In JoVE (3)

Other Publications (270)

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

 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

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

Journal of Pediatric Surgery. Jan, 2002  |  Pubmed ID: 11781979

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

Journal of Pediatric Surgery. Jan, 2002  |  Pubmed ID: 11781980

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

American Journal of Obstetrics and Gynecology. Mar, 2002  |  Pubmed ID: 11904620

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

European Radiology. Dec, 2002  |  Pubmed ID: 12439572

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

Prenatal Diagnosis. Mar, 2003  |  Pubmed ID: 12627417

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

Monochorionic Diamniotic Twins: Complications and Management Options

Current Opinion in Obstetrics & Gynecology. Apr, 2003  |  Pubmed ID: 12634610

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

American Journal of Obstetrics and Gynecology. Mar, 2003  |  Pubmed ID: 12634668

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

Cancer. Jul, 2003  |  Pubmed ID: 12872366

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

Fetal Diagnosis and Therapy. Jan-Feb, 2004  |  Pubmed ID: 14646424

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

Radiology. Feb, 2004  |  Pubmed ID: 14699185

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

Pediatric Pulmonology. Feb, 2004  |  Pubmed ID: 14730653

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

Pediatric Surgery International. Apr, 2004  |  Pubmed ID: 15083328

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

The New England Journal of Medicine. Jul, 2004  |  Pubmed ID: 15238624

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

American Journal of Obstetrics and Gynecology. Sep, 2004  |  Pubmed ID: 15467550

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

American Journal of Obstetrics and Gynecology. Nov, 2004  |  Pubmed ID: 15547520

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

American Journal of Obstetrics and Gynecology. Dec, 2004  |  Pubmed ID: 15592278

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

Obstetrics and Gynecology Clinics of North America. Mar, 2005  |  Pubmed ID: 15644293

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

American Journal of Obstetrics and Gynecology. Feb, 2005  |  Pubmed ID: 15696010

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

Journal of Pediatric Surgery. Jan, 2005  |  Pubmed ID: 15868554

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

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Jun, 2005  |  Pubmed ID: 15925062

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

Anesthesia and Analgesia. Jul, 2005  |  Pubmed ID: 15976241

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

Neurourology and Urodynamics. 2005  |  Pubmed ID: 15977258

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

Best Practice & Research. Clinical Obstetrics & Gynaecology. Jun, 2005  |  Pubmed ID: 15985252

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

Seminars in Perinatology. Apr, 2005  |  Pubmed ID: 16050527

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

BJOG : an International Journal of Obstetrics and Gynaecology. Nov, 2005  |  Pubmed ID: 16225578

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

Clinical Obstetrics and Gynecology. Dec, 2005  |  Pubmed ID: 16286838

Diagnosis and Management of Heterokaryotypic Monochorionic Twins

American Journal of Medical Genetics. Part A. Feb, 2006  |  Pubmed ID: 16411235

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

Journal of Pediatric Surgery. Feb, 2006  |  Pubmed ID: 16481263

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

American Journal of Obstetrics and Gynecology. Mar, 2006  |  Pubmed ID: 16522413

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?

American Journal of Obstetrics and Gynecology. Mar, 2006  |  Pubmed ID: 16522414

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

American Journal of Obstetrics and Gynecology. Mar, 2006  |  Pubmed ID: 16522415

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

Current Opinion in Obstetrics & Gynecology. Apr, 2006  |  Pubmed ID: 16601482

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

American Journal of Obstetrics and Gynecology. Jul, 2006  |  Pubmed ID: 16626602

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

Current Opinion in Obstetrics & Gynecology. Jun, 2006  |  Pubmed ID: 16735838

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

International Urogynecology Journal and Pelvic Floor Dysfunction. Jun, 2006  |  Pubmed ID: 16738743

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

International Urogynecology Journal and Pelvic Floor Dysfunction. Jun, 2006  |  Pubmed ID: 16738750

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)

American Journal of Obstetrics and Gynecology. Dec, 2006  |  Pubmed ID: 16769018

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

Radiology. Dec, 2006  |  Pubmed ID: 17053198

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

Seminars in Fetal & Neonatal Medicine. Dec, 2006  |  Pubmed ID: 17056307

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

Neurourology and Urodynamics. 2007  |  Pubmed ID: 17009249

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

International Urogynecology Journal and Pelvic Floor Dysfunction. Jun, 2007  |  Pubmed ID: 17031489

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

Gynecologic and Obstetric Investigation. 2007  |  Pubmed ID: 17095874

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

Placenta. Jul, 2007  |  Pubmed ID: 17098282

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

Fetal Diagnosis and Therapy. 2007  |  Pubmed ID: 17139173

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

Gynecologic and Obstetric Investigation. 2007  |  Pubmed ID: 17159352

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

Anesthesiology. Jan, 2007  |  Pubmed ID: 17197857

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

American Journal of Obstetrics and Gynecology. Mar, 2007  |  Pubmed ID: 17346548

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

American Journal of Obstetrics and Gynecology. Apr, 2007  |  Pubmed ID: 17403419

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

Pediatric Pulmonology. Jun, 2007  |  Pubmed ID: 17469148

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

Radiology. Aug, 2007  |  Pubmed ID: 17641375

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

Gynecologic and Obstetric Investigation. 2007  |  Pubmed ID: 17934311

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

Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. Dec, 2007  |  Pubmed ID: 18022473

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

American Journal of Obstetrics and Gynecology. Dec, 2007  |  Pubmed ID: 18060944

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

Neonatology. 2008  |  Pubmed ID: 17703103

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

American Journal of Obstetrics and Gynecology. Jan, 2008  |  Pubmed ID: 17826727

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)

Fetal Diagnosis and Therapy. 2008  |  Pubmed ID: 17934305

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

Best Practice & Research. Clinical Obstetrics & Gynaecology. Feb, 2008  |  Pubmed ID: 18082455

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

American Journal of Obstetrics and Gynecology. Jan, 2008  |  Pubmed ID: 18166318

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

Radiology. Apr, 2008  |  Pubmed ID: 18258812

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

Prenatal Diagnosis. Apr, 2008  |  Pubmed ID: 18302309

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

Prenatal Diagnosis. Jun, 2008  |  Pubmed ID: 18435415

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

Pediatric Pulmonology. Jun, 2008  |  Pubmed ID: 18435480

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

Current Opinion in Anaesthesiology. Jun, 2008  |  Pubmed ID: 18458544

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

Current Opinion in Anaesthesiology. Jun, 2008  |  Pubmed ID: 18458545

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

American Journal of Obstetrics and Gynecology. Nov, 2008  |  Pubmed ID: 18533114

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

American Journal of Obstetrics and Gynecology. Nov, 2008  |  Pubmed ID: 18539256

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

American Journal of Obstetrics and Gynecology. Nov, 2008  |  Pubmed ID: 18539257

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

Pediatric Pulmonology. Aug, 2008  |  Pubmed ID: 18615670

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

Prenatal Diagnosis. Jul, 2008  |  Pubmed ID: 18634116

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

Prenatal Diagnosis. Sep, 2008  |  Pubmed ID: 18646240

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

Fetal Diagnosis and Therapy. 2008  |  Pubmed ID: 18648203

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

Reproductive Biology and Endocrinology : RB&E. 2008  |  Pubmed ID: 18796153

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

Pediatric Surgery International. Dec, 2008  |  Pubmed ID: 19009301

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]

Bulletin De L'Académie Nationale De Médecine. Nov, 2008  |  Pubmed ID: 19445375

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

Seminars in Fetal & Neonatal Medicine. Feb, 2009  |  Pubmed ID: 18845492

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

American Journal of Obstetrics and Gynecology. Feb, 2009  |  Pubmed ID: 19006783

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

European Urology. Jun, 2009  |  Pubmed ID: 19111382

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

Pediatric Pulmonology. Feb, 2009  |  Pubmed ID: 19137593

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

International Urogynecology Journal and Pelvic Floor Dysfunction. Apr, 2009  |  Pubmed ID: 19139799

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

Obstetrics and Gynecology. Feb, 2009  |  Pubmed ID: 19155907

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?

Journal of Pediatric Surgery. Jan, 2009  |  Pubmed ID: 19159719

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

Prenatal Diagnosis. Mar, 2009  |  Pubmed ID: 19177458

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

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Apr, 2009  |  Pubmed ID: 19185969

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

American Journal of Obstetrics and Gynecology. Apr, 2009  |  Pubmed ID: 19318149

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

Methods and Findings in Experimental and Clinical Pharmacology. Jan-Feb, 2009  |  Pubmed ID: 19357795

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

Prenatal Diagnosis. Jul, 2009  |  Pubmed ID: 19365875

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

American Journal of Obstetrics and Gynecology. May, 2009  |  Pubmed ID: 19375567

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

International Urogynecology Journal and Pelvic Floor Dysfunction. Sep, 2009  |  Pubmed ID: 19479177

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

Radiology. Aug, 2009  |  Pubmed ID: 19508989

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

Clinics in Perinatology. Jun, 2009  |  Pubmed ID: 19559323

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

Obstetrics and Gynecology. Aug, 2009  |  Pubmed ID: 19622964

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

Gynecologic and Obstetric Investigation. 2009  |  Pubmed ID: 19729939

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

The Journal of Urology. Nov, 2009  |  Pubmed ID: 19762041

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

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. Nov, 2009  |  Pubmed ID: 19776249

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

Prenatal Diagnosis. Dec, 2009  |  Pubmed ID: 19816885

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

Neurourology and Urodynamics. Apr, 2010  |  Pubmed ID: 19731305

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

American Journal of Obstetrics and Gynecology. Jan, 2010  |  Pubmed ID: 19801144

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

Seminars in Fetal & Neonatal Medicine. Feb, 2010  |  Pubmed ID: 19913467

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

American Journal of Obstetrics and Gynecology. Feb, 2010  |  Pubmed ID: 20035915

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

International Urogynecology Journal. May, 2010  |  Pubmed ID: 20082065

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

American Journal of Obstetrics and Gynecology. Jan, 2010  |  Pubmed ID: 20096254

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

Human Gene Therapy. Feb, 2010  |  Pubmed ID: 20136405

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

Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography. Mar, 2010  |  Pubmed ID: 20138468

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

International Urogynecology Journal. Jul, 2010  |  Pubmed ID: 20204323

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

International Urogynecology Journal. Jul, 2010  |  Pubmed ID: 20204327

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

Pediatric Pulmonology. Apr, 2010  |  Pubmed ID: 20232469

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

Pediatric Radiology. May, 2010  |  Pubmed ID: 20352401

Twin Anemia Polycythemia Sequence from a Prenatal Perspective

Prenatal Diagnosis. May, 2010  |  Pubmed ID: 20373492

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

Journal of Pediatric Surgery. Apr, 2010  |  Pubmed ID: 20385271

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

The Journal of Urology. Jun, 2010  |  Pubmed ID: 20400143

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

Fetal Diagnosis and Therapy. 2010  |  Pubmed ID: 20413975

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

The International Journal of Developmental Biology. 2010  |  Pubmed ID: 20446274

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

American Journal of Obstetrics and Gynecology. Sep, 2010  |  Pubmed ID: 20522408

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

Prenatal Diagnosis. Jul, 2010  |  Pubmed ID: 20572114

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

Histology and Histopathology. Sep, 2010  |  Pubmed ID: 20607652

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

Molecular Therapy : the Journal of the American Society of Gene Therapy. Dec, 2010  |  Pubmed ID: 20664525

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

Radiology. Oct, 2010  |  Pubmed ID: 20713614

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

Prenatal Diagnosis. Nov, 2010  |  Pubmed ID: 20734348

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

International Journal of Pediatrics. 2010  |  Pubmed ID: 20811613

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)

Prenatal Diagnosis. Dec, 2010  |  Pubmed ID: 21064195

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

BMJ Case Reports. 2010  |  Pubmed ID: 22778376

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 20215733

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 20881369

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 20962504

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 21063073

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

International Urogynecology Journal. Jan, 2011  |  Pubmed ID: 21140130

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)

Journal of Perinatal Medicine. Mar, 2011  |  Pubmed ID: 21142846

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 21150176

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

Neurourology and Urodynamics. Jan, 2011  |  Pubmed ID: 21181958

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

Journal of Pediatric Surgery. Jan, 2011  |  Pubmed ID: 21238635

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

Fetal Diagnosis and Therapy. 2011  |  Pubmed ID: 21325858

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

International Urogynecology Journal. Sep, 2011  |  Pubmed ID: 21562913

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

Amniopatch for Iatrogenic Rupture of the Fetal Membranes

Prenatal Diagnosis. Jul, 2011  |  Pubmed ID: 21656529

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

Prenatal Diagnosis. Jul, 2011  |  Pubmed ID: 21656530

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

Prenatal Diagnosis. Oct, 2011  |  Pubmed ID: 21898469

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

Early Human Development. Sep, 2011  |  Pubmed ID: 21907109

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

Prenatal Diagnosis. Nov, 2011  |  Pubmed ID: 21915885

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 Diagnosis. Jan, 2012  |  Pubmed ID: 22052745

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

Fetal Diagnosis and Therapy. 2012  |  Pubmed ID: 22156583

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

Methods in Molecular Biology (Clifton, N.J.). 2012  |  Pubmed ID: 22228011

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

Fetal Diagnosis and Therapy. 2012  |  Pubmed ID: 22248756

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

Seminars in Fetal & Neonatal Medicine. Apr, 2012  |  Pubmed ID: 22297025

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

Journal of Pediatric Surgery. Feb, 2012  |  Pubmed ID: 22325377

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

International Urogynecology Journal. Apr, 2012  |  Pubmed ID: 22395289

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

Circulation. Cardiovascular Imaging. May, 2012  |  Pubmed ID: 22455877

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

Neurourology and Urodynamics. Apr, 2012  |  Pubmed ID: 22517067

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

Prenatal Diagnosis. Jul, 2012  |  Pubmed ID: 22517500

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

International Urogynecology Journal. Oct, 2012  |  Pubmed ID: 22527542

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

International Urogynecology Journal. May, 2012  |  Pubmed ID: 22527748

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 Diagnosis and Therapy. 2012  |  Pubmed ID: 22613961

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

Best Practice & Research. Clinical Obstetrics & Gynaecology. Oct, 2012  |  Pubmed ID: 22682617

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

Prenatal Diagnosis. Oct, 2012  |  Pubmed ID: 22763612

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

Fetal Diagnosis and Therapy. 2012  |  Pubmed ID: 22777088

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

European Journal of Anaesthesiology. Oct, 2012  |  Pubmed ID: 22935956

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

American Journal of Obstetrics and Gynecology. Aug, 2012  |  Pubmed ID: 22939166

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

Acta Obstetricia Et Gynecologica Scandinavica. Oct, 2012  |  Pubmed ID: 22984776

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

Medical Engineering & Physics. Sep, 2012  |  Pubmed ID: 22998894

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

Deutsches Ärzteblatt International. Sep, 2012  |  Pubmed ID: 23093990

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

American Journal of Obstetrics and Gynecology. Sep, 2012  |  Pubmed ID: 23103301

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

European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery ... [et Al] = Zeitschrift Für Kinderchirurgie. Oct, 2012  |  Pubmed ID: 23114980

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

Prenatal Diagnosis. Dec, 2012  |  Pubmed ID: 23132095

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?

British Medical Bulletin. 2013  |  Pubmed ID: 23184854

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

European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery. Jan, 2013  |  Pubmed ID: 23355689

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

Prenatal Diagnosis. Apr, 2013  |  Pubmed ID: 23457008

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

Journal of Pediatric Surgery. Mar, 2013  |  Pubmed ID: 23480900

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

Prenatal Diagnosis. Apr, 2013  |  Pubmed ID: 23512492

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

Prenatal Diagnosis. Apr, 2013  |  Pubmed ID: 23568832

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

BMJ Open. 2013  |  Pubmed ID: 23604346

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

Prenatal Diagnosis. May, 2013  |  Pubmed ID: 23703584

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

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Jun, 2013  |  Pubmed ID: 23801588

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).

Does Website Based Information Add Any Value in Counselling Mothers Expecting a Baby with Severe Congenital Diaphragmatic Hernia?

Prenatal Diagnosis. Jun, 2013  |  Pubmed ID: 23813901

We aimed to measure whether website provided information about congenital diaphragmatic hernia (CDH) and fetal therapy for severe cases provides added value compared to clinical counseling of parents.

Preoperative Prediction of the Individualized Risk of Early Fetal Death After Laser Therapy in Twin-to-twin Transfusion Syndrome

Prenatal Diagnosis. Nov, 2013  |  Pubmed ID: 23813911

The aim of this study is to evaluate the independent and combined value of gestational age, fetal weight, fetoplacental Doppler, and myocardial performance index for the prediction of individual risk of early (≤7 days) intrauterine fetal death (IUFD) after laser therapy in twin-to-twin transfusion syndrome (TTTS).

The 2012 Malcolm Ferguson-Smith Young Investigator Award

Prenatal Diagnosis. Jul, 2013  |  Pubmed ID: 23824976

Is General Anaesthesia for Caesarean Section Associated with Postpartum Haemorrhage? Systematic Review and Meta-analysis

Acta Anaesthesiologica Scandinavica. Oct, 2013  |  Pubmed ID: 24003971

Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality. The odds for PPH were about eight times higher following general anaesthesia compared with neuraxial anaesthesia in a recent retrospective study. We aimed to conduct a systematic review and meta-analysis of the effect of type of anaesthesia (general vs. neuraxial) on estimated blood loss and transfusion requirements after caesarean section.

A Surgical Technique for Homogenous Renal Distribution of Substances in Rats

European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes. 2013  |  Pubmed ID: 24081026

Intra-arterial injection of mesenchymal stem cells has been proven to result in a superior nephroprotection compared to intravenous injection. This avoids initial passage through filter organs such as the lung, liver and spleen. The aim of the present study was to investigate whether suprarenal aortic delivery results in a homogenous distribution to both kidneys. Chinese ink was used to evaluate the renal distribution pattern for the comparison of two retrograde intra-aortic injection methods. In the first, the aorta caudal to the renal branches was temporarily clamped and Chinese ink was injected at the level of the renal arteries. In the second, a distal aortic clamp was combined with alternated clamping of the contralateral arteries. Immediately after injection, kidneys were harvested for histological analysis. Amniotic fluid stem cells labeled with LacZ were injected in the aorta by alternated clamping of the renal arteries in order to track the cells in a rat ischemia/reperfusion model. Without renal artery clamping, intra-aortic administration resulted in a delivery of the ink into the right kidney, whereas administration with alternated clamping of the contralateral renal artery, together with distal aortic artery clamping, resulted in a more homogenous distribution of the ink in both kidneys. Moreover, LacZ-positive cells were found in both kidneys after 6 h of injection. In conclusion, the retrograde administration of Chinese ink in two steps is a fast and reproducible technique, which results in a more homogenous distribution of the stain in both kidneys than a single administration combined by only clamping the aorta.

Expression of a Distinct Set of Chemokine Receptors in Adipose Tissue-Derived Stem Cells is Responsible for In Vitro Migration Toward Chemokines Appearing in the Major Pelvic Ganglion Following Cavernous Nerve Injury

Sexual Medicine. Aug, 2013  |  Pubmed ID: 25356281

Adipose tissue-derived stem cells (ADSCs) herald tremendous promise for clinical application in a wide range of injuries and diseases. Several preclinical reports demonstrate their efficacy in the treatment of cavernous nerve (CN) injury-induced erectile dysfunction in rats. It was recently illustrated that these effects were established as a result of ADSC migration to the major pelvic ganglion (MPG) where these cells induced neuroregeneration in loco.

Calculation of Membrane Tension in Selected Sections of the Pelvic Floor

International Urogynecology Journal. Apr, 2014  |  Pubmed ID: 24146072

A mathematical model to estimate membrane tensions (Mt) at the urogenital hiatus and midpelvis in patients with and without prolapse is proposed. For that purpose the complex structures of the pelvic floor were simplified and, based on assumptions concerning geometry and loading conditions, Laplace's law was used to calculate Mt. The pelvic cavity is represented by an ellipsoid in which the midpelvic and hiatal sections are described by an ellipse. The downwards forces within the pelvis (F(in)) are in equilibrium with the support forces within its walls (F(w)). F(in) is the abdominal pressure (PABD) multiplied by the area A of the ellipse. The force inside the tissues (F(w)) is distributed along the circumference of the ellipse C. The Mt can be approximated as Mt = (PABD.A)/C (N/m). Mt-α accounts for the angle α which describes tissue orientation with respect to the anatomical section and is calculated as Mt-α = Mt/sin(α).

A Pictorial Essay on Fetal Rabbit Anatomy Using Micro-ultrasound and Magnetic Resonance Imaging

Prenatal Diagnosis. Jan, 2014  |  Pubmed ID: 24151193

With this pictorial essay, we aimed to provide gestational age specific reference ranges of relevant fetal structures using micro-ultrasound, as well as its correlation with postmortem MRI and whole body sections.

In Vivo Assessment of the Biomechanical Properties of the Uterine Cervix in Pregnancy

Prenatal Diagnosis. Jan, 2014  |  Pubmed ID: 24155152

Measuring the stiffness of the cervix might be useful in the prediction of preterm delivery or successful induction of labor. For that purpose, a variety of methods for quantitative determination of physical properties of the pregnant cervix have been developed. Herein, we review studies on the clinical application of these new techniques. They are based on the quantification of mechanical, optical, or electrical properties associated with increased hydration and loss of organization in collagen structure. Quasi-static elastography determines relative values of stiffness; hence, it can identify differences in deformability. Quasi-static elastography unfortunately cannot quantify in absolute terms the stiffness of the cervix. Also, the current clinical studies did not demonstrate the ability to predict the time point of delivery. In contrast, measurement of maximum deformability of the cervix (e.g. quantified with the cervical consistency index) provided meaningful results, showing an increase in compliance with gestational age. These findings are consistent with aspiration measurements on the pregnant ectocervix, indicating a progressive decrease of stiffness along gestation. Cervical consistency index and aspiration measurements therefore represent promising techniques for quantitative assessment of the biomechanical properties of the cervix.

A Prospective Study of the Clinical Utility of Prenatal Chromosomal Microarray Analysis in Fetuses with Ultrasound Abnormalities and an Exploration of a Framework for Reporting Unclassified Variants and Risk Factors

Genetics in Medicine : Official Journal of the American College of Medical Genetics. Jun, 2014  |  Pubmed ID: 24177055

To evaluate the clinical utility of chromosomal microarrays for prenatal diagnosis by a prospective study of fetuses with abnormalities detected on ultrasound.

Optimizing Study Design for Interobserver Reliability: IUGA-ICS Classification of Complications of Prostheses and Graft Insertion

International Urogynecology Journal. Jun, 2014  |  Pubmed ID: 24196654

Results of interobserver reliability studies for the International Urogynecological Association-International Continence Society (IUGA-ICS) Complication Classification coding can be greatly influenced by study design factors such as participant instruction, motivation, and test-question clarity. We attempted to optimize these factors.

Fetal Heart Pathology on Postmortem 3-T Magnetic Resonance Imaging

Prenatal Diagnosis. Mar, 2014  |  Pubmed ID: 24243492

Postmortem magnetic resonance imaging (pmMRI) is increasingly used in perinatology, typically as an alternative or complement to conventional necropsy for central nervous system anomalies. Overall, it provides reliable information on structural malformations but was shown to be of limited use in examining the fetal heart.

Development and Use of a High-fidelity Simulator for Fetal Endotracheal Balloon Occlusion (FETO) Insertion and Removal

Prenatal Diagnosis. Feb, 2014  |  Pubmed ID: 24284906

Objectives The objective of this article is to describe the development of an anatomically accurate simulator in order to aid the training of a perinatal team in the insertion and removal of a fetal endoscopic tracheal occlusion (FETO) balloon in the management of prenatally diagnosed congenital diaphragmatic hernia. Methods An experienced perinatal team collaborated with a medical sculptor to design a fetal model for the FETO procedure. Measurements derived from 28-week fetal magnetic resonance imaging were used in the development of an anatomically precise simulated airway within a silicone rubber preterm fetal model. Clinician feedback was then used to guide multiple iterations of the model with serial improvements in the anatomic accuracy of the simulator airway. Results An appropriately sized preterm fetal mannequin with a high-fidelity airway was developed. The team used this model to develop surgical skills with balloon insertion, and removal, and to prepare the team for an integrated response to unanticipated delivery with the FETO balloon still in situ. Conclusions This fetal mannequin aided in the ability of a fetal therapy unit to offer the FETO procedure at their center for the first time. This model may be of benefit to other perinatal centers planning to offer this procedure.

Growth Discordance

Best Practice & Research. Clinical Obstetrics & Gynaecology. Feb, 2014  |  Pubmed ID: 24361179

Poor growth is a common problem in twin pregnancies, and management poses some unique challenges as the wellbeing of both twins have to be taken into account at all times. The decision to deliver the twins to prevent an intrauterine demise of the growth-restricted twin will, therefore, depends on the chances of intact postnatal survival of both twins. In monochorionic twins, management is complicated further by the fact that the wellbeing of one twin critically depends on that of the other twin because of the shared circulation. In the event of demise of the growth-restricted twin, the larger twin may also die or sustain brain damage because of an acute exsanguination into the feto-placental unit of its demised co-twin. In the pre-viable period, invasive fetal therapy may, therefore, be indicated to protect the appropriately growing twin.

Functional Assessment of Hyperoxia-induced Lung Injury After Preterm Birth in the Rabbit

American Journal of Physiology. Lung Cellular and Molecular Physiology. Feb, 2014  |  Pubmed ID: 24375793

The objective of this study was to document early neonatal (7 days) pulmonary outcome in the rabbit model for preterm birth and hyperoxia-induced lung injury. Preterm pups were delivered at 28 days (term = 31 days; early saccular phase of lung development) by cesarean section, housed in an incubator, and gavage fed for 7 days. Pups were divided into the following groups: 1) normoxia (21% O2; normoxia group) and 2) and hyperoxia (>95% O2; hyperoxia group). Controls were pups born at term who were housed in normoxic conditions (control group). Outcome measures were survival, pulmonary function tests using the whole body plethysmograph and forced oscillation technique, and lung morphometry. There was a significant difference in survival of preterm pups whether they were exposed to normoxia (83.3%) or hyperoxia (55.9%). Hyperoxic exposure was associated with increased tissue damping and elasticity and decreased static compliance compared with normoxic controls (P < 0.01). Morphometry revealed an increased linear intercept and increased mean wall transection length, which translates to larger alveoli with septal thickening in hyperoxia compared with normoxia (P < 0.01). In conclusion, the current experimental hyperoxic conditions to which preterm pups are exposed induce the typical clinical features of bronchopulmonary dysplasia. This model will be used to study novel preventive or therapeutic interventions.

In Case You Missed It: the Prenatal Diagnosis Section Editors Bring You the Most Significant Advances of 2013

Prenatal Diagnosis. Jan, 2014  |  Pubmed ID: 24382791

Mesh Contraction: in Vivo Documentation of Changes in Apparent Surface Area Utilizing Meshes Visible on Magnetic Resonance Imaging in the Rabbit Abdominal Wall Model

International Urogynecology Journal. Jun, 2014  |  Pubmed ID: 24448724

Our aim was to analyze the apparent contraction of meshes in vivo after abdominal wall reconstruction and evaluate histological and biomechanical properties after explantation.

Biomechanics of the Rat Vagina During Pregnancy and Postpartum: a 3-dimensional Ultrasound Approach

International Urogynecology Journal. Jul, 2014  |  Pubmed ID: 24452620

The vagina and surrounding structures have been shown to remodel during pregnancy. Our objective was to characterize the biomechanical properties of the vagina in the rodent model in vivo utilizing three-dimensional (3D) ultrasound.

A Novel Translational Model of Percutaneous Fetoscopic Endoluminal Tracheal Occlusion - Baboons (Papio Spp.)

Fetal Diagnosis and Therapy. 2014  |  Pubmed ID: 24480792

Percutaneous fetoscopic endoluminal reversible tracheal occlusion (FETO) was developed to prevent the pulmonary complications of fetal congenital diaphragmatic herniation. There is an urgent need to establish the closest to human translational model of FETO in order to improve fetal outcomes and to determine new clinical approaches and applications.

Immunological Ignorance Allows Long-term Gene Expression After Perinatal Recombinant Adeno-associated Virus-mediated Gene Transfer to Murine Airways

Human Gene Therapy. Jun, 2014  |  Pubmed ID: 24548076

Gene therapy of the lung has the potential to treat life-threatening diseases such as cystic fibrosis and α(1)-antitrypsin or surfactant deficiencies. A major hurdle for successful gene therapy is the development of an immune response against the transgene and/or viral vector. We hypothesized that by targeting the airways in the perinatal period, induction of an immune response against the vector particle could be prevented because of immaturity of the immune system, in turn allowing repeated gene transfer later in adult life to ensure long-term gene expression. Therefore, we readministered recombinant adeno-associated viral vector serotype 5 (rAAV2/5) to mouse airways 3 and 6 months after initial perinatal gene transfer. Our findings demonstrate that perinatal rAAV2/5-mediated gene transfer to the airways avoids a strong immune response. This immunological ignorance allows the readministration of an autologous vector later in adult life, resulting in efficient and stable gene transfer up to 7 months, without evidence of a decrease in transgene expression. Together, these data provide a basis to further explore perinatal gene therapy for pulmonary conditions with adequate gene expression up to 7 months.

Fetal Surgery in Complicated Monoamniotic Pregnancies: Case Series and Systematic Review of the Literature

Prenatal Diagnosis. Jun, 2014  |  Pubmed ID: 24596242

This study aimed to analyze perinatal outcome in monoamniotic (MA) pregnancies that underwent antenatal surgical interventions for fetal complications.

Fetoscopic Laser Coagulation of the Vascular Equator Versus Selective Coagulation for Twin-to-twin Transfusion Syndrome: an Open-label Randomised Controlled Trial

Lancet (London, England). Jun, 2014  |  Pubmed ID: 24613024

Monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome are typically treated with fetoscopic laser coagulation. Postoperative complications can occur due to residual vascular anastomoses on the placenta. We aimed to assess the efficacy and safety of a novel surgery technique that uses laser coagulation of the entire vascular equator (Solomon technique).

Perception and Knowledge About Stem Cell and Tissue Engineering Research: a Survey Amongst Researchers and Medical Practitioners in Perinatology

Stem Cell Reviews. Aug, 2014  |  Pubmed ID: 24647632

Stem cell and tissue engineering (SC&TE) research remain controversial. Polemics are potential hurdles for raising public funds for research and clinical implementation. In view of future applications of SC&TE in perinatal conditions, we aimed to measure the background knowledge, perceptions or beliefs on SC&TE research among clinicians and academic researchers with perinatal applications on the department's research agenda.

Influence of Reproductive Status on Tissue Composition and Biomechanical Properties of Ovine Vagina

PloS One. 2014  |  Pubmed ID: 24709913

To undertake a comprehensive analysis of the biochemical tissue composition and passive biomechanical properties of ovine vagina and relate this to the histo-architecture at different reproductive stages as part of the establishment of a large preclinical animal model for evaluating regenerative medicine approaches for surgical treatment of pelvic organ prolapse.

Exome Sequencing Identifies ZFPM2 As a Cause of Familial Isolated Congenital Diaphragmatic Hernia and Possibly Cardiovascular Malformations

European Journal of Medical Genetics. May-Jun, 2014  |  Pubmed ID: 24769157

Using exome sequencing we identify a heterozygous nonsense mutation in ZFPM2 as a cause of familial isolated congenital diaphragmatic hernia in 2 affected siblings. This mutation displays variable phenotypic expression being present in a third sibling with a mild diaphragmatic eventration and a cardiovascular malformation. The same variant is seen in 2 additional family members, both of whom are asymptomatic, thus highlighting that ZFPM2 haploinsufficiency is associated with reduced penetrance. Our finding adds further evidence for ZFPM2 having a role in diaphragm and cardiovascular development.

Routine Isolation and Expansion Late Mid Trimester Amniotic Fluid Derived Mesenchymal Stem Cells in a Cohort of Fetuses with Congenital Diaphragmatic Hernia

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Jul, 2014  |  Pubmed ID: 24798073

To assess the feasibility of routine isolation and expansion of amniotic fluid derived mesenchymal stem cells (AF-MSC) in fetuses diagnosed with isolated congenital diaphragmatic hernia (CDH).

Residual Anastomoses in Twin-twin Transfusion Syndrome After Laser: the Solomon Randomized Trial

American Journal of Obstetrics and Gynecology. Sep, 2014  |  Pubmed ID: 24813598

Residual anastomoses after fetoscopic laser surgery for twin-to-twin transfusion syndrome (TTTS) may lead to severe postoperative complications, including recurrent TTTS and twin anemia-polycythemia sequence (TAPS). A novel technique (Solomon technique) using laser coagulation of the entire vascular equator was recently investigated in a randomized controlled trial (Solomon trial) and compared with the Standard selective laser technique. The aim of this secondary analysis was to evaluate the occurrence and characteristics of residual anastomoses in placentas included in the Solomon trial.

The Challenge of Implementing Laparoscopic Sacrocolpopexy

International Urogynecology Journal. Sep, 2014  |  Pubmed ID: 24846152

Vaginal-vault prolapse is effectively treated using sacrocolpopexy (SCP). A randomized trial demonstrated that it can be performed as effectively via laparoscopy (LSCP) as via laparotomy and with less morbidity. This evidence begs the question of how units offering abdominal sacrocolpopexy will implement LSCP. Several limitations need to be overcome. LSCP initially requires longer operating time; however, that decreases with surgeon experience. To decrease operation time, suture training can be implemented ahead. Following a 15-h suturing lab, trainees achieved comparable operation times after 30 cases. Dissection is another critical time-consuming step and is difficult to model. Proficiency is more dependent on patient characteristics, though this component is poorly studied. One experience showed it takes 60 procedures to effectively limit complications. The large number of patients required for surgeon training for this relative infrequent operation creates a problem, thus limiting the number of centers available for training surgeons within a reasonable period.

Analysis of the Learning Process for Laparoscopic Sacrocolpopexy: Identification of Challenging Steps

International Urogynecology Journal. Sep, 2014  |  Pubmed ID: 24846153

We earlier demonstrated that the operation time of laparoscopic sacrocolpopexy (LSCP) by an experienced surgeon drops significantly after 30 cases to reach a steady state after 90. We now aimed to define the learning curve and to identify the most challenging steps for a trainee learning LSCP.

Assessment of Pulmonary Vascular Reactivity to Oxygen Using Fractional Moving Blood Volume in Fetuses with Normal Lung Development and Pulmonary Hypoplasia in Congenital Diaphragmatic Hernia

Prenatal Diagnosis. Oct, 2014  |  Pubmed ID: 24863699

The objective of this study is to evaluate whether assessment pulmonary vascular reactivity in response to maternal hyperoxygenation using fractional moving blood volume (FMBV) is associated with lesser variability between individual measurements than what is observed with direct Doppler measurements.

Medical and Regenerative Solutions for Congenital Diaphragmatic Hernia: a Perinatal Perspective

European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery ... [et Al] = Zeitschrift Fur Kinderchirurgie. Jun, 2014  |  Pubmed ID: 24937193

In the EU-27, 2,100 babies with congenital diaphragmatic hernia (CDH) are born annually. CDH is fatal in 30% of them. Experimental fetal surgery in severe cases results in a survival rate of 50 to 60% at its best. Failure is due to insufficient lung growth, persistent pulmonary hypertension or prematurity induced by the procedure. For nonsurvivors alternative strategies are required. Survivors undergo anatomical repair, but large diaphragmatic defects are closed using a patch. At present the used materials are less than ideal, mainly because of recurrence and chest deformation. To overcome the above limitations, alternative medical therapies (pharmacologic or cell therapy) that are more potent and less invasive are needed. Also a more functional postnatal repair may be possible when using novel scaffolds or engineered constructs. We see a prominent place for autologous amniotic fluid-derived stem cells for these novel strategies, which could be prenatally harvested following appropriate patient selection by noninvasive imaging.

Absence of Intestinal Inflammation and Postoperative Ileus in a Mouse Model of Laparoscopic Surgery

Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. Sep, 2014  |  Pubmed ID: 24966010

Postoperative ileus (POI) is characterized by impaired gastrointestinal motility resulting from intestinal handling-associated inflammation. The introduction of laparoscopic surgery has dramatically reduced the duration of POI. However, it remains unclear to what extent this results in a reduction of intestinal inflammation. The aim of the present study is to compare the degree of intestinal inflammation and gastrointestinal transit following laparoscopic surgery and open abdominal surgery.

Speckle Tracking Echocardiography in Fetuses Diagnosed with Congenital Diaphragmatic Hernia

Prenatal Diagnosis. Dec, 2014  |  Pubmed ID: 25043615

The aim of this study is to evaluate cardiac function in fetuses with congenital diaphragmatic hernia (CDH) using speckle tracking.

The 2013 Malcolm Ferguson-Smith Young Investigator Award

Prenatal Diagnosis. Aug, 2014  |  Pubmed ID: 25087736

Acute in Vivo Response to an Alternative Implant for Urogynecology

BioMed Research International. 2014  |  Pubmed ID: 25136633

To investigate in vivo the acute host response to an alternative implant designed for the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP).

Hysteropexy in the Treatment of Uterine Prolapse Stage 2 or Higher: a Multicenter Randomized Controlled Non-inferiority Trial Comparing Laparoscopic Sacrohysteropexy with Vaginal Sacrospinous Hysteropexy (LAVA-trial, Study Protocol)

BMC Women's Health. Sep, 2014  |  Pubmed ID: 25231240

Pelvic organ prolapse is a common health problem: the lifetime risk of undergoing surgery for pelvic organ prolapse by the age of 85 years is 19%. Pelvic organ prolapse has significant negative effects on a woman's quality of life. Worldwide, vaginal hysterectomy is the leading treatment method for patients with symptomatic uterovaginal prolapse. Several studies have shown that vaginal sacrospinous hysteropexy and laparoscopic sacrohysteropexy are safe and effective alternatives in treating uterine descent. To date, it is unclear which of these techniques leads to the best operative result and the highest patient satisfaction. Therefore, we conducted the LAVA trial.

Full Thickness Abdominal Wall Defect in Growing Rats As a Model for Congenital Diaphragmatic Hernia Prosthetic Repair

Journal of Pediatric Surgery. Oct, 2014  |  Pubmed ID: 25280646

Large congenital diaphragmatic hernia may require prosthetic correction. Acellular collagen matrices were introduced to avoid complications owing to the use of synthetic patches. We tested 3 different ACM for reconstruction of an abdominal wall defect in an animal model that mimics the fast growth during infancy.

Prenatal Management of the Fetus with Isolated Congenital Diaphragmatic Hernia in the Era of the TOTAL Trial

Seminars in Fetal & Neonatal Medicine. Dec, 2014  |  Pubmed ID: 25447987

Congenital diaphragmatic hernia (CDH) may be isolated or associated with other structural anomalies, the latter with poor prognosis. The defect allows viscera to herniate through the defect into the chest, competing for space with the developing lungs. At birth, pulmonary hypoplasia leads to respiratory insufficiency and persistent pulmonary hypertension that is lethal in up to 30% of patients. When isolated, survival chances can be predicted by antenatal measurement of lung size and liver herniation. Chromosomal microarrays and exome sequencing contribute to understanding genetic factors underlying isolated CDH. Prenatal intervention aims at stimulating lung development, clinically achieved by percutaneous fetal endoscopic tracheal occlusion (FETO) under local anesthesia. The Tracheal Occlusion To Accelerate Lung growth trial ( is an international randomized trial investigating the role of fetal therapy for severe and moderate pulmonary hypoplasia. Despite an apparent increase in survival following FETO, the search for lesser invasive and more potent prenatal interventions must continue.

High-frequency Micro-ultrasound: a Novel Method to Assess External Urethral Sphincter Function in Rats Following Simulated Birth Injury

Neurourology and Urodynamics. Mar, 2015  |  Pubmed ID: 24436081

We evaluated external urethral sphincter (EUS) function using high-frequency micro-ultrasound (US) in rats that were either uninjured (Control, C) or underwent vaginal distension (VD) as a substitute for vaginal birth injury induced stress urinary incontinence (SUI).

Expanding the Phenotypic Spectrum of PORCN Variants in Two Males with Syndromic Microphthalmia

European Journal of Human Genetics : EJHG. Apr, 2015  |  Pubmed ID: 25026905

Variants in PORCN are a cause of Goltz-Gorlin syndrome or Focal Dermal Hypoplasia, an X-linked dominant disorder affecting heterozygous females and until now considered to be embryonic lethal in males. Exome sequencing was performed in a family in which two male siblings were characterized by microphthalmia and additional congenital anomalies including diaphragmatic hernia, spina bifida and cardiac defects. Surprisingly, we identified a maternally inherited variant in PORCN present in both males as well as in two female siblings. This represents the first finding of a PORCN variant in non-mosaic males affected with Goltz-Gorlin syndrome. The apparently asymptomatic mother showed extreme skewing of X-inactivation (90%), an asymptomatic female sibling showed skewing of 88%, and the second female sibling affected with cutis aplasia of the scalp showed X-inactivation considered within the normal range.

Prenatal Diagnosis and Patient Preferences in Patients with Neural Tube Defects Around the Advent of Fetal Surgery in Belgium and Holland

Fetal Diagnosis and Therapy. 2015  |  Pubmed ID: 25301576

We review the characteristics and prenatal choices of patients recently evaluated for neural tube defects (NTD) at two tertiary units. The prenatal diagnosis of NTD allows parents to consider all prenatal options. In selected cases of spina bifida aperta this also includes fetal surgery, which we started offering after combined 'in-house' and 'exported' training.

Prediction of Neonatal Respiratory Function and Pulmonary Hypertension in Fetuses with Isolated Congenital Diaphragmatic Hernia in the Fetal Endoscopic Tracleal Occlusion Era: a Single-center Study

Fetal Diagnosis and Therapy. 2015  |  Pubmed ID: 25402437

To correlate prenatal indicators of pulmonary hypoplasia with neonatal lung function and pulmonary hypertension (PHT) in isolated congenital diaphragmatic hernia (iCDH).

Host Reaction to Vaginally Inserted Collagen Containing Polypropylene Implants in Sheep

American Journal of Obstetrics and Gynecology. Apr, 2015  |  Pubmed ID: 25446700

We aimed to characterize the effect of vaginal or abdominal mesh insertion and of different collagen augmentation of polypropylene mesh in a sheep model. Outcome measures were passive and active biomechanical properties and semiquantitative morphometry.

Unique Tracheal Fluid MicroRNA Signature Predicts Response to FETO in Patients With Congenital Diaphragmatic Hernia

Annals of Surgery. Dec, 2015  |  Pubmed ID: 25563880

Our objective was to determine the fetal in vivo microRNA signature in hypoplastic lungs of human fetuses with severe isolated congenital diaphragmatic hernia (CDH) and changes in tracheal and amniotic fluid of fetuses undergoing fetoscopic endoluminal tracheal occlusion (FETO) to reverse severe lung hypoplasia due to CDH.

In Case You Missed It: the Prenatal Diagnosis Editors Bring You the Most Significant Advances of 2014

Prenatal Diagnosis. Jan, 2015  |  Pubmed ID: 25594313

Laser Ablation of Posterior Urethral Valves by Fetal Cystoscopy

Fetal Diagnosis and Therapy. 2015  |  Pubmed ID: 25614247

To report the results of fetal cystoscopic laser ablation of posterior urethral valves (PUV) in a consecutive series in two referral centers.

Safe and Effective Cryopreservation Methods for Long-term Storage of Human-amniotic-fluid-derived Stem Cells

Prenatal Diagnosis. May, 2015  |  Pubmed ID: 25641322

Stem cells (SCs) can be isolated from amniotic fluid (AF) for a variety of perinatal applications. In view of this, we compared different cryopreservation protocols for these AFSCs.

Three-dimensional Analysis of Implanted Magnetic-resonance-visible Meshes

International Urogynecology Journal. Oct, 2015  |  Pubmed ID: 25800904

Our primary objective was to develop relevant algorithms for quantification of mesh position and 3D shape in magnetic resonance (MR) images.

Experimental Evaluation of Tracheo-Amniotic Shunting for Induced Congenital High Airway Obstruction in a Sheep Model

Fetal Diagnosis and Therapy. 2015  |  Pubmed ID: 25895676

To evaluate the feasibility of tracheo-amniotic shunting in a sheep model for congenital high airway obstruction syndrome.

Cross-linked Xenogenic Collagen Implantation in the Sheep Model for Vaginal Surgery

Gynecological Surgery. 2015  |  Pubmed ID: 25960708

The properties of meshes used in reconstructive surgery affect the host response and biomechanical characteristics of the grafted tissue. Whereas durable synthetics induce a chronic inflammation, biological grafts are usually considered as more biocompatible. The location of implantation is another determinant of the host response: the vagina is a different environment with specific function and anatomy. Herein, we evaluated a cross-linked acellular collagen matrix (ACM), pretreated by the anti-calcification procedure ADAPT® in a sheep model for vaginal surgery. Ten sheep were implanted with a cross-linked ACM, and six controls were implanted with a polypropylene (PP; 56 g/m(2)) control. One implant was inserted in the lower rectovaginal septum, and one was used for abdominal wall defect reconstruction. Grafts were removed after 180 days; all graft-related complications were recorded, and explants underwent bi-axial tensiometry and contractility testing. Half of ACM-implanted animals had palpable induration in the vaginal implantation area, two of these also on the abdominal implant. One animal had a vaginal exposure. Vaginal ACMs were 63 % less stiff compared to abdominal ACM explants (p = 0.01) but comparable to vaginal PP explants. Seven anterior vaginal ACM explants showed areas of graft degradation on histology. There was no overall difference in vaginal contractility. Considering histologic degradation in the anterior vaginal implant as representative for the host, posterior ACM explants of animals with degradation had a 60 % reduced contractility as compared to PP (p = 0.048). Three abdominal implants showed histologic degradation; those were more compliant than non-degraded implants. Vaginal implantation with ACM was associated with graft-related complications (GRCs) and biomechanical properties comparable to PP. Partially degraded ACM had a decreased vaginal contractility.

The Use of Human Amniotic Fluid Stem Cells As an Adjunct to Promote Pulmonary Development in a Rabbit Model for Congenital Diaphragmatic Hernia

Prenatal Diagnosis. Sep, 2015  |  Pubmed ID: 25976324

This study aimed to evaluate the potential benefit of intra-tracheal injection of human amniotic fluid stem cells (hAFSC) on pulmonary development combined with TO in a rabbit model for CDH.

Medical Interventions to Reverse Pulmonary Hypoplasia in the Animal Model of Congenital Diaphragmatic Hernia: A Systematic Review

Pediatric Pulmonology. Aug, 2015  |  Pubmed ID: 25994108

We aimed to systematically review all published pre-clinical research on prenatal medical treatment of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Background The neonatal mortality due to isolated CDH remains high. Whether fetal endoscopic tracheal occlusion (FETO) reduces mortality is still to be demonstrated. Therefore more potent preferentially medical therapy would be welcomed. Methods We searched MEDLINE (Pubmed), Embase and the Web of Science including all studies from the earliest date (1951) to December 2013. Article quality was assessed using the modified CAMRADES checklist. Inclusion criteria were those animal studies addressing prenatal medical interventions and principal variables were confirmation of a diaphragmatic defect, lung to body weight ratio (LBWR), formal airway morphometry or DNA/protein content. Results In total 983 articles were identified. Following abstract review, 96 articles were assessed by two authors in agreement with a third for eligibility. Of these, 43 were included in the final analysis. The median number of study quality checklist items (maximum 10) scored was 4 (IQ range: 2-5). Thirty (69.8%) of studies were in the nitrofen rat. The majority were treated with vitamins or glucocorticoids. Single studies reported some improvement in lung morphology with alternative therapies. It was impossible to identify a pattern in animal model selection or creation, mode, time point or duration of treatment and readouts. Only one study reported a sample size calculation. Conclusion Comparison in pre-clinical studies in CDH is challenging due to methodological variation. Agreed standardized methods need to be applied in future investigation of new medical therapies.

Molecular Signature of Amniotic Fluid Derived Stem Cells in the Fetal Sheep Model of Myelomeningocele

Journal of Pediatric Surgery. Sep, 2015  |  Pubmed ID: 26026346

Abnormal cord development results in spinal cord damage responsible for myelomeningocele (MMC). Amniotic fluid-derived stem cells (AFSCs) have emerged as a potential candidate for applications in regenerative medicine. However, their differentiation potential is largely unknown as well as the molecular signaling orchestrating the accurate spinal cord development. Fetal lambs underwent surgical creation of neural tube defect and its subsequent repair. AFSCs were isolated, cultured and characterized at the 12th (induction of MMC), 16th (repair of malformation), and 20th week of gestation (delivery). After performing open hysterectomy, AF collections on fetuses with sham procedures at the same time points as the MMC creation group have been used as controls. Cytological analyses with the colony forming unit assay, XTT and alkaline-phosphatase staining, qRT-PCR gene expression analyses (normalized with aged match controls) and NMR metabolomics profiling were performed. Here we show for the first time the metabolomics and molecular signature variation in AFSCs isolated in the sheep model of MMC, which may be used as diagnostic tools for the in utero identification of the neural tube damage. Intriguingly, PAX3 gene involved in the murine model for spina bifida is modulated in AFSCs reaching the peak of expression at 16 weeks of gestation, 4 weeks after the intervention. Our data strongly suggest that AFSCs reorganize their differentiation commitment in order to generate PAX3-expressing progenitors to counteract the MMC induced in the sheep model. The gene expression signature of AFSCs highlights the plasticity of these cells reflecting possible alterations of embryonic development.

The 2014 Malcolm Ferguson-Smith Young Investigator Award

Prenatal Diagnosis. Jun, 2015  |  Pubmed ID: 26041253

In Vivo Evidence by Magnetic Resonance Volumetry of a Gestational Age Dependent Response to Tracheal Occlusion for Congenital Diaphragmatic Hernia

Prenatal Diagnosis. Nov, 2015  |  Pubmed ID: 26135752

We aimed to assess in vivo changes in lung and liver volumes in fetuses with isolated congenital diaphragmatic hernia, either expectantly managed or treated in utero.

Diaphragm Repair with a Novel Cross-Linked Collagen Biomaterial in a Growing Rabbit Model

PloS One. 2015  |  Pubmed ID: 26147985

Neonates with congenital diaphragmatic hernia and large defects often require patch closure. Acellular collagen matrices (ACM) have been suggested as an alternative to synthetic durable patches as they are remodeled by the host or could also be used for tissue engineering purposes.

Computer-assisted Surgical Planning and Intraoperative Guidance in Fetal Surgery: a Systematic Review

Prenatal Diagnosis. Dec, 2015  |  Pubmed ID: 26235960

Fetal surgery has become a clinical reality, with interventions for twin-to-twin transfusion syndrome (TTTS) and spina bifida demonstrated to improve outcome. Fetal imaging is evolving, with the use of 3D ultrasound and fetal MRI becoming more common in clinical practise. Medical imaging analysis is also changing, with technology being developed to assist surgeons by creating 3D virtual models that improve understanding of complex anatomy, and prove powerful tools in surgical planning and intraoperative guidance. We introduce the concept of computer-assisted surgical planning, and present the results of a systematic review of image reconstruction for fetal surgical planning that identified six articles using such technology. Indications from other specialities suggest a benefit of surgical planning and guidance to improve outcomes. There is therefore an urgent need to develop fetal-specific technology in order to improve fetal surgical outcome.

Amniotic Fluid Derived Stem Cells with a Renal Progenitor Phenotype Inhibit Interstitial Fibrosis in Renal Ischemia and Reperfusion Injury in Rats

PloS One. 2015  |  Pubmed ID: 26295710

Mesenchymal stem cells derived from human amniotic fluid (hAFSCs) are a promising source for cellular therapy, especially for renal disorders, as a subpopulation is derived from the fetal urinary tract. The purpose of this study was to evaluate if hAFSCs with a renal progenitor phenotype demonstrate a nephroprotective effect in acute ischemia reperfusion (I/R) model and prevent late stage fibrosis.

Transcriptome Analysis of the Preterm Rabbit Lung After Seven Days of Hyperoxic Exposure

PloS One. 2015  |  Pubmed ID: 26317699

The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD.

High-Resolution (1)H NMR Spectroscopy Discriminates Amniotic Fluid of Fetuses with Congenital Diaphragmatic Hernia from Healthy Controls

Journal of Proteome Research. Nov, 2015  |  Pubmed ID: 26348471

Lung hypoplasia in congenital diaphragmatic hernia (CDH) is a life-threatening birth defect. Severe cases can be offered tracheal occlusion to boost prenatal lung development, although defining those to benefit remains challenging. Metabonomics of (1)H NMR spectra collected from amniotic fluid (AF) can identify general changes in diseased versus healthy fetuses. AF embodies lung secretions and hence might contain pulmonary next to general markers of disease in CDH fetuses. AF from 81 healthy and 22 CDH fetuses was collected. NMR spectroscopy was performed at 400 MHz to compare AF from fetuses with CDH against controls. Several advanced feature extraction methods based on statistical tests that explore spectral variability, similarity, and dissimilarity were applied and compared. This resulted in the identification of 30 spectral regions, which accounted for 80% variability between CDH and controls. Combination with automated classification discriminates AF from CDH versus healthy fetuses with up to 92% accuracy. Within the identified spectral regions, isoleucine, leucine, valine, pyruvate, GABA, glutamate, glutamine, citrate, creatine, creatinine, taurine, and glucose were the most concentrated metabolites. As the metabolite pattern of AF changes with fetal development, we have excluded metabolites with a high age-related variability and repeated the analysis with 12 spectral regions, which has resulted in similar classification accuracy. From this analysis, it was possible to distinguish between AF from CDH fetuses versus healthy controls independent of gestational age.


Journal of Pediatric Gastroenterology and Nutrition. Oct, 2015  |  Pubmed ID: 26439575

Congenital diaphragmatic hernia (CDH) is a rare condition characterized by a congenital defect in the diaphragm. Abdominal organs are displaced into the thorax through the diaphragmatic defect, hereby causing lung hypoplasia. Survivors also present with long-term functional gastro-intestinal morbidity such as gastro-esophageal reflux, esophageal dysfunction and poor nutritional status. Congenital esophageal dysmotility and surgical disruption of the esophago-gastric junction (EGJ) may contribute to this esophageal dysfunction. The aim of this study was to characterize esophageal function in young infants born with CDH.

Paracetamol Pharmacokinetics and Metabolism in Young Women

BMC Anesthesiology. Nov, 2015  |  Pubmed ID: 26566962

There is relevant between individual variability in paracetamol clearance in young women. In this pooled study, we focused on the population pharmacokinetic profile of intravenous paracetamol metabolism and its covariates in young women.

Immediate Postoperative Changes in Synthetic Meshes - In Vivo Measurements

Journal of the Mechanical Behavior of Biomedical Materials. Mar, 2015  |  Pubmed ID: 26594782

Immediate post-operative structural changes in implanted synthetic meshes are believed to contribute to graft related complications. Our aim was to observe in vivo dimensional changes at the pore level.

Interventional Photoacoustic Imaging of the Human Placenta with Ultrasonic Tracking for Minimally Invasive Fetal Surgeries

Medical Image Computing and Computer-assisted Intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. Oct, 2015  |  Pubmed ID: 28101537

Image guidance plays a central role in minimally invasive fetal surgery such as photocoagulation of inter-twin placental anastomosing vessels to treat twin-to-twin transfusion syndrome (TTTS). Fetoscopic guidance provides insufficient sensitivity for imaging the vasculature that lies beneath the fetal placental surface due to strong light scattering in biological tissues. Incomplete photocoagulation of anastamoses is associated with postoperative complications and higher perinatal mortality. In this study, we investigated the use of multi-spectral photoacoustic (PA) imaging for better visualization of the placental vasculature. Excitation light was delivered with an optical fiber with dimensions that are compatible with the working channel of a fetoscope. Imaging was performed on an ex vivo normal term human placenta collected at Caesarean section birth. The photoacoustically-generated ultrasound signals were received by an external clinical linear array ultrasound imaging probe. A vein under illumination on the fetal placenta surface was visualized with PA imaging, and good correspondence was obtained between the measured PA spectrum and the optical absorption spectrum of deoxygenated blood. The delivery fiber had an attached fiber optic ultrasound sensor positioned directly adjacent to it, so that its spatial position could be tracked by receiving transmissions from the ultrasound imaging probe. This study provides strong indications that PA imaging in combination with ultrasonic tracking could be useful for detecting the human placental vasculature during minimally invasive fetal surgery.

The Effect of Transplacental Administration of Glucagon-Like Peptide-1 on Fetal Lung Development in the Rabbit Model of Congenital Diaphragmatic Hernia

Fetal Diagnosis and Therapy. 2016  |  Pubmed ID: 26277998

Glucagon-like peptide-1 (GLP-1) increases surfactant protein expression in type 2 pneumocytes. Herein, we determine if transplacental GLP-1 treatment accelerates lung growth in the fetal rabbit model of congenital diaphragmatic hernia (DH).

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model

Fetal Diagnosis and Therapy. 2016  |  Pubmed ID: 26375032

Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone.

Thrombin Generation by Fetoscopic Trauma to the Fetal Membranes: An in Vivo and in Vitro Study

Fetal Diagnosis and Therapy. 2016  |  Pubmed ID: 26426691

We first aimed to investigate in vivo thrombin generation induced by fetoscopy, and second we used term membrane explants for measurement of thrombin generation, thrombin receptor location and induction of selected matrix metalloproteinases (MMPs) in tissue culture.

Prenatal Interventions to Prevent Bronchopulmonary Dysplasia in Animal Models: a Systematic Review

The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2016  |  Pubmed ID: 26456571

The objective of this study is to identify and systematically review in vivo animal studies on antenatal medical interventions to prevent bronchopulmonary dysplasia.

Pulmonary Transcriptome Analysis in the Surgically Induced Rabbit Model of Diaphragmatic Hernia Treated with Fetal Tracheal Occlusion

Disease Models & Mechanisms. Feb, 2016  |  Pubmed ID: 26744354

Congenital diaphragmatic hernia (CDH) is a malformation leading to pulmonary hypoplasia, which can be treated in utero by fetal tracheal occlusion (TO). However, the changes of gene expression induced by TO remain largely unknown but could be used to further improve the clinically used prenatal treatment of this devastating malformation. Therefore, we aimed to investigate the pulmonary transcriptome changes caused by surgical induction of diaphragmatic hernia (DH) and additional TO in the fetal rabbit model. Induction of DH was associated with 378 upregulated genes compared to controls when allowing a false-discovery rate (FDR) of 0.1 and a fold change (FC) of 2. Those genes were again downregulated by consecutive TO. But DH+TO was associated with an upregulation of 157 genes compared to DH and controls. When being compared to control lungs, 106 genes were downregulated in the DH group and were not changed by TO. Therefore, the overall pattern of gene expression in DH+TO is more similar to the control group than to the DH group. In this study, we further provide a database of gene expression changes induced by surgical creation of DH and consecutive TO in the rabbit model. Future treatment strategies could be developed using this dataset. We also discuss the most relevant genes that are involved in CDH.

In Case You Missed It: the Prenatal Diagnosis Editors Bring You the Most Significant Advances of 2015

Prenatal Diagnosis. Jan, 2016  |  Pubmed ID: 26777520

Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits

Neonatology. 2016  |  Pubmed ID: 26866610

Caffeine is a commonly used drug for apnea of prematurity. It may, however, also have a beneficial effect on bronchopulmonary dysplasia (BPD), which is the most common complication of extreme preterm birth.

Evaluating Alternative Materials for the Treatment of Stress Urinary Incontinence and Pelvic Organ Prolapse: A Comparison of the In Vivo Response to Meshes Implanted in Rabbits

The Journal of Urology. Jul, 2016  |  Pubmed ID: 26880411

Serious complications can develop with the mesh implants used for stress urinary incontinence and pelvic organ prolapse surgery. We evaluated 2 materials currently in clinical use and 2 alternative materials using a rabbit abdominal model to assess host response and biomechanical properties of the materials before and after implantation.

Fetoscopic Versus Open Repair for Spina Bifida Aperta: A Systematic Review of Outcomes

Fetal Diagnosis and Therapy. 2016  |  Pubmed ID: 26901156

To compare outcomes of fetoscopic spina bifida aperta repair (FSBAR) with the results of the open approach (OSBAR) as in the Management Of Myelomeningocele Study (MOMS).

Fetal Tracheal Occlusion for Severe Pulmonary Hypoplasia in Isolated Congenital Diaphragmatic Hernia: A Systematic Review and Meta-analysis of Survival

Annals of Surgery. Dec, 2016  |  Pubmed ID: 26910202

To evaluate fetal survival after tracheal occlusion in fetuses with severe pulmonary hypoplasia and isolated congenital diaphragmatic hernia (CDH).

Urine of Preterm Neonates As a Novel Source of Kidney Progenitor Cells

Journal of the American Society of Nephrology : JASN. Sep, 2016  |  Pubmed ID: 26940093

In humans, nephrogenesis is completed prenatally, with nephrons formed until 34 weeks of gestational age. We hypothesized that urine of preterm neonates born before the completion of nephrogenesis is a noninvasive source of highly potent stem/progenitor cells. To test this hypothesis, we collected freshly voided urine at day 1 after birth from neonates born at 31-36 weeks of gestational age and characterized isolated cells using a single-cell RT-PCR strategy for gene expression analysis and flow cytometry and immunofluorescence for protein expression analysis. Neonatal stem/progenitor cells expressed markers of nephron progenitors but also, stromal progenitors, with many single cells coexpressing these markers. Furthermore, these cells presented mesenchymal stem cell features and protected cocultured tubule cells from cisplatin-induced apoptosis. Podocytes differentiated from the neonatal stem/progenitor cells showed upregulation of podocyte-specific genes and proteins, albumin endocytosis, and calcium influx via podocyte-specific transient receptor potential cation channel, subfamily C, member 6. Differentiated proximal tubule cells showed upregulation of specific genes and significantly elevated p-glycoprotein activity. We conclude that urine of preterm neonates is a novel noninvasive source of kidney progenitors that are capable of differentiation into mature kidney cells and have high potential for regenerative kidney repair.

Gynaecological Endoscopic Surgical Education and Assessment. A Diploma Programme in Gynaecological Endoscopic Surgery

European Journal of Obstetrics, Gynecology, and Reproductive Biology. Apr, 2016  |  Pubmed ID: 26946312

In recent years, training and education in endoscopic surgery has been critically reviewed. Clinicians, both surgeons as gynaecologist who perform endoscopic surgery without proper training of the specific psychomotor skills are at higher risk to increased patient morbidity and mortality. Although the apprentice-tutor model has long been a successful approach for training of surgeons, recently, clinicians have recognised that endoscopic surgery requires an important training phase outside the operating theatre. The Gynaecological Endoscopic Surgical Education and Assessment programme (GESEA), recognises the necessity of this structured approach and implements two separated stages in its learning strategy. In the first stage, a skill certificate on theoretical knowledge and specific practical psychomotor skills is acquired through a high stake exam; in the second stage, a clinical programme is completed to achieve surgical competence and receive the corresponding diploma. Three diplomas can be awarded: (a) the Bachelor in Endoscopy; (b) the Minimally Invasive Gynaecological Surgeon (MIGS); and (c) the Master level. The Master level is sub-divided into two separate diplomas: the Master in Laparoscopic Pelvic Surgery and the Master in Hysteroscopy. The complexity of modern surgery has increased the demands and challenges to surgical education and the quality control. This programme is based on the best available scientific evidence and it counteracts the problem of the traditional surgical apprentice tutor model. It is seen as a major step toward standardization of endoscopic surgical training in general.

Transplacental Sildenafil Rescues Lung Abnormalities in the Rabbit Model of Diaphragmatic Hernia

Thorax. Jun, 2016  |  Pubmed ID: 26987998

The management of congenital diaphragmatic hernia (DH) would benefit from an antenatal medical therapy, which addresses both lung hypoplasia and persistent pulmonary hypertension. We aimed at evaluating the pulmonary effects of sildenafil in the fetal rabbit model for DH.

The Impact of Entry Technique and Access Diameter on Prelabour Rupture of Membranes Following Primary Fetoscopic Laser Treatment for Twin-Twin Transfusion Syndrome

Fetal Diagnosis and Therapy. 2016  |  Pubmed ID: 27073886

To evaluate the impact of entry method and access diameter at fetoscopic surgery for twin-twin transfusion syndrome in twin pregnancies with at least one survivor. The outcomes evaluated were prelabour rupture of membranes (PROM) and birth <4 weeks, preterm birth (PTB) <28 weeks, and latency to birth.

Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update

Neonatology. 2016  |  Pubmed ID: 27077664

In 2010, the congenital diaphragmatic hernia (CDH) EURO Consortium published a standardized neonatal treatment protocol. Five years later, the number of participating centers has been raised from 13 to 22. In this article the relevant literature is updated, and consensus has been reached between the members of the CDH EURO Consortium. Key updated recommendations are: (1) planned delivery after a gestational age of 39 weeks in a high-volume tertiary center; (2) neuromuscular blocking agents to be avoided during initial treatment in the delivery room; (3) adapt treatment to reach a preductal saturation of between 80 and 95% and postductal saturation >70%; (4) target PaCO2 to be between 50 and 70 mm Hg; (5) conventional mechanical ventilation to be the optimal initial ventilation strategy, and (6) intravenous sildenafil to be considered in CDH patients with severe pulmonary hypertension. This article represents the current opinion of all consortium members in Europe for the optimal neonatal treatment of CDH.

A Minimum of 1-year Follow-up for MiniArc Single Incision Slings Compared to Monarc Transobturator Slings: An Analysis to Evaluate Durability of Continence and Medium-term Outcomes

Neurourology and Urodynamics. May, 2016  |  Pubmed ID: 27148678

To compare efficacy and safety of two commercially available single incision slings (SIS) and trans-obturator vaginal tapes (TOT), namely MiniArc™ and Monarc™ slings, and report the results at 5-year follow-up.

Tissue Response to Collagen Containing Polypropylene Meshes in an Ovine Vaginal Repair Model

Acta Biomaterialia. Jul, 2016  |  Pubmed ID: 27163402

Pelvic Organ Prolapse (POP) is the herniation of pelvic organs into the vagina. Despite broad acceptance of mesh use in POP surgical repair, the complication rate is unacceptable. We hypothesized that collagen-containing polypropylene (PP) mesh types could modulate mesh-tissue integration and reduce long-term inflammation, thereby reducing mesh-associated complications. This study compared the long-term tissue response to an unmodified PP mesh and two collagen containing meshes in an ovine model which has similar pelvic anatomy and vaginal size to human. Three commercially available macroporous PP meshes, uncoated PP mesh (Avaulta Solo) (PP), the same textile PP mesh layered with a sheet of cross-linked porcine acellular matrix (Avaulta Plus) (PP-ACM) and a different yet also macroporous PP (Sofradim) mesh coated with solubilized atelocollagen (Ugytex) (PP-sCOL) were implanted in the ovine vagina and tissue explanted after 60 and 180days. The macrophage phenotype and response to implanted meshes, and vascularity were quantified by immunostaining and morphometry. We quantified changes in extracellular matrix composition biochemically and collagen organisation and percentage area around the interface of the mesh implants by Sirius Red birefringence and morphometry. PP-ACM induced a more sustained inflammatory response, indicated by similar CD45(+) leukocytes but reduced CD163(+) M2 macrophages at 60days (P<0.05). PP-sCOL increased Von Willebrand Factor (vWF)-immunoreactive vessel profiles after 60days. At the micro-molecular level, collagen birefringence quantification revealed significantly fewer mature collagen fibrils (red, thick fibrils) at the mesh-tissue interface than control tissue for all mesh types (P<0.001) but still significantly greater than the proportion of immature (green thin fibrils) at 60days (P<0.05). The proportion of mature collagen fibrils increased with time around the mesh filaments, particularly those containing collagen. The total collagen percent area at the mesh interface was greatest around the PP-ACM mesh at 60days (P<0.05). By 180days the total mature and immature collagen fibres at the interface of the mesh filaments resembled that of native tissue. In particular, these results suggest that both meshes containing collagen evoke different types of tissue responses at different times during the healing response yet both ultimately lead to physiological tissue formation approaching that of normal tissue.

Slic-Seg: A Minimally Interactive Segmentation of the Placenta from Sparse and Motion-corrupted Fetal MRI in Multiple Views

Medical Image Analysis. Dec, 2016  |  Pubmed ID: 27179367

Segmentation of the placenta from fetal MRI is challenging due to sparse acquisition, inter-slice motion, and the widely varying position and shape of the placenta between pregnant women. We propose a minimally interactive framework that combines multiple volumes acquired in different views to obtain accurate segmentation of the placenta. In the first phase, a minimally interactive slice-by-slice propagation method called Slic-Seg is used to obtain an initial segmentation from a single motion-corrupted sparse volume image. It combines high-level features, online Random Forests and Conditional Random Fields, and only needs user interactions in a single slice. In the second phase, to take advantage of the complementary resolution in multiple volumes acquired in different views, we further propose a probability-based 4D Graph Cuts method to refine the initial segmentations using inter-slice and inter-image consistency. We used our minimally interactive framework to examine the placentas of 16 mid-gestation patients from MRI acquired in axial and sagittal views respectively. The results show the proposed method has 1) a good performance even in cases where sparse scribbles provided by the user lead to poor results with the competitive propagation approaches; 2) a good interactivity with low intra- and inter-operator variability; 3) higher accuracy than state-of-the-art interactive segmentation methods; and 4) an improved accuracy due to the co-segmentation based refinement, which outperforms single volume or intensity-based Graph Cuts.

Evaluating Fetal Head Dimension Changes During Labor Using Open Magnetic Resonance Imaging

Journal of Perinatal Medicine. May, 2016  |  Pubmed ID: 27219097

Fetal skull molding is important for the adaptation of the head to the birth canal during vaginal delivery. Importantly, the fetal head must rotate around the maternal symphysis pubis. The goals of this analysis were to observe a human birth in real-time using an open magnetic resonance imaging (MRI) scanner and describe the fetal head configuration during expulsion.

Laparoscopic Versus Robotic-assisted Sacrocolpopexy for Pelvic Organ Prolapse: a Systematic Review

Gynecological Surgery. 2016  |  Pubmed ID: 27226787

The use of robot-assisted surgery (RAS) has gained popularity in the field of gynaecology, including pelvic floor surgery. To assess the benefits of RAS, we conducted a systematic review of randomized controlled trials comparing laparoscopic and robotic-assisted sacrocolpopexy. The Cochrane Library (1970-January 2015), MEDLINE (1966 to January 2015), and EMBASE (1974 to January 2015) were searched, as well as and the International Clinical Trials Registry Platform. We identified two randomized trials (n = 78) comparing laparoscopic with robotic sacrocolpopexy. The Paraiso 2011 study showed that laparoscopic was faster than robotic sacrocolpopexy (199 ± 46 vs. 265 ± 50 min; p < .001), yet in the ACCESS trial, no difference was present (225 ± 62.3 vs. 246.5 ± 51.3 min; p = .110). Costs for using the robot were significantly higher in both studies, however, in the ACCESS trial, only when purchase and maintenance of the robot was included (LSC US$11,573 ± 3191 vs. RASC US$19,616 ± 3135; p < .001). In the Paraiso study, RASC was more expensive even without considering those costs (LSC US$ 14,342 ± 2941 vs. RASC 16,278 ± 3326; p = 0.008). Pain was reportedly higher after RASC, although at different time points after the operation. There were no differences in anatomical outcomes, pelvic floor function, and quality of life. The experience with RASC was tenfold lower than that with LSC in both studies. The heterogeneity between the two studies precluded a meta-analysis. Based on small randomized studies, with surgeons less experienced in RAS than in laparoscopic surgery, robotic surgery significantly increases the cost of a laparoscopic sacrocolpopexy. RASC would be more sustainable if its costs would be lower. Though RASC may have other benefits, such as reduction of the learning curve and increased ergonomics or dexterity, these remain to be demonstrated.

Airway Tissue Engineering for Congenital Laryngotracheal Disease

Seminars in Pediatric Surgery. Jun, 2016  |  Pubmed ID: 27301606

Regenerative medicine offers hope of a sustainable solution for severe airway disease by the creation of functional, immunocompatible organ replacements. When considering fetuses and newborns, there is a specific spectrum of airway pathologies that could benefit from cell therapy and tissue engineering applications. While hypoplastic lungs associated with congenital diaphragmatic hernia (CDH) could benefit from cellular based treatments aimed at ameliorating lung function, patients with upper airway obstruction could take advantage from a de novo tissue engineering approach. Moreover, the international acceptance of the EXIT procedure as a means of securing the precarious neonatal airway, together with the advent of fetal surgery as a method of heading off postnatal co-morbidities, offers the revolutionary possibility of extending the clinical indication for tissue-engineered airway transplantation to infants affected by diverse severe congenital laryngotracheal malformations. This article outlines the necessary basic components for regenerative medicine solutions in this potential clinical niche.

Lung Size and Liver Herniation Predict the Need for Extra Corporeal Membrane Oxygenation but Not Pulmonary Hypertension in Isolated Congenital Diaphragmatic Hernia: a Systematic Review and Meta-analysis

Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. Jun, 2016  |  Pubmed ID: 27312047

To identify antenatal predictors of persistent pulmonary hypertension (PPH) and need for extracorporeal membrane oxygenation (ECMO) in fetuses with congenital diaphragmatic hernia (CDH).

The 2015 Malcolm Ferguson-Smith Young Investigator Award

Prenatal Diagnosis. Jul, 2016  |  Pubmed ID: 27381265

Gynaecological Endoscopic Surgical Education and Assessment. A Diploma Programme in Gynaecological Endoscopic Surgery

Gynecological Surgery. 2016  |  Pubmed ID: 27478427

In recent years, training and education in endoscopic surgery has been critically reviewed. Clinicians, both surgeons as gynaecologist who perform endoscopic surgery without proper training of the specific psychomotor skills, are at higher risk to increased patient morbidity and mortality. Although the apprentice-tutor model has long been a successful approach for training of surgeons, recently, clinicians have recognised that endoscopic surgery requires an important training phase outside the operating theatre. The Gynaecological Endoscopic Surgical Education and Assessment programme (GESEA) recognises the necessity of this structured approach and implements two separated stages in its learning strategy. In the first stage, a skill certificate on theoretical knowledge and specific practical psychomotor skills is acquired through a high-stake exam; in the second stage, a clinical programme is completed to achieve surgical competence and receive the corresponding diploma. Three diplomas can be awarded: (a) the Bachelor in Endoscopy, (b) the Minimally Invasive Gynaecological Surgeon (MIGS) and (c) the Master level. The Master level is sub-divided into two separate diplomas: the Master in Laparoscopic Pelvic Surgery and the Master in Hysteroscopy. The complexity of modern surgery has increased the demands and challenges to surgical education and the quality control. This programme is based on the best available scientific evidence, and it counteracts the problem of the traditional surgical apprentice-tutor model. It is seen as a major step toward standardisation of endoscopic surgical training in general.

Esophageal Atresia: Future Directions for Research on the Digestive Tract

European Journal of Pediatric Surgery : Official Journal of Austrian Association of Pediatric Surgery ... [et Al] = Zeitschrift Fur Kinderchirurgie. Aug, 2016  |  Pubmed ID: 27533315

Esophageal atresia (EA) is a congenital malformation defined by the discontinuity of the esophagus occurring in 2.4 in 10,000 births. As survival rates are high, the significant medical morbidity became more relevant. Short-term and long-term morbidities involve the respiratory and gastrointestinal system in the majority of the patients. The impact of this morbidity seems large enough to inspire researchers to develop experimental animal models that may help understanding the pathogenesis and pathophysiology. These models can also be used to explore potential surgical therapies. We reviewed the clinical and experimental literature focusing on esophageal morbidity in EA. Although the consequences of esophageal motility disorders are very relevant in the clinical setting, research remains largely underexplored. Consequently, we suggest integrating motility function assessment in the existing research models.

Proton-pump Inhibitor Omeprazole Attenuates Hyperoxia Induced Lung Injury

Journal of Translational Medicine. Aug, 2016  |  Pubmed ID: 27567616

The administration of supplemental oxygen to treat ventilatory insufficiency may lead to the formation of reactive oxygen species and subsequent tissue damage. Cytochrome P4501A1 (CYP1A1) can modulate hyperoxic lung injury by a currently unknown mechanism. Our objective was to evaluate the effect of administration of omeprazole on the induction of CYP1A1 and its influence on hyperoxic lung injury in an established preterm rabbit model.

A Novel Translational Model for Fetoscopic Intratracheal Delivery of Nanoparticles in Piglets

Prenatal Diagnosis. Oct, 2016  |  Pubmed ID: 27567969

The aim of this study was to assess the feasibility of fetal tracheal injection in the late-gestational pig to target the airways.

Connexin 43 is Overexpressed in Human Fetal Membrane Defects After Fetoscopic Surgery

Prenatal Diagnosis. Oct, 2016  |  Pubmed ID: 27568096

We examined whether surgically induced membrane defects elevate connexin 43 (Cx43) expression in the wound edge of the amniotic membrane (AM) and drives structural changes in collagen that affects healing after fetoscopic surgery.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

International Journal of Molecular Sciences. Oct, 2016  |  Pubmed ID: 27783043

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Current Controversies in Prenatal Diagnosis 1: in Utero Therapy for Spina Bifida is Ready for Endoscopic Repair

Prenatal Diagnosis. Dec, 2016  |  Pubmed ID: 27862078

Enantiomer-specific Ketorolac Pharmacokinetics in Young Women, Including Pregnancy and Postpartum Period

Bosnian Journal of Basic Medical Sciences. Nov, 2016  |  Pubmed ID: 27968707

Racemic ketorolac clearance (CL) is significantly higher at delivery, but S-ketorolac disposition determines the analgesic effects. The aim of this study was to investigate the effect of pregnancy and postpartum period on enantiomer-specific (S and R) intravenous (IV) ketorolac pharmacokinetics (PKs). Data in women shortly following cesarean delivery (n=39) were pooled with data in a subgroup of these women that was reevaluated in the later postpartum period (postpartum group, n=8/39) and with eight healthy female volunteers. All women received single IV bolus of 30 mg ketorolac tromethamine. Five plasma samples were collected at 1, 2, 4, 6, and 8 hours and plasma concentrations were determined using high performance liquid chromatography. Enantiomer-specific PKs were calculated using PKSolver. Unpaired analysis showed that distribution volume at steady state (Vss, L/kg) for S- and R-ketorolac was significantly higher in women shortly following cesarean delivery (n=31) compared to postpartum group (n=8) or to healthy female volunteers (n=8). CL, CL to body weight, and CL to body surface area (CL/BSA) for S- and R-ketorolac were also significantly higher in women following delivery. In addition, S/R-ketorolac CL/BSA ratio was significantly higher at delivery. Paired PK analysis in eight women shortly following delivery and in postpartum group showed the same pattern. Finally, the simultaneous increase in CL and Vss resulted in similar estimates for elimination half-life in both unpaired and paired analysis. In conclusion, pregnancy affects S-, R-, and S/R-ketorolac disposition. This is of clinical relevance since S-ketorolac (analgesia) CL is even more increased compared to R-ketorolac CL, and S/R-ketorolac CL ratio is higher following delivery compared to postpartum period or to healthy female volunteers.

Vascular Endothelial Growth Factor Up-regulation in Human Amniotic Fluid Stem Cell Enhances Nephroprotection After Ischemia-Reperfusion Injury in the Rat

Critical Care Medicine. Jan, 2017  |  Pubmed ID: 27548820

To evaluate if the up-regulation of vascular endothelial growth factor strengthens the protective effect of amniotic fluid stem cells in a renal ischemia-reperfusion injury model.

Comparative Anatomy of the Ovine and Female Pelvis

Gynecologic and Obstetric Investigation. Jan, 2017  |  Pubmed ID: 28125816

Pelvic organ prolapse affects half of vaginally parous women. Several animal models are used to study its pathophysiology and treatment. Sheep are interesting because they develop spontaneously prolapse with similar risk factors as women and can be used for vaginal surgery. This study describes ovine pelvis anatomy and compares it to women's pelvis to provide anatomical tools for translational researchers.

GIFT-Cloud: A Data Sharing and Collaboration Platform for Medical Imaging Research

Computer Methods and Programs in Biomedicine. Feb, 2017  |  Pubmed ID: 28187889

Clinical imaging data are essential for developing research software for computer-aided diagnosis, treatment planning and image-guided surgery, yet existing systems are poorly suited for data sharing between healthcare and academia: research systems rarely provide an integrated approach for data exchange with clinicians; hospital systems are focused towards clinical patient care with limited access for external researchers; and safe haven environments are not well suited to algorithm development. We have established GIFT-Cloud, a data and medical image sharing platform, to meet the needs of GIFT-Surg, an international research collaboration that is developing novel imaging methods for fetal surgery. GIFT-Cloud also has general applicability to other areas of imaging research.

Pericardio-Amniotic Shunting for Incomplete Pentalogy of Cantrell

Fetal Diagnosis and Therapy. Feb, 2017  |  Pubmed ID: 28196368

A 27-year-old woman, gravida 2, para 0, presented with an incomplete Pentalogy of Cantrell with an omphalocele, diaphragmatic hernia, and a pericardial defect at 32 weeks' gestation. A large pericardial effusion compressed the lungs and had led to a reduced lung growth with an observed-to-expected total lung volume of 28% as measured by MRI. The effusion disappeared completely after the insertion of a pericardio-amniotic shunt at 33 weeks. After birth, the newborn showed no signs of pulmonary hypoplasia and underwent a surgical correction of the defect. Protracted wound healing and a difficult withdrawal from opioids complicated the neonatal period. The child was discharged on postnatal day 105 in good condition. This case demonstrates that in case of Pentalogy of Cantrell with large pericardial effusion, the perinatal outcome might be improved by pericardio-amniotic shunting.

In Case You Missed It: the Prenatal Diagnosis Editors Bring You the Most Significant Advances of 2016

Prenatal Diagnosis. Feb, 2017  |  Pubmed ID: 28205301

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