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Twin-to-twin-transfusion syndrome (TTTS) is the most important cause of handicap and death in monochorionic twin pregnancies. It is caused by a certain pattern of anastomoses between the two fetal circulations leading to an unbalanced blood and fluid transfer. This leads to severe amniotic fluid discordance and variable degrees of cardiac dysfunction. Untreated, this condition has a very poor survival rate. Fetoscopic laser has been shown to be the best first line treatment, which aims to dichorionise the placenta therefore arresting the inter-twin transfusion. Fetoscopic laser is a causative therapy, which aims to functionally create a dichorionized placenta hence arresting inter-twin transfusion. This is achieved by percutaneous sono-endoscopic coagulation of placental anastomoses. In addition, redundant amniotic fluid is drained. Fetoscopic laser coagulation of chorionic plate anastomoses is safe and effective. There is level I evidence that it is the best treatment modality, in particular when the placental surface is lined along the vascular equator. A recent meta-analysis confirmed an increased fetal survival and decreased risk for neonatal and pediatric neurologic morbidity. Laser therapy is the first line therapy for TTTS. The technique is quite standardized and safe and effective in experienced hands. Herein we describe the technique and current instrumentation used for this procedure. ispartof: FACTS VIEWS AND VISION IN OBGYN vol:11 issue:3 pages:197-205 ispartof: location:Belgium status: published

OBJECTIVE: To determine the prevalence of pulmonary hypertension(PAH) in left-sided congenital diaphragmatic hernia(CDH); how we could predict it; and how PAH contributed to the model for mortality prediction.; STUDY DESIGN: Retrospective analysis in three European centers. The primary outcome was the presence of PAH on postnatal day(d)1,7, and at discharge. Studied predictors of PAH were: observed/expected-lung/head-ratio(o/e LHR), liver-herniation, FETO, and gestational age(GA) at delivery. The combined effect of pre-and postnatal variables on mortality was modeled by Cox regression.; RESULTS: Of the 197 neonates, 56(28.4%) died. At d1, 67.5%(133/197) had PAH and 61.9% (101/163) by d7. Overall, 6.4% (9/141) had PAH at discharge.At d1, o/eLHR(OR 0.96) and FETO(OR 2.99) independently correlated to PAH(AUC:0.74). At d7, PAH significantly correlated only with the use of FETO (OR 3.9;AUC:0.65). None were significant for PAH at discharge.Combining the occurrence of PAH with antenatal biomarkers improved mortality prediction(p=0.02), in a model including o/eLHR(HR:0.94), FETO(HR:0.35), liver herniation(HR:16.78), and PAH(HR:15.95).; CONCLUSIONS: Antenatal prediction of PAH was only moderate. The postnatal occurrence of PAH further increases the risk of death. Whereas this may be used to counsel parents in the postnatal period, our study demonstrates there is a need to find more accurate antenatal predictors for PAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

OBJECTIVES: the MOMS randomized trial has demonstrated that prenatal spina bifida aperta (SBA) repair via open approach is safe and effective for both mother and fetus, yet half of the infants have incomplete reversal of hindbrain herniation and no improvement in neuromotor function. One contributing factor may be the incompleteness of the neurosurgical repair causing persistent in utero leakage of cerebrospinal fluid (CSF) and exposure of the spinal cord to the amniotic fluid until birth. We aim to investigate the neurostructural and neurofunctional efficacy of the watertightness of prenatal SBA repair. METHODS: a superiority study was conducted in the validated SBA fetal lamb model and powered (n=7 per group). Outcomes of lambs undergoing watertight or non-watertight multilayer repairs through an open approach were compared to those in unrepaired SBA lambs at delivery (term=145 days). At ~75-day fetal lambs underwent standardized induction of lumbar SBA. At ~100 days, they were assigned to one of the three groups and subsequently to either watertight or non-watertight layered repair group based on an intraoperative watertightness test using subcutaneous fluoresceine injection. Finally, at 1-2 postnatal days, we assessed reversal of hindbrain herniation on Magnetic Resonance Imaging (MRI) as primary outcome. Secondary proxies of neuroprotection were CSF leakage at the repair site; hindlimb motor function based on joint movement score, locomotor grade and Motor Evoked Potentials (MEP); neuroprotection score encompassing live birth, hindbrain herniation reversal, absent CSF leakage and joint score =9/15; and brain and spinal cord histology and immunohistochemistry. As the watertightness test is not clinically usable, we developed a potential surrogate intraoperative quality score and assessed its relationship with improved outcomes. This four-point scoring system is based on visual assessment of the quality of the skin repair (suture inter-run distance =3mm, absence of tear and ischemia). RESULTS: Compared to unrepaired lambs, watertight repair was neuroprotective in 5/7 lambs (neuroprotection score of 4/4), as evidenced by a 100% reversal of hindbrain herniation on MRI; lower CSF leakage rate (14%); better hindlimb motor function evidenced by higher joint movement score, locomotor grade, and MEP area-under-the-curve and peak-to-peak amplitude; higher neuronal density in the hippocampus and corpus callosum; and higher reactive astrogliosis at the SBA lesion epicenter. Conversely, non-watertight SBA repair did not achieve the same level of neuroprotection (1/7) due to non-significant 86% hindbrain herniation reversal, no motor function improvement, high CSF leakage (43%), low brain neuron count in both regions and low spinal astroglial cell area at the epicenter. Like watertight layered repair, a high quality score (=2/3) was associated with improved outcomes yet watertightness test and quality score could not be used interchangeably due to results discrepancies. CONCLUSIONS: A watertight layered fetal SBA repair improves brain and spinal cord structure and function in the fetal lamb model. This translational research has important clinical implication and neurosurgical technique that achieves watertightness should be adopted in all fetal centers to improve neuroprotection. Future clinical studies could assess whether the high quality of the repair correlates with clinical outcomes for neuroprotection. This article is protected by copyright. All rights reserved.

Congenital diaphragmatic hernia can be diagnosed in the prenatal period and its severity can be measured by fetal imaging. There is now level I evidence that, in selected cases, Fetoscopic Endoluminal Tracheal Occlusion with a balloon increases survival to discharge from the neonatal unit as well as the risk for prematurity. Both effects are dependent on the time point of tracheal occlusion. Fetoscopic Endoluminal Tracheal Occlusion may also lead to iatrogenic death when the balloon cannot be timely retrieved. The implementation of the findings from our clinical studies, may also vary based on local conditions. These may be different in terms of available skill set, access to fetal therapy, as well as outcome based on local neonatal management. We encourage prior benchmarking of local outcomes with optimal postnatal management, based on large enough numbers and using identical criteria as in the recent trials. We propose to work further on prenatal prediction methods, and the improvement of fetal intervention. In this manuscript, we describe a research agenda from a fetal medicine perspective. This research should be in parallel with innovation in neonatal and pediatric (surgical) management of this condition.

Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.

Objective To assess the safety of Partial-Amniotic-Insufflation-of-heated-humidified-CO2 (hPACI) during fetoscopic spina bifida repair (fSB-repair). Method A simulated fSB-repair through an exteriorized uterus under hPACI was performed in 100-day fetal lambs (term = 145 days) under a laboratory anesthesia protocol (n = 5; group 1) which is known to induce maternal-fetal acidosis and hypercapnia. Since these may not occur clinically, we applied a clinical anesthesia protocol (n = 5; group 2), keeping maternal parameters within physiological conditions, that is, controlled maternal arterial carbon dioxide (CO2) pressure (pCO(2) = 30 mmHg), blood pressure (>= 67 mmHg), and temperature (37.1-39.8 degrees C). Our superiority study used fetal pH as the primary outcome. Results Compared to group 1, controlled anesthesia normalized fetal pH (7.23 +/- 0.02 vs. 7.36 +/- 0.02, p < 0.001), pCO(2) (70.0 +/- 9.1 vs. 43.0 +/- 1.0 mmHg, p = 0.011) and bicarbonate (27.8 +/- 1.1 vs. 24.0 +/- 0.9 mmol/L, p = 0.071) at baseline. It kept them within clinically acceptable limits (pH >= 7.23, pCO(2) = 120 min of hPACI as opposed to

Congenital Diaphragmatic Hernia (CDH) is a rare congenital anomaly characterized by a defect in the diaphragm, which permits abdominal organs to herniate into the thorax. This causes lung hypoplasia and at birth, children with CDH experience respiratory distress and pulmonary hypertension. Despite optimal neonatal treatment, CDH is still associated with a high mortality and morbidity. In severe cases, Fetal Intervention (FETO) may alter the natural course of this disease. Herein we describe the rationale, action mechanism and technique to perform this intervention. Despite hope giving results, this technique remains investigational for left sided CDH. However, an increased survival may come at the cost of increased morbidity. Children born with CDH are at increased risk for long and short-term morbidity, including neurodevelopmental problems. Until now, there are still uncertainties about the severity and prevalence of neurologic morbidity. Furthermore, it remains uncertain if these problems are already present prenatally and if a prenatal intervention influence this.

Objective: To compare the host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold to the response to PP mesh in an animal model of vaginal POP surgery. Design: A study employing a sheep model Setting: KU Leuven Center for Surgical Technologies Population: 14 parous female Mule sheep Methods: P4HB scaffolds were surgically implanted in the posterior vaginal wall of sheep. The comparative PP mesh data were obtained from an identical protocol. Main outcome measures: Gross necropsy, histological and biomechanical evaluation of explants, and the in vivo P4HB scaffold degradation were evaluated at 60- and 180-days post-implantation. Results: Gross necropsy revealed no implant related adverse events using P4HB scaffolds. The tensile stiffness of the P4HB explants increased at 180-days (12.498 ± 2.66 N/mm (P=0.019)) as compared to 60-days (4.585 ± 1.57 N/mm) post-implantation, while P4HB degraded gradually. P4HB scaffolds exhibited excellent tissue integration with dense connective tissue and a moderate initial host response. P4HB scaffolds induced a significantly higher M2/M1 ratio (1.70 ± 0.67 SD, score 0-4), as compared to PP mesh (0.99 ± 0.78 SEM, score 0-4) at 180-days. Conclusions: P4HB scaffold facilitated a gradual load transfer to vaginal tissue over time. The fully absorbable P4HB scaffold, in comparison to PP mesh, has a favorable host response with comparable load bearing capacity. If these results are also observed at longer follow-up, a clinical study for vaginal POP surgery may be warranted to demonstrate efficacy. Key words: Pelvic organ prolapse, vaginal surgery, Poly-4-hydroxybutyrate, degradable scaffold, host response, biomechanics.