Longitudinal MRI Evaluation of Brain Development in Fetuses with Congenital Diaphragmatic Hernia around the Time of Fetal Endotracheal Occlusion.

BACKGROUND AND PURPOSE: Congenital diaphragmatic hernia is associated with high mortality and morbidity, including evidence suggesting neurodevelopmental comorbidities after birth. The aim of this study was to document longitudinal changes in brain biometry and the cortical folding pattern in fetuses with congenital diaphragmatic hernia compared with healthy fetuses. MATERIALS AND METHODS: This is a retrospective cohort study including fetuses with isolated congenital diaphragmatic hernia between January 2007 and May 2019, with at least 2 MR imaging examinations. For controls, we used images from fetuses who underwent MR imaging for an unrelated condition that did not compromise fetal brain development and fetuses from healthy pregnant women. Biometric measurements and 3D segmentations of brain structures were used as well as qualitative and quantitative grading of the supratentorial brain. Brain development was correlated with disease-severity markers. RESULTS: Forty-two fetuses were included, with a mean gestational age at first MR imaging of 28.0 (SD, 2.1) weeks and 33.2 (SD, 1.3) weeks at the second imaging. The mean gestational age in controls was 30.7 (SD, 4.2) weeks. At 28 weeks, fetuses with congenital diaphragmatic hernia had abnormal qualitative and quantitative maturation, more extra-axial fluid, and larger total skull volume. By 33 weeks, qualitative grading scores were still abnormal, but quantitative scoring was in the normal range. In contrast, the extra-axial fluid volume remained abnormal with increased ventricular volume. Normal brain parenchymal volumes were found. CONCLUSIONS: Brain development in fetuses with congenital diaphragmatic hernia around 28 weeks appears to be delayed. This feature is less prominent at 33 weeks. At this stage, there was also an increase in ventricular and extra-axial space volume.

Safety and efficacy of smart tracheal occlusion device in diaphragmatic hernia lamb model.

OBJECTIVE: To investigate the efficacy and safety of the 'smart' tracheal occlusion (Smart-TO) device in fetal lambs with diaphragmatic hernia (DH). METHODS: DH was created in fetal lambs on gestational day 70 (term, 145 days). Fetuses were allocated to either pregnancy continuation until term (DH group) or fetoscopic endoluminal tracheal occlusion (TO), performed using the Smart-TO balloon on gestational day 97 (DH + TO group). On gestational day 116, the presence of the balloon was confirmed on ultrasound, then the ewe was walked around a 3.0-Tesla magnetic resonance scanner for balloon deflation, which was confirmed by ultrasound immediately afterwards. At term, euthanasia was performed and the fetus retrieved. Efficacy of occlusion was assessed by the lung-to-body-weight ratio (LBWR) and lung morphometry. Safety parameters included tracheal side effects assessed by morphometry and balloon location after deflation. The unoccluded DH lambs served as a comparator. RESULTS: Six fetuses were included in the DH group and seven in the DH + TO group. All balloons deflated successfully and were expelled spontaneously from the airways. In the DH + TO group, in comparison to controls, the LBWR at birth was significantly higher (1.90 (interquartile range (IQR), 1.43-2.55) vs 1.07 (IQR, 0.93-1.46); P = 0.005), while on lung morphometry, the alveolar size was significantly increased (mean linear intercept, 47.5 (IQR, 45.6-48.1) vs 41.9 (IQR, 38.8-46.1) µm; P = 0.03); whereas airway complexity was lower (mean terminal bronchiolar density, 1.56 (IQR, 1.0-1.81) vs 2.23 (IQR, 2.14-2.40) br/mm2 ; P = 0.005). Tracheal changes on histology were minimal in both groups, but more noticeable in fetal lambs that underwent TO than in unoccluded lambs (tracheal score, 2 (IQR, 1-3) vs 0 (0-1); P = 0.03). CONCLUSIONS: In fetal lambs with DH, TO using the Smart-TO balloon is effective and safe. Occlusion can be reversed non-invasively and the deflated intact balloon expelled spontaneously from the fetal upper airways. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

New device permitting non-invasive reversal of fetal endoscopic tracheal occlusion: ex-vivo and in-vivo study.

OBJECTIVE: One of the drawbacks of fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia is the need for a second invasive intervention to re-establish airway patency. The 'Smart-TO' device is a new balloon for FETO that deflates spontaneously when placed in a strong magnetic field, therefore overcoming the need for a second procedure. The safety and efficacy of this device have not yet been demonstrated. The aim of this study was to investigate the reversibility, local side effects and occlusiveness of the Smart-TO balloon, both in a simulated in-utero environment and in the fetal lamb model. METHODS: First, the reversibility of tracheal occlusion by the Smart-TO balloon was tested in a high-fidelity simulator. Following videoscopic tracheoscopic balloon insertion, the fetal mannequin was placed within a 1-L water-filled balloon to mimic the amniotic cavity. This was held by an operator in front of their abdomen, and different fetal and maternal positions were simulated to mimic the most common clinical scenarios. Following exposure to the magnetic field generated by a 1.5-T magnetic resonance (MR) machine, deflation of the Smart-TO balloon was assessed by tracheoscopy. In cases of failed deflation, the mannequin was reinserted into a water-filled balloon for additional MR exposure, up to a maximum of three times. Secondly, reversibility, occlusiveness and local effects of the Smart-TO balloon were tested in vivo in fetal lambs. Tracheal occlusion was performed in fetal lambs on gestational day 95 (term, 145 days), either using the balloon currently used in clinical practice (Goldbal2) (n = 5) or the Smart-TO balloon (n = 5). On gestational day 116, the presence of the balloon was assessed by tracheoscopy. Deflation was performed by puncture (Goldbal2) or MR exposure (Smart-TO). Six unoccluded fetal lambs served as controls. Following euthanasia, the lung-to-body-weight ratio (LBWR), lung morphometry and tracheal circumference were assessed. Local tracheal changes were measured using a hierarchical histologic scoring system. RESULTS: Ex vivo, Smart-TO balloon deflation occurred after a single MR exposure in 100% of cases in a maternal standing position with the mannequin at a height of 95 cm (n = 32), 55 cm (n = 8) or 125 cm (n = 8), as well as when the maternal position was 'lying on a stretcher' (n = 8). Three out of eight (37.5%) balloons failed to deflate at first exposure when the maternal position was 'sitting in a wheelchair'. Of these, two balloons deflated after a second MR exposure, but one balloon remained inflated after a third exposure. In vivo, all Smart-TO balloons deflated successfully. The LBWR in fetal lambs with tracheal occlusion by a Smart-TO balloon was significantly higher than that in unoccluded controls, and was comparable with that in the Goldbal2 group. There were no differences in lung morphometry and tracheal circumference between the two balloon types. Tracheal histology showed minimal changes for both balloons. CONCLUSIONS: In a simulated in-utero environment, the Smart-TO balloon was effectively deflated by exposure of the fetus in different positions to the magnetic field of a 1.5-T MR system. There was only one failure, which occurred when the mother was sitting in a wheelchair. In healthy fetal lambs, the Smart-TO balloon is as occlusive as the clinical standard Goldbal2 system and has only limited local side effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Laser for twin-to-twin transfusion syndrome: a guide for endoscopic surgeons.

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.

Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta-analysis.

OBJECTIVE: To assess the neurodevelopmental outcome of children with spina bifida aperta (SBA) treated prenatally as compared to those treated postnatally. METHODS: We performed a systematic review of the literature in PubMed/MEDLINE, EMBASE, Web of Science and The Cochrane Library, comparing the neurological outcome of infants with SBA treated prenatally vs postnatally. Only randomized controlled trials (RCTs) and non-randomized prospective controlled studies were included. The primary outcome assessed was neurodevelopmental impairment at the age of 1 year or later. Secondary outcomes were preterm birth, need for ventriculoperitoneal (VP) shunt by 12 months of age, absence of signs of hindbrain herniation at the first postnatal magnetic resonance imaging (MRI) evaluation and independent ambulation evaluated at 30 months. RESULTS: Of 11 359 studies identified through the electronic search, six met the inclusion criteria and were assessed in full text and two, one RCT and one prospective cohort study, were ultimately included in the meta-analysis. Sensitivity analysis did not show any difference between the outcomes of the RCT alone and those of the pooled RCT and prospective cohort study. This allowed neurodevelopmental assessment of 213 children between 14 and 53 months of age. Neurodevelopment was assessed by the Bayley Scales of Infant Development II (BSID-II) mental development index corrected for chronological age, with a cut-off of ≥ 70 (representing no more than 2 SD below the mean). The presence of neurodevelopmental impairment was similar between children who underwent prenatal (25/105 (23.8%)) and those who had postnatal (30/108 (27.8%)) repair of SBA (odds ratio (OR), 0.82 (95% CI, 0.43-1.56); P = 0.54), although the risk of prematurity was higher in the prenatal-repair group (OR, 17.62 (95% CI, 7.60-40.87); P < 0.0001). For every two fetuses operated on before birth, there was, compared with those operated on after birth, one additional premature birth (number needed to harm = 2 (95% CI, 1-3)). The need for VP shunt placement by 12 months of age was lower in the prenatal-repair group (45/109 (41.3%)) than in children that had postnatal repair (93/112 (83.0%); OR, 0.14 (95% CI, 0.08-0.26); P < 0.0001). Data on neurodevelopmental impairment in children with a shunt were available only for patients from the prenatal-surgery group of the RCT; in this subgroup, the likelihood for impairment was similar between children who did (7/39 (17.9%)) and those who did not (4/48 (8.3%)) have shunt placement (P = 0.21). At first postnatal MRI evaluation, no signs of hindbrain herniation were detected in 28/88 (31.8%) children who were operated on prenatally compared with 4/89 (4.5%) who had postnatal repair (OR, 9.45 (95% CI, 3.12-28.64); P < 0.0001). Independent ambulation at 30 months was achieved by 41/109 (37.6%) children who underwent prenatal repair compared with 21/111 (18.9%) who had postnatal repair (OR, 2.59 (95% CI, 1.39-4.86); P = 0.003). CONCLUSION: The risk of neurodevelopmental impairment in infants with SBA was similar between those who underwent prenatal and those who had postnatal surgical repair, despite an increased risk of prematurity in the prenatally repaired group. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Adverse Effects of Carbetocin versus Oxytocin in the Prevention of Postpartum Haemorrhage after Caesarean Section: A Randomized Controlled Trial.

PURPOSE: To compare the incidence of nausea, vomiting, and arterial hypotension between carbetocin and oxytocin to prevent haemorrhage after caesarean section (CS). METHODS: A randomized controlled trial in term pregnant women undergoing planned CS. Groups were randomized to carbetocin or oxytocin. Blood pressure (BP), heart rate, presence of nausea/vomitus, and need for vasopressors were evaluated throughout surgery. Preoperative and postoperative haemoglobin and haematocrit levels were compared. RESULTS: Fifty-eight women were randomized (carbetocin n = 32; oxytocin n = 26). Both medications had hypotensive effect, difference in BP for carbetocin versus oxytocin: systolic (14.4 ± 2.4 mmHg versus 8.5 ± 1.8 mmHg); diastolic (7.8 ± 1.6 mmHg versus 8.9 ± 3.0 mmHg) without significant difference between the drugs (p = 0.1 and p = 0.7). Both groups had similar needs for vasopressors. The presence of nausea was not rare, but the difference was not statistically significant (p = 0.4). Average blood loss was slightly lower in the carbetocin group but not statistically significant (p = 0.8). CONCLUSION: In planned CS, a possible clinical significant lower incidence of nausea after carbetocin was noted but this was not statistically significant. There were no differences regarding BP, heart rate, the need for vasopressor, and blood loss. The study was registered in the International Journal of Clinical Trials (ISRCTN 95504420, 2/2017).