Fetoscopic Tracheal Occlusion Research Articles

Fetoscopic Tracheal Occlusion for Isolated Severe Left Diaphragmatic Hernia: A Systematic Review and Meta-Analysis.

Background: We aimed to conduct a systematic review and meta-analysis to evaluate the fetoscopic tracheal occlusion in patients with isolated severe and left-sided diaphragmatic hernia. Methods: Cochrane Library, Embase, and PubMed (Medline) databases were searched from inception to February 2024 with no filters or language restrictions. We included studies evaluating the outcomes of fetoscopic intervention compared to expectant management among patients with severe congenital diaphragmatic hernia exclusively on the left side. A random-effects pairwise meta-analysis was performed using RStudio version 4.3.1. Results: In this study, we included 540 patients from three randomized trials and five cohorts. We found an increased likelihood of neonatal survival associated with fetoscopic tracheal occlusion (Odds Ratio, 5.07; 95% Confidence Intervals, 1.91 to 13.44; p < 0.01) across general and subgroup analyses. Nevertheless, there were higher rates of preterm birth (OR, 5.62; 95% CI, 3.47-9.11; p < 0.01) and preterm premature rupture of membranes (OR, 7.13; 95% CI, 3.76-13.54; p < 0.01) in fetal endoscopic tracheal occlusion group compared to the expectant management. Conclusions: Our systematic review and meta-analysis demonstrated the benefit of fetoscopic tracheal occlusion in improving neonatal and six-month postnatal survival in fetuses with severe left-sided CDH. Further studies are still necessary to evaluate the efficacy of tracheal occlusion for isolated right-sided CDH, as well as the optimal timing to perform the intervention.

Do FETO CDH survivors need the same follow-up program as non-FETO patients?

Congenital diaphragmatic hernia (CDH) survivors are at risk of developing significant chronic health conditions and disabilities. The main purpose of this study was to compare the outcomes of CDH infants at 2years of age (2y) according to whether the infants had undergone fetoscopic tracheal occlusion (FETO) during the prenatal period and characterize the relationship between morbidity at 2y and perinatal characteristics. Retrospective cohort single center study. Eleven years of clinical follow-up data (from 2006 to 2017) were collected. Prenatal and neonatal factors as well as growth, respiratory, and neurological evaluations at 2y were analyzed. One hundred and fourteen CDH survivors were evaluated. Failure to thrive (FTT) was present in 24.6% of patients, gastroesophageal reflux disease (GERD) in 22.8%, 28.9% developed respiratory problems, and 22% had neurodevelopment disabilities. Prematurity and birth weight < 2500g were related to FTT and respiratory morbidity. Time to reach full enteral nutrition and prenatal severity markers seemed to influence all outcomes, but FETO therapy itself only had an effect on respiratory morbidity. Some variables related to postnatal severity (ECMO, patch closure, days on mechanic ventilation, and vasodilator treatment) were associated with almost all outcomes. Conclusion: CDH patients have specific morbidities at 2y, most of them related to lung hypoplasia severity. Only respiratory problems were related to FETO therapy itself. The implementation of a specific multidisciplinary follow-up program for CDH patients is essential to provide them the best standard of care, but, more severe patients, regardless of whether they received prenatal therapy, need a more intensive follow-up. What is Known: • Antenatal fetoscopic endoluminal tracheal occlusion (FETO) increases survival in more severe congenital diaphragmatic hernia patients. • Congenital diaphragmatic hernia survivors are at risk of developing significant chronic health conditions and disabilities. Very limited data are available about the follow-up in patients with congenital diaphragmatic hernia and FETO therapy. What is New: • CDH patients have specific morbidities at 2 years of age, most of them related to lung hypoplasia severity. • FETO patients present more respiratory problems at 2 years of age but they don't have an increased incidence of other morbidities. More severe patients, regardless of whether they received prenatal therapy, need a more intensive follow-up.

Postnatal care setting and survival after fetoscopic tracheal occlusion for severe congenital diaphragmatic hernia: A systematic review and meta-analysis

BackgroundFetoscopic endoluminal tracheal occlusion (FETO) was recently shown to improve postnatal survival in a multicenter, randomized controlled trial of infants with severe congenital diaphragmatic hernia (CDH). However, the external validity of this study remains unclear given a lack of standardization in postnatal management approaches. The purpose of this study was to evaluate the impact of an integrated prenatal and postnatal care setting on survival outcomes in severe CDH after FETO. Study designA systematic review, meta-analysis, and individual participant analysis of FETO outcomes in severe CDH were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was survival to discharge. Subgroup analyses of patients managed in integrated versus nonintegrated settings were performed to identify predictors of outcome. ResultsThe review generated five studies (n = 192) for the meta-analysis of FETO versus expectant prenatal management. These data revealed a significant survival benefit after FETO that was restricted to an integrated setting (OR 2.97, 95% Confidence Interval 1.69–4.26). There were nine studies (n = 150) for the individual participant analysis, which showed that FETO managed in an integrated setting had significantly increased survival rates when compared to FETO treated in a nonintegrated setting (70.7% vs. 45.7%, p = 0.003). Multi-level logistic regression identified increased availability of extracorporeal membrane oxygenation (ECMO) as the strongest determinant of postnatal survival (OR=18.8, p = 0.049). ConclusionThis systematic review shows that institutional integration of prenatal and postnatal care is associated with the highest overall survival in children with severe CDH. These data highlight the importance of a standardized, multidisciplinary approach, including access to ECMO, as a critical postnatal component in optimizing FETO outcomes in CDH.

Challenges and Pitfalls: Performing Clinical Trials in Patients With Congenital Diaphragmatic Hernia.

Congenital diaphragmatic hernia (CDH) is a rare developmental defect of the lungs and diaphragm, with substantial morbidity and mortality. Although internationally established treatment guidelines have been developed, most recommendations are still expert opinions. Trials in patients with CDH, more in particular randomized controlled trials, are rare. Only three multicenter trials in patients with CDH have been completed, which focused on fetoscopic tracheal occlusion and ventilation mode. Another four are currently recruiting, two with a focus on perinatal transition and two on the treatment of pulmonary hypertension. Herein, we discuss major challenges and pitfalls when performing a clinical trial in infants with CDH. It is essential to select the correct intervention and dose, select the appropriate population of CDH patients, and also define a relevant endpoint that allows a realistic duration and sample size. New statistical approaches might increase the feasibility of randomized controlled trials in patients with CDH. One should also timely perform the trial when there is still equipoise. But above all, awareness of policymakers for the relevance of investigator-initiated trials is essential for future clinical research in this rare disease.

Sonographic pulmonary response after tracheal occlusion in fetuses with severe isolated congenital diaphragmatic hernia.

To report the longitudinal lung growth and prognosis of fetuses with severe left sided congenital diaphragmatic hernia (CDH) treated with fetoscopic tracheal occlusion (FETO) in a single institution. Fetal lung size (observed-to-expected lung area to head circumference [o/e-LHR]) was measured in seven consecutive fetuses with isolated severe left-sided CDH who underwent FETO. Fetal lung growth was used to prognosticate survival and need for ECMO. Seven consecutive fetuses had a FETO procedure in the timeframe of this study. A total of 44 longitudinal ultrasound were performed to evaluate lung development. FETO was performed at GA 28.5 ± 0.5 weeks. Five (71.4%) infants survived to one-year follow-up and ECMO was needed in three patients (42.8%). Fetal lung response was observed in all fetuses; mean o/e-LHR increased from 22.5% ± 1.4 before FETO to 44.4% ± 9.8 before delivery. Infants who survived had a higher percentage of fetal lung growth (21.8%) than those who died (8.25%). Our study supports the hypothesis that FETO promotes fetal lung growth in fetuses with severe left-sided CDH, and the fetal pulmonary response seems to be associated with improved outcomes after the procedure.

Right ventricular analysis of fetuses with congenital diaphragmatic hernia shows increased risk of neonatal death

Cardiac deformation analysis (CDA) is a novel ultrasound (US) technique used to assess fetal cardiac shape and contractility. This study aims to correlate CDA with observed/expected lung-to-head ratio (O/E LHR) in the prediction of adverse neonatal outcome in fetuses with isolated congenital diaphragmatic hernia (CDH) no treated with fetoscopic tracheal occlusion.

Single-Center Outcome of Fetoscopic Tracheal Balloon Occlusion for Severe Congenital Diaphragmatic Hernia

(Obstet Gynecol. 2020;135:511–521) Congenital diaphragmatic hernia, caused by the absence of the diaphragm or part of the diaphragm, leads to impaired fetal lung development as the abdominal contents move into the chest cavity. This is commonly managed with high-frequency oscillatory ventilation, pulmonary vasodilators, and extracorporeal membrane oxygenation, but the survival rate is &lt;20% in cases with an observed lung/head ratio of &lt;25% and intrathoracic liver herniation. In temporary fetoscopic tracheal balloon occlusion (FETO), the lungs are stretched and increase growth in airways and lung vasculature takes place. FETO has demonstrated increased survival rates, but is also associated with adverse outcomes such as preterm labor, rupture of membranes, and preterm birth. This study aimed to determine feasibility of FETO in cases of severe congenital diaphragmatic hernia.

OP17.08: Optimal full matching for survival outcomes in severe left diaphragmatic hernia with and without fetoscopic tracheal occlusion

OP17.08: Optimal full matching for survival outcomes in severe left diaphragmatic hernia with and without fetoscopic tracheal occlusion

Reproducibility of fetal lung-to-head ratio in left diaphragmatic hernia across the North American Fetal Therapy Network (NAFTNet).

To determine the antenatal sonographic lung area measurement method in left congenital diaphragmatic hernia (CDH) with the highest interrater agreement among North American Fetal Therapy Network (NAFTNet) centers within and outside the fetoscopic tracheal occlusion (FETO) consortium and in comparison with a European "expert" reviewer (ER). Nineteen members from nine FETO consortium centers and 29 reviewers from 17 non-FETO centers reviewed ultrasound clips of the chest from 13 fetuses with isolated left CDH and were asked to select a static plane for lung area measurement using anteroposterior (AP), longest, and trace methods. Interrater agreement in lung area measurements was determined using intraclass correlation coefficient (ICC). Bland-Altman analysis was used to evaluate mean difference (bias) between NAFTNet reviewers and ER. Among FETO centers, agreement was highest using trace (ICC 0.94; 95% CI, 0.83-0.98), followed by longest (ICC 0.89; 95% CI, 0.75-0.97) and lowest for A-P (ICC 0.83; 95% CI, 0.67-0.94). Similar trends were noted in non-FETO centers. When compared with ER, bias was lowest for trace: 14±38mm2 and 19±36mm2 for FETO and non-FETO centers, respectively. The trace method demonstrated the highest interrater agreement and lowest bias for lung area estimation in left CDH across NAFTNet.

Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia.

BackgroundCongenital diaphragmatic hernia (CDH) is a fetal defect comprising an incomplete diaphragm and the herniation of abdominal organs into the chest cavity that interfere with fetal pulmonary development. Though the most promising treatment for CDH is via interventional fetoscopic tracheal occlusion (TO) surgery in-utero, it has produced mixed results due to the static nature of the inserted occlusion. We hypothesize that a suitable noninvasively-actuatable, cyclic-release tracheal occlusion device can be developed to enable dynamic tracheal occlusion (dTO) implementation.ObjectiveTo conduct an in-vitro proof-of-concept investigation of the construction of thermo-responsive polymer valves designed for targeted activation within a physiologically realizable temperature range as a first step towards potential development of a noninvasively-actuatable implantable device to facilitate dynamic tracheal occlusion (dTO) therapy.MethodsSix thermo-responsive polymer valves, with a critical solution temperature slightly higher than normal physiological body temperature of 37°C, were fabricated using a copolymer of n-isopropylacrylamide (NIPAM) and dimethylacrylamide (DMAA). Three of the valves underwent ethylene oxide (EtO) sterilization while the other three served as controls for EtO-processing compatibility testing. Thermal response actuation of the valves and their steady-state flow performances were evaluated using water and caprine amniotic fluid.ResultsAll six valves consisting of 0.3-mole fraction of DMAA were tested for thermal actuation of caprine amniotic fluid flow at temperatures ranging from 30–44°C. They all exhibited initiation of valve actuation opening at ~40°C with full completion at ~44°C. The overall average coefficient of variation (CV) for the day-to-day flow performance of the valves tested was less than 12%. Based on a Student t-test, there was no significant difference in the operational characteristics for the EtO processed versus the non-EtO processed valves tested.ConclusionsWe successfully fabricated and demonstrated physiological realizable temperature range operation of thermo-responsive polymer valves in-vitro and their suitability for standard EtO sterilization processing, a prerequisite for future in-vivo surgical implantation testing.

181: Survival after fetoscopic tracheal occlusion for diaphragmatic hernia: The importance of the care setting

Fetoscopic tracheal occlusion (FETO) is an experimental prenatal treatment intended to improve the respiratory morbidity and mortality associated with severe congenital diaphragmatic hernia (CDH)). In the US all CDH programs that employ FETO have standardized pediatric care paths that include extracorporeal membrane oxygenation (ECMO). We sought to compare US-FETO outcomes to healthcare settings where ECMO is not uniformly available. Infant outcome after FETO from a feasibility study at our center (NCT:02710968) and another US Center (Belfort et al., 2017) were aggregated. Similar data were extracted from all published non-US FETO series that are available in PubMed. Gestational age (GA) at FETO, balloon removal and delivery, length of occlusion as well as side of hernia, observed to expected lung to head ratio (O/E LHR), delivery details and neonatal and infant survival were compared between the two healthcare settings. FETO outcome from 21 CDH infants from the US were compared to 71 reported in six studies from Europe and Brazil. Baseline characteristics and CDH severity were similar between cohorts (table). In the US FETO and balloon removal occurred one week later respectively (p<0.05). Balloon removal was achieved prenatally by fetoscopy more frequently in the US cases (p<0.05). Remaining procedure details were similar. Following balloon removal there were differences in the rate of preterm birth <34 weeks (21/71 vs 2/21) and delivery gestational age (35 vs 36+1 weeks gestation; both p<0.05) in the two care settings. Neonatal survival was higher in the US cohort (p<0.0001), but higher infant survival did not reach significance, Among all significantly divergent variables logistic regression identified the healthcare setting as the primary determinant of neonatal death (r2 0.28, B=-2.772, p<0.004). Survival after FETO for CDH is significantly dependent on the healthcare setting suggesting that postnatal therapies such as ECMO are complementary to overcome the pulmonary hypertension and hypoplasia of severe CDH. Neonatal survival is higher after FETO in ECMO centers. Our findings indicate that randomized trials of fetal therapy for CDH must be powered based on to the specific healthcare setting where this treatment is subsequently intended to be used.

180: Outcome after fetoscopic tracheal occlusion treatment of congenital diaphragmatic hernia

180: Outcome after fetoscopic tracheal occlusion treatment of congenital diaphragmatic hernia

Cirugía fetal para hernia diafragmática congénita en América Latina

La hernia diafragmática congénita es una anomalía en la formación del diafragma, asociada a elevada mortalidad neonatal secundaria a hipoplasia pulmonar e hipertensión arterial pulmonar neonatal. El diagnóstico se realiza por ultrasonido, generalmente en la semana 20 de gestación, y es mandatorio solicitar estudios genéticos (cariotipo y microarreglos) debido al alto riesgo de asociación con anomalías cromosómicas y monogénicas. En casos aislados, la estimación del tamaño pulmonar en combinación con la identificación de herniación hepática es el mejor parámetro predictivo de supervivencia neonatal. En los casos con hipoplasia pulmonar grave, la oclusión traqueal fetoscópica ha demostrado una mejoría en la tasa de supervivencia en 30% con respecto a la probabilidad basal. En este artículo, se resume las indicaciones, criterios de selección, técnica y resultados de la oclusión traqueal fetoscópica, destacando las diferencias de tasa de supervivencia neonatal que existen en América Latina.

OC14.07: Ultrasound‐measured lung size in severe congenital diaphragmatic hernia (CDH) after fetoscopic tracheal occlusion (FETO)

OC14.07: Ultrasound‐measured lung size in severe congenital diaphragmatic hernia (CDH) after fetoscopic tracheal occlusion (FETO)

P15.07: Fetoscopic tracheal occlusion for congenital diaphragmatic hernia in Japan: the feasibility and preliminary results of lung volume analyses

P15.07: Fetoscopic tracheal occlusion for congenital diaphragmatic hernia in Japan: the feasibility and preliminary results of lung volume analyses

Fetoscopic tracheal occlusion for severe congenital diaphragmatic hernia: retrospective study

The temporary fetal tracheal occlusion performed by fetoscopy accelerates lung development and reduces neonatal mortality. The aim of this paper is to present an anesthetic experience in pregnant women, whose fetuses have diaphragmatic hernia, undergoing fetoscopic tracheal occlusion (FETO). Retrospective, descriptive study, approved by the Institutional Ethics Committee. Data were obtained from medical and anesthetic records. FETO was performed in 28 pregnant women. Demographic characteristics: age 29.8±6.5; weight 68.64±12.26; ASA I and II. Obstetric: IG 26.1±1.10 weeks (in FETO); 32.86±1.58 (reversal of occlusion); 34.96±2.78 (delivery). Delivery: cesarean section, vaginal delivery. Fetal data: Weight (g) in the occlusion and delivery times, respectively (1045.82±222.2 and 2294±553); RPC in FETO and reversal of occlusion: 0.7±0.15 and 1.32±0.34, respectively. Preoperative maternal anesthesia included ranitidine and metoclopramide, nifedipine (VO) and indomethacin (rectal). Preanesthetic medication with midazolam IV. Anesthetic techniques: combination of 0.5% hyperbaric bupivacaine (5-10mg) and sufentanil; continuous epidural predominantly with 0.5% bupivacaine associated with sufentanil, fentanyl, or morphine; general. In 8 cases, there was need to complement via catheter, with 5 submitted to PC and 3 to BC. Thirteen patients required intraoperative sedation; ephedrine was used in 15 patients. Fetal Anesthesia: fentanyl 10 to 20mg·kg-1 and pancuronium 0,1-0,2mg·kg-1 (IM). Neonatal survival rate was 60.7%. FETO is a minimally invasive technique for severe congenital diaphragmatic hernia repair. Combined blockade associated with sedation and fetal anesthesia proved safe and effective for tracheal occlusion.

Fetal imaging and therapy for CDH—Current status

In congenital diaphragmatic hernia (CDH), herniation of the abdominal organs into the fetal chest causes pulmonary hypoplasia and pulmonary hypertension, the main causes of neonatal mortality. As antenatal ultrasound screening improves, the risk of postnatal death can now be better predicted, allowing for the identification of fetuses that might most benefit from a prenatal intervention. Fetoscopic tracheal occlusion is being evaluated in a large international randomized controlled trial. We present the antenatal imaging approaches that can help identify fetuses that might benefit from antenatal therapy, and review the evolution of fetal surgery for CDH to date.

Fetoscopic tracheal occlusion for severe congenital diaphragmatic hernia: retrospective study

Background and objectivesThe temporary fetal tracheal occlusion performed by fetoscopy accelerates lung development and reduces neonatal mortality. The aim of this paper is to present an anesthetic experience in pregnant women, whose fetuses have diaphragmatic hernia, undergoing fetoscopic tracheal occlusion (FETO). MethodRetrospective, descriptive study, approved by the Institutional Ethics Committee. Data were obtained from medical and anesthetic records. ResultsFETO was performed in 28 pregnant women. Demographic characteristics: age 29.8±6.5; weight 68.64±12.26; ASA I and II. Obstetric: IG 26.1±1.10 weeks (in FETO); 32.86±1.58 (reversal of occlusion); 34.96±2.78 (delivery). Delivery: cesarean section, vaginal delivery. Fetal data: Weight (g) in the occlusion and delivery times, respectively (1045.82±222.2 and 2294±553); RPC in FETO and reversal of occlusion: 0.7±0.15 and 1.32±0.34, respectively. Preoperative maternal anesthesia included ranitidine and metoclopramide, nifedipine (VO) and indomethacin (rectal). Preanesthetic medication with midazolam IV. Anesthetic techniques: combination of 0.5% hyperbaric bupivacaine (5–10mg) and sufentanil; continuous epidural predominantly with 0.5% bupivacaine associated with sufentanil, fentanyl, or morphine; general. In 8 cases, there was need to complement via catheter, with 5 submitted to PC and 3 to BC. Thirteen patients required intraoperative sedation; ephedrine was used in 15 patients. Fetal anesthesia: fentanyl 10–20mg.kg−1 and pancuronium 0.1–0.2mg.kg−1 (IM). Neonatal survival rate was 60.7%. ConclusionFETO is a minimally invasive technique for severe congenital diaphragmatic hernia repair. Combined blockade associated with sedation and fetal anesthesia proved safe and effective for tracheal occlusion.

Congenital diaphragmatic hernia-influence of fetoscopic tracheal occlusion on outcomes and predictors of survival.

The morbidity of infants with congenital diaphragmatic hernia (CDH) who had undergone foetal endoscopic tracheal occlusion (FETO) to those who had not was compared and predictors of survival regardless of antenatal intervention were identified. FETO was undertaken on the basis of the lung to head ratio or the position of the liver. A retrospective review of the records of 78 CDH infants was undertaken to determine the lung-head ratio (LHR) at referral and prior to birth, maximum oxygen saturation in the labour suite and neonatal outcomes. The 43 FETO infants were born earlier (mean 34 versus 38weeks) (p < 0.001). They had a lower mean LHR at referral (0.65 versus 1.24) (p < 0.001) but not prior to birth and did not have a higher mortality than the 35 non-FETO infants. The FETO infants required significantly longer durations of ventilation (median: 15 versus 6days) and supplementary oxygen (28 versus 8days) and hospital stay (29 versus 16days). Overall, the best predictor of survival was the OI in the first 24h. The FETO group had increased morbidity, but not mortality. The lowest oxygenation index in the first 24h was the best predictor of survival regardless of antenatal intervention. • Randomised controlled trials have demonstrated that foetal endotracheal occlusion (FETO) in high risk infants with congenital diaphragmatic hernia is associated with a higher survival rate. • Mortality is greater in foetuses who underwent FETO and delivered prior to 35weeks of gestation. What is New: • Infants who had undergone FETO compared to those who had not had significantly longer durations of mechanical ventilation, supplementary oxygen and hospital stay. • Regardless of antenatal intervention, the lowest oxygenation index in the first 24h was the best predictor of survival.

Prophylactic use of the Arabin cervical pessary in fetuses with severe congenital diaphragmatic hernia treated by fetoscopic endoluminal tracheal occlusion (FETO): preliminary experience.

The aim of this study was to describe whether the prophylactic use of a cervical pessary decreases the rate of premature birth in congenital diaphragmatic hernia (CDH) fetuses treated with fetoscopic tracheal occlusion (FETO). The study concerns a consecutive series of cases with CDH and FETO and a group of CDH without FETO. In a subgroup of the FETO group, a prophylactic cervical pessary was inserted the day following the procedure. Gestational age (GA) at birth was the primary outcome. Fifty-nine fetuses with FETO and 47 expectantly managed were included. The last 15 FETO had a cervical pessary inserted. The median GA at delivery in the FETO group with pessary was 35.1 weeks and was not different from that in the FETO group without a pessary (34.3 weeks; p = 0.28) but was below that in the expectantly managed group (38.3 weeks; p < 0.001). Early results suggest that prophylactic use of an Arabin cervical pessary does not prolong gestation of CDH fetuses treated with FETO. © 2015 John Wiley & Sons, Ltd.