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The New England Journal of Medicine Jul 2021Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data from randomized trials are lacking.
METHODS
In this open-label trial conducted at centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with severe isolated congenital diaphragmatic hernia on the left side to FETO at 27 to 29 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcome was infant survival to discharge from the neonatal intensive care unit. We used a group-sequential design with five prespecified interim analyses for superiority, with a maximum sample size of 116 women.
RESULTS
The trial was stopped early for efficacy after the third interim analysis. In an intention-to-treat analysis that included 80 women, 40% of infants (16 of 40) in the FETO group survived to discharge, as compared with 15% (6 of 40) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). Survival to 6 months of age was identical to the survival to discharge (relative risk, 2.67; 95% CI, 1.22 to 6.11). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (47% vs. 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs. 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. In an analysis that included 11 additional participants with data that were available after the trial was stopped, survival to discharge was 36% among infants in the FETO group and 14% among those in the expectant care group (relative risk, 2.65; 95% CI, 1.21 to 6.09).
CONCLUSIONS
In fetuses with isolated severe congenital diaphragmatic hernia on the left side, FETO performed at 27 to 29 weeks of gestation resulted in a significant benefit over expectant care with respect to survival to discharge, and this benefit was sustained to 6 months of age. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT01240057.).
Topics: Adult; Balloon Occlusion; Female; Fetal Membranes, Premature Rupture; Fetal Therapies; Fetoscopy; Gestational Age; Hernias, Diaphragmatic, Congenital; Humans; Intention to Treat Analysis; Obstetric Labor, Premature; Patient Acuity; Pregnancy; Premature Birth; Trachea; Watchful Waiting
PubMed: 34106556
DOI: 10.1056/NEJMoa2027030 -
The New England Journal of Medicine Jul 2021Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease.
METHODS
In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age.
RESULTS
In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk , 1.27; 95% confidence interval [CI], 0.99 to 1.63; two-sided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal.
CONCLUSIONS
This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO performed at 30 to 32 weeks of gestation over expectant care with respect to survival to discharge or the need for oxygen supplementation at 6 months. FETO increased the risks of preterm, prelabor rupture of membranes and preterm birth. (Funded by the European Commission and others; TOTAL ClinicalTrials.gov number, NCT00763737.).
Topics: Adult; Balloon Occlusion; Female; Fetal Membranes, Premature Rupture; Fetal Therapies; Fetoscopy; Gestational Age; Hernias, Diaphragmatic, Congenital; Humans; Intention to Treat Analysis; Obstetric Labor, Premature; Patient Acuity; Pregnancy; Premature Birth; Trachea; Watchful Waiting
PubMed: 34106555
DOI: 10.1056/NEJMoa2026983 -
European Journal of Human Genetics :... Dec 2021Congenital diaphragmatic hernia (CDH) is a life-threatening malformation characterised by failure of diaphragmatic development with lung hypoplasia and persistent... (Review)
Review
Congenital diaphragmatic hernia (CDH) is a life-threatening malformation characterised by failure of diaphragmatic development with lung hypoplasia and persistent pulmonary hypertension of the newborn (PPHN). The incidence is 1:2000 corresponding to 8% of all major congenital malformations. Morbidity and mortality in affected newborns are very high and at present, there is no precise prenatal or early postnatal prognostication parameter to predict clinical outcome in CDH patients. Most cases occur sporadically, however, genetic causes have long been discussed to explain a proportion of cases. These range from aneuploidy to complex chromosomal aberrations and specific mutations often causing a complex phenotype exhibiting multiple malformations along with CDH. This review summarises the genetic variations which have been observed in syndromic and isolated cases of congenital diaphragmatic hernia.
Topics: Genetic Testing; Hernia, Diaphragmatic; Humans; Mutation; Vitamin A
PubMed: 34621023
DOI: 10.1038/s41431-021-00972-0 -
Journal of Perinatal Medicine Jan 2023Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary... (Review)
Review
Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary development and those with sickle cell disease. Our research group, therefore, has focused on the early origins of chronic respiratory disease. This has included assessing antenatal diagnostic techniques and potentially therapeutic interventions in infants with congenital diaphragmatic hernia. Undertaking physiological studies, we have increased the understanding of the premature baby's response to resuscitation and evaluated interventions in the delivery suite. Mechanical ventilation modes have been optimised and randomised controlled trials (RCTs) with short- and long-term outcomes undertaken. Our studies highlighted respiratory syncytial virus lower respiratory tract infections (LRTIs) and other respiratory viral LRTIs had an adverse impact on respiratory outcomes of prematurely born infants, who we demonstrated have a functional and genetic predisposition to respiratory viral LRTIs. We have described the long-term respiratory outcomes for children with sickle cell disease and importantly identified influencing factors. In conclusion, it is essential to undertake long term follow up of infants at high risk of chronic respiratory morbidity if effective preventative strategies are to be developed.
Topics: Child; Humans; Infant; Anemia, Sickle Cell; Lung; Respiration Disorders; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Hernias, Diaphragmatic, Congenital
PubMed: 35786507
DOI: 10.1515/jpm-2022-0257 -
Diagnostics (Basel, Switzerland) Feb 2021Diaphragmatic hernia (DH) is a defect, which can be congenital or can develop later in life. Moreover, chromosomal and genetic abnormalities, environmental exposures,...
Diaphragmatic hernia (DH) is a defect, which can be congenital or can develop later in life. Moreover, chromosomal and genetic abnormalities, environmental exposures, and nutritional deficiencies may be related to the development of congenital DH. In contrast, the risk factors of acquired DH include traumas, such as blunt injuries due to traffic accidents and surgical procedures. We report the case of a 71-year-old man admitted to our gastroenterology department for the treatment of esophageal varices. Four days after the endoscopic treatment, the patient vomited severely and reported severe right upper abdominal pain. He was diagnosed with DH, and surgical fixation was performed. The diaphragmatic injury lesion was located on the estimated needle track of percutaneous radiofrequency ablation, which was performed through the thoracic diaphragm with artificial pleural effusion for hepatocellular carcinoma.
PubMed: 33672980
DOI: 10.3390/diagnostics11020307 -
World Journal of Emergency Surgery :... Jul 2023Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. (Review)
Review
BACKGROUND
Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable.
METHODS
A bibliographic search using major databases was performed using the terms "emergency surgery" "diaphragmatic hernia," "traumatic diaphragmatic rupture" and "congenital diaphragmatic hernia." GRADE methodology was used to evaluate the evidence and give recommendations.
RESULTS
CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients.
CONCLUSIONS
Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.
Topics: Humans; Diaphragm; Hernias, Diaphragmatic, Congenital; Tomography, X-Ray Computed; Thorax; Hernia, Hiatal; Thoracic Injuries
PubMed: 37496073
DOI: 10.1186/s13017-023-00510-x -
American Journal of Obstetrics &... Sep 2022Antenatal diagnosis of abnormal pulmonary development has improved significantly over recent years because of progress in imaging techniques. Two-dimensional ultrasound... (Review)
Review
Antenatal diagnosis of abnormal pulmonary development has improved significantly over recent years because of progress in imaging techniques. Two-dimensional ultrasound is the mainstay of investigation of pulmonary pathology during pregnancy, providing good prognostication in conditions such as congenital diaphragmatic hernia; however, it is less validated in other high-risk groups such as those with congenital pulmonary airway malformation or preterm premature rupture of membranes. Three-dimensional assessment of lung volume and size is now possible using ultrasound or magnetic resonance imaging; however, the use of these techniques is still limited because of unpredictable fetal motion, and such tools have also been inadequately validated in high-risk populations other than those with congenital diaphragmatic hernia. The advent of advanced, functional magnetic resonance imaging techniques such as diffusion and T2* imaging, and the development of postprocessing pipelines that facilitate motion correction, have enabled not only more accurate evaluation of pulmonary size, but also assessment of tissue microstructure and perfusion. In the future, fetal magnetic resonance imaging may have an increasing role in the prognostication of pulmonary abnormalities and in monitoring current and future antenatal therapies to enhance lung development. This review aims to examine the current imaging methods available for assessment of antenatal lung development and to outline possible future directions.
Topics: Female; Hernias, Diaphragmatic, Congenital; Humans; Infant, Newborn; Lung; Lung Diseases; Lung Volume Measurements; Pregnancy; Prenatal Diagnosis
PubMed: 35858660
DOI: 10.1016/j.ajogmf.2022.100693 -
Ultrasound in Obstetrics & Gynecology :... Jun 2023It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
It is debated whether fetal endoscopic tracheal occlusion (FETO) is beneficial to fetuses with congenital diaphragmatic hernia (CDH) and whether FETO has different effects in moderate and severe CDH. We conducted a systematic review and meta-analysis including the latest evidence to assess the overall effects of FETO on clinical outcomes of CDH.
METHODS
We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang Database to retrieve eligible studies published before 8 September 2022. No language or study design restrictions were applied. Studies were included if CDH fetuses underwent FETO surgery and were compared with a cohort that underwent expectant management, with at least one outcome reported. The primary outcomes were mortality at 1, 6 and 12 months after birth, rates of pulmonary hypertension, use of extracorporeal membrane oxygenation (ECMO) and prematurity. Meta-analysis was conducted to obtain pooled odds ratios (ORs) and mean differences. The quality of included studies and pooled evidence was also assessed.
RESULTS
A total of 1187 CDH fetuses from 20 studies were included in the quantitative synthesis. FETO significantly reduced 1-month (OR, 0.56 (95% CI, 0.34-0.93); P = 0.02, number needed to treat (NNT) = 7.67) and 6-month (OR, 0.34 (95% CI, 0.18-0.65); P = 0.0009, NNT = 5.26) CDH mortality (moderate/low quality of evidence). Subgroup analysis suggested that the effects of FETO on the rates of pulmonary hypertension and ECMO usage were significant in severe CDH (low/moderate quality of evidence) but not in moderate CDH (low/very low quality of evidence). FETO was also associated with an increased risk of preterm prelabor rupture of membranes before 37 weeks' gestation (OR, 4.94 (95% CI, 2.25-10.88); P < 0.0001, number needed to harm (NNH) = 3.13) and preterm birth before 37 weeks (OR, 5.24 (95% CI, 3.33-8.23); P < 0.00001, NNH = 2.79) (high/moderate quality of evidence). However, FETO was not associated with severe complications, such as preterm birth before 32 weeks, placental abruption or chorioamnionitis (very low/low quality of evidence).
CONCLUSIONS
FETO is associated with a reduction in mortality, rate of pulmonary hypertension and ECMO usage in severe CDH, while it reduces only the risk of mortality in moderate CDH. Although FETO increases the risk of late prematurity, it does not result in extreme prematurity. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Hernias, Diaphragmatic, Congenital; Fetoscopy; Hypertension, Pulmonary; Premature Birth; Placenta; Fetus; Trachea
PubMed: 36704940
DOI: 10.1002/uog.26164 -
Anaesthesia Apr 2021Over the last three decades, advances in early diagnosis of fetal anomalies, imaging and surgical techniques have led to a huge expansion in fetal surgery. A small... (Review)
Review
Over the last three decades, advances in early diagnosis of fetal anomalies, imaging and surgical techniques have led to a huge expansion in fetal surgery. A small number of specialist centres perform fetal surgery, which involves high-risk anaesthesia for the mother and fetus. The anaesthetist plays an integral role within the large multispecialty and multidisciplinary team, involved in planning and delivering care for complex surgical procedures. This article reviews three fetal surgical procedures, congenital diaphragmatic hernia, myelomeningocele repair and ex-utero intrapartum treatment for airway obstruction. The underlying fetal pathology, surgical management, anaesthetic considerations and risks for both the mother and fetus are described for each. Fundamental to this is the understanding that clear communication and collaboration between all team members is vital to ensure successful outcomes of patients, the mother and the fetus.
Topics: Airway Obstruction; Anesthetics; Female; Fetus; Hernias, Diaphragmatic, Congenital; Humans; Laryngoscopy; Meningomyelocele; Prenatal Diagnosis
PubMed: 33682103
DOI: 10.1111/anae.15423 -
Prenatal Diagnosis Mar 2022Congenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses... (Review)
Review
Congenital diaphragmatic hernia (CDH) is often detectable prenatally. Advances in genetic testing have made it possible to obtain a molecular diagnosis in many fetuses with CDH. Here, we review the aneuploidies, copy number variants (CNVs), and single genes that have been clearly associated with CDH. We suggest that array-based CNV analysis, with or without a chromosome analysis, is the optimal test for identifying chromosomal abnormalities and CNVs in fetuses with CDH. To identify causative sequence variants, whole exome sequencing (WES) is the most comprehensive strategy currently available. Whole genome sequencing (WGS) with CNV analysis has the potential to become the most efficient and effective means of identifying an underlying diagnosis but is not yet routinely available for prenatal diagnosis. We describe how to overcome and address the diagnostic and clinical uncertainty that may remain after genetic testing, and review how a molecular diagnosis may impact recurrence risk estimations, mortality rates, and the availability and outcomes of fetal therapy. We conclude that after the prenatal detection of CDH, patients should be counseled about the possible genetic causes of the CDH, and the genetic testing modalities available to them, in accordance with generally accepted guidelines for pretest counseling in the prenatal setting.
Topics: Clinical Decision-Making; DNA Copy Number Variations; Female; Hernias, Diaphragmatic, Congenital; Humans; Pregnancy; Prenatal Diagnosis; Uncertainty
PubMed: 35037267
DOI: 10.1002/pd.6099