JoVE 50392

We describe examination of fetal cardiac function with contemporary functional fetal echocardiography and fetoplacental Doppler ultrasound using the VisualSonics VEVO 2100 microultrasound in a surgically induced model of intrauterine fetal growth restriction in a rabbit.

Other articles by Jan Deprest on PubMed

Pulmonary Effects of in Utero Tracheal Occlusion Are Dependent on Gestational Age in a Rabbit Model of Diaphragmatic Hernia

The authors investigated the effect of gestational age on lung development and maturation after in utero tracheal occlusion (TO) in a rabbit model of congenital diaphragmatic hernia (CDH).

Ex Vivo Testing of a Temperature- and Pressure-controlled Amnio-irrigator for Fetoscopic Surgery

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.

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

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.

Postnatal Cranial Ultrasonographic Findings in Feto-fetal Transfusion Syndrome

Our objective was a retrospective evaluation of cranial US in survivors of twin pregnancy with feto-fetal transfusion syndrome (FFTS), with knowledge of prenatal treatment and neonatal/postnatal clinical data. In 18 pregnancies with FFTS (January 1996 to May 2000), pregnancy management and outcome, and neonatal clinical/neurological data and follow-up (age of 3-7 months) were documented when available. Postnatal cranial US abnormalities were differentiated in prenatal and peri/postnatal lesions, respectively, in "donor" and "recipient." The statistical analysis used was Mann Whitney U test and Fisher's exact test. Overall pregnancy survival rate was 19 of 36 (53%); mors in utero occurred in five twin members. Gestational age at birth was significantly lower in FFTS after laser coagulation (13 of 18; p<0.05). Initial (

Antenatal Urodynamic Studies in the Fetal Lamb: Experimental Protocol and Preliminary Results

To set up a fetal lamb model for intrauterine fetal urodynamic studies.

Monochorionic Diamniotic Twins: Complications and Management Options

Monochorionic compared with dichorionic twins have disproportionately high fetal loss rates, perinatal mortality and morbidity. This is because of the unpredictable vascular anastomoses and the often asymmetrical distribution of the single placenta between both twins.

Increased Polymorphonuclear Infiltration and Iatrogenic Amniotic Band After Closure of Fetoscopic Access Sites with a Bioactive Membrane in the Rabbit at Midgestation

This study was undertaken to evaluate the efficacy and safety of closing the fetoscopy access site in a midgestational rabbit model by using a commercially available bioactive membrane.

Significance of Secondary Ultrasonographic Endometrial Thickening in Postmenopausal Tamoxifen-treated Women

Complete Chorioamniotic Membrane Separation. Case Report and Review of the Literature

We present a patient who developed complete chorioamniotic membrane separation (CMS) in two consecutive pregnancies. The first pregnancy ended with an intrauterine fetal death at 25 weeks of gestation. The entire separated amniotic sac had twisted around the umbilical cord. In the subsequent pregnancy, a complete CMS was diagnosed at 34 weeks of gestation. In both pregnancies, the patient underwent an early 2nd-trimester genetic amniocentesis. A review of the literature shows that extensive CMS is associated with miscarriage, in utero fetal death, umbilical cord complications, and preterm delivery. Most reported cases occurred after invasive intrauterine procedures.

Fetal Sheep with Tracheal Occlusion: Monitoring Lung Development with MR Imaging and B-mode US

To assess the accuracy of magnetic resonance (MR) imaging in determining fetal lung volume (FLV) and to observe fetal lung development with B-mode ultrasonography (US) and MR imaging.

Pulmonary Effects of Gastroschisis in a Fetal Rabbit Model

Respiratory insufficiency is a significant cause of mortality and morbidity among infants with anterior abdominal wall defects (AWD). The aim of this study was to evaluate the pulmonary effects in a fetal rabbit model where gastroschisis was induced at midgestation. Gastroschisis (GAS) was created in 20 rabbit fetuses on day 22 or 23 of gestation (pseudoglandular phase; term = 31-32 days). The amniotic sacs of 13 fetuses were subjected to hysterotomy and amniotomy only (HYST), while 13 underwent a sham laparotomy which was immediately closed by sutures (SHAM). Eleven nonoperated littermates served as internal controls (CTR). Fetuses were harvested by cesarean section on day 31 of gestation prior to respiration. Pulmonary response was evaluated by left lung to body weight ratio (LWBWR), airway morphometry, and density of type II pneumocytes, as evaluated by the number of surfactant protein B-positive cells. Fetuses from the GAS group had significantly lower body weights than did CTR (P = 0.0129). Of these fetuses, 27% were growth-restricted, i.e., with a body weight under the 10th percentile of the CTR population. There were no differences in left lung weight and LWBWR among the GAS and CTR groups. Moreover, the GAS group had similar alveolar size, alveolar wall thickness, and type II cell density as CTR fetuses. Only mean terminal bronchiolar density (MTBD), which is inversely related to the alveolar space, was slightly increased in the GAS group, but without reaching significance (P = 0.0821). No effect on lung growth and maturation could be demonstrated in this study.

Lung Growth Induced by Prenatal Instillation of Perfluorocarbon into the Fetal Rabbit Lung

The study's aim was to evaluate whether prenatal instillation of perfluorooctylbromide (PFOB, a perfluorocarbon) into the lungs of fetal rabbits leads to increased lung growth. Hysteroamniotomy was performed in eight pregnant New Zealand white rabbits on gestational day 27. In each mother, four fetuses were randomized to undergo either 1) endotracheal intubation and intrapulmonary instillation of 1 ml PFOB, 2) intrapulmonary instillation of 1 ml 0.9% NaCl solution (saline), 3) no fetal manipulation (control), or 4) tracheal occlusion (TO). The distribution of PFOB was documented radiographically. The fetuses were born by cesarean section after 48 h, sacrificed, weighed, and their lungs excised. Fetal lung to body weight ratios (FLBW) were determined, and the lungs were snap frozen for histomorphologic analysis and lung tissue distillation. On macroscopic inspection, PFOB-filled and tracheally-occluded lungs were markedly larger than saline-filled and control lungs. Mean FLBW was higher in fetuses treated with intrapulmonary instillation of PFOB (0.037+/-0.009), compared with fetuses receiving saline (0.027+/-0.008) or the unmanipulated controls (0.028+/-0.008). FLBW was highest after TO (0.049+/-0.008). After 48 h, in-vivo radiographs did not demonstrate any residual PFOB. Average dry fetal left lung weight (in g) was much higher in the TO (0.064+/-0.029) and PFOB (0.062+/-0.016) fetuses compared with the saline (0.054+/-0.017) and control (0.043+/-0.012) groups. Alveolar architecture on microscopy was similar between all groups, although the alveolar septae appeared thicker and more cellular after PFOB treatment and TO. We concluded that prenatal intrapulmonary PFOB instillation leads to increased lung growth in the late gestation rabbit model. Although PFOB instillation resulted in lower wet FLBW than TO, the increase in dry lung weight is comparable. This novel technique may be a less invasive and less noxious treatment strategy for pulmonary hypoplasia associated with diaphragmatic hernia.

Endoscopic Laser Surgery Versus Serial Amnioreduction for Severe Twin-to-twin Transfusion Syndrome

Monochorionic twin pregnancies complicated by severe twin-to-twin transfusion syndrome at midgestation can be treated by either serial amnioreduction (removal of large volumes of amniotic fluid) or selective fetoscopic laser coagulation of the communicating vessels on the chorionic plate. We conducted a randomized trial to compare the efficacy and safety of these two treatments.

Effect of Tracheal Occlusion on Peripheric Pulmonary Vessel Muscularization in a Fetal Rabbit Model for Congenital Diaphragmatic Hernia

This study was undertaken to evaluate the effects on peripheric pulmonary vessel muscularization by tracheal occlusion (TO) performed at different gestational ages in fetal rabbits with surgically induced diaphragmatic hernia.

Fetoscopic Surgery in Triplet Pregnancies: a Multicenter Case Series

The purpose of this study was to evaluate the feasibility of fetoscopic surgery in complicated monochorionic and dichorionic triplet pregnancies.

Host Response After Reconstruction of Abdominal Wall Defects with Porcine Dermal Collagen in a Rat Model

The purpose of this study was to compare the inflammatory response after implantation of Pelvicol with Prolene in a rat model.

Invasive Antenatal Interventions in Complicated Multiple Pregnancies

Multiple pregnancies still pose challenging problems for modern medicine. Complications in monochorionic multiple pregnancies have sparked a revival of fetoscopy as a means surgery on the placenta and umbilical cord. As such, fetoscopic laser coagulation is currently the best first-line treatment for severe twin-to-twin transfusion syndrome. Also, fetoscopic or ultrasound-guided cord coagulation seems to be an effective technique for selective feticide in monochorionic twins, albeit with still considerably higher fetal loss rates compared with selective feticide by potassium chloride injection in dichorionic twins.

Persistent Elevation of Cell-free Fetal DNA Levels in Maternal Plasma After Selective Laser Coagulation of Chorionic Plate Anastomoses in Severe Midgestational Twin-twin Transfusion Syndrome

This study was undertaken to determine whether laser thermocoagulation for twin-twin transfusion syndrome (TTTS) causes increased cell-free fetal DNA levels in maternal plasma, potentially as a result of placental injury.

Postnatal Lung Mechanics, Lung Composition, and Surfactant Synthesis After Tracheal Occlusion Vs Prenatal Intrapulmonary Instillation of Perfluorocarbon in Fetal Rabbits

Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO.

Viable Cervical Pregnancy with Levonorgestrel Containing Intrauterine Device, Treated Successfully with Methotrexate and Mifepristone

Remifentanil for Fetal Immobilization and Maternal Sedation During Fetoscopic Surgery: a Randomized, Double-blind Comparison with Diazepam

Obstetric endoscopy procedures are routinely performed at our institution to treat selected complications of monochorionic twin gestation. We perform these procedures under combined spinal epidural anesthesia plus maternal sedation. In the absence of general anesthesia, fetal immobilization is not achieved. We hypothesized that remifentanil would induce adequate maternal sedation and provide fetal immobilization, which is equal or superior to that induced by diazepam. Fifty-four second trimester pregnant women were included in this randomized, double-blind trial. After combined spinal epidural anesthesia, maternal sedation was initiated using either incremental doses of diazepam or a continuous infusion of remifentanil. Maternal sedation, hemodynamics, side effects, and fetal hemodynamics and immobilization were evaluated before, during, and for 60 min after surgery. Remifentanil produced adequate maternal sedation with mild but clinically irrelevant respiratory depression (respiratory rate 13 +/- 4 breaths/min and Pco(2) 38.6 +/- 4 mm Hg at 40 min of surgery), whereas diazepam resulted in a more pronounced maternal sedation but no respiratory depression (respiratory rate 18 +/- 3 breaths/min and Pco(2) 32.7 +/- 3 mm Hg at 40 min of surgery). Compared with diazepam, fetal immobilization with remifentanil occurred faster and was more pronounced, resulting in improved surgical conditions; the number of gross body and limb movements was 12 +/- 4 (diazepam) versus 2 +/- 1 (remifentanil) at 40 min of surgery. Because of this, the mean (range) duration of surgery was significantly shorter in the remifentanil-treated patients, 60 (54-71) min versus 80 (60-90) min in the diazepam group. We conclude that remifentanil produces improved fetal immobilization with good maternal sedation and only minimal effects on maternal respiration.

Improved Surgical Outcome by Modification of Porcine Dermal Collagen Implant in Abdominal Wall Reconstruction in Rats

We earlier showed in rats that fascial repair with Pelvicol, a porcine dermal collagen implant, was associated with a lesser inflammatory response but lower tensile strength in the early postoperative period as compared to Prolene. Herein we wanted to evaluate whether creation of pores in Pelvicol, facilitating ingrowth of fibrous tissue and vessels, would result in a higher tensile strength at d30 without compromising longer term results.

Laparoscopic Hysterectomy for Benign Diseases

Despite more than 1000 publications on laparoscopic hysterectomy (LH), its role remains difficult to define. LH is not there to replace vaginal hysterectomy, but may be an alternative for abdominal hysterectomy when there are (relative) contraindications for vaginal hysterectomy, including concomitant oophorectomy, previous pelvic surgery and/or risk for adhesions, the larger uterus and nulliparity, and some oncological indications. Randomized trials have demonstrated that, compared to abdominal hysterectomy, LH shortens hospital stay and induces less postoperative pain and quicker recovery at the expense of a longer operation time. LH carries a higher risk for adjacent organ injury, and may be cost-effective, despite higher direct costs, because of the shorter hospital stay and quicker recovery.

Fetal Intervention for Congenital Diaphragmatic Hernia: the European Experience

Fetuses with CDH presenting with liver herniation and a lung area-to-head circumference ratio of less than 1.0 have a high chance for neonatal death due to pulmonary hypoplasia. Fetal tracheal occlusion (TO) prevents egress of lung liquid, which triggers lung growth. In animal experiments, we were able to develop a minimally invasive technique for Fetoscopic Endoluminal Tracheal Occlusion (FETO) with a detachable balloon. In 2001, we demonstrated feasibility of FETO by percutaneous access in fetuses with severe CDH. In a retrospective multicenter review, we obtained LHR measurements and position of the liver in 134 cases of isolated left-sided CDH between 24 and 28 weeks. Eleven patients (8%) with LHR < 1.4 opted for termination. Overall survival of liveborn babies was 47% (58/123). LHR and position of the liver correlated both to survival. Combination of both variables predicted neonatal outcome better: liver up and LHR < 1.0 predicted a survival of 9%. When LHR < 0.6, there were no survivors irrespective of liver position. We could successfully perform endotracheal placement of the balloon in 20 cases at a median gestational age of 26 weeks. The mean duration of the operation was 22 (range 5-54) minutes. In 11 (55%) of these patients, there was postoperative prelabor (ie, <37 weeks) amniorrhexis. Membranes ruptured before 32 weeks in 35%, with a decreasing trend as experience increased. Ultrasound scans after FETO demonstrated an increase in the echogenicity of the lungs within 48 hours 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 after surgery. The median gestation at delivery was 33.2 (range 27-38) weeks, and in 14 (70%) this occurred after 32 weeks. Surgical repair of the diaphragmatic hernia could be done in 13 babies, and in all but 1 the defect was extensive and required the insertion of a patch. Survival to discharge was 50%. These 10 long-term surviving babies are now aged 7 to 26 (median 19) months without known neurologic morbidity. Eight babies died in the neonatal period due to complications of the underlying disease. Two nonsurvivors died from other causes but with appropriately developed lungs. Improved survival coincided with increasing experience, in turn related to reduced incidence of postoperative amniorrhexis, later delivery, and a change in the policy on the timing of removal of the balloon from intrapartum to the prenatal period. Survival in eligible contemporary controls was 1/12 (8%). The presence of liver herniation and a low lung-to-head ratio (LHR <1.0) is a good predictor of poor prognosis at different tertiary centers around the world. Severe CDH may be successfully treated with FETO, which is minimally invasive and may improve postnatal survival.

Comparison of Host Response to Polypropylene and Non-cross-linked Porcine Small Intestine Serosal-derived Collagen Implants in a Rat Model

To compare the host response, architectural integration and tensile strength of polypropylene and porcine small intestine submucosa-derived implants in a rat model.

Percutaneous Fetal Endoscopic Tracheal Occlusion (FETO) for Severe Left-sided Congenital Diaphragmatic Hernia

Diagnosis and Management of Heterokaryotypic Monochorionic Twins

The diagnosis, management, and outcome of six consecutive heterokaryotypic monochorionic twins were evaluated. All suspected cases, based on discordant ultrasound findings, underwent amniocentesis of both sacs. Two cases also had chorionic villous sampling (CVS). Dual amniocentesis was superior to CVS in diagnosing heterokaryotypic monochorionic twins. In four cases, the X-chromosome was involved and autosomal aneuploidy was noted in the others. In five cases, the anomalous twin was selectively reduced by cord coagulation. All pregnancies ended with a phenotypically normal liveborn and all children are developing normally at 1-7 years of age.

Current Consequences of Prenatal Diagnosis of Congenital Diaphragmatic Hernia

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.

Pregnancy and Infant Outcome of 80 Consecutive Cord Coagulations in Complicated Monochorionic Multiple Pregnancies

This study was undertaken to document pregnancy and infant outcome after cord coagulation with laser and/or bipolar as a technique for selective feticide in complicated monochorionic multiple pregnancies.

Intertwin Anastomoses in Monochorionic Placentas After Fetoscopic Laser Coagulation for Twin-to-twin Transfusion Syndrome: is There More Than Meets the Eye?

This study was undertaken to detect missed anastomoses on the chorionic surface as well as hidden connections in the depth of the cotyledons in placentas after laser coagulation for twin-to-twin transfusion syndrome (TTTS) and to correlate these findings to clinical outcome.

Prevalence and Management of Late Fetal Complications Following Successful Selective Laser Coagulation of Chorionic Plate Anastomoses in Twin-to-twin Transfusion Syndrome

This study was undertaken to report on the prevalence and management of late complications in twin-to-twin transfusion syndrome (TTTS) treated by laser therapy when both twins are alive 1 week after surgery.

Prenatal Intervention for Isolated Congenital Diaphragmatic Hernia

We aim to review the recent literature regarding early prenatal prediction of outcome in babies diagnosed with isolated congenital diaphragmatic hernia, as well as results of fetal therapy for this condition.

Circulating Cell-free Fetal Messenger RNA Levels After Fetoscopic Interventions of Complicated Pregnancies

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.

Prenatal Intervention for Isolated Congenital Diaphragmatic Hernia

We aim to review the recent literature regarding early prenatal prediction of outcome in babies diagnosed with isolated congenital diaphragmatic hernia, as well as results of fetal therapy for this condition.

The Biology Behind Fascial Defects and the Use of Implants in Pelvic Organ Prolapse Repair

Implant materials are increasingly being used in an effort to reduce recurrence after prolapse repair with native tissues. Surgeons should be aware of the biology behind both the disease as well as the host response to various implants. We will discuss insights into the biology behind hernia and abdominal fascial defects. Those lessons from "herniology" will, wherever possible, be applied to pelvic organ prolapse (POP) problems. Then we will deal with available animal models, for both the underlying disease and surgical repair. Then we will go over the features of implants and describe how the host responds to implantation. Methodology of such experiments will be briefly explained for the clinician not involved in experimentation. As we discuss the different materials available on the market, we will summarize some results of recent experiments by our group.

Clinical Implications of the Biology of Grafts: Conclusions of the 2005 IUGA Grafts Roundtable

With few exceptions, the current expansion of graft utilization in pelvic reconstructive surgery is not a product of evidence-based medicine. Abdominal sacrocolpopexy and suburethral sling procedures are two situations under which synthetic graft utilization is indicated, based on randomized prospective trials and reported clinical outcomes. Otherwise, indications and contraindications for graft utilization are unclear. Current published data on the biology of synthetic and biologic grafts are limited and overall not very helpful to the reconstructive surgeon who is faced with the selection of a graft for use during a reconstructive procedure. This Roundtable presented the opportunity for a series of basic science researchers to present their data to a group of reconstructive surgeons and provide publishable background information on the various currently available grafts. The occurrence of healing abnormalities after graft implantation is becoming increasingly recognized as a potentially serious problem. To date, definitions and a classification system for healing abnormalities do not exist. Based on the input from basic scientists and experienced surgeons, a simple classification is suggested based on the site of healing abnormality, timing relative to graft implantation, presence of inflammatory changes, and the viscera into which the graft is exposed. Many opportunities for clinical and basic science research exist. As the use of grafts in reconstructive surgery is expanded, surgeons are encouraged to familiarize themselves with currently published data, and determine whether a graft should, or should not be, utilized during a reconstructive procedure, and if so, the type of graft best indicated in each specific clinical situation.

Fetal Lung-to-head Ratio in the Prediction of Survival in Severe Left-sided Diaphragmatic Hernia Treated by Fetal Endoscopic Tracheal Occlusion (FETO)

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.

Fetal Body Volume: Use at MR Imaging to Quantify Relative Lung Volume in Fetuses Suspected of Having Pulmonary Hypoplasia

To retrospectively determine an algorithm based on fetal body volume (FBV) by using magnetic resonance (MR) imaging to calculate relative lung volume in fetuses with normally developed lungs and prospectively assess the use of this algorithm in predicting pulmonary hypoplasia in the late second and early third trimesters for fetuses at risk for pulmonary hypoplasia.

Fetoscopic Surgery: Encouraged by Clinical Experience and Boosted by Instrument Innovation

Today, modern ultrasound equipment and the wide implementation of screening programmes allow the timely diagnosis of many congenital anomalies. For some of these, fetal surgery may be a life-saving option. In Europe, open fetal surgery became poorly accepted because of its invasiveness and the high incidence of postoperative premature labour and rupture of the fetal membranes. In the 1990s, the merger of fetoscopy and advanced video-endoscopic surgery formed the basis for endoscopic fetal surgery. We review the current applications of fetal surgery via both methods of access. The first clinical fetoscopic surgeries were interventions on the umbilical cord and the placenta, often referred to as obstetrical endoscopy. The outcome of a randomized clinical trial demonstrating that fetoscopic laser coagulation of chorionic plate vessels is the most effective treatment for twin-twin transfusion syndrome (TTTS) has revived interest in endoscopic fetal therapy. Operating on the fetus is another more challenging enterprise. Clinical fetal surgery programmes were virtually non-existent in Europe until minimally invasive fetoscopic surgery made such operations clinically possible as well as maternally acceptable. At present, most experience has been gathered with fetal tracheal occlusion as a therapy for severe congenital diaphragmatic hernia. As in other fields, minimally invasive surgery has pushed back boundaries and now allows safe operations to be performed on the fetal patient. Whereas minimal access seems to solve the problem of preterm labour, all procedures remain invasive, and carry a risk to the mother and a substantial risk of preterm prelabour rupture of the membranes (PPROM). The latter problem may prove to be a bottleneck for further developments, although treatment modalities are currently being evaluated.

Cytokine Production Following Experimental Implantation of Xenogenic Dermal Collagen and Polypropylene Grafts in Mice

We earlier showed that xenogenic Pelvicol (Bard, Olen, Belgium) implants induce a lesser inflammatory response than Prolene (Johnson and Johnson, Dilbeek, Belgium). The purpose of this study was to determine cytokine profiles in the host immune responses to Pelvicol in a mouse model. The hypothesis was that Pelvicol would induce a "T-helper2" (Th2) rather than T-helper1 (Th1) type of inflammatory response.

Tensile Strength and Host Response Towards Different Polypropylene Implant Materials Used for Augmentation of Fascial Repair in a Rat Model

We compared inflammatory response, fibrosis and biomechanical properties of different polypropylene materials from one manufacturer (Tyco Healthcare) in a rat model for primary fascial repair. Full-thickness abdominal wall defects were primarily repaired using 'overlay' technique. Multifilament implants were Surgipro SPM and SPMW, the latter a wider-weave type of the former. Monofilament SPMM implants and polypropylene suture repair (Surgipro II) served as controls. Explants were evaluated macroscopically and changes in thickness, shrinkage and tensile strength were measured. Inflammatory and connective tissue response was assessed on haematoxylin-eosin and Movat stains. Immunohistochemistry was done to localise rat macrophages/monocytes. Multifilament materials induced a shorter acute inflammatory response and more pronounced chronic inflammatory reaction compared to monofilament implants. Macrophages could be found deep in interstices 7.5 by 12.5 microm. No difference in collagen deposition and neovascularisation was observed. At 90 days time point, explants reconstructed with tighter woven multifilament SPM were weaker than sutured or SPMM controls. Overall shrinkage of 10% was comparable for all groups.

Tensile Strength and Host Response Towards Silk and Type I Polypropylene Implants Used for Augmentation of Fascial Repair in a Rat Model

We compared host response, architectural integration and tensile strength of two different macroporous silk constructs to a polypropylene type I implant in a rat model for augmentation of primary fascial defect repair.

Modeling Severely Discordant Hematocrits and Normal Amniotic Fluids After Incomplete Laser Therapy in Twin-to-twin Transfusion Syndrome

Our objective was to explain the clinical presentations of sustained arteriovenous anastomotic transfusion of blood after incomplete laser therapy in twin-to-twin transfusion syndrome (TTTS). We extended our mathematical model of TTTS by adding the dynamics of hematocrit, and simulated incomplete laser therapy, first, by leaving one patent opposite arteriovenous anastomosis from the recipient to the donor and, second, by leaving one patent arteriovenous anastomosis from the donor to the recipient. In both simulations we reproduced the clinical observation of severe hematocrit discordance preceding delayed amniotic fluid imbalance. In conclusion, incomplete laser therapy may cause a severe circulatory imbalance between the twins which presents predominantly as discordant hematocrits rather than discordant amniotic fluid volumes as in primary TTTS. These results imply that the anemia-polycythemia sequence is a sensitive mechanism to identify transfusion reversal after complicated laser therapy, confirming the suggested role of middle cerebral artery peak systolic velocity Doppler measurements as a useful method of follow-up.

T2 Quantifications of Lungs in the Fetal Lamb with Experimentally-induced Congenital Diaphragmatic Hernia

As an aid to evaluate lung hypoplasia, we investigated the difference between T2 value in fetal lungs of lambs with surgically-induced left-sided diaphragmatic hernia (DH) and gestational age (GA)-matched control littermates (normal [NL]).

Posterior Intravaginal Slingplasty with Preservation of the Uterus: a Modified Surgical Technique in a Young Myelomeningocele Patient

We report a case of uterine prolapse in a young woman, treated by posterior intravaginal slingplasty with preservation of the uterus as a feasible and safe surgical procedure. Posterior intravaginal slingplasty is commonly used to correct vaginal vault prolapse, but may be a valuable alternative to correct uterine prolapse. We compare this technique to other techniques to correct uterine prolapse.

Determination of the Full Dose-response Relation of Intrathecal Bupivacaine, Levobupivacaine, and Ropivacaine, Combined with Sufentanil, for Labor Analgesia

Ropivacaine and levobupivacaine are local anesthetics that produce less motor block and greater sensory-motor separation when compared with equal milligram doses of bupivacaine. Although minimum local analgesic concentration studies suggested that they are less potent than bupivacaine, full dose-response studies have not been performed. The current trial describes the dose-response relation of levobupivacaine, ropivacaine, and bupivacaine, combined with sufentanil, when used for intrathecal labor analgesia.

Enhancing Sealing of Fetal Membrane Defects Using Tissue Engineered Native Amniotic Scaffolds in the Rabbit Model

The purpose of this study was to compare the efficacy of native engineered amniotic scaffolds (AS) and polyesterurethane scaffolds (DegraPol) and document wound healing response when sealing iatrogenic fetal membrane defects in the rabbit model.

Fetal Gene Transfer with Lentiviral Vectors: Long-term in Vivo Follow-up Evaluation in a Rat Model

The purpose of this study was to evaluate the long-term expression of a transgene and subsequent immune response after the injection of lentiviral vectors in a fetal rats.

Lung Tissue Mechanics Predict Lung Hypoplasia in a Rabbit Model for Congenital Diaphragmatic Hernia

Several animal models have been proposed to study the pathophysiology of congenital diaphragmatic hernia (CDH). Surgical induction of CDH in fetal rabbits during the pseudoglandular phase has been shown to induce severe pulmonary hypoplasia, but functional studies in this model are scarce. We aimed to measure neonatal pulmonary impedance and related it to the severity of lung hypoplasia. CDH was surgically created in rabbits at 23 days of gestation. Following cesarean delivery at term (31 days) pups were subjected to measurement of total lung capacity (TLC), lung to body weight ratio (LBWR) and lung impedance by forced oscillation technique (FOT). Airway resistance (R(aw)), tissue elastance (H(L)), tissue damping (G(L)), and hysteresivity (eta) (G(L)/H(L)) were calculated from impedance data. Twelve CDH fetuses and 15 controls were available for final analysis. LBWR and TLC were significantly lower in the CDH group compared to gestational and age matched controls (P<0.001). R(aw), H(L), and G(L) were significantly increased in CCDH fetuses. eta and H(L) best reflected lung hypoplasia (LBWR) (r(2) = 0.42 and 0.43; P=0.001), indicating a dominant contribution of lung tissue mechanics to CDH-induced lung hypoplasia. We successfully introduced lung impedance measurement by FOT in neonatal rabbits. Following surgical induction of CDH in the pseudoglandular phase, they have, next to morphological evidence of pulmonary hypoplasia, changes in lung mechanics. Our results for lung tissue mechanics support the concept of delayed pulmonary tissue modeling. We propose to employ functional studies in future experiments when evaluating prenatal interventions aimed at reversing pulmonary hypoplasia.

Lung Volumes in Fetuses with Congenital Diaphragmatic Hernia: Comparison of 3D US and MR Imaging Assessments

To prospectively compare three-dimensional (3D) ultrasonography (US) and magnetic resonance (MR) imaging in the assessment of lung volumes in fetuses with congenital diaphragmatic hernia.

The Baboon As a Research Model for the Study of Endometrial Biology, Uterine Receptivity and Embryo Implantation

The process of embryo implantation includes attachment of the embryo to the endometrium and penetration through the epithelial layer, decidualization of the basement membrane, invasion of the uterine stroma and access to blood supply. This implantation process is very different in humans when compared to pigs, cattle or rodents. The process of invasion in humans where the embryo gets embedded in decidual tissue and in spiral arteries is more aggressive, but otherwise similar to the process of implantation and invasion in non-human primates such as rhesus monkeys and baboons. For ethical reasons, it is unacceptable to study directly the process of embryo implantation in women, and to this day, this remains one of the 'black boxes' of reproductive science. Indeed for many clinicians practicing reproductive medicine, in fertility centers, the most difficult question and of concern asked by patients is: 'Why do my healthy appearing embryos not implant: is there a problem with my endometrium or uterus?' The olive baboon (Papio anubis anubis) is an excellent animal model for reproductive research. In contrast with smaller non-human primates like rhesus monkeys or cynomolgus monkeys, it is possible in baboons to use transcervical uterine probes (curettes, catheters and hysteroscopic equipment) to perform endometrial biopsy, embryo flushing or transfer and hysteroscopy in a non-invasive way. This can be done easily in multiparous baboons during menstruation, but may be more difficult at the end of the follicular phase (maximal perineal swelling impedes vaginal/cervical access) or during the luteal phase (narrow cervix), in nulliparous baboons and in animals with abnormal internal genitals. In this paper we present an overview regarding the potential of the baboon model to study in vivo uterine receptivity and embryo implantation using invasive and non-invasive approaches.

Prenatal Cleft Lip and Maxillary Alveolar Defect Repair in a 2-step Fetal Lamb Model

As there is no satisfying animal model simulating the complex cleft lip and palate anatomy in a standardized defect on one hand, and comprising the possibilities for extensive surgical procedures on the other hand, an improved fetal lamb model for cleft surgery was developed.

Placental Sharing, Birthweight Discordance, and Vascular Anastomoses in Monochorionic Diamniotic Twin Placentas

The purpose of this study was to examine the relationship between placental territory and birthweight discordance and vascular anastomoses in monochorionic diamniotic twin placentas from pregnancies that were not complicated by twin-to-twin transfusion syndrome with 2 liveborn twins.

Effect of Maternal Administration of Betamethasone on Peripheral Arterial Development in Fetal Rabbit Lungs

Glucocorticoids promote lung maturation and reduce the incidence of respiratory distress syndrome in premature newborns. We hypothesized that betamethasone (BM), which is known to induce thinning of the alveolar walls, would also thin the arterial media and adventitia of intra-parenchymatic vessels in developing rabbit lungs.

Fetal Lung Volume After Endoscopic Tracheal Occlusion in the Prediction of Postnatal Outcome

The objective of the study was to investigate the volume response of the contralateral lung in the prediction of postnatal outcome in fetuses with congenital diaphragmatic hernia (CDH) treated by fetoscopic endotracheal occlusion (FETO).

Chorionic Membrane Separation Following Fetoscopy. A Role for Collagen Plugging of the Fetoscopic Access Site? Commentary on Chang Et Al: Transient Chorioamniotic Membrane Separation After Fetoscope Guide Laser Therapy for Twin-twin Transfusion Syndrome: a Case Report (Fetal Diagn Ther 2007;22:180-182)

Prediction of Outcome in Isolated Congenital Diaphragmatic Hernia and Its Consequences for Fetal Therapy

Congenital diaphragmatic hernia (CDH) can be diagnosed in the prenatal period either as part of other anomalies or as an isolated birth defect. The clinical impact of this surgically correctable anatomical defect lies in its impairment of lung development. Currently, up to 30% of babies with isolated CDH die from the consequences of lung hypoplasia and/or pulmonary hypertension. Antenatal prediction of outcome essentially relies on the measurement of lung development by the so-called lung area to head circumference ratio (LHR). By expressing observed LHR as a proportion of what is normally expected (O/E LHR) at a certain time point in gestation, a prediction of outcome can be made. When O/E LHR is less than 25% of the normal, postnatal death is very likely. In these cases, an antenatal intervention that can improve lung development is currently offered. Currently, this is done by percutaneous fetal endoscopic tracheal occlusion (FETO) with a balloon at 26-28 weeks, and reversal of occlusion at 34 weeks. The feasibility and safety of percutaneous FETO have been established and the procedure seems to improve outcome in severe CDH. The lung response to, and outcome after, FETO depend on pre-existing lung size respectively gestational age at birth. Prenatal decision making can therefore be stratified according to measured lung size.

Fate of Collagen-based Implants Used in Pelvic Floor Surgery: a 2-year Follow-up Study in a Rabbit Model

The purpose of this study was to compare the long-term host response to 2 different collagen matrices versus macroporous polypropylene mesh.

Fetal Body Volume at MR Imaging to Quantify Total Fetal Lung Volume: Normal Ranges

To prospectively determine normal ranges of total fetal lung volume (TFLV) based on fetal body volume (FBV) and to determine whether prediction of TFLV based on such ranges is independent of fetal biometric indexes.

Monochorionic and Dichorionic Twin Pregnancies Discordant for Fetal Anencephaly: a Systematic Review of Prenatal Management Options

The aim of this study was to evaluate the effect of selective feticide (SF) compared to expectant management (EM) on perinatal outcome in dichorionic and monochorionic twins discordant for anencephaly. For this purpose, we conducted a systematic review of literature and added ten unpublished cases. As a result, we found that in dichorionic twins, mean gestational age (GA) at birth in the SF group was 38.0 weeks versus 34.9 weeks (P = 0.0002). Mean birth weight was 2922 g in the SF group versus 2474 g (P = 0.03). In monochorionic twins, mean GA at birth was 35.2 weeks versus 32.7 weeks (P = 0.1). Mean birth weight was 2711 g versus 1667 g (P = 0.0001). We conclude that while SF does not reduce perinatal mortality, it does result in significantly longer gestations and higher birth weight, and appears to be the management of choice in dichorionic twins discordant for anencephaly. In monochorionic twins, SF also increases birth weight, but in view of the complexity of this group, no clear recommendations can be made.

Enrichment of Collagen Plugs with Platelets and Amniotic Fluid Cells Increases Cell Proliferation in Sealed Iatrogenic Membrane Defects in the Foetal Rabbit Model

The purpose of this study was to evaluate cell proliferation in platelet-enriched collagen plugs with and without addition of amniotic fluid-derived heterologous foetal cells to seal an iatrogenic membrane defect in the foetal rabbit model.

Effects of Maternal Retinoic Acid Administration in a Congenital Diaphragmatic Hernia Rabbit Model

Maternal retinoid administration has beneficial effects on lung development in the nitrofen rodent toxic model of congenital diaphragmatic hernia (DH). We wanted to investigate the effects in a surgical model, where the retinoid signaling pathway is not primarily disrupted by the toxic agent. We created DH in fetal rabbits at day 23 of gestation, administrated to the does all trans-retinoic acid (ATRA) or vehicle (VHC) intramuscularly for 8 consecutive days and harvested normal and operated (DH) fetuses at 31 d (n = 7 in each group). Normal lungs exposed to ATRA had increased surfactant protein mRNA levels without change in type II pneumocyte density. There was no measurable effect on lung-to-body weight ratio and airway morphometry by ATRA. In DH lungs (DH/VHC) surfactant protein mRNA levels were increased, as well as the density of type II pneumocytes. When supplemented with ATRA (DH/ATRA) these parameters returned to normal (VHC). Cell proliferation or apoptosis were not influenced by ATRA supplementation. In conclusion, maternal ATRA supplementation does not affect gross anatomic, morphologic or proliferation indices in hypoplastic lungs related to surgically induced DH in rabbit. However, ATRA lowers surfactant protein expression and normalizes type I/II pneumocyte ratio to what is observed in normal lungs.

Anesthesia for Fetal Surgery

To look at different anesthetic approaches to different surgical techniques used in fetal procedures and the influence of maternal and fetal factors on anesthetic management.

Fetal Surgery for Anesthesiologists

We aimed to review the current clinical status and advances in endoscopic and open surgical interventions on the fetus in terms of indications, technical aspects and reported outcomes.

The Outcome of Monochorionic Diamniotic Twin Gestations in the Era of Invasive Fetal Therapy: a Prospective Cohort Study

The purpose of this study was to document pregnancy and neonatal outcome of monochorionic diamniotic twin pregnancies.

The Role of Ultrasound Examination in the First Trimester and at 16 Weeks' Gestation to Predict Fetal Complications in Monochorionic Diamniotic Twin Pregnancies

The purpose of this study was to determine the value of ultrasound examination in the first trimester and at 16 weeks to predict fetal complications in monochorionic diamniotic (MCDA) twin pregnancies, defined as the occurrence of either twin-to-twin transfusion syndrome, severe discordant growth, or intrauterine death.

Clinical Outcome and Placental Characteristics of Monochorionic Diamniotic Twin Pairs with Early- and Late-onset Discordant Growth

The purpose of this study was to examine the clinical and placental characteristics of monochorionic diamniotic twin pregnancies with early-onset discordant growth diagnosed at 20 weeks, late-onset discordant growth diagnosed at 26 weeks or later, and concordant growth.

Effects of Betamethasone on Peripheral Arterial Development in Term Fetal Rabbit

Glucocorticoids are given antenatally to promote pulmonary epithelial maturation and prevent respiratory distress syndrome in premature newborns. In contrast to airway changes, effects on vessels are less documented. We hypothesized that antenatal betamethasone (BM) administration promotes vascular development. Does received either a course of BM = 0.05 mg/kg/day (18 does, 70 fetuses), BM = 0.1 mg/kg/day (20 does, 75 fetuses), or saline (11 does, 92 fetuses) starting on d25, 26 (canalicular stage), d27, d28 (saccular stage), and d29 (alveolar stage) of gestation. In total 236 fetuses from 49 does were examined at term (d31) in terms of vascular development. Lung specimens were weighed and formalin fixed for morphometry. We determined differences in fetal body, liver and lung weight, proportionate medial thickness, muscularization of intra-acinar vessels, number of vessels under 100 microm, as well as immunoreactivity to Flk-1 in vascular smooth muscle and endothelial cells. A dose-dependent reduction in neonatal body and organ weight was observed in fetuses exposed to BM at d25. In contrast, term liver weight increased after late administration of BM (d28, 29). There was a dose- and time-dependent thinning of the pulmonary arterial media, which coincided with a decreased proportion of intra- and pre-acinar muscularized arteries (ED

Prenatal Diagnosis, Prediction of Outcome and in Utero Therapy of Isolated Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) can be associated with genetic or structural anomalies with poor prognosis. In isolated cases, survival is dependent on the degree of lung hypoplasia and liver position. Cases should be referred in utero to tertiary care centers familiar with this condition both for prediction of outcome as well as timed delivery. The best validated prognostic indicator is the lung area to head circumference ratio. Ultrasound is used to measure the lung area of the index case, which is then expressed as a proportion of what is expected normally (observed/expected LHR). When O/E LHR is < 25% survival chances are < 15%. Prenatal intervention, aiming to stimulate lung growth, can be achieved by temporary fetal endoscopic tracheal occlusion (FETO). A balloon is percutaneously inserted into the trachea at 26-28 weeks, and reversal of occlusion is planned at 34 weeks. Growing experience has demonstrated the feasibility and safety of the technique with a survival rate of about 50%. The lung response to, and outcome after FETO, is dependent on pre-existing lung size as well gestational age at birth. Early data show that FETO does not increase morbidity in survivors, when compared to historical controls. Several trials are currently under design.

In Utero Acquired Limb Ischemia in Monochorionic Twins with and Without Twin-to-twin Transfusion Syndrome

To report on the occurrence of in utero acquired limb ischemia in two referral institutions managing monochorionic (MC) twins with and without twin-to-twin transfusion syndrome (TTTS) and estimate its prevalence.

Feasibility of in Utero Telemetric Fetal ECG Monitoring in a Lamb Model

If fetal ECG (fECG) devices could be miniaturized sufficiently, one could consider their implantation at the time of fetal surgery to allow permanent monitoring of the fetus and timely intervention in the viable period. We set up an experiment to evaluate the feasibility of in utero direct fECG monitoring and telemetric transmission using a small implantable device in a lamb model.

Immunohistochemistry Using an Antibody to Unphosphorylated Connexin 43 to Identify Human Myometrial Interstitial Cells

Myometrial smooth myocytes contract as a result of electrical signalling via a process called excitation-contraction coupling. This process is understood in great detail at the cellular level but the generation and coordination of electrical signals throughout the myometrium are incompletely understood. Recent evidence concerning the vital role of interstitial cells of Cajal in tissue-level signalling in gastrointestinal tract, and the presence of similar cells in urinary tract smooth muscle may be relevant for future research into myometrial contractility but there remains a lack of evidence regarding these cells in the myometrium.

Maternal Administration of Betamethasone Inhibits Proliferation Induced by Fetal Tracheal Occlusion in the Nitrofen Rat Model for Congenital Diaphragmatic Hernia: a Placebo-controlled Study

Fetal tracheal occlusion (TO) is offered to fetuses with severe pulmonary hypoplasia due to congenital diaphragmatic hernia (CDH). TO induces lung growth, but even when performed minimally invasive, there is a risk for iatrogenic preterm delivery. Whenever this is anticipated, maternal glucocorticoids (GC) may be given to enhance lung maturation. The pulmonary effects of GC in fetuses with CDH that underwent TO are yet poorly defined. Therefore, we conducted a placebo-controlled study in the nitrofen (NF) rat model for CDH.

[Antenatal Prediction of Pulmonary Hypoplasia and Intrauterine Treatment by Endoscopic Fetal Tracheal Occlusion in Severe Isolated Congenital Diaphragmatic Hernia]

Congenital diaphragmatic hernia (CDH) affects one in 2500 to 5000 births and can be detected in utero by means of ultrasound screening Associated structural problems aggravate the prognosis. The survival rate is 70% or more for cases managed in tertiary care centers. The commonest causes of neonatal death in this setting are pulmonary hypoplasia and pulmonary hypertension. Prenatal imaging findings can now accurately predict postnatal outcome, based mainly on ultrasound determination of the lung-to-head ratio and liver position. This information can be used to counsel patients. In severe cases, prenatal intervention can reverse pulmonary hypoplasia. We review current data on prenatal prediction of neonatal survival. We also discuss experimental and clinical data on the benefits of fetal tracheal occlusion. The TOTAL trial (Tracheal Occlusion To Accelerate Lung growth) is currently ongoing in Europe.

Antenatal Prediction of Lung Volume and In-utero Treatment by Fetal Endoscopic Tracheal Occlusion in Severe Isolated Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a severe malformation with an overall survival between 30% and 90%. Survival in the presence of associated malformations is very low. The condition should be detected in ultrasound screening programmes, but whether and how prenatal imaging can accurately predict outcome remains a matter of debate. Predictions based on the lung area:head circumference ratio and liver position are best studied. This information is highly relevant in counselling patients, leaving to severe cases the option of termination of pregnancy as experimental prenatal intervention aiming to reverse pulmonary hypoplasia. The purpose of this review is to update current knowledge regarding predictive value of prenatal assessment in terms of neonatal survival. We will also discuss experimental evidence and clinical data regarding fetal tracheal occlusion.

Cefazolin Pharmacokinetics in Maternal Plasma and Amniotic Fluid During Pregnancy

To study cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy.

Medium-term Anatomic and Functional Results of Laparoscopic Sacrocolpopexy Beyond the Learning Curve

Limited prospective data on the anatomic and functional outcome after laparoscopic sacrocolpopexy (LSC) are available in the literature.

The Effect of Fetal Tracheal Occlusion on Lung Tissue Mechanics and Tissue Composition

Fetal tracheal occlusion (TO) is currently used to treat severe cases of congenital diaphragmatic hernia (DH). Clinical and experimental studies suggest an improved postnatal outcome, but lung tissue mechanics after TO have not been studied. We determined the effect of TO on mechanical impedance and lung tissue components in a rabbit model for DH. At 23 days of gestation (term = 31 days) either a sham thoracotomy or a diaphragmatic defect was induced. DH fetuses were randomly assigned to undergo 5 days later TO. Fetuses were delivered by term cesarean section to determine lung to body weight ratio (LBWR), dynamic lung mechanics and lung impedance. Airway resistance (R(aw)), elastance (H(L)), tissue damping (G(L)) and hysteresivity (G(L)/H(L)) were calculated from impedance data. Collagen I and III and elastin were quantified histologically. LBWR was significantly increased by TO compared to DH (P < 0.001) and resistance and compliance of the respiratory system (R(rs), C(rs)) were improved as well. TO resulted in a significant decrease of R(aw) comparable to observations in sham-fetuses, without effect on lung tissue mechanics H(L), G(L) and hysteresivity. This coincides with a significant decrease of collagen I, III and elastin in comparison to DH fetuses. In this first report on lung tissue mechanics in a rabbit model of DH, TO had a substantial effect on tissue morphology yet this was not mirrored in lung mechanics. We conclude that the effect of TO on lung mechanics without in utero reversal of occlusion, is dominated by airway remodeling.

Experimental Comparison of Abdominal Wall Repair Using Different Methods of Enhancement by Small Intestinal Submucosa Graft

To assess the biomechanical properties of full-thickness abdominal wall defects, either using Native tissues, with or without Overlay, and by substitution of the Defect by small intestinal submucosa mesh.

Risk Factors for Neurodevelopment Impairment in Twin-twin Transfusion Syndrome Treated with Fetoscopic Laser Surgery

To estimate the risk factors for adverse long-term neurodevelopment outcome in twin-twin transfusion syndrome treated with laser surgery.

Survival After Laser Surgery for Twin-to-twin Transfusion Syndrome: when Are They out of the Woods?

Severe, progressive twin-to-twin transfusion syndrome (TTTS) is associated with near-100% mortality if left untreated. Endoscopic laser ablation of placental vessels (ELA) is associated with 75% to 80% survival of at least one twin. The actuarial risk of fetal demise after ELA has not yet been described.

Ultrasound Prediction of Intertwin Birth Weight Discordance in Monochorionic Diamniotic Twin Pregnancies

To estimate the accuracy of ultrasound to predict birth weight (BW) and BW discordance in monochorionic diamniotic (MCDA) twin pregnancies.

The Effect of Extracellular Adenosine Triphosphate on the Spontaneous Contractility of Human Myometrial Strips

Extracellular ATP is involved in cell-cell signalling in a variety of tissues but its effects in tissue level signalling in the myometrium have been poorly studied to date. We hypothesised that extracellular ATP was involved in the control of myometrial contractile frequency and/or force.

Assessment of Fetal Cardiac Function Before and After Therapy for Twin-to-twin Transfusion Syndrome

We sought to assess fetal cardiac function in monochorionic twins before and after therapy for twin-to-twin transfusion syndrome (TTTS) and compare it with control subjects.

Cefazolin Plasma Protein Binding Saturability During Pregnancy

This article aims to document cefazolin (CFZ) plasma binding and its covariates during pregnancy and compare these observations with previously reported observations in nonpregnant adults. Maternal CFZ plasma samples were collected during in utero surgery. The unbound CFZ fraction was reported by median and range. Correlation (Spearman) and multiple regression were used to identify covariates (total CFZ concentration, albuminemia, gestational age) of the unbound CFZ fraction. Observations during pregnancy were compared with observations in nonpregnant adults (unpaired t test, multiple regression). Plasma (N = 130) samples were collected during 30 interventions. The median unbound CFZ fraction was 0.25 (range 0.14-0.41). Correlations between the unbound CFZ fraction and total CFZ plasma concentration (0.46), time after administration (-0.38), albuminemia (-0.39) and gestational age (-0.19) were statistically significant. The median unbound CFZ fraction was higher during pregnancy when compared to observations in nonpregnant adults (0.25 vs. 0.19, P < 0.001). In a multiple-regression model, total plasma CFZ concentration and albuminemia were covariates of the unbound CFZ fraction (r(2) = 0.4). The concept of saturability of CFZ plasma protein binding has been confirmed during pregnancy, but the free CFZ fraction is higher, likely explained by the lower albuminemia during pregnancy.

The Effect of Maternal Betamethasone and Fetal Tracheal Occlusion on Pulmonary Vascular Morphometry in Fetal Rabbits with Surgically Induced Diaphragmatic Hernia: a Placebo Controlled Morphologic Study

We studied the vascular effects of betamethasone (BM) and/or tracheal occlusion (TO) in fetal rabbits with surgically induced congenital diaphragmatic hernia (CDH).

The Pregnancy and Long-term Neurodevelopmental Outcome of Monochorionic Diamniotic Twin Gestations: a Multicenter Prospective Cohort Study from the First Trimester Onward

We sought to document the pregnancy and neurodevelopmental outcome in monochorionic diamniotic twin pregnancies and to identify risk factors for death and impairment.

Implementation of Laparoscopic Sacrocolpopexy--a Single Centre's Experience

The aim of this study was to describe the learning curve of a single surgeon to achieve the ability to perform a complication-free and anatomically successful laparoscopic sacrocolpopexy (LSC).

Evidence and Patterns in Lung Response After Fetal Tracheal Occlusion: Clinical Controlled Study

To prospectively assess changes in lung volume in fetuses with isolated severe congenital diaphragmatic hernia (CDH) after fetoscopic endoluminal tracheal occlusion (FETO) compared with those in fetuses with CDH of variable severity who were expectantly managed.

Changing Perspectives on the Perinatal Management of Isolated Congenital Diaphragmatic Hernia in Europe

Congenital diaphragmatic hernia (CDH) should be diagnosed in the prenatal period and prompt referral to a tertiary referral center for imaging, genetic testing, and multidisciplinary counseling. Individual prediction of prognosis is based on the absence of additional anomalies, lung size, and liver herniation. In severe cases, a prenatal endotracheal balloon procedure is currently being offered at specialized centers. Fetal intervention is now also offered to milder cases within a trial, hypothesizing that this may reduce the occurrence of bronchopulmonary dysplasia in survivors. Postnatal management has been standardized by European high-volume centers for the purpose of this and other trials.

Impaction After Partial Expulsion of a Neglected Pessary

Vaginal pessaries are effective for treating pelvic organ prolapse, and severe complications are rare. We describe an exceptional case of pessary impaction with partial expulsion.

Porous Acellular Porcine Dermal Collagen Implants to Repair Fascial Defects in a Rat Model: Biomechanical Evaluation Up to 180 Days

To investigate the biomechanical properties of porous collagen matrices in a rat abdominal wall defect model.

Medium Term Outcome of Laparoscopic Sacrocolpopexy with Xenografts Compared to Synthetic Grafts

We compared the medium term anatomical and subjective outcome, and graft related complications after sacrocolpopexy for apical vaginal prolapse using xenogenic or polypropylene grafts.

Insulin-like Growth Factor-II Regulates Maternal Hemodynamic Adaptation to Pregnancy in Rats

The relationship between maternal plasma volume (PV) expansion and fetal growth is well established, but the underlying mechanisms remain unclear. Here, we examined the influence of maternal body weight and fetoplacental mass on gestational PV increment in the rat. Because IGF-I and IGF-II have growth-promoting and vasoactive properties, their relationship to PV expansion and fetoplacental growth was also studied. In normal rats, the gradual expansion of PV (+35% at day 22, i.e., term) was accompanied by a rise in circulating IGF-II (+45%) and a considerable drop in IGF-I (-73%). Increased maternal body weight induced by an obesogenic diet did not influence PV and circulating IGFs compared with rats on the standard diet. Combining the results from both diets, circulating IGF-II was the principal correlate of PV. A second experiment examined the effect of fetoplacental mass reduction by surgically removing half of the gestational sacs at day 16. This procedure reduced maternal PV and circulating IGF-II at term by 14% and 20%, respectively. We then investigated the effect of a constant infusion of IGF-II (1 mgxkg(-1)xday(-1)) from day 16, which raised circulating IGF-II by 38% and found increased PV (+19%) and a larger placental trophospongial area (+29%) at term. Our results indicate that the placenta, the primary source of IGF-II synthesis in pregnancy, drives PV expansion, and that IGF-II is among the regulatory factors of the gestational PV increment. Further studies should clarify whether IGF-II directly affects vascular function and/or indirectly promotes the secretion of placenta-derived vasoactive substances.

Methods for Prenatal Assessment of Fetal Cardiac Function

Fetal cardiac function is increasingly recognized as a marker of disease severity and prognosis in selected fetal conditions. Magnetic resonance imaging (MRI) has been used in experimental (animal) fetal cardiology but the lack of a noninvasive fetal electrocardiogram (ECG) to trigger image acquisition remains a major limiting factor precluding its application in humans. Fetal medicine specialists are therefore limited to ultrasound to evaluate human fetal cardiac function. In this review, we aim to provide a complete overview of the different ultrasound techniques that can be used for fetal cardiac function assessment and we discuss their (theoretical) strengths and shortcomings. Conventional methods include M-mode assessment of ventricular contractility and Doppler assessment of the precordial veins and cardiac output (CO). More recent techniques such as the measurement of the myocardial performance index (MPI), myocardial motion analysis with tissue Doppler, speckle tracking and three-dimensional (3D) ultrasound techniques are also discussed.

Sacrocolpopexy Using Xenogenic Acellular Collagen in Patients at Increased Risk for Graft-related Complications

We studied the long-term anatomical and functional outcome following sacrocolpopexy for apical vaginal prolapse using xenogenic grafts in a population at increased risk for graft-related complications (GRCs).

Amniotic Fluid Markers of Fetal Cardiac Dysfunction in Twin-to-twin Transfusion Syndrome

The objective of the study was to determine whether cardiac troponin T (cTnT) and natriuretic peptides can be isolated from the amniotic fluid (AF) of pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) and whether they correlate with fetal echocardiographic findings and recipient survival.

Fetal Surgery is a Clinical Reality

An increasing number of fetal anomalies are being diagnosed prior to birth, some of them amenable to fetal surgical intervention. We discuss the current clinical status and recent advances in endoscopic and open surgical interventions. In Europe, fetoscopic interventions are widely embraced, whereas the uptake of open fetal surgery is much less. The indications for each access modality are different, hence they cannot substitute each other. Although the stage of technical experimentation is over, most interventions remain investigational. Today there is level I evidence that fetoscopic laser surgery for twin-to-twin transfusion syndrome is the preferred therapy, but this operation actually takes place on the placenta. In terms of surgery on the fetus, an increasingly frequent indication is severe congenital diaphragmatic hernia as well as myelomeningocele. Overall maternal safety is high, but rupture of the membranes and preterm delivery remain a problem. The increasing application of fetal surgery and its mediagenicity has triggered the interest to embark on fetal surgical therapy, although the complexity as well as the overall rare indications are a limitation to sufficient experience on an individual basis. We plead for increased exchange between high volume units and collaborative studies; there may also be a case for self-regulation. Inclusion of patients into trials whenever possible should be encouraged rather than building up casuistic experience.

Albumin As an Adjunct to Tracheal Occlusion in Fetal Rats with Congenital Diaphragmatic Hernia: a Placebo-controlled Study

We sought to investigate effects of intratracheal albumin injection prior to tracheal occlusion (TO) on lung proliferation in fetal rats with nitrofen-induced congenital diaphragmatic hernia.

Validity, Reliability and Responsiveness of a Dutch Version of the Prolapse Quality-of-life (P-QoL) Questionnaire

We aimed to test validity, reliability and responsiveness of a Dutch version of a prolapse quality-of-life questionnaire (P-QoL).

Injectable Candidate Sealants for Fetal Membrane Repair: Bonding and Toxicity in Vitro

This study was undertaken to test injectable surgical sealants that are biocompatible with fetal membranes and that are to be used eventually for the closure of iatrogenic membrane defects.

A Ray of Light for Fetal Therapy

Prospective Assessment of Fetal Cardiac Function with Speckle Tracking in Healthy Fetuses and Recipient Fetuses of Twin-to-twin Transfusion Syndrome

The aim of this study was to assess speckle tracking-derived fetal cardiac function in a normal population and in recipient fetuses of twin-to-twin transfusion syndrome (TTTS).

Single Incision Mini-sling Versus a Transobutaror Sling: a Comparative Study on MiniArc and Monarc Slings

A retrospective, dual-center, cohort study on the single incision MiniArc sling and the transobturator Monarc sling in the treatment of stress urinary incontinence is presented. We hypothesized that both systems would perform equally well.

Prevalence of Major Levator Abnormalities in Symptomatic Patients with an Underactive Pelvic Floor Contraction

Major levator ani abnormalities (LAA) may lead to abnormal pelvic floor muscle contraction (pfmC) and secondarily to stress urinary incontinence (SUI), prolapse, or fecal incontinence (FI).

Preterm Rabbit Lung Tissue Mechanics: Maturational Changes and Effect of Antenatal Steroids

Describe lung tissue and central airway mechanics using forced oscillation in preterm rabbits at different gestational ages and after maternal administration of betamethasone (BM).

Tracheal Side Effects Following Fetal Endoscopic Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia

Twin Anemia Polycythemia Sequence from a Prenatal Perspective

To describe the prevalence, management and outcome of spontaneous twin anemia polycythemia sequence (TAPS) diagnosed in the prenatal period.

Neonatal Tracheal Changes Following in Utero Fetoscopic Balloon Tracheal Occlusion in Severe Congenital Diaphragmatic Hernia

To report postnatal tracheal changes after in utero fetoscopic balloon tracheal occlusion in severe congenital diaphragmatic hernia (CDH).

Clinicopathological Study of Patients Requiring Reintervention After Sacrocolpopexy with Xenogenic Acellular Collagen Grafts

We describe the operative and histopathological findings of patients requiring reintervention because of symptomatic vault prolapse or graft related complications following sacrocolpopexy using xenografts.

Monochorionic Diamniotic Twin Pregnancies: Natural History and Risk Stratification

About 30% of monochorionic twin pregnancies are complicated by twin-to-twin transfusion syndrome (TTTS), isolated discordant growth, twin anemia-polycythemia sequence, congenital defects or intrauterine demise. About 15% will be eligible for invasive fetal therapy, either fetoscopic laser treatment for TTTS or fetoscopic or ultrasound-guided umbilical cord coagulation for a severe congenital defect in one twin or severe discordant growth with imminent demise of the growth-restricted twin. Ultrasound examination in the first and early second trimester can differentiate the monochorionic twins at high risk for adverse outcome from those likely to be uneventful, which may be useful for patient counselling and planning of care.

On the Origin of Amniotic Stem Cells: of Mice and Men

A common characteristic of mammals is the development of extraembryonic supporting tissues and organs that are required for embryonic implantation, survival and development in utero. The amnion is the innermost extraembryonic membrane that eventually surrounds the fetus of amniotes, and contains the amniotic fluid. Next to its function in in utero development, the amnion has been shown to have an important potential for clinical applications. It is mainly used as a dressing to stimulate healing in skin and ocular wounds. Moreover, cells derived from the amniotic membrane and amniotic fluid have been reported to possess stem cell features, like pluripotent differentiation ability. Little is known about the early development of this membrane in humans. The mouse is a powerful genetic model organism that can be used to address the dynamics and the developmental origin of amnion and amnion-derived stem cells. Here, we discuss some fundamental differences in amnion development in the disc-shaped primate embryo and in the cup-shaped mouse embryo. We emphasize the consequences that this may have on the derivation of amniotic "stem" cells. After revision of the different isolation procedures of amniotic (fluid) derived "stem" cells from rodents, we reveal striking differences in the sources used to derive these cells across studies. The profound differences in the development of the extraembryonic membranes and cavities between primates and rodents may result in comparing cell types of different developmental origins, eventually leading to missinterpretations.

The Outcome of Twin Reversed Arterial Perfusion Sequence Diagnosed in the First Trimester

The aim of this study was to document the mortality of twin reversed arterial perfusion (TRAP) sequence from the first trimester to planned intervention at 16-18 weeks.

The Making of Fetal Surgery

Fetal diagnosis prompts the question for fetal therapy in highly selected cases. Some conditions are suitable for in utero surgical intervention. This paper reviews historically important steps in the development of fetal surgery. The first invasive fetal intervention in 1963 was an intra-uterine blood transfusion. It took another 20 years to understand the pathophysiology of other candidate fetal conditions and to develop safe anaesthetic and surgical techniques before the team at the University of California at San Francisco performed its first urinary diversion through hysterotomy. This procedure would be abandoned as renal and pulmonary function could be just as effectively salvaged by ultrasound-guided insertion of a bladder shunt. Fetoscopy is another method for direct access to the feto-placental unit. It was historically used for fetal visualisation to guide biopsies or for vascular access but was also abandoned following the introduction of high-resolution ultrasound. Miniaturisation revived fetoscopy in the 1990 s, since when it has been successfully used to operate on the placenta and umbilical cord. Today, it is also used in fetuses with congenital diaphragmatic hernia (CDH), in whom lung growth is triggered by percutaneous tracheal occlusion. It can also be used to diagnose and treat urinary obstruction. Many fetal interventions remain investigational but for a number of conditions randomised trials have established the role of in utero surgery, making fetal surgery a clinical reality in a number of fetal therapy programmes. The safety of fetal surgery is such that even non-lethal conditions, such as myelomeningocoele repair, are at this moment considered a potential indication. This, as well as fetal intervention for CDH, is currently being investigated in randomised trials.

Morphologic Changes and Methodological Issues in the Rabbit Experimental Model for Diaphragmatic Hernia

Fetal lung development may be impaired by some congenital anomalies or in utero events. Animal models are used to understand the pathophysiology of these diseases and explore therapeutic strategies. Our group has an interest in the prenatal management of congenital diaphragmatic hernia (CDH). Isolated CDH remains associated with a 30% mortality because of lung hypoplasia and pulmonary hypertension. On day 23 of gestation (pseudoglandular stage) CDH was created in both ovarian-end fetuses (n= 28) in 14 time-mated pregnant white rabbits (hybrid of Dendermonde and New-Zealand White). At term (day 30) all survived operated fetuses and size-matched controls were harvested. Fetuses/lungs were assigned randomly to formalin fixation either under pressure of 25 cm H2O (CDH25 n=5; CTR25 n=5) or without (0 cm H2O (CDH0 n=7; CTR0 n=7). Fetuses and lungs were first weighed, and then the lungs were processed for morphometry. Pulmonary development was evaluated by lung-to-body weight ratio (LBWR) and airway and vascular morphometry. Surgical induction of CDH does reduce the LBWR to hypoplastic levels. The contralateral lung weight is 81% of what is expected, whereas the ipsilateral lung is only 46% of the normal. This was accompagnied by a loss of conducting airway generations, precisely, terminal bronchioles (TB), which were surrounded by less alveoli. The ipsilateral CDH lung demonstrated a thickened media in the peripheral arteries as well. As a result, in the severely hypoplastic ipsilateral lung, an airway fixation pressure of 25 H2O has no significant effect on the morphometric indices. The contralateral lung has a normal amount of alveoli around a single TB, which also behave like alveoli of the normal lung, i.e. expand under pressure fixation. The present study on severely hypoplastic lungs that never respirated, shows that in contrast to normal lungs, the morphometric indices are not significantly influenced by a difference in fixation pressure. Increasing fixation pressure seems to expand the lung only when sufficient alveolated parenchyma is present.

Efficient Gene Transfer into the Mouse Lung by Fetal Intratracheal Injection of RAAV2/6.2

Fetal gene therapy is one of the possible new therapeutic strategies for congenital or perinatal diseases with high mortality or morbidity. We developed a novel delivery strategy to inject directly into the fetal mouse trachea. Intratracheal (i.t.) injection at embryonic day 18 (E18) was more efficient in targeting the fetal lung than conventional intra-amniotic (i.a.) delivery. Viral vectors derived from adeno-associated virus serotype 6.2, with tropism for the airway epithelium and not earlier tested in the fetal mouse lung, were injected into the fetal trachea. Bioluminescence (BL) imaging (BLI) was combined with magnetic resonance (MR) imaging (MRI) for noninvasive and accurate localization of transgene expression in vivo. Histological analysis for β-galactosidase (β-gal) revealed 17.5% of epithelial cells transduced in the conducting airways and 1.5% in the alveolar cells. Stable gene expression was observed up to 1 month after injection. This study demonstrates that direct injection of rAAV2/6.2 in the fetal mouse trachea is superior to i.a. delivery for transducing the lung. Second, as stable gene transfer was detected up to 1 postnatal month, this approach may be useful to evaluate fetal gene therapy for pulmonary diseases such as cystic fibrosis, requiring both substantial numbers of transduced cells as well as prolonged gene expression to obtain a stable phenotypic effect.

Cross-sectional Study of Tracheomegaly in Children After Fetal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia

To measure tracheal dimensions in children with congenital diaphragmatic hernia (CDH) who had undergone fetoscopic endoluminal tracheal occlusion (FETO) or were treated expectantly during gestation.

MR Volumetry of the Normal Fetal Kidney: Reference Values

The aim of this study is to provide reference values for normal fetal kidney growth based on magnetic resonance (MR) volumetry. Differences in side and gender will be investigated.

The Fetal Heart in Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome is a severe complication occurring in 10% of monochorionic twin pregnancies. The disease is usually explained as due to an intrauterine imbalance in intertwin blood exchange, which leads to a volume depleted-donor twin and an overfilled recipient twin. The recipient has signs of cardiac dysfunction, which can be measured using echocardiography or blood and amniotic fluid derived biomarkers. Whereas cardiac dysfunction typically progresses in pregnancies treated with amniodrainage, it usually disappears within a few weeks after fetoscopic laser coagulation of the connecting intertwin anastomoses. Nevertheless, recipients remain at a increased risk of pulmonary stenosis. In this paper, we summarize the cardiac alterations in twin-to-twin transfusion syndrome, describe the changes seen after fetal therapy, list the newly proposed staging systems based on fetal cardiac function, and make recommendations about the use of fetal echocardiography in the evaluation and followup of pregnancies complicated by twin-to-twin transfusion syndrome.

Targeted Array Comparative Genomic Hybridisation (array CGH) Identifies Genomic Imbalances Associated with Isolated Congenital Diaphragmatic Hernia (CDH)

Congenital diaphragmatic hernia (CDH) is a congenital birth defect affecting around 1/3000 births. We propose that a significant number of isolated CDH cases have an underlying genetic cause, and that a subset of these result from copy number variations (CNVs) identifiable by array CGH.

Fetoscopic Imaging of Isolated Cleft Lip

Changes in Lung Tissue Perfusion in the Prediction of Survival in Fetuses with Congenital Diaphragmatic Hernia Treated with Fetal Endoscopic Tracheal Occlusion

To assess the impact of lung perfusion by fractional moving blood volume (FMBV) for the prediction of survival in fetuses with congenital diaphragmatic hernia (CDH) treated with fetal endoscopic tracheal occlusion (FETO).

Prognostic Value of Pulmonary Doppler to Predict Response to Tracheal Occlusion in Fetuses with Congenital Diaphragmatic Hernia

Pulmonary Doppler may play an important role in the prediction of survival and postnatal morbidity in fetuses with congenital diaphragmatic hernia treated with fetoscopic tracheal occlusion (FETO). Spectral Doppler indexes such as pulsatility index and peak early diastolic reversed flow could help to refine the selection of fetuses that might benefit from fetal therapy. When combined with lung-to-head ratio (LHR), these Doppler indices allow to discriminate cases with moderate-to-high survival rates from fetuses with extremely low chances to survive after FETO. In addition, they discriminate groups with a high or low risk of serious neonatal morbidity in surviving fetuses. After therapy, the combined evaluation of the relative increase of LHR with the increase in lung tissue perfusion by power Doppler seems to improve the prediction of fetal survival. In conclusion, while LHR remains the strongest predictive index, Doppler measurements allow to substantially improve the accuracy in the prediction of the chances of survival of fetuses with congenital diaphragmatic hernia treated with FETO.

Examining the Relationship Between the Lung-to-head Ratio Measured on Ultrasound and Lung Volumetry by Magnetic Resonance in Fetuses with Isolated Congenital Diaphragmatic Hernia

In fetuses with isolated congenital diaphragmatic hernia (CDH), lung development can be measured by the lung-to-head ratio (LHR) using ultrasound as well as by lung volumetry determined by fetal magnetic resonance imaging (MRI). We aimed to investigate their relationship as well as to analyze the factors that may have an impact on it.

Prenatal Anatomical Imaging in Fetuses with Congenital Diaphragmatic Hernia

The role of prenatal ultrasound and magnetic resonance imaging in the diagnosis and management of congenital diaphragmatic hernia (CDH) is reviewed. Topics include morphologic imaging and vascular assessment of the developing lung, the value of imaging parameters as prognostic predictors in CDH and the role of imaging following percutaneous fetoscopic endoluminal tracheal occlusion.

An International Urogynecological Association (IUGA) / International Continence Society (ICS) Joint Terminology and Classification of the Complications Related Directly to the Insertion of Prostheses (meshes, Implants, Tapes) & Grafts in Female Pelvic Floor Surgery

a terminology and standardized classification has yet to be developed for those complications arising directly from the insertion of synthetic (prostheses) and biological (grafts) materials in female pelvic floor surgery.

Twin-to-twin Transfusion Syndrome (TTTS)

Twin-to-twin transfusion syndrome (TTTS) is a severe complication of monochorionic (MC) twin pregnancies, characterized by the development of unbalanced chronic blood transfer from one twin, defined as donor twin, to the other, defined as recipient, through placental anastomoses. If left untreated, TTTS is associated with very high perinatal mortality and morbidity rates, due to a combination of fetal and/or obstetric complications. The reported prevalence is 10-15% of all MC twins, or about 1 in 2000 pregnancies. This consensus document reviews available evidence and offers practical guidance to clinicians by providing recommendations on various aspects concerning diagnosis and management of TTTS.

Recent Developments in the Genetic Factors Underlying Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a birth defect affecting around 1 in 3,000 births and is associated with high mortality and morbidity. It has become increasingly apparent that genetic factors underlie many forms of CDH. We review the recent developments in the area of the genetics of CDH, including potential candidate genes supported by evidence from animal models. We also discuss the possible role in the pathogenesis of CDH of defective retinoid signalling and abnormal mesenchymal cell function.

An International Urogynecological Association (IUGA)/International Continence Society (ICS) Joint Terminology and Classification of the Complications Related Directly to the Insertion of Prostheses (meshes, Implants, Tapes) and Grafts in Female Pelvic Floor Surgery

A terminology and standardized classification has yet to be developed for those complications arising directly from the insertion of synthetic (prostheses) and biological (grafts) materials in female pelvic floor surgery.

Technical Aspects of Fetal Endoscopic Tracheal Occlusion for Congenital Diaphragmatic Hernia

In isolated congenital diaphragmatic hernia, prenatal prediction is made based on measurements of lung size and the presence of liver herniation into the thorax. A subset of fetuses likely to die in the postnatal period is eligible for fetal intervention that can promote lung growth. Rather than anatomical repair, this is now attempted by temporary fetal endoscopic tracheal occlusion (FETO). Herein we describe purpose-designed instruments that were developed thanks to a grant from the European Commission. The feasibility and safety of FETO have now been demonstrated in several active fetal surgery programs. The most frequent complication of the procedure is preterm premature rupture of the membranes, which is probably iatrogenic in nature. It does have an impact on gestational age at delivery and complicates balloon removal. FETO is associated with an apparent increase in survival compared with same severity controls, although this needs to be evaluated in a formal trial. The time has come to do so.

Fetal Surgery for Congenital Diaphragmatic Hernia is Back from Never Gone

Over half of the cases of congenital diaphragmatic hernia are picked up prenatally. Prenatal assessment aims to rule out associated anomalies and to make an individual prognosis. Prediction of outcome is based on measurements of lung size and vasculature as well as on liver herniation. A subset of fetuses likely to die in the postnatal period is eligible for a fetal intervention that can promote lung growth. Two randomized trials have shown that fetal surgery using open anatomical repair or tracheal occlusion via hysterostomy has no benefit. Since then, a percutaneous fetoscopic technique has been introduced, which has been shown to be safe and seems to improve survival when compared to historical controls. Rupture of the fetal membranes and early delivery, nevertheless, remain an issue, but are less likely as compared to earlier experience. Improved outcomes are confirmed in two other studies published in this issue of Fetal Diagnosis and Therapy. This paper summarizes the experimental and clinical history of fetal surgery for congenital diaphragmatic hernia. It stresses the need for another randomized trial. This trial started in Europe and patients should be asked whether they would like to participate.

Shrinkage and Biomechanical Evaluation of Lightweight Synthetics in a Rabbit Model for Primary Fascial Repair

The experiment evaluated different lightweights (<32 g/m(2)) in terms of shrinkage and biomechanics.

Amniopatch for Iatrogenic Rupture of the Fetal Membranes

With the increased use of invasive fetal procedures, the number of women facing post-procedure membrane rupture is increasing. Here we review the use of platelets and fresh frozen plasma for sealing iatrogenic fetal membrane defects by describing the mechanisms of action of the amniopatch procedure as well as published experience. In cases of iatrogenic preterm pre-labour rupture of the membranes, amniopatch effectively seals the fetal membranes in over two-thirds of cases. There is a risk of 16% of in utero fetal death, which may occur at varying intervals from the procedure and often for unknown reasons. Amniopatch has also been used as a treatment of chorionic membrane separation. In summary, current experience suggests that in cases of early onset but persistent amniotic fluid leakage following an invasive fetal procedure, amniopatch is an option.

Prenatal Assessment and Management of Sacrococcygeal Teratoma

Sacrococcygeal teratoma (SCT) is one of the most common tumors in newborns with a birth prevalence of up to 1 in 21,700 births. Routine fetal anomaly screening programs allow for prenatal diagnosis in many cases. Fetal ultrasound with Doppler evaluation and more recently magnetic resonance imaging may be used to document the extent of the tumor as well as identifying the population at risk for serious fetal complications. Rapidly growing SCT and highly vascularized tumors are more likely to have hemodynamic repercussions. Fetal hydrops is usually considered as a poor prognostic marker and a potential indicator for fetal intervention. Newborns with SCT require stabilization prior to early surgical resection. In case of malignancy additional chemotherapy may be required. SCT may result in significant morbidity, either directly or as a consequence of surgical therapy. Careful postnatal follow-up is required for timely identification and treatment of complications as well as recurrence. This paper aims to review the perinatal management of this condition.

The 2010 Malcolm Ferguson-Smith Young Investigator Award

Results of Fetal Endoscopic Tracheal Occlusion for Congenital Diaphragmatic Hernia and the Set Up of the Randomized Controlled TOTAL Trial

In isolated congenital diaphragmatic hernia, lung size and/or the position of the liver are predictive of neonatal outcome. Percutaneous Fetal Endoscopic Tracheal Occlusion (FETO) by a balloon can be undertaken to prompt lung growth in the worst cases. The feasibility and safety of FETO is no longer at stake, and it is associated with an apparent increase in neonatal survival. The gestational age at birth, the pre-existing lung size, the ability to remove the balloon prior to birth, and the lung response are predicting outcome. The most frequent complication is preterm premature rupture of the membranes, and as a consequence preterm delivery, which also complicates balloon removal. We have set up a randomized trial for the formal evaluation of FETO in Europe, including criteria for fetoscopy centers. Training of European as well as North American centers is taking place, so that the procedure could be safely and more widely offered.

The Correlation Between Lung Volume and Liver Herniation Measurements by Fetal MRI in Isolated Congenital Diaphragmatic Hernia: a Systematic Review and Meta-analysis of Observational Studies

We conducted a meta-analysis to assess the correlation of lung volume and liver position measured by magnetic resonance imaging (MRI) with survival until discharge in fetuses with isolated congenital diaphragmatic hernia (CDH).

A Longer Tracheal Occlusion Period Results in Increased Lung Growth in the Nitrofen Rat Model

Prenatal tracheal occlusion (TO) promotes lung growth and is applied clinically in fetuses with severe congenital diaphragmatic hernia. Limited data are available regarding the effect of duration of TO on lung development. Our objective was to evaluate the effects of long (2 and 2.5 days) versus short (1 day) TO on lung development in rats with nitrofen-induced diaphragmatic hernia.

Fetoscopic Laser Surgery for Twin-to-twin Transfusion Syndrome After 26 Weeks of Gestation

To compare the outcomes of twin-to-twin transfusion syndrome (TTTS) cases treated with fetoscopic laser coagulation of vascular anastomoses before 25 + 6 weeks of gestation and between 26 and 28 weeks of gestation.

Array-based Approaches in Prenatal Diagnosis

The diagnostic benefits of array comparative genomic hybridisation (CGH) have been demonstrated, with this technique now being applied as the first-line test for patients with intellectual disabilities and/or multiple congenital anomalies in numerous laboratories. There are no technical barriers preventing the introduction of array CGH to prenatal diagnosis. The question is rather how this is best implemented, and for whom. The challenges lie in the interpretation of copy number variations, particularly those which exhibit reduced penetrance or variable expression, and how to deal with incidental findings, which are not related to the observed foetal anomalies, or unclassified variants which are currently of uncertain clinical significance. Recently, applications of array technologies to the field of pre-implantation genetic diagnosis have also been demonstrated. It is important to address the ethical questions raised concerning the genome-wide analysis of prenatal samples to ensure the maximum benefit for patients. We provide an overview of the recent developments on the use of array CGH in the prenatal setting, and address the challenges posed.

Fetoscopic Release of an Amniotic Band with Risk of Amputation: Case Report and Review of the Literature

Amniotic bands can cause limb amputation as well as intrauterine fetal demise. Fetoscopic release of amniotic bands has been shown to rescue limb function. Herein, we describe an interesting case of an amniotic band wrapped around the right forearm as well as the umbilical cord, which was released by fetoscopy. Following the procedure, the blood flow in the forearm was restored and the edema gradually reduced. Full functionality of the arm was confirmed after birth, though the esthetic problem of the imprint of the band on the arm persisted. Furthermore, we review the available literature regarding fetoscopic interventions in amniotic band syndrome.

Long Term Respiratory Outcomes of Congenital Diaphragmatic Hernia, Esophageal Atresia, and Cardiovascular Anomalies

Intrathoracic congenital malformations may be associated with long-term pulmonary morbidity. This certainly is the case for congenital diaphragmatic hernia, esophageal atresia and cardiac and aortic arch abnormalities. These conditions have variable degrees of impaired development of both the airways and lung vasculature, with a postnatal impact on lung function and bronchial reactivity. Pulmonary complications are themselves frequently associated to non-pulmonary morbidities, including gastrointestinal and orthopaedic complications. These are best recognized in a structured multidisciplinary follow-up clinic so that they can be actively managed.

Antenatal Management of Isolated Congenital Diaphragmatic Hernia Today and Tomorrow: Ongoing Collaborative Research and Development. Journal of Pediatric Surgery Lecture

The diagnosis of congenital diaphragmatic hernia should be made prenatally in virtually all cases where routine maternal ultrasonography is available. At that time, the prognosis can be predicted based on whether it is isolated and assessment of lung size and/or the position of the liver. Prenatal intervention may be offered in those selected fetuses that have a predicted poor outcome. The aim of this procedure is to reverse the key determinant of survival-pulmonary hypoplasia. Percutaneous fetal endoscopic tracheal occlusion by a balloon is a minimally invasive procedure that has been shown safe and yields a 50% survival rate in severe cases. The outcome can be predicted by the gestational age at birth, the lung size before and after balloon placement, and whether the balloon has been removed prenatally. Currently, the added value of prenatal intervention is being investigated in the Tracheal Occlusion To Accelerate Lung Growth trial ((TOTAL); a European and North American collaboration). Future developments may include better prediction of outcome by more complex algorithms reflecting combinations of prenatal predictors, gene expression profiling to reflect lung development and response to tracheal occlusion, and alternative prenatal strategies for salvaging the worst cases. Fetuses with severe hypoplasia usually require postnatal operative repair using prosthetic patches, and tissue engineering offers the potential for ex utero culture.

A Standardized Description of Graft-containing Meshes and Recommended Steps Before the Introduction of Medical Devices for Prolapse Surgery. Consensus of the 2nd IUGA Grafts Roundtable: Optimizing Safety and Appropriateness of Graft Use in Transvaginal Pelvic Reconstructive Surgery

Over the past decade, a huge number of new implants and ancillary devices have been introduced to the market. Most of these have become clinically available with little or no clinical data or research. This is a less-than-ideal situation, and this subgroup of the ad hoc IUGA roundtable conference wants to open the discussion to change this, by proposing a pragmatic minimum clearance track for new products being introduced to the market. It consists of an accurate and more standardized product description, data on the biological properties gathered in animal experiments, anatomical cadaveric studies, and upfront clinical studies followed by a compulsory registry on the first 1,000 patients implanted. Ideally, manufacturers should support well-designed prospective (randomized) clinical trials that can support the claimed benefits of the new product.

Morphological and Functional Adaptation of the Maternal Heart During Pregnancy

Pregnancy provides a unique model to study the adaptation of the heart in a physiological situation of transient load changes. The aim of this study was to assess the performance of the left ventricle (LV) in normal, uncomplicated pregnancies while considering the actual LV load and shape.

International Urogynecological Association (IUGA)/International Continence Society (ICS) Joint Terminology and Classification of the Complications Related to Native Tissue Female Pelvic Floor Surgery

A terminology and standardized classification has yet to be developed for those complications related to native tissue female pelvic floor surgery.

Fetal Pyelectasis and Corkscrew-shaped Ureters: an Association Observed in Postmortem Fetal Imaging Studies of Osteochondrodysplasia and Trisomy 21

Biomechanical Effects of Polyglecaprone Fibers in a Polypropylene Mesh After Abdominal and Rectovaginal Implantation in a Rabbit

To investigate the biomechanical effects of polyglecaprone fibers in lightweight meshes implanted into the vaginal and abdominal wall of parous rabbits.

An International Urogynecological Association (IUGA)/International Continence Society (ICS) Joint Terminology and Classification of the Complications Related to Native Tissue Female Pelvic Floor Surgery

A terminology and standardized classification has yet to be developed for those complications related to native tissue female pelvic floor surgery.

Comparison of Doppler-based and Three-dimensional Methods for Fetal Cardiac Output Measurement

Fetal cardiac output is conventionally measured using two-dimensional (2D) and Doppler ultrasound (Doppler). New methods based on 3D measurements of ventricular size in systole and diastole have been proposed. Our aim was to validate these tools against the conventional Doppler-based methods.

Minimally Invasive Fetal Therapy

The implementation of systematic pregnancy screening programmes, and the increased use and improving quality of medical imaging techniques, have lead to earlier detection and better understanding of the natural history of fetal anomalies. Where most fetal conditions are adequately treatable after birth, some disorders progress during fetal life and can lead to severe morbidity or fetal and neonatal demise. This inherently raises the question of prenatal therapy. Some fetal conditions are amenable for fetal surgical intervention, part of them by minimal access. We provide an overview of the rationale for, the technical aspects of, and (if available) the outcomes of the most common minimally invasive prenatal therapies. These include intrauterine transfusion, fetal cardiac procedures, interventions for lower urinary tract obstruction, thoracic and pulmonary pathology, fetoscopic laser of placental vessels for twin-to-twin transfusion syndrome, and selective reduction in complicated monochorionic twin pregnancies.

Cytogenetic and Morphological Analysis of Early Products of Conception Following Hystero-embryoscopy from Couples with Recurrent Pregnancy Loss

Our knowledge about miscarriages mainly concerns pregnancies of at least 8 weeks' gestation. Information about the morphology and the genetic determinants of early aborted embryos remains limited. In addition, it is known that aneuploidies account for less than half of recurrent spontaneous abortions. We hypothesized that (recurrent) early pregnancy losses might have other genetic causes.

Risk of Perinatal Death in Early-onset Intrauterine Growth Restriction According to Gestational Age and Cardiovascular Doppler Indices: a Multicenter Study

To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses.

The Pharmacokinetics of a High Intravenous Dose of Paracetamol After Caesarean Delivery: the Effect of Gestational Age

Pregnancy affects intravenous paracetamol pharmacokinetics, but there are no studies on covariates of intravenous paracetamol pharmacokinetics around delivery.

IUGA/ICS Terminology and Classification of Complications of Prosthesis and Graft Insertion-rereading Will Revalidate

Twin-twin Transfusion Syndrome: the Good News Is; There is Still Room for Improvement …

Contractions, a Risk for Premature Rupture of Fetal Membranes: A New Protocol with Cyclic Biaxial Tension

This study aims at investigating the effect of repeated mechanical loading on the rupture and deformation properties of fetal membranes. Ten membranes delivered by cesarean sections were tested using a custom-built inflation device which provides a multi-axial stress state. For each membrane, a group of samples was first cyclically stretched by application of pressure ranging between 10 and 40mmHg. After cycles, samples were subjected to inflation up to rupture. Differences between mechanical parameters from cycled and uncycled samples were analyzed. Ten cycles at 40% of mean critical membrane tension-representative of mean physiologic contractions-did not affect strength and stiffness of fetal membranes but reduced the work to rupture, thus indicating that contractions might increase the risk of premature rupture of the membrane. Cyclic testing demonstrated a large hysteresis loop and irreversible deformation on the first cycle, followed by rapid stabilization on subsequent cycles. In 80% of tests, amnion ruptured first and at the periphery of the sample, under uniaxial strain state. Chorion ruptured at higher deformation levels in the middle, under biaxial strain state.

Intrauterine Surgery-choices and Limitations

The past decade has seen much progress in intrauterine surgery. Randomized trials have documented the benefit of some procedures of this type for the unborn child.

The Vascular Anastomoses in Monochorionic Twin Pregnancies and Their Clinical Consequences

Monochorionic twin pregnancies are at increased risk of adverse outcome because of the vascular anastomoses that connect the 2 fetal circulation systems. The shared circulation is responsible for some unique complications in monochorionic twins, such as the twin-to-twin transfusion syndrome, the twin anemia polycythemia sequence, the twin reversed arterial perfusion sequence, and monoamniotic twinning. Another consequence of the shared circulation is that the well-being of one twin critically depends on that of the other. In this review, we will describe the technique of placental injection. Further, we will discuss the role of the vascular anastomoses in each of the complications described above and provide an update on their management.

Regenerative Medicine for Congenital Diaphragmatic Hernia: Regeneration for Repair

Regenerative medicine has developed recently as a new field of science aiming at restoring organ and tissue damage through the use of autologous constructs. Cellular therapies and relatively simple tissue engineering reconstructions have recently been successfully applied into patients. For babies born with congenital diaphragmatic hernia, regenerative medicine may play a role both in developing a myogenic patch capable of restoring muscle function and promoting regeneration of hypoplastic lungs that characterised those patients. The latter is particularly attractive because it may change the long-term outcome of those children. We aim here to discuss recent advancement in the field, looking in particular at the future clinical prospective of those exciting therapeutic strategies.

Sonographic Evaluation of Vascular Pulmonary Reactivity Following Oxygen Administration in Fetuses with Normal Lung Development

This study aimed to establish nomograms for sonographic assessment of fetal pulmonary vascular reactivity following maternal hyperoxygenation.

Placenta As a Reservoir of Stem Cells: an Underutilized Resource?

Both embryonic and adult tissues are sources of stem cells with therapeutic potential but with some limitations in the clinical practice such as ethical considerations, difficulty in obtaining and tumorigenicity. As an alternative, the placenta is a foetal tissue that can be obtained during gestation and at term, and it represents a reservoir of stem cells with various potential.

Antireflux Surgery After Congenital Diaphragmatic Hernia Repair: a Plea for a Tailored Approach

OBJECTIVES: Preventive antireflux surgery (ARS) at the moment of congenital diaphragmatic hernia (CDH) repair has been suggested by some authors, particularly in subgroups with a liver herniated in the chest or patch requirement. We evaluated the incidence and associated factors of gastro-oesophageal reflux disease (GERD) and the need for subsequent ARS in our CDH patients. METHODS: We retrospectively reviewed our CDH database. Demographics, prenatal assessment of severity, prenatal treatment, type of repair, intraoperative findings and incidences of gastro-oesophageal reflux and ARS were recorded. RESULTS: CDH repair was performed in 77 infants between July 1993 and November 2009. Eight died after repair. Seven were lost to follow-up. The median follow-up was 4.0 (0.16-14.88) years. Fourteen of these 62 patients were prenatally treated with fetoscopic endoluminal tracheal occlusion (FETO) because of severe pulmonary hypoplasia. After CDH repair, GERD was diagnosed in 31 patients. In all of them, medical antireflux treatment was started. Thirteen (42%) patients needed ARS at a median age of 64 (37-264) days. One year after starting medical treatment, 14 (45%) patients were completely off antireflux medication. In CDH subgroups with patch repair, liver herniated in the chest or previous FETO, the incidences of gastro-oesophageal reflux and ARS were 61 and 32%, 73 and 38% and 71 and 43%, respectively. Univariable analysis of associated potentially predisposing factors shows that patch repair, liver herniated in the chest, pulmonary hypertension, high-frequency oscillatory ventilation and FETO are associated with subsequent ARS. On multivariable analysis, liver herniated in the chest was the only independent predictor for both gastro-oesophageal reflux and ARS. CONCLUSIONS: Of all CDH patients, 50% developed gastro-oesophageal reflux and 21% required ARS. For both, liver in the chest was the only independent predictor. Routine ARS in certain subgroups at the time of CDH repair seems not to be justified. Foetal endoluminal tracheal occlusion creates a new cohort of survivors with an increased risk for undergoing ARS. The surgical group, in particular, reflects a more complex gastro-oesophageal reflux physiopathology.

A Morphometric Study of the Human Fetal Heart on Post-mortem 3-tesla Magnetic Resonance Imaging

To report on the feasibility of assessing cardiac structures on post-mortem 3-tesla MRI (pmMRI) and to provide morphometric data in fetuses without cardiac abnormalities.

Tracheal Occlusion Alters Pulmonary Circulation in the Fetal Lamb with Normally Developing Lungs

Tracheal occlusion (TO) promotes fetal lung growth through an increase in intraluminal pressure. Although evidence suggests that fetal TO (FETO) decreases the occurrence of pulmonary hypertension in severe congenital diaphragmatic hernia, controversies on its effect on the pulmonary circulation remain. Therefore, we investigated the effects of FETO on the lung hemodynamics in a chronically catheterized fetal lamb model.

Amniopatch Procedure After Previable Iatrogenic Rupture of the Membranes: a Two-center Review

This study aimed to analyze success rates and pregnancy outcomes of amniopatch procedures for previable iatrogenic preterm prelabour rupture of the membranes (PPROM) with associated oligohydramnios.

Psychosocial Aspects of Invasive Fetal Therapy As Compared to Prenatal Diagnosis and Risk Assessment

To explore the psychosocial impact of invasive fetal therapy (FT).

Concerning the Timing of Antibiotic Administration in Women Undergoing Caesarean Section: a Systematic Review and Meta-analysis

To assess the effects on maternal infectious morbidity and neonatal outcomes of the timing of antibiotic prophylaxis in women undergoing caesarean section. A recent National Institute for Health and Clinical Excellence (NICE) guideline reported that antibiotic administration before skin incision reduces the risk of maternal infection; this recommendation was based on a meta-analysis, however one including trials that were not double blind and not including a trial published recently.

Routine Clonal Expansion of Mesenchymal Stem Cells Derived from Amniotic Fluid for Perinatal Applications

INTRODUCTION: Stem cells isolated from amniotic fluid are a promising source for autologous perinatal cell therapy. The aim of this study was to develop a routine isolation, selection and expansion protocol of clonal stem cell lines from redundant clinical amniocentesis samples. MATERIALS AND METHODS: Amniotic fluids were collected between 15-22 weeks of gestation and stem cells were isolated by CD117 based and mechanical selection protocols. Stem cells were characterized by mesenchymal stem cell marker expression and differentiation protocols. Cells were manipulated with a lentiviral vector system expressing the β-galactosidase reporter gene and were injected into immunodeficient newborn mouse pups. Qualitative assessment was performed to detect the infused cells after 1 week. RESULTS: 78 Clonal amniotic fluid stem cell populations were successfully isolated by mechanical selection from 21 consecutive amniocentesis samples. They were positive for mesenchymal stem cell CD markers and could be differentiated into the different lineages. Stem cells were stably labeled using β-galactosidase and were detected in the lungs and hearts of the neonatal mice. CONCLUSION: We demonstrate that mesenchymal stem cells can be routinely isolated and clonally expanded from mid-gestation human amniotic fluid using mechanical isolation. They can easily be transduced and be tested for perinatal treatment in animal models. This article is protected by copyright. All rights reserved.

Collagen Plug Sealing of Iatrogenic Fetal Membrane Defects After Fetoscopic Surgery for Congenital Diaphragmatic Hernia

We aimed to investigate the efficacy of collagen plugs in reducing the risk of preterm premature rupture of the membranes (PPROM) after fetoscopic surgery for Congenital Diaphragmatic Hernia (CDH).

simple hit counter