A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia.
ABSTRACT Experimental and clinical data suggest that fetal endoscopic tracheal occlusion to induce lung growth may improve the outcome of severe congenital diaphragmatic hernia. We performed a randomized, controlled trial comparing fetal tracheal occlusion with standard postnatal care.
Women carrying fetuses that were between 22 and 27 weeks of gestation and that had severe, left-sided congenital diaphragmatic hernia (liver herniation and a lung-to-head ratio below 1.4), with no other detectable anomalies, were randomly assigned to fetal endoscopic tracheal occlusion or standard care. The primary outcome was survival at the age of 90 days; the secondary outcomes were measures of maternal and neonatal morbidity.
Of 28 women who met the entry criteria, 24 agreed to randomization. Enrollment was stopped after 24 patients had been enrolled because of the unexpectedly high survival rate with standard care and the conclusion of the data safety monitoring board that further recruitment would not result in significant differences between the groups. Eight of 11 fetuses (73 percent) in the tracheal-occlusion group and 10 of 13 (77 percent) in the group that received standard care survived to 90 days of age (P=1.00). The severity of the congenital diaphragmatic hernia at randomization, as measured by the lung-to-head ratio, was inversely related to survival in both groups. Premature rupture of the membranes and preterm delivery were more common in the group receiving the intervention than in the group receiving standard care (mean [+/-SD] gestational age at delivery, 30.8+/-2.0 weeks vs. 37.0+/-1.5 weeks; P<0.001). The rates of neonatal morbidity did not differ between the groups.
Tracheal occlusion did not improve survival or morbidity rates in this cohort of fetuses with congenital diaphragmatic hernia.
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ABSTRACT: Rapid advances in perinatal medicine have resulted in increased number of various tracheo-bronchial interventions on fetal and neonatal airways. The present study was performed to compile normative data for external dimensions of the trachea at varying gestational age. Using anatomical dissection, digital image analysis (NIS-Elements BR 3.0) and statistical analysis (ANOVA, regression analysis), a range of measurements (prebifurcation and bifurcation lengths, proximal and distal external transverse diameters, proximal external cross-sectional area, and external volume) for the trachea in 73 spontaneously aborted fetuses (39 male, 34 female) aged 14-25 weeks was examined. No significant male-female differences were found (P > 0.05). The prebifurcation and bifurcation lengths ranged from 8.14 ± 1.90 to 20.77 ± 0.50 mm and from 2.23 ± 0.25 to 5.77 ± 0.76 mm, according to the functions y = -54.291 + 23.940 × ln (Age) ± 1.681 (R (2) = 0.78) and y = -10.756 + 4.860 × ln (Age) ± 0.731 (R (2) = 0.44), respectively. Their relative growth, expressed as the bifurcation-to-prebifurcation length ratio, was stable from the age of 16 weeks and attained the value 0.22 ± 0.05. The proximal external transverse diameter of the trachea was greater (36 fetuses, 49.3%), smaller (34 fetuses, 46.6%) or similar (3 fetuses, 4.1%), when compared to the distal external transverse diameter. The values for proximal and distal transverse diameters ranged from 2.39 ± 0.04 to 5.20 ± 0.17 mm and from 2.42 ± 0.20 to 4.93 ± 0.08 mm, expressed by the functions: y = -9.659 + 4.574 × ln (Age) ± 0.313 (R (2) = 0.79) and y = -10.897 + 4.984 × ln (Age) ± 0.327 (R (2) = 0.81). The values of proximal external cross-sectional area ranged from 3.38 ± 0.12 to 15.98 ± 1.04 mm(2), according to the linear function y = -11.798 + 1.077 × Age ± 1.463 (R (2) = 0.78). The values of external volume of the trachea ranged from 34.3 ± 11.6 to 370.6 ± 94.1 mm(3) and generated the quadratic function y = -154.589 + 0.858 × Age(2) ± 34.196 (R (2) = 0.87). The tracheal parameters do not show male-female differences. The developmental dynamics of prebifurcation and bifurcation lengths and proximal and distal external transverse diameters of the trachea follow linear functions dependent on the natural logarithm of fetal age, its external cross-sectional area-according to a linear function, and its external volume-according to a quadratic function.Anatomia Clinica 10/2011; 34(4):317-23. · 0.93 Impact Factor
Article: A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia.[show abstract] [hide abstract]
ABSTRACT: Severe pulmonary hypoplasia and pulmonary arterial hypertension are associated with reduced survival in congenital diaphragmatic hernia (CDH). We aimed to determine whether fetal endoscopic tracheal occlusion (FETO) improves survival in cases of severe isolated CDH. Between May 2008 and July 2010, patients whose fetuses had severe isolated CDH (lung-to-head ratio < 1.0, liver herniation into the thoracic cavity and no other detectable anomalies) were assigned randomly to FETO or to no fetal intervention (controls). FETO was performed under maternal epidural anesthesia supplemented with fetal intramuscular anesthesia. Tracheal balloon placement was achieved with ultrasound guidance and fetoscopy between 26 and 30 weeks of gestation. All cases that underwent FETO were delivered by the EXIT procedure. Postnatal therapy was the same for both treated fetuses and controls. The primary outcome was survival to 6 months of age. Other maternal and neonatal outcomes were also evaluated. Twenty patients were enrolled randomly to FETO and 21 patients to standard postnatal management. The mean gestational age at randomization was similar in both groups (P = 0.83). Delivery occurred at 35.6 ± 2.4 weeks in the FETO group and at 37.4 ± 1.9 weeks in the controls (P < 0.01). In the intention-to-treat analysis, 10/20 (50.0%) infants in the FETO group survived, while 1/21 (4.8%) controls survived (relative risk (RR), 10.5 (95% CI, 1.5-74.7), P < 0.01). In the received-treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived (RR, 10.0 (95% CI, 1.4-70.6) P < 0.01). FETO improves neonatal survival in cases with isolated severe CDH.Ultrasound in Obstetrics and Gynecology 12/2011; 39(1):20-7. · 3.01 Impact Factor
Article: Congenital diaphragmatic hernia.[show abstract] [hide abstract]
ABSTRACT: Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted.Orphanet Journal of Rare Diseases 01/2012; 7:1. · 5.83 Impact Factor