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• W3200605280 abstract "Congenital diaphragmatic hernia (CDH) occurs in about one-to-four per 10,000 live births, with 85% of defects on the left side.1Langham Jr., MR Kays DW Ledbetter DJ et al.Congenital diaphragmatic hernia. Epidemiology and outcome.Clin Perinatol. 1996; 23: 671-688Abstract Full Text PDF PubMed Google Scholar CDH is the result of incomplete closure of the diaphragmatic muscle during embryonic development, causing herniation of abdominal content into the thoracic cavity, resulting in lung hypoplasia, abnormal pulmonary vascular development, and subsequent pulmonary hypertension. Despite advances in diagnostic abilities, which allow for better assessment of disease severity and improvements in prenatal care, CDH still is associated with a high rate of neonatal mortality, primarily due to pulmonary hypertension and respiratory failure. While advances in medical management and surgical repair after birth have led to improved survival, in utero intervention offers another promising treatment modality, promoting lung development and decreasing the risk of lung damage. Recently, Deprest et al published their experience, The Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia, using fetoscopic endoluminal tracheal occlusion (FETO) for the treatment of severe left diaphragmatic hernia, with promising survival outcome.2Deprest JA Nicolaides KH Benachi A et al.Randomized trial of fetal surgery for severe left diaphragmatic hernia.N Engl J Med. 2021; 385: 107-118Crossref PubMed Scopus (134) Google Scholar This was a randomized, open-label trial conducted at specialized centers with experience using FETO and fetal surgery. A FETO procedure involves the placement of a balloon in the trachea of the fetus above the carina to occlude the airway and stimulate lung growth, including volume and function.3Perrone EE Deprest JA. Fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia: A narrative review of the history, current practice, and future directions.Transl Pediatr. 2021; 10: 1448-1460Crossref PubMed Scopus (9) Google Scholar Eligible candidates were healthy women aged 18 years and older carrying singleton fetuses, with isolated severe left-sided CDH defined as an observed-to-expected lung-to-head ratio of less than 25.0%, with gestational age less than 29 weeks six days at the time of study randomization. Fetoscopic tracheal balloon placement was performed between 27 weeks zero days and 29 weeks six days' gestation. Balloon removal, via puncture, was scheduled between 34 weeks zero days to 34 weeks six days' gestation. All postnatal care was standardized using the same consensus guidelines. The trial was stopped early for efficacy after the third interim analysis. The results of the study demonstrated an improved survival to discharge from the neonatal intensive care unit in the FETO intervention group (16 of 40 patients or 40%), versus the expectant management group (six of 40 patients or 15%). Survival rates at six months of age reflected similar results. The intervention does carry risk, with increased incidence of premature rupture of membranes (47% in FETO v 11% in expectant management group). The incidence of preterm birth also was higher in the FETO intervention group (75% v 29%). Despite an increased rate of preterm birth, the survival rate still was higher in the intervention group. A separate study of FETO intervention by the same authors for moderate left CDH, diagnosed at observed-to-expected lung-to-head ratios of 25.0%-to-34.9%, did not show a significant benefit of FETO to expectant management with regard to either survival, discharge from the intensive care unit, or the need for supplemental oxygen at six months of age.4Deprest JA Benachi A Gratacos E et al.Randomized trial of fetal surgery for moderate left diaphragmatic hernia.N Engl J Med. 2021; 385: 119-129Crossref PubMed Scopus (82) Google Scholar The results of these two studies suggested that fetuses with severe left CDH may benefit more from FETO intervention than those with moderate disease. While fetal interventional procedures offer significant outcome improvements for fetal diseases, they also pose a significant risk for both the mother and the fetus. The procedure carries risks of preterm labor (2.6- times higher in the FETO group compared with the expectant management group), premature birth (4.5- times higher), and the need for emergent removal of the tracheal balloon; all of which require special preparation by the anesthesia team taking care of both mother and fetus.2Deprest JA Nicolaides KH Benachi A et al.Randomized trial of fetal surgery for severe left diaphragmatic hernia.N Engl J Med. 2021; 385: 107-118Crossref PubMed Scopus (134) Google Scholar The anesthetic technique ranges from local to full general anesthesia (GA), depending on the type of procedure. Local anesthesia can be used successfully for minimally invasive procedures like FETO, in which only a skin incision is required to place a single fetoscope, and the procedure does not cause noxious stimuli to the fetus.5Nelson O Simpao AF Tran KM et al.Fetal anesthesia: Intrauterine therapies and immediate postnatal anesthesia for noncardiac surgical interventions.Curr Opin Anaesthesiol. 2020; 33: 368-373Crossref PubMed Scopus (4) Google Scholar For more complex minimally invasive procedures, either sedation or monitored anesthesia care is used, with minimal complications.6Patel D Adler AC Hassanpour A et al.Monitored anesthesia care versus general anesthesia for intrauterine fetal interventions: Analysis of conversions and complications for 480 cases.Fetal Diagn Ther. 2020; 47: 597-603Crossref PubMed Scopus (3) Google Scholar Regional anesthetics (RA), such as epidural, may be used for longer procedures or as an adjunct to facilitate maternal comfort. More involved fetal surgical interventions, such as open midgestation surgery requiring hysterotomy, are done under RA or GA with an epidural for postoperative pain control.7Weber SU Kranke P. Anesthesia for predelivery procedures: Ex-utero intrapartum treatment/intrauterine transfusion/surgery of the fetus.Curr Opin Anaesthesiol. 2019; 32: 291-297Crossref PubMed Scopus (6) Google Scholar Historically, the lack of a maternal requirement for GA to tolerate minimally invasive and open midgestational fetal procedures has called into question whether there is a need for fetal anesthesia and analgesia. However, a growing body of evidence suggests that preventing the fetal stress response to pain can enhance fetal outcomes and may limit preterm labor.8Lee SJ Ralston HJ Drey EA et al.Fetal pain: A systematic multidisciplinary review of the evidence.JAMA. 2005; 294: 947-954Crossref PubMed Scopus (312) Google Scholar, 9Van de Velde M De Buck F Fetal and maternal analgesia/anesthesia for fetal procedures.Fetal Diagn Ther. 2012; 31: 201-209Crossref PubMed Scopus (46) Google Scholar, 10Anand KJ Maze M. Fetuses, fentanyl, and the stress response: Signals from the beginnings of pain?.Anesthesiology. 2001; 95: 823-825Crossref PubMed Scopus (30) Google Scholar There are several methods to provide fetal anesthesia and analgesia. They include transplacental transfer, direct intramuscular, direct intravascular, and direct intracardiac injections. Transplacental transfer of medications from mother to fetus can be unreliable because bioavailability is highly variable and subject to lipid solubility, protein binding, and placental perfusion. Intravascular and intracardiac drugs can be administered via the umbilical or other large fetal vein and guarantee drug availability. However, there is a risk of bleeding and injury to the fetus from the injection needle. Intramuscular injections are done under ultrasound guidance in the buttock or an extremity and carry the least risk of bleeding and injury.11Brusseau R Mizrahi-Arnaud A. Fetal anesthesia and pain management for intrauterine therapy.Clin Perinatol. 2013; 40: 429-442Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar The most common medications used in fetal procedures include paralytic agents, such as vecuronium to facilitate muscle relaxation, fentanyl for analgesia, and atropine to prevent bradycardia from noxious stimuli.12Tran KM Chatterjee D. New trends in fetal anesthesia.Anesthesiol Clin. 2020; 38: 605-619Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar It is important to note that anesthetic complications in both the mother and fetus can arise. Anesthetic complications for the mother include the failure of sedation or RA requiring conversion to GA, pulmonary edema from tocolytic agent use, maternal hemodynamics changes, and postpartum hemorrhage.13Olutoye OO Olutoye OA. EXIT procedure for fetal neck masses.Curr Opin Pediatr. 2012; 24: 386-393Crossref PubMed Scopus (31) Google Scholar Pregnant women are at a higher risk for aspiration and airway complications compared with the general population.6Patel D Adler AC Hassanpour A et al.Monitored anesthesia care versus general anesthesia for intrauterine fetal interventions: Analysis of conversions and complications for 480 cases.Fetal Diagn Ther. 2020; 47: 597-603Crossref PubMed Scopus (3) Google Scholar,14Sviggum HP Kodali BS. Maternal anesthesia for fetal surgery.Clin Perinatol. 2013; 40: 413-427Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar Therefore, airway equipment and medications for a rapid-sequence induction and intubation always should be available. Open midgestation surgery requires high-dose anesthetic agents to maintain uterine relaxation, which may lead to a decrease in blood pressure. The drop in blood pressure may impair placental blood flow if not promptly treated with vasopressors.15Manrique S Maiz N Garcia I et al.Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.Eur J Anaesthesiol. 2019; 36: 175-184Crossref PubMed Scopus (16) Google Scholar In addition, the high dose of volatile anesthetic agents used for GA to induce uterine relaxation may cause fetal hemodynamic instability via decreased cardiac output and bradycardia. The fetal myocardium is particularly sensitive to the myocardial depressant effects of volatile anesthetic agents. Therefore, the fetal heart rate and, when possible, fetal echocardiography, are strictly monitored both intraoperatively and postoperatively. Placental blood flow should be optimized by the maintenance of stable hemodynamics, maximizing oxygen therapy, and the prevention of preterm labor with tocolytic agents.16Kodali BS Bharadwaj S. Foetal surgery: Anaesthetic implications and strategic management.Indian J Anaesth. 2018; 62: 717-723Crossref PubMed Scopus (7) Google Scholar Fetal surgery requires a multidisciplinary team of highly skilled surgical, anesthesia, nursing, and ancillary staff in order to ensure both the mother and the fetus safely tolerate the procedure. Anesthesiologists will continue to play a key role in facilitating prenatal interventions for both mother and fetus. However, it is important to note that despite the advances in prenatal and postnatal management of CDH, survivors often suffer from significant long-term morbidity.17Lally KP American Academy of Pediatrics Section on Surgery; American Academy of Pediatrics Committee on Fetus and NewbornPostdischarge follow-up of infants with congenital diaphragmatic hernia.Pediatrics. 2008; 121: 627-632Crossref PubMed Scopus (201) Google Scholar These long-term sequelae include gastrointestinal, pulmonary, musculoskeletal, as well as neurodevelopmental issues, well into childhood. Gastrointestinal disease includes gastroesophageal reflux, failure to thrive, oral aversion, and small bowel occlusion. Due to lung dysplasia, patients often have frequent upper respiratory tract infections and/or obstructive lung disease (wheezing and asthma), requiring chronic bronchodilator and steroid treatment. Chest asymmetry, scoliosis, and pectus excavatum further contribute to poor long-term lung function, though most scoliosis is moderate and does not require surgical correction.18Morini F Valfre L Bagolan P. Long-term morbidity of congenital diaphragmatic hernia: A plea for standardization.Semin Pediatr Surg. 2017; 26: 301-310Crossref PubMed Scopus (47) Google Scholar,19Wang Y Honeyford K Aylin P et al.One-year outcomes for congenital diaphragmatic hernia.BJS Open. 2019; 3: 305-313Crossref PubMed Scopus (22) Google Scholar Survivors of CDH also have been found to have mild-to-severe neurodevelopmental delay compared with the general population at two years of age and can persist well into childhood, with motor function more affected than mental function.20Church JT Mon R Wright T et al.Neurodevelopmental outcomes in CDH survivors: A single institution's experience.J Pediatr Surg. 2018; 53: 1087-1091Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar As survival improves with FETO, there have been reports of tracheomegaly associated with the intervention. It still is unclear whether the increase in airway diameter causes respiratory pathology, but these findings warrant further follow-up.21McHugh K Afaq A Broderick N et al.Tracheomegaly: A complication of fetal endoscopic tracheal occlusion in the treatment of congenital diaphragmatic hernia.Pediatr Radiol. 2010; 40: 674-680Crossref PubMed Scopus (38) Google Scholar, 22Breysem L Debeer A Claus F et al.Cross-sectional study of tracheomegaly in children after fetal tracheal occlusion for severe congenital diaphragmatic hernia.Radiology. 2010; 257: 226-232Crossref PubMed Scopus (30) Google Scholar, 23Speggiorin S Fierens A McHugh K et al.Bronchomegaly as a complication of fetal endoscopic tracheal occlusion. A caution and a possible solution.J Pediatr Surg. 2011; 46: e1-e3Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar, 24Enriquez G Cadavid L Garces-Inigo E et al.Tracheobronchomegaly following intrauterine tracheal occlusion for congenital diaphragmatic hernia.Pediatr Radiol. 2012; 42: 916-922Crossref PubMed Scopus (15) Google Scholar In conclusion, prenatal procedural interventions to improve survival in CDH are an important facet of the overall treatment of the disease, but it is not the only area of focus by the medical community. Further research needs to be directed at the medical management of subsequent childhood comorbidities to ensure good quality of life for survivors. None." @default.
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• W3200605280 title "Congenital Diaphragmatic Hernia: Fetal Therapies to Increase Survival Are Only the Beginning" @default.
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