Self-reported respiratory and gastrointestinal outcomes in children with isolated congenital diaphragmatic hernia: A prospective multicentre study.

OBJECTIVE: To evaluate medium-term self-reported respiratory and gastrointestinal (GI) outcomes in children with congenital diaphragmatic hernia (CDH). DESIGN: Self-reported respiratory and GI outcomes correlated with prenatal severity indicators. SETTING: Prospective study at three fetal medicine units. POPULATION: Families of children prenatally diagnosed with isolated, left-sided CDH surviving for >1 year. METHODS: Families received validated questionnaires for GI outcomes (Infant Gastroesophageal Reflux Questionnaire Revised, I-GERQ-R, for infants aged <2 years, or Paediatric Gastro-oesophageal Symptom and Quality of Life Questionnaire, PGSQ, for children aged aged 2-8 years or >9 years) and respiratory outcomes (preschool respiratory outcome questionnaire, for children aged ≤5 years, or the International Study of Asthma and Allergies in Childhood asthma questionnaire, for children aged 6-8 years or ≥9 years). Prenatal data collected from the medical records included lung size (percentage observed/expected lung-to-head ratio, O/E LHR %), liver position, fetal endoluminal tracheal occlusion (FETO) gestational age (GA) at delivery, and perinatal data included birthweight, location, patch repair and respiratory support. MAIN OUTCOME MEASURES: The GI and respiratory scores were correlated with O/E LHR using linear and logistic regression models. Univariate analysis was used to evaluate associations with perinatal variables. RESULTS: We obtained 142 responses from 342 families (representing a response rate of 45%). The baseline characteristics of participants and non-participants were comparable. No correlations between perinatal variables and respiratory or GI scores were identified. Children aged ≤5 years with lower O/E LHR values reported higher respiratory scores (P = 0.0175); this finding was not reported in older children. Overall, the children who underwent FETO (n = 51) had GI (P = 0.290) and respiratory (P = 0.052) scores that were comparable with those of children who were expectantly managed. CONCLUSIONS: Families and children with prenatally diagnosed CDH reported fewer respiratory symptoms with increasing age. There was no correlation between O/E LHR or the use of FETO and self-reported outcomes.

High-fidelity, low-cost synthetic training model for fetoscopic spina bifida repair.

BACKGROUND: Fetoscopic spina bifida repair is increasingly being practiced, but limited skill acquisition poses a barrier to widespread adoption. Extensive training in relevant models, including both ex vivo and in vivo models may help. To address this, a synthetic training model that is affordable, realistic, and that allows skill analysis would be useful. OBJECTIVE: This study aimed to create a high-fidelity model for training in the essential neurosurgical steps of fetoscopic spina bifida repair using synthetic materials. In addition, we aimed to obtain a cheap and easily reproducible model. STUDY DESIGN: We developed a 3-layered, silicon-based model that resemble the anatomic layers of a typical myelomeningocele lesion. It allows for filling of the cyst with fluid and conducting a water tightness test after repair. A compliant silicon ball mimics the uterine cavity and is fixed to a solid 3-dimensional printed base. The fetal back with the lesion (single-use) is placed inside the uterine ball, which is reusable and repairable to allow for practicing port insertion and fixation multiple times. Following cannula insertion, the uterus is insufflated and a clinical fetoscopic or robotic or prototype instruments can be used. Three skilled endoscopic surgeons each did 6 simulated fetoscopic repairs using the surgical steps of an open repair. The primary outcome was surgical success, which was determined by water tightness of the repair, operation time <180 minutes and an Objective Structured Assessment of Technical Skills score of ≥18 of 25. Skill retention was measured using a competence cumulative sum analysis of a composite binary outcome of surgical success. Secondary outcomes were cost and fabrication time of the model. RESULTS: We made a model that can be used to simulate the neurosurgical steps of spina bifida repair, including anatomic details, port insertion, placode release and descent, undermining of skin and muscular layer, and endoscopic suturing. The model was made using reusable 3-dimensional printed molds and easily accessible materials. The 1-time startup cost was €211, and each single-use, simulated myelomeningocele lesion cost €9.5 in materials and 50 minutes of working time. Two skilled endoscopic surgeons performed 6 simulated, 3-port fetoscopic repairs, whereas a third used a Da Vinci surgical robot. Operation times decreased by more than 30% from the first to the last trial. Six experiments per surgeon did not show an obvious Objective Structured Assessment of Technical Skills score improvement. Competence cumulative sum analysis confirmed competency for each surgeon. CONCLUSION: This high-fidelity, low-cost spina bifida model allows simulated dissection and closure of a myelomeningocele lesion. VIDEO ABSTRACT.

3D vs. 2D simulated fetoscopy for spina bifida repair: a quantitative motion analysis.

3D imaging technology is becoming more prominent every day. However, more validation is needed to understand the actual benefit of 3D versus conventional 2D vision. This work quantitatively investigates whether experts benefit from 3D vision during minimally invasive fetoscopic spina bifida (fSB) repair. A superiority study was designed involving one expert team ([Formula: see text] procedures prior) who performed six 2D and six 3D fSB repair simulations in a high-fidelity animal training model, using 3-port access. The 6D motion of the instruments was recorded. Among the motion metrics are total path length, smoothness, maximum speed, the modified Spectral Arc Length (SPARC), and Log Dimensionless Jerk (LDLJ). The primary clinical outcome is operation time (power 90%, 5% significance) using Sealed Envelope Ltd. 2012. Secondary clinical outcomes are water tightness of the repair, CO[Formula: see text] insufflation volume, and OSATS score. Findings show that total path length and LDLJ are considerably different. Operation time during 3D vision was found to be significantly shorter compared to 2D vision ([Formula: see text] vs. [Formula: see text] min; p [Formula: see text] 0.026). These results suggest enhanced performance with 3D vision during interrupted suturing in fetoscopic SBA repair. To confirm these results, a larger-scale follow-up study involving multiple experts and novice surgeons is recommended.

Duration of fetoscopic spina bifida repair does not affect the central nervous system in fetal lambs.

BACKGROUND: Prenatal spina bifida aperta repair improves neurologic outcomes yet comes with a significant risk of prematurity and uterine scar-related complications. To reduce such complications, different fetoscopic techniques, for example, with varying numbers of ports, are being explored. This has an effect on the duration of the procedure, potentially affecting central nervous system development. Both the condition and anesthesia can affect the central nervous system, particularly the hippocampus, a region crucial for prospective and episodic memory. Previous animal studies have shown the potential influence of anesthesia, premature delivery, and maternal surgery during pregnancy on this area. OBJECTIVE: This study aimed to compare the effects of 2- vs 3-port fetoscopic spina bifida aperta repair in the fetal lamb model using neuron count of the hippocampus as the primary outcome. STUDY DESIGN: Based on the hippocampal neuron count from previous lamb experiments, we calculated that we required 5 animals per group to achieve a statistical power of ≥ 80%. A spina bifida aperta defect was developed in fetal lambs at 75 days of gestation (term: 145 days). At 100 days, fetuses underwent either a 2-port or 3-port fetoscopic repair. At 143 days, all surviving fetuses were delivered by cesarean delivery, anesthetized, and transcardially perfused with a mixture of formaldehyde and gadolinium. Next, they underwent neonatal brain and spine magnetic resonance imaging after which these organs were harvested for histology. Hippocampus, frontal cortex, caudate nucleus, and cerebellum samples were immunostained to identify neurons, astrocytes, microglia, and markers associated with cell proliferation, myelination, and synapses. The degree of hindbrain herniation and the ventricular diameter were measured on magnetic resonance images and volumes of relevant brain and medulla areas were segmented. RESULTS: Both treatment groups included 5 fetuses and 9 unoperated littermates served as normal controls. The durations for both skin-to-skin (341±31 vs 287±40 minutes; P=.04) and fetal surgery (183±30 vs 128±22; P=.01) were longer for the 2-port approach than for the 3-port approach. There was no significant difference in neuron density in the hippocampus, frontal cortex, and cerebellum. In the caudate nucleus, the neuron count was higher in the 2-port group (965±156 vs 767±92 neurons/mm2; P=.04). There were neither differences in proliferation, astrogliosis, synaptophysin, or myelin. The tip of the cerebellar vermis was closer to the foramen magnum in animals undergoing the 2-port approach than in animals undergoing the 3-port approach (-0.72±0.67 vs -2.47±0.91 mm; P=.009). There was no significant difference in the ratio of the hippocampus, caudate nucleus, or cerebellar volume to body weight. For the spine, no difference was noted in spine volume-to-body weight ratio for the lower (L1-L2), middle (L3-L4), and higher (L5-L6) levels. Compared with controls, in repaired animals, the cerebellar vermis tip laid closer to the foramen magnum, parietal ventricles were enlarged, and medulla volumes were reduced. CONCLUSION: In the experimental spina bifida fetal lamb model, a 2-port repair took 40% longer than a 3-port repair. However, there was no indication of any relevant morphologic differences in the fetal brain.

Implementation and Assessment of a Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program.

Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.

Characterization of Suboptimal Responses to Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

INTRODUCTION: The aim of the study was to characterize the changes in fetal lung volume following fetoscopic endoluminal tracheal occlusion (FETO) that are associated with infant survival and need for extracorporeal membrane oxygenation (ECMO) in congenital diaphragmatic hernia (CDH). METHODS: Fetuses with CDH who underwent FETO at a single institution were included. CDH cases were reclassified by MRI metrics [observed-to-expected total lung volume (O/E TLV) and percent liver herniation]. The percent changes of MRI metrics after FETO were calculated. ROC-derived cutoffs of these changes were derived to predict infant survival to discharge. Regression analyses were done to determine the association between these cutoffs with infant survival and ECMO need, adjusted for site of CDH, gestational age at delivery, fetal sex, and CDH severity. RESULTS: Thirty CDH cases were included. ROC analysis demonstrated that post-FETO increases in O/E TLV had an area under the curve of 0.74 (p = 0.035) for the prediction of survival to hospital discharge; a cutoff of less than 10% was selected. Fetuses with a <10% post-FETO increase in O/E TLV had lower survival to hospital discharge [44.8% vs. 91.7%; p = 0.018] and higher ECMO use [61.1% vs. 16.7%; p = 0.026] compared to those with an O/E TLV increase ≥10%. Similar results were observed when the analyses were restricted to left-sided CDH cases. A post-FETO <10% increase in O/E TLV was independently associated with lower survival at hospital discharge (aOR: 0.073, 95% CI: 0.008-0.689; p = 0.022) and at 12 months of age (aOR: 0.091, 95% CI: 0.01-0.825; p = 0.036) as well as with higher ECMO use (aOR: 7.88, 95% CI: 1.31-47.04; p = 0.024). CONCLUSION: Fetuses with less than 10% increase in O/E TLV following the FETO procedure are at increased risk for requiring ECMO and for death in the postnatal period when adjusted for gestational age at delivery, CDH severity, and other confounders.

Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model.

OBJECTIVE: Fetal surgery for spina bifida aperta (SBA) by open hysterotomy typically repairs anatomical native tissue in layers. Increasingly, fetoscopic repair is performed using a dural patch followed by skin closure. We studied the host response to selected commercially available patches currently being used in a fetal rabbit model for spina bifida repair. METHODS: SBA was surgically induced at 23-24 days of gestation (term = 31 days). Fetal rabbits were assigned to unrepaired (SBA group), or immediate repair with Duragen™ or Durepair™. Non-operated littermates served as normal controls. At term, spinal cords underwent immunohistochemical staining including Nissl and glial fibrillary acidic protein. We hypothesized that spinal cord coverage with a dural patch and skin closure would preserve motor neuron density within the non-inferiority limit of 201.65 cells/mm2 and reduce inflammation compared to unrepaired SBA fetuses. RESULTS: Motor neuron density assessed by Nissl staining was conserved both by Duragen (n = 6, 89.5; 95% CI -158.3 to -20.6) and Durepair (n = 6, 37.0; 95% CI -132.6 to -58.5), whereas density of GFAP-positive cells to quantify inflammation was lower than in unrepaired SBA-fetuses (SBA 2366.0 ± 669.7 cells/mm2 vs. Duragen 1274.0 ± 157.2 cells/mm2 ; p = 0.0002, Durepair 1069.0 ± 270.7 cells/mm2 ; p < 0.0001). CONCLUSIONS: Covering the rabbit spinal cord with either Duragen or Durepair followed by skin closure preserves motor neuron density and reduces the inflammatory response.

Effects of cumulative duration of repeated anaesthesia exposure on foetal brain development in the ovine model.

OBJECTIVE: Anaesthesia is required in 0.4-1% of pregnant women, and prolonged and repeated exposures to anaesthesia may be required. It is unknown whether these exposures may result in foetal neurotoxicity in humans. As sheep have a gestation comparable to that of humans, the objective of this study was to analyse the neurodevelopmental outcome of ovine foetuses that had been exposed in utero to repeated and prolonged anaesthesia. DESIGN: Randomized controlled preclinical study. SETTING: Anaesthesia for non-obstetric surgery during pregnancy. ANIMALS: Twenty-four healthy pregnant Swifter ewes. INTERVENTIONS: The ewes were randomized to no anaesthesia exposure (control-group), single exposure (at gestational age 68-70 days), or repeated exposure (at gestational age 68-70 days and 96-98 days) to 2.5 h of sevoflurane anaesthesia and maternal laparotomy. All lambs were delivered at approximately term gestation (gestational age: 140-143 days). MEASUREMENTS: The primary outcome was neuron density in the frontal cortex 24 h after birth for the control-group versus the repeated-exposure-group. Key secondary outcome was the time needed to achieve the milestone of standing. Secondary outcomes included other neurobehavioural assessments (e.g., motoric milestones) and histological parameters quantified in multiple brain regions (neuron density, total cell density, proliferation, inflammation, synaptogenesis, astrocytes and myelination). MAIN RESULTS: Neuron density in the frontal cortex did not differ between groups (mean ±â€¯standard deviation: control-group: 403 ±â€¯39, single-exposure group: 436 ±â€¯23 and repeated-exposure-group: 403 ±â€¯40 neurons/mm2, control-group versus repeated-exposure-group: p = 0.986, control-group versus single-exposure-group: p = 0.097). No significant difference was observed for the time needed to achieve the milestone of standing. Only very limited differences were observed for other histological outcome parameters and neurobehavioural assessments. CONCLUSIONS: There is no evidence for foetal neuronal injury or neurobehavioural impairments after a cumulative duration of 5 h repetitive prenatal anaesthesia in sheep.

Turner syndrome-omphalocele association: Incidence, karyotype, phenotype and fetal outcome.

OBJECTIVE: Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith-Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes. METHOD: Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound. RESULTS: 680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive. CONCLUSION: TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester.

Minimally Invasive Fetal Surgery and the Next Frontier.

Most patients with congenital anomalies do not require prenatal intervention. Furthermore, many congenital anomalies requiring surgical intervention are treated adequately after birth. However, there is a subset of patients with congenital anomalies who will die before birth, shortly after birth, or experience severe postnatal complications without fetal surgery. Fetal surgery is unique in that an operation is performed on the fetus as well as the pregnant woman who does not receive any direct benefit from the surgery but rather lends herself to risks, such as hemorrhage, abruption, and preterm labor. The maternal risks involved with fetal surgery have limited the extent to which fetal interventions may be performed but have, in turn, led to technical innovations that have significantly advanced the field. This review will examine congenital abnormalities that can be treated with minimally invasive fetal surgery and introduce the next frontier of prenatal management of fetal surgical pathology.

Arterial Embolization and Methylene Blue Injection into the Aberrant Artery in Two Infants with Intralobar Sequestration.

Bronchopulmonary sequestration is a rare congenital lung dysplasia. An intralobar sequestration (ILS) is a nonfunctional mass within the lung parenchyma without bronchial communication and with aberrant systemic arterial blood supply. Surgical resection or close observation can be proposed in the management of asymptomatic and low-risk ILS, but there is a lack of consensus. Endovascular embolization before thoracoscopic resection of ILS has been described to limit perioperative bleeding. Another technique previously reported is the injection of methylene blue in the feeding artery to macroscopically mark the sequestration from the healthy lung. In that way, a nonanatomical resection can be performed instead of a lobectomy without the risk of leaving abnormal lung tissue in place. We describe the first two cases of these two techniques combined: a 3-year-old girl with an ILS in the right lower lobe with an artery originating from the abdominal aorta, and a 14-month-old girl with an ILS in the right lower lobe with an artery coming from the celiac trunk. The combination of embolization and injection of methylene blue in the aberrant artery leads to a clear macroscopic demarcation of the blue-colored ILS from the healthy lung parenchyma and allowed safe nonanatomical resection of the ILS without risk of bleeding or compromising normal lung tissue.

The Cellular and Molecular Effects of Fetoscopic Endoluminal Tracheal Occlusion in Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is a complex disease associated with pulmonary hypoplasia and pulmonary hypertension. Great strides have been made in our ability to care for CDH patients, specifically in the prenatal improvement of lung volume and morphology with fetoscopic endoluminal tracheal occlusion (FETO). While the anatomic effects of FETO have been described in-depth, the changes it induces at the cellular and molecular level remain a budding area of CDH research. This review will delve into the cellular and molecular effects of FETO in the developing lung, emphasize areas in which further research may improve our understanding of CDH, and highlight opportunities to optimize the FETO procedure for improved postnatal outcomes.

Natural history of posterior fetal cephaloceles and incidence of progressive cephalocele herniation.

OBJECTIVE: In utero repair of fetal posterior cephaloceles (meningocele and encephalocele) is being performed based on the premise that fetal surgery prevents progressive herniation of neural tissue and brain damage during pregnancy. However, the extent to which progressive herniation occurs during pregnancy, specifically from prenatal diagnosis to after delivery, is not well known. The objective of this study was to describe the natural history of patients with fetal cephaloceles focusing on the incidence of progressive herniation. METHODS: The authors conducted a retrospective cohort study of all patients referred to their center for posterior fetal cephalocele between 2006 and 2021. All patients underwent prenatal and postnatal MRI. Progressive herniation (primary outcome) was defined as an increase in the absolute volume of neural tissue within the cephalocele of > 5% or new herniation of a critical structure into the cephalocele. Total brain and cephalocele volumes were calculated to determine herniation progression from prenatal to postnatal MRI. Information on the presence of hydrocephalus, epilepsy, and developmental delay (secondary outcomes) was collected at 1 year of age. RESULTS: Twenty patients met all study criteria. Ten patients (50%; 95% CI 0.27-0.73) demonstrated progressive herniation from prenatal to postnatal MRI. Three patients with progressive herniation were diagnosed with a meningocele prenatally and had an encephalocele postnatally. Two patients without progression had meningocele identified prenatally that regressed and became atretic by birth. Both prenatal hindbrain herniation (p = 0.03) and prenatal microcephaly (p = 0.05) were predictive of progressive herniation. The rates of hydrocephalus (44%), epilepsy (44%), and developmental delay (63%) were not associated with the occurrence of progressive herniation in this study. CONCLUSIONS: In this study, progressive herniation was not a rare event (50%). Fetal hindbrain herniation and fetal microcephaly were associated with the occurrence of progressive herniation. These results support further investigations into why progressive herniation occurs in utero and if progressive cerebral herniation in utero plays a significant role in determining clinical outcome.

Fetoscopic insufflation of heated-humidified carbon dioxide during simulated spina bifida repair is safe under controlled anesthesia in the fetal lamb.

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 (pCO2  = 30 mmHg), blood pressure (≥67 mmHg), and temperature (37.1-39.8°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), pCO2 (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, pCO2  ≤ 70 mmHg, bicarbonate ≤ 30 mm/L) for ≥120 min of hPACI as opposed to ≤30 min in group one. Fetal pO2 and lactate were comparable between groups and generally within normal range. Fetal brain histology demonstrated fewer apoptotic cells and higher neuronal density in the prefrontal cortex in group two. There was no difference in fetal membrane inflammation, which was mild. CONCLUSION: Fetoscopic insufflation of heated-humidified CO2 during simulated fSB-repair through an exteriorized uterus can be done safely under controlled anesthesia.

Prenatal ultrasonographic markers for prediction of complex gastroschisis and adverse perinatal outcomes: a systematic review and meta-analysis.

OBJECTIVE: We sought to perform a meta-analysis of the predictive value of antenatal ultrasonographic markers of bowel dilation, gastric dilation, polyhydramnios and abdominal circumference that predict complex gastroschisis and adverse perinatal outcomes DATA SOURCES: PubMed, Web of Science, Scopus and Embase were searched for relevant articles up to December 2020. Studies reporting prenatal ultrasonographic markers including intra-abdominal bowel dilation (IABD), extra-abdominal bowel dilation (EABD), bowel wall thickness, polyhydramnios, abdominal circumference <5th percentile, gastric dilation (GD) and bowel dilation not otherwise specified (BD-NOS) were included. The primary outcome was prediction of complex gastroschisis; secondary outcomes were length of hospital stay for newborn, time to full enteral feeding, postnatal mortality rate, incidence of necrotising enterocolitis and short bowel syndrome. RESULTS: Thirty-six studies were included in this meta-analysis. We found significant associations between complex gastroschisis and IABD (OR=5.42; 95% CI 3.24 to 9.06), EABD (OR=2.27; 95% CI 1.40 to 3.66), BD-NOS (OR=6.27; 95% CI 1.97 to 19.97), GD (OR=1.88; 95% CI 1.22 to 2.92) and polyhydramnios (OR=6.93; 95% CI 3.39 to 14.18). Second trimester IABD and EABD have greater specificity for the prediction of complex gastroschisis than third trimester values with specificity of 95.6% (95% CI 58.1 to 99.7) and 94.6% (95% CI 86.7 to 97.9) for the second trimester IABD and EABD, respectively. CONCLUSION: Prenatal ultrasonographic markers, especially the second trimester IABD and EABD, can identify fetuses that develop complex gastroschisis. Furthermore, these specific ultrasonographic markers can identify those babies at the highest risk for severe complications of this congenital anomaly and hence selected for future antenatal interventions.

Surgical data science - from concepts toward clinical translation.

Recent developments in data science in general and machine learning in particular have transformed the way experts envision the future of surgery. Surgical Data Science (SDS) is a new research field that aims to improve the quality of interventional healthcare through the capture, organization, analysis and modeling of data. While an increasing number of data-driven approaches and clinical applications have been studied in the fields of radiological and clinical data science, translational success stories are still lacking in surgery. In this publication, we shed light on the underlying reasons and provide a roadmap for future advances in the field. Based on an international workshop involving leading researchers in the field of SDS, we review current practice, key achievements and initiatives as well as available standards and tools for a number of topics relevant to the field, namely (1) infrastructure for data acquisition, storage and access in the presence of regulatory constraints, (2) data annotation and sharing and (3) data analytics. We further complement this technical perspective with (4) a review of currently available SDS products and the translational progress from academia and (5) a roadmap for faster clinical translation and exploitation of the full potential of SDS, based on an international multi-round Delphi process.

Neonatal and fetal therapy of congenital diaphragmatic hernia-related pulmonary hypertension.

Congenital diaphragmatic hernia (CDH) is a complex malformation characterised by a triad of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. Much of the mortality and morbidity in CDH is largely accounted for by PH, especially when persistent beyond the neonatal period and refractory to available treatment. Gentle ventilation, haemodynamic optimisation and pulmonary vasodilation constitute the foundations of neonatal treatment of CDH-related PH (CDH-PH). Moreover, early prenatal diagnosis, the ability to assess severity and the developmental nature of the condition generate the perfect rationale for fetal therapy. Shortcomings of currently available clinical therapies in combination with increased understanding of CDH pathophysiology have spurred experimental drug trials, exploring new therapeutic mechanisms to tackle CDH-PH. We herein discuss clinically available neonatal and fetal therapies specifically targeting CDH-PH and review the most promising experimental treatments and future research avenues.