Surfactant Therapy in Congenital Diaphragmatic Hernia and Fetoscopic Endoluminal Tracheal Occlusion.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population. METHODS: A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression. RESULTS: Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use. CONCLUSIONS: Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO.

Fetal cardiovascular changes during open and fetoscopic in-utero spina bifida closure.

OBJECTIVE: Fetoscopic closure of spina bifida using heated and humidified carbon dioxide gas (hhCO2) has been associated with lower maternal morbidity compared with open closure. Fetal cardiovascular changes during these surgical interventions are poorly defined. Our objective was to compare fetal bradycardia (defined as fetal heart rate (FHR) < 110 bpm for 10 min) and changes in umbilical artery (UA) Doppler parameters during open vs fetoscopic closure. METHODS: This was a prospective cohort study of 22 open and 46 fetoscopic consecutive in-utero closures conducted between 2019 and 2023. Both cohorts had similar preoperative counseling and clinical management. FHR and UA Doppler velocimetry were obtained systematically during preoperative assessment, every 5 min during the intraoperative period, and during the postoperative assessment. FHR, UA pulsatility index (PI) and UA end-diastolic flow (EDF) were segmented into hourly periods during surgery, and the lowest values were averaged for analysis. Umbilical vein maximum velocity was measured in the fetoscopic cohort. At each timepoint at which FHR was recorded, maternal heart rate and systolic and diastolic blood pressure were measured. RESULTS: Fetal bradycardia occurred in 4/22 (18.2%) cases of open closure and 21/46 (45.7%) cases of fetoscopic closure (P = 0.03). FHR decreased gradually in both cohorts after administration of general anesthesia and decreased further during surgery. FHR was significantly lower during hour 2 of surgery in the fetoscopic-repair cohort compared with the open-repair cohort. The change in FHR from baseline in the final stage of fetal surgery was significantly more pronounced in the fetoscopic-repair cohort compared with the open-repair cohort (mean, -32.4 (95% CI, -35.7 to -29.1) bpm vs -23.5 (95% CI, -28.1 to -18.8) bpm; P = 0.002). Abnormal UA-EDF (defined as absent or reversed EDF) occurred in 3/22 (13.6%) cases in the open-repair cohort and 23/46 (50.0%) cases in the fetoscopic-repair cohort (P = 0.004). There were no differences in UA-EDF or UA-PI between closure techniques at the individual stages of assessment. CONCLUSIONS: We observed a decrease in FHR and abnormalities in UA Doppler parameters during both open and fetoscopic spina bifida closure. Fetal bradycardia was more prominent during fetoscopic closure following hhCO2 insufflation, but FHR recovered after cessation of hhCO2. Changes in FHR and UA Doppler parameters during in-utero spina bifida closure were transient, no cases required emergency delivery and no fetoscopic closure was converted to open closure. These observations should inform algorithms for the perioperative management of fetal bradycardia associated with in-utero spina bifida closure. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal bradycardia in open versus fetoscopic prenatal repair of spina bifida.

OBJECTIVE: To compare the occurrence of fetal bradycardia in open versus fetoscopic fetal spina bifida surgery. METHODS: This is a single-institution retrospective cohort study of patients undergoing open (n = 25) or fetoscopic (n = 26) spina bifida repair between 2017 and 2022. From October 2017 to June 2020, spina bifida repairs were performed via an open classical hysterotomy, and from November 2020 to June 2022 fetoscopic repairs were performed following transition to this technique. Fetal heart rate (FHR) in beats per minute (bpm) was recorded via echocardiography every 15 min during the procedure. Cohort characteristics, fetal bradycardia and maternal physiologic parameters were compared between the groups. RESULTS: Fetuses undergoing an open repair more frequently developed bradycardia defined as <110 bpm (32% vs. 3.8%, p = 0.008), and a trend was observed for FHR decreases more than 25 bpm from baseline (20% vs. 3.8%, p = 0.073). Profound bradycardia less than 80 bpm was rare, occurring in only three operations (two in open, one in fetoscopic repair) with two fetuses (one in each group) requiring emergency cesarean delivery. CONCLUSION: When compared to open fetal surgery, fetal bradycardia occurred less frequently in fetoscopic surgery despite a significantly greater anesthetic exposure and the use of the intraamniotic carbon dioxide insufflation.

Fetoscopic laser coagulation for twin-to-twin transfusion syndrome: a comparison of flexible 1.0/1.2 mm fetoscopes with curved sheaths of 2.7/3.3 mm2 vs. 2 mm fetoscopic lens technique with sheaths of 6.6/11.3 mm2.

OBJECTIVES: Fetoscopic laser coagulation of placental anastomoses is usually performed for a treatment of twin-to-twin transfusion syndrome (TTTS). A common complication of fetoscopic laser coagulation for TTTS is preterm preliminary rupture of fetal membranes (PPROM) aggravating the neonatal outcome significantly. However, use of an flexible 1 mm fetoscope with an curved sheath could reduce iatrogenic damage of the amniotic membrane and improve neonatal outcomes after laser treatment. The aim of this study was to compare neonatal outcomes using this flexible fetoscope with curved sheath vs. use of a standard lens technique. METHODS: Outcomes were retrospective analyzed after use of a standard lens fetoscope of 2 mm (sheath 6.63 mm2 or 11.27 mm2 for anterior placenta) and a flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2) in two German centers of fetal surgery, performed during 2006-2019. RESULTS: Neonatal outcome of 247 TTTS patients were analyzed including the rates of double and single fetal survival. The survival of at least one fetus was 97.2 % in the group with the ultrathin technique (n=154) compared to 88.3 % (n=93) in the group with the standard lens fetoscope (p=0.008). Survival of both fetuses was not different between groups (81.0 vs. 75.3 %). The procedure to delivery interval was significantly increased using the ultrathin fetoscope (89.1±35.0 d vs. 71.4±35.4 d, p=0.001) resulting in an increased gestational age at delivery by 11 days on average (231.9±28.1 d vs. 221.1±32.7 d, p=0.012). CONCLUSIONS: Fetal survival can be significantly increased following TTTS using flexible fetoscope of 1 mm or 1.2 mm (sheath 2.65 mm2 or 3.34 mm2).

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Tracheomalacia and tracheomegaly in infants and children with congenital diaphragmatic hernia managed with and without fetoscopic endoluminal tracheal occlusion (FETO): a multicentre, retrospective cohort study.

BACKGROUND: Temporary fetoscopic endoluminal tracheal occlusion (FETO) promotes lung growth and increases survival in selected fetuses with congenital diaphragmatic hernia (CDH). FETO is performed percutaneously by inserting into the trachea a balloon designed for vascular occlusion. However, reports on the potential postnatal side-effects of the balloon are scarce. This study aimed to evaluate the prevalence of tracheomalacia in infants with CDH managed with and without FETO and other consequences related to the use of the balloon. METHODS: In this multicentre, retrospective cohort study, we included infants who were live born with CDH, either with FETO or without, who were managed postnatally at four centres (UZ Leuven, Leuven, Belgium; Antoine Béclère, Clamart, France; BCNatal, Barcelona, Spain; and HCor-Heart Hospital, São Paulo, Brazil) between April 5, 2002, and June 2, 2021. We primarily assessed the prevalence of all (symptomatic and asymptomatic) tracheomalacia as reported in medical records among infants with and without FETO. Secondarily we assessed the prevalence of symptomatic tracheomalacia and its resolution as reported in medical records, and compared tracheal diameters as measured on postnatal x-rays. Crude and adjusted risk ratios (aRRs) and 95% CIs were calculated via modified Poisson regression models with robust error variances for potential association between FETO and tracheomalacia. Variables included in the adjusted model were the side of the hernia, observed-to-expected lung-to-head ratio, and gestational age at birth. Crude and adjusted mean differences and 95% CIs were calculated via linear regression models to assess the presence and magnitude of association between FETO and tracheal diameters. In infants who had undergone FETO we also assessed the localisation of balloon remnants on x-rays, and the methods used for reversal of occlusion and potential complications associated with balloon remnants as documented in clinical records. Finally we investigated whether the presence of balloon remnants was influenced by the interval between balloon removal and delivery. FINDINGS: 505 neonates were included in the study, of whom 287 had undergone FETO and 218 had not. Tracheomalacia was reported in 18 (6%) infants who had undergone FETO and in three (1%) who had not (aRR 6·17 [95% CI 1·83-20·75]; p=0·0030). Tracheomalacia was first reported in the FETO group at a median of 5·0 months (IQR 0·8-13·0). Symptomatic tracheomalacia was reported in 13 (5%) infants who had undergone FETO, which resolved in ten (77%) children by 55·0 months (IQR 14·0-83·0). On average, infants who had undergone FETO had a 31·3% wider trachea (with FETO tracheal diameter 7·43 mm [SD 1·24], without FETO tracheal diameter 5·10 mm [SD 0·84]; crude mean difference 2·32 [95% CI 2·11-2·54]; p<0·0001; adjusted mean difference 2·62 [95% CI 2·35-2·89]; p<0·0001). At birth, the metallic component was visible within the body in 75 (37%) of 205 infants with available thoraco-abdominal x-rays: it was located in the gastrointestinal tract in 60 (80%) and in the lung in 15 (20%). No side-effects were reported for any of the infants during follow-up. The metallic component was more likely to be in the lung than either outside the body or the gastrointestinal tract when the interval between occlusion reversal and birth was less than 24 h. INTERPRETATION: Although FETO was associated with an increased tracheal diameter and an increased probability of tracheomalacia, symptomatic tracheomalacia typically resolved over time. There is a higher risk of retention of metallic balloon components if reversal of the occlusion occurs less than 24 h before delivery. Finally, there were no reported side-effects of the metallic component of the balloon persisting in the body during follow-up. Longer-term follow-up is needed to ensure that no tracheal problems arise later in life. FUNDING: None.

Cirurgias intrauterinas: alternativa de intervenção para as cardiopatias congênitas / Intrauterine surgeries: intervetion alternative for congenital cardiopathies

As cardiopatias congênitas são anormalidades estruturais ou funcionais do sistema cardiovascular, advindas desde o nascimento, mesmo que diagnosticadas posteriormente. Entre as malformações congênitas, as cardiopatias são as principais causas de mortalidade infantil nos Estados Unidos e em outros países desenvolvidos. Com o intuito de reduzir os efeitos progressivos dessas patologias, a intervenção intrauterina tem se destacado como opção terapêutica diante de resultados iniciais satisfatórios. O presente artigo teve por objetivo demonstrar a evolução da cirurgia intrauterina para correção cardíaca, a partir da avaliação dos benefícios ao feto e visando a riscos mínimos e aceitáveis para a mãe. Foi realizada uma pesquisa na base de dados Publisher Medline (PubMed), Scientific Electronic Library Online (SciELO) e Biblioteca Virtual da Saúde (BVS), incluindo artigos publicados entre 2008 e 2018; além da pesquisa efetuada no Manual de Medicina Fetal da SOGIMIG ­ 2018. Os critérios de elegibilidade são amplos. São necessários equipe multidisciplinar, equipamentos sofisticados e aperfeiçoamento da técnica, dessa forma dificulta-se a realização das cirurgias. Entretanto, diante dos resultados já demonstrados, a cirurgia intrauterina apresenta-se como alternativa terapêutica promissora.(AU)

The congenital cardiopathies are structural or functional abnormalities of the cardiovascular system, originated from birth, even when previously diagnosed. Among the congenic malformations, the cardiopathies are the main causes of infant mortality in the United States and in other developed countries. In order to reduce the progressive effects of these pathologies, intrauterine intervention has been highlighted as a therapeutic option in contempt of satisfactory initial results. This article has as goal to demonstrate the evolution of the intrauterine surgery for cardiac correction, based on the evaluation of the benefits to the fetus and aiming at minimum and acceptable risks to the mother. A research was made based on the Publisher Medline (PubMed) data base, Scientific Electronic Library Online (SciELO) and Biblioteca Virtual da Saúde (BVS), including published articles between 2008 and 2018. Beyond the research made on The fetal medicine manual from SOGIMIG ­ 2018. The eligibility criteria are broad. It is necessary a multidisciplinary team, sophisticated equipments and technique improvement, therefore interfering in the performance of surgeries. However, in contempt of the already demonstrated results the intrauterine surgery presents itself as a therapeutic promising alternative.(AU)

Mirror Syndrome after Fetoscopic Laser Treatment - A Case Report / Síndrome do espelho após tratamento laser por fetoscopia - caso clínico

Abstract Mirror syndrome is a rare disease with unknown pathophysiology that can be present in different diseases that can cause fetal hydrops. The prognosis is usually bad with a high perinatal mortality. We report an unusual form of mirror syndrome that manifested itself only after a successful treatment for fetal hydrops (caused by twin-twin transfusion syndrome, in Quinteros stage IV) was performed. This syndrome was controlled by medical treatment, and despite the usually bad prognosis seen in these cases, we could extend the pregnancy from the 23rd to the 34th week of gestation, resulting in the birth of 2 live infants.

Resumo A síndrome do espelho é uma doença rara, de fisiopatologia desconhecida, que se manifesta em situações obstétricas responsáveis pela presença de hidrópsia fetal. Habitualmente o prognóstico é reservado, uma vez que se associa a elevadas taxas de mortalidade perinatal. O presente caso clínico trata de uma situação de síndrome do espelho que se manifestou, atipicamente, após o tratamento eficaz para a hidrópsia fetal associada à síndrome de transfusão feto-fetal. Apesar do mau prognóstico associado a estas situações, conseguiu-se controlar a situação apenas com tratamento médico e, desta forma, prolongar a gravidez durante 12 semanas.

Complicações maternas decorrentes das cirurgias endoscópicas em Medicina fetal / Maternal complications following endoscopic surgeries in fetal Medicine

OBJETIVO: descrever as complicações maternas decorrentes dos procedimentos endoscópicos terapêuticos em Medicina fetal, realizados em um centro universitário no Brasil. MÉTODOS: estudo observacional retrospectivo que incluiu gestantes atendidas no período de Abril de 2007 a Maio de 2010. Esses casos foram submetidos aos seguintes procedimentos: ablação vascular placentária com laser (AVPL) por síndrome de transfusão feto-fetal (STFF) grave; oclusão traqueal fetal (OTF) e retirada de balão traqueal por via endoscópica por hérnia diafragmática congênita (HDC) grave e AVPL, com ou sem cauterização bipolar do cordão umbilical, por síndrome da perfusão arterial reversa (SPAR) em gêmeo acárdico. As principais variáveis descritas para cada condição clínica/tipo de cirurgia foram as complicações maternas e a sobrevida (alta do berçário) do neonato/lactente. RESULTADOS: cinquenta e seis gestantes foram submetidas a 70 procedimentos: STFF grave (34 pacientes; 34 cirurgias); HDC grave (16 pacientes; 30 cirurgias) e SPAR (6 pacientes; 6 cirurgias). Entre as 34 gestantes tratadas com AVPL por STFF, duas (2/34=5,9 por cento) apresentaram perda de líquido amniótico para a cavidade peritoneal e sete (7/34=20,6 por cento) tiveram abortamento após os procedimentos. A sobrevida de pelo menos um gêmeo foi de 64,7 por cento (22/34). Entre as 30 intervenções realizadas para HDC, houve perda de líquido amniótico para a cavidade peritoneal materna em um caso (1/30=3,3 por cento) e rotura prematura pré-termo de membranas após três (3/30=30 por cento) fetoscopias para retirada do balão traqueal. A sobrevida com alta do berçário foi de 43,8 por cento (7/16). Entre os seis casos de SPAR, houve sangramento materno para a cavidade peritoneal após uma cirurgia (1/6=16,7 por cento) e a sobrevida com alta do berçário foi de 50 por cento (3/6). CONCLUSÕES: em concordância com os dados disponíveis na literatura, em nosso centro, os benefícios relacionados às intervenções endoscópicas terapêuticas em casos de STFF, HDC e SPAR parecem superar os riscos de complicações maternas que, raramente, foram consideradas graves.

PURPOSE: to describe the maternal complications due to therapeutic endoscopic procedures in fetal Medicine performed at an university center in Brazil. METHODS: retrospective observational study including patients treated from April 2007 to May 2010 who underwent laser ablation of placental vessels (LAPV) for severe twin-twin transfusion syndrome (TTTS); fetal tracheal occlusion (FETO) and endoscopic removal of tracheal balloon in cases of severe congenital diaphragmatic hernia (CDH); LAPV with or without bipolar coagulation of the umbilical cord in cases of twin reversed arterial perfusion (TRAP) sequence. The main variables described for each disease/type of surgery were maternal complications and neonatal survival (discharge from nursery). RESULTS: fifty-six patients underwent 70 procedures: Severe TTTS (34 patients; 34 surgeries); severe CDH (16 patients; 30 surgeries), and TRAP sequence (6 patients; 6 surgeries). Among 34 women who underwent LAPV for TTTS, two (2/34=5.9 percent) experienced amniotic fluid leakage to the peritoneal cavity and seven (7/34=20.6 percent) miscarried after the procedure. Survival of at least one twin was 64.7 percent (22/34). Among 30 interventions performed in cases of CDH, there was amniotic fluid leakage into the maternal peritoneal cavity in one patient (1/30=3.3 percent) and premature preterm rupture of membranes after three (3/30=30 percent) fetoscopies for removal of the tracheal balloon. Infant survival with discharge from nursery was 43.8 percent (7/16). Among six cases of TRAP sequence, there was bleeding into the peritoneal cavity after surgery in one patient (1/6=16.7 percent) and neonatal survival with discharge from nursery was 50 percent (3/6). CONCLUSIONS: in agreement with the available data in literature, at our center, the benefits related to therapeutic endoscopic interventions for TTTS, CDH and TRAP sequence seem to overcome the risks of maternal complications, which were rarely considered severe.