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Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues
Journal of Pediatric Surgery (2008) 43, E29–E32
www.elsevier.com/locate/jpedsurg
Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues Daniele De Luca a,⁎, Maria Pia De Carolis a , Arnaldo Capelli b , Francesca Gallini a , Gaetano Draisci c , Raffaella Pinto c , Vincenzo Arena b a
Neonatal Intensive Care Unit, Department of Paediatrics, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy b Institute of Pathology, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy c Department of Anaesthesiology and Intensive Care, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy
Index words: Tracheal agenesis; Resuscitation; Newborn
Abstract An exceptional case of tracheal agenesis with no communication with the esophagus is described. This malformation needs surgical airway approach and is hardly classifiable. We analyzed the literature and our institutional data: this resulted to be the first case of such anatomical variant. Genetic and pathological issues are reviewed: recent genetic data seem to explain this malformation. We also reviewed the available literature about prenatal presentation. Because prenatal diagnosis is difficult to achieve and current guidelines for neonatal resuscitation do not provide any recommendation, the resuscitative team may not be prepared for managing such a case. Usefulness of uncommon resuscitative maneuvers is discussed: a promptly performed surgical tracheotomy is the only mean to ventilate such a baby. © 2008 Elsevier Inc. All rights reserved.
Tracheal agenesis (TA) is an uncommon malformation that critical care physicians may encounter in the delivery room. It usually presents with severe neonatal respiratory distress and absent or exceedingly weak cry that shortly precede cardiorespiratory arrest. An ideal surgical therapy is still not defined [1], and available guidelines from the Neonatal Resuscitation Program do not provide any recommendation about such cases [2]. Nevertheless, most TA babies could temporarily be ventilated through a tracheoesophageal fistula by insertion of an endotracheal ⁎ Corresponding author. Divisione di Neonatologia, Dpt. di Scienze Pediatriche, Policlinico Universitario “A. Gemelli”, Università Cattolica del Sacro Cuore, 00168 Roma, Italia. Tel.: +39 0630154169; fax: +39 063383211. E-mail address: [email protected] (D. De Luca). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.10.004
tube (ETT) in the esophagus [1,3]. We report an exceptional case of TA without communication with the esophagus in which surgical tracheotomy was performed. Such anomaly is hardly classifiable; we discuss about possible classification, resuscitative, and genetic issues.
1. Case report A 1500-g male neonate was born at 29 weeks' gestation. Fetal ascites, polyhydramnios, and left lung hyperechogenicity were present; and a diagnosis of cystic adenomatous malformation was presumed. Amniocentesis provided a normal XY karyotype. Because nonreassuring cardiotocogram was recorded, fetal magnetic resonance
E30 imaging was not carried out and an emergency cesarean delivery was performed. Immediately after birth, the baby showed severe respiratory distress, increasing cyanosis, no audible crying, and progressively ineffective breathing. He was initially bagmask ventilated, then a first attempt of intubation was performed because of the insurgence of bradycardia and worsening of arterial oxygen saturation. The larynx visualization was good, but endotracheal intubation was not possible because the tube did not advance beyond the vocal cords and a high resistance was felt in the subglottis. The presence of a membrane was supposed, and several unsuccessful attempts to intubate the neonate were performed by skilled neonatologists and anesthesiologists using ETT of various diameters. Within the attempts, bag-mask
D. De Luca et al. ventilation and external chest compressions (3:1 ratio) were provided: mean arterial oxygen saturation and heart rate were ∼50% and 60 beats per minute, respectively. Pediatric otolaryngologists were then emergently summoned to the delivery room. In the meantime, the presence of tracheoesophageal fistula was hoped and esophagus intubation was tried, without any improvement. At about 15 minutes from birth, the emergency tracheotomy was performed. On surgical exploration, the larynx was identified; but continuation into trachea was absent: only the distal part of trachea was present. An ETT was placed in the distal trachea, and ventilation was started. External chest compressions were continued while several doses of adrenaline were administered. Volume expanders and sodium bicarbonate were also given. Despite all resuscitative efforts, no improvement in
Fig. 1 A, Posterior view of hypopharynx and larynx. The aditus ad laringem and a normally developed epiglottis are visible. Normal piriform fossae and corniculate cartilages are also evident. B, Postfixation examination. The trachea blindly ended in a cartilaginous cup without any connection with the larynx. C, Macroscopic view of histologic section: normally developed tracheal arches and upper part of the trachea ending blindly in a cartilaginous cup. It is visible in the posterior part, the cricoid cartilage (arrowhead) and the anterior part of the thyroid cartilage (arrow). D, The tissue between the blind end of the trachea and the inferior part of the larynx was composed of connective and muscular tissue with no recognizable anatomical organization.
Tracheal agenesis without esophageal fistula vital parameter was noticed. Blood gas analysis was performed (30 minutes) showing extreme mixed acidosis (pH 6.6; CO2, 145 mm Hg; base excess, −25 μmol/L), whereas heart rate was decreasing to 40 beats per minute. After 35 minutes, taking into account the severe malformation, the prematurity, the prolonged resuscitation, and the gas analysis results, all physicians agreed to stop resuscitation; and the baby was allowed to die. Postmortem examination (Fig. 1) revealed a normal larynx that ended in a blind pouch 3 mm below the level of the true vocal cords. In the mediastinum, there was a slightly dilated stump of trachea that was 14 mm long with a blind proximal end, from which arose confluent bronchi of smaller-than-normal caliber, but with otherwise normal pulmonary architecture. There was no tracheoesophageal fistula, and the lungs were normally developed. No malformation in other organs was seen.
2. Discussion Tracheal agenesis is a rare congenital anomaly. Since it was initially described in 1900, only 150 cases have been published in the English literature [4]. Its incidence is approximately 1:50,000; and 52% of patients were preterm infants [5]. Our University Hospital is a tertiary referral center with availability of neonatal critical and surgical care. Reviewing our database, we only found 1 case of TA with tracheoesophageal fistula in the last 30 years. In the absence of communication with the esophagus, TA becomes an even more devastating malformation. Such a case can be ventilated only with surgical approach similarly to laryngeal atresia [3]. Tracheal agenesis and esophageal atresia in rats have been recently associated with Nog, a gene encoding a bone morphogenetic protein antagonist [6]. Two classification schemes are available [7,8]. The Floyd classification is the more used and divides TA into 3 types depending on the degree of distal tracheobronchial development: fistulous connections to the esophagus are always present but variously developed [7]. Recent genetic data seem to explain the different findings in the Floyd classification. In fact, impairment in Nog posttranscriptional process may lead to tracheoesophageal fistula and abnormal tracheal elongations: the degree of trachea development determines the resulting type of TA [6]. If there is an arrested elongation with resultant failure to fuse with the larynx, Floyd type 1 TA results. Type 2 occurs if the respiratory diverticula fuse to form the carina but tracheal elongation does not occur. In these types, a tracheoesophageal fistula is present; and it can be high or low positioned. If the respiratory diverticula totally fail to fuse, type 3 TA occurs; and 2 distinct bronchoesophageal fistulae are present [7]. Faro et al [8] made a more complex classification of TA in 7 types: A, total pulmonary agenesis; B, TA with main bronchi arising directly from esophagus; C, TA with fused
E31 main bronchi and bronchoesophageal fistula; D, TA with larynx joined by atresic strand to distal trachea that has a fistulous connection with the esophagus; E, upper TA with large direct tracheoesophageal communication; F, TA with no communication with esophagus; and G, short segment TA. Our case is difficult to classify according to the Floyd classification, but all its findings correspond to the Faro TA type F. This seems to be the more rare type of TA [8], and the role of Nog in such uncommon variant remains to be clarified. There is a wide spectrum of prenatal TA findings: lung hyperechogenicity, flattened diaphragms, dilated airways, oligo-/polyhydramnios, ascites/hydrops, and large breathing movements [9,10]. There have been attempts to present this association as “congenital high airway obstruction syndrome” [9]. Tracheal agenesis is also associated with abnormalities of cardiovascular, gastrointestinal, and urinary tract [1]. In 26% of cases, other respiratory malformations are present. Interestingly, TA-associated lung anomalies may vary from lung hypoplasia to adenomatous cystic malformation, abnormal lobulation, and lung hyperplasia [1]. No explanation for this wide spectrum of anomalies is available, but lung hypoplasia is a main cause of mortality and could be predicted prenatally. In fact, some cases of TA with fistula show oligohydramnios; and this is consistent with data on fetal lung development [9]. Fetal signs being generic and variable, a prenatal diagnosis is difficult to achieve without performing a fetal magnetic resonance imaging. In our case, the absence of a prenatal diagnosis made the emergency unexpected. Moreover, TA is an uncommon anomaly and no recommendations are provided in the current Neonatal Resuscitation Program guidelines [2]. A definite diagnosis of TA may be achieved only with autopsy or radiology. Meanwhile, when intubation appears impossible, uncommon resuscitative maneuvers, such as esophagus intubation and tracheotomy, should be tried. When a tracheoesophageal communication is absent, tracheotomy remains the only achievable approach. Nevertheless, this is an explicative case in which the absence of prenatal diagnosis made all resuscitation attempts worthless. In fact, ventilation through the esophagus was impossible and tracheotomy proved useless because of the severe established hypoxic damage. The fate of TA neonates is doubtless severe especially if a fistula is absent, although data about long-term outcome are not available. Nowadays, prenatal diagnosis of TA is to be considered necessary to give some real chances of survival: in fact, when a diagnosis is suspected, the woman should be transferred to selected centers with extracorporeal membrane oxygenation facilities. An alternative may be performing the “ex utero intrapartum treatment” (EXIT), using placental circulation during hysterotomy: this would require the presence of pediatric surgical team to perform the delivery room tracheotomy and the subsequent surgical correction. Three children have survived after this experimental procedure, and this is the largest available population of surviving babies [11]. More recent data
E32 confirm that survival may be enabled by means of EXIT [12]. To our knowledge, only one case survived for a long time without EXIT procedure, undergoing several corrective surgeries [13]. An ideal surgical approach to repair TA is not definite, and ethical framework should also be considered when TA is associated with other congenital malformations. We describe this case as a reminder for critical care physicians managing unexpected emergencies in the delivery room. Our case demonstrates that ventilating a TA baby can be completely impossible without a tracheotomy; therefore, a prenatal diagnosis is mandatory to manage these cases and ensure the best survival chances.
Acknowledgment This work was partially supported by grants from Università Cattolica del Sacro Cuore, Milan, Italy. The authors thanks Mr Egidio Stigliano and Ms Chiara Campana for their precious technical support.
References [1] van Veenendaal MB, Liem KD, Marres HAM. Congenital absence of the trachea. Eur J Pediatr 2000;159:8-13.
D. De Luca et al. [2] International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: neonatal resuscitation. Pediatrics 2006;117:e978-88. [3] Saleeby MG, Vustar M, Algren J. Tracheal agenesis: a rare disease with unique airway considerations. Anesth Analg 2003;97:50-2. [4] Heimann K, Bartz C, Naami A, et al. Three new cases of congenital agenesis of the trachea. Eur J Pediatr 2007;166:79-82, doi:10.1007/ s00431-006-0210-4. [5] De José Maria B, Drudis R, Monclus E, et al. Management of tracheal agenesis. Paediatr Anaesth 2000;10:441-4. [6] Que J, Choi M, Ziel JW, et al. Morphogenesis of the trachea and oesophagus: current players and new roles for noggin and Bmps. Differentiation 2006;74:422-37. [7] Floyd J, Campbell DCJ, Dominy DE. Agenesis of the trachea. Am Rev Respir Dis 1962;86:557-60. [8] Faro RS, Goodwin CD, Organ Jr CH, et al. Tracheal agenesis. Ann Thorac Surg 1979;28:295-9. [9] Hedrick MH, Ferro MM, Filly RA, et al. Congenital high airway obstruction syndrome (CHAOS): a potential for perinatal intervention. J Pediatr Surg 1994;29:271-4. [10] Kassanos D, Christodoulou CN, Agapitos E, et al. Prenatal ultrasonographic detection of the tracheal atresia sequence. Ultrasound Obstet Gynecol 1997;10:133-6. [11] Lim F, Crombleholme T, Hedrick HL, et al. Congenital high airway obstruction syndrome: natural history and management. J Pediatr Surg 2003;38:940-5. [12] Shimabukuro F, Sakumoto K, Masamoto H, et al. A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature. Am J Perinatol 2007;24:197-201. [13] Baroncini-Cornea S, Fae F, Gargiulo G, et al. Tracheal agenesis: management of the first 10 months of age. Paediatr Anaesth 2004;14: 774-7.
www.elsevier.com/locate/jpedsurg
Tracheal agenesis without esophageal fistula: genetic, resuscitative, and pathological issues Daniele De Luca a,⁎, Maria Pia De Carolis a , Arnaldo Capelli b , Francesca Gallini a , Gaetano Draisci c , Raffaella Pinto c , Vincenzo Arena b a
Neonatal Intensive Care Unit, Department of Paediatrics, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy b Institute of Pathology, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy c Department of Anaesthesiology and Intensive Care, University Hospital “A. Gemelli”-Catholic University of the Sacred Heart, 00168 Rome, Italy
Index words: Tracheal agenesis; Resuscitation; Newborn
Abstract An exceptional case of tracheal agenesis with no communication with the esophagus is described. This malformation needs surgical airway approach and is hardly classifiable. We analyzed the literature and our institutional data: this resulted to be the first case of such anatomical variant. Genetic and pathological issues are reviewed: recent genetic data seem to explain this malformation. We also reviewed the available literature about prenatal presentation. Because prenatal diagnosis is difficult to achieve and current guidelines for neonatal resuscitation do not provide any recommendation, the resuscitative team may not be prepared for managing such a case. Usefulness of uncommon resuscitative maneuvers is discussed: a promptly performed surgical tracheotomy is the only mean to ventilate such a baby. © 2008 Elsevier Inc. All rights reserved.
Tracheal agenesis (TA) is an uncommon malformation that critical care physicians may encounter in the delivery room. It usually presents with severe neonatal respiratory distress and absent or exceedingly weak cry that shortly precede cardiorespiratory arrest. An ideal surgical therapy is still not defined [1], and available guidelines from the Neonatal Resuscitation Program do not provide any recommendation about such cases [2]. Nevertheless, most TA babies could temporarily be ventilated through a tracheoesophageal fistula by insertion of an endotracheal ⁎ Corresponding author. Divisione di Neonatologia, Dpt. di Scienze Pediatriche, Policlinico Universitario “A. Gemelli”, Università Cattolica del Sacro Cuore, 00168 Roma, Italia. Tel.: +39 0630154169; fax: +39 063383211. E-mail address: [email protected] (D. De Luca). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2007.10.004
tube (ETT) in the esophagus [1,3]. We report an exceptional case of TA without communication with the esophagus in which surgical tracheotomy was performed. Such anomaly is hardly classifiable; we discuss about possible classification, resuscitative, and genetic issues.
1. Case report A 1500-g male neonate was born at 29 weeks' gestation. Fetal ascites, polyhydramnios, and left lung hyperechogenicity were present; and a diagnosis of cystic adenomatous malformation was presumed. Amniocentesis provided a normal XY karyotype. Because nonreassuring cardiotocogram was recorded, fetal magnetic resonance
E30 imaging was not carried out and an emergency cesarean delivery was performed. Immediately after birth, the baby showed severe respiratory distress, increasing cyanosis, no audible crying, and progressively ineffective breathing. He was initially bagmask ventilated, then a first attempt of intubation was performed because of the insurgence of bradycardia and worsening of arterial oxygen saturation. The larynx visualization was good, but endotracheal intubation was not possible because the tube did not advance beyond the vocal cords and a high resistance was felt in the subglottis. The presence of a membrane was supposed, and several unsuccessful attempts to intubate the neonate were performed by skilled neonatologists and anesthesiologists using ETT of various diameters. Within the attempts, bag-mask
D. De Luca et al. ventilation and external chest compressions (3:1 ratio) were provided: mean arterial oxygen saturation and heart rate were ∼50% and 60 beats per minute, respectively. Pediatric otolaryngologists were then emergently summoned to the delivery room. In the meantime, the presence of tracheoesophageal fistula was hoped and esophagus intubation was tried, without any improvement. At about 15 minutes from birth, the emergency tracheotomy was performed. On surgical exploration, the larynx was identified; but continuation into trachea was absent: only the distal part of trachea was present. An ETT was placed in the distal trachea, and ventilation was started. External chest compressions were continued while several doses of adrenaline were administered. Volume expanders and sodium bicarbonate were also given. Despite all resuscitative efforts, no improvement in
Fig. 1 A, Posterior view of hypopharynx and larynx. The aditus ad laringem and a normally developed epiglottis are visible. Normal piriform fossae and corniculate cartilages are also evident. B, Postfixation examination. The trachea blindly ended in a cartilaginous cup without any connection with the larynx. C, Macroscopic view of histologic section: normally developed tracheal arches and upper part of the trachea ending blindly in a cartilaginous cup. It is visible in the posterior part, the cricoid cartilage (arrowhead) and the anterior part of the thyroid cartilage (arrow). D, The tissue between the blind end of the trachea and the inferior part of the larynx was composed of connective and muscular tissue with no recognizable anatomical organization.
Tracheal agenesis without esophageal fistula vital parameter was noticed. Blood gas analysis was performed (30 minutes) showing extreme mixed acidosis (pH 6.6; CO2, 145 mm Hg; base excess, −25 μmol/L), whereas heart rate was decreasing to 40 beats per minute. After 35 minutes, taking into account the severe malformation, the prematurity, the prolonged resuscitation, and the gas analysis results, all physicians agreed to stop resuscitation; and the baby was allowed to die. Postmortem examination (Fig. 1) revealed a normal larynx that ended in a blind pouch 3 mm below the level of the true vocal cords. In the mediastinum, there was a slightly dilated stump of trachea that was 14 mm long with a blind proximal end, from which arose confluent bronchi of smaller-than-normal caliber, but with otherwise normal pulmonary architecture. There was no tracheoesophageal fistula, and the lungs were normally developed. No malformation in other organs was seen.
2. Discussion Tracheal agenesis is a rare congenital anomaly. Since it was initially described in 1900, only 150 cases have been published in the English literature [4]. Its incidence is approximately 1:50,000; and 52% of patients were preterm infants [5]. Our University Hospital is a tertiary referral center with availability of neonatal critical and surgical care. Reviewing our database, we only found 1 case of TA with tracheoesophageal fistula in the last 30 years. In the absence of communication with the esophagus, TA becomes an even more devastating malformation. Such a case can be ventilated only with surgical approach similarly to laryngeal atresia [3]. Tracheal agenesis and esophageal atresia in rats have been recently associated with Nog, a gene encoding a bone morphogenetic protein antagonist [6]. Two classification schemes are available [7,8]. The Floyd classification is the more used and divides TA into 3 types depending on the degree of distal tracheobronchial development: fistulous connections to the esophagus are always present but variously developed [7]. Recent genetic data seem to explain the different findings in the Floyd classification. In fact, impairment in Nog posttranscriptional process may lead to tracheoesophageal fistula and abnormal tracheal elongations: the degree of trachea development determines the resulting type of TA [6]. If there is an arrested elongation with resultant failure to fuse with the larynx, Floyd type 1 TA results. Type 2 occurs if the respiratory diverticula fuse to form the carina but tracheal elongation does not occur. In these types, a tracheoesophageal fistula is present; and it can be high or low positioned. If the respiratory diverticula totally fail to fuse, type 3 TA occurs; and 2 distinct bronchoesophageal fistulae are present [7]. Faro et al [8] made a more complex classification of TA in 7 types: A, total pulmonary agenesis; B, TA with main bronchi arising directly from esophagus; C, TA with fused
E31 main bronchi and bronchoesophageal fistula; D, TA with larynx joined by atresic strand to distal trachea that has a fistulous connection with the esophagus; E, upper TA with large direct tracheoesophageal communication; F, TA with no communication with esophagus; and G, short segment TA. Our case is difficult to classify according to the Floyd classification, but all its findings correspond to the Faro TA type F. This seems to be the more rare type of TA [8], and the role of Nog in such uncommon variant remains to be clarified. There is a wide spectrum of prenatal TA findings: lung hyperechogenicity, flattened diaphragms, dilated airways, oligo-/polyhydramnios, ascites/hydrops, and large breathing movements [9,10]. There have been attempts to present this association as “congenital high airway obstruction syndrome” [9]. Tracheal agenesis is also associated with abnormalities of cardiovascular, gastrointestinal, and urinary tract [1]. In 26% of cases, other respiratory malformations are present. Interestingly, TA-associated lung anomalies may vary from lung hypoplasia to adenomatous cystic malformation, abnormal lobulation, and lung hyperplasia [1]. No explanation for this wide spectrum of anomalies is available, but lung hypoplasia is a main cause of mortality and could be predicted prenatally. In fact, some cases of TA with fistula show oligohydramnios; and this is consistent with data on fetal lung development [9]. Fetal signs being generic and variable, a prenatal diagnosis is difficult to achieve without performing a fetal magnetic resonance imaging. In our case, the absence of a prenatal diagnosis made the emergency unexpected. Moreover, TA is an uncommon anomaly and no recommendations are provided in the current Neonatal Resuscitation Program guidelines [2]. A definite diagnosis of TA may be achieved only with autopsy or radiology. Meanwhile, when intubation appears impossible, uncommon resuscitative maneuvers, such as esophagus intubation and tracheotomy, should be tried. When a tracheoesophageal communication is absent, tracheotomy remains the only achievable approach. Nevertheless, this is an explicative case in which the absence of prenatal diagnosis made all resuscitation attempts worthless. In fact, ventilation through the esophagus was impossible and tracheotomy proved useless because of the severe established hypoxic damage. The fate of TA neonates is doubtless severe especially if a fistula is absent, although data about long-term outcome are not available. Nowadays, prenatal diagnosis of TA is to be considered necessary to give some real chances of survival: in fact, when a diagnosis is suspected, the woman should be transferred to selected centers with extracorporeal membrane oxygenation facilities. An alternative may be performing the “ex utero intrapartum treatment” (EXIT), using placental circulation during hysterotomy: this would require the presence of pediatric surgical team to perform the delivery room tracheotomy and the subsequent surgical correction. Three children have survived after this experimental procedure, and this is the largest available population of surviving babies [11]. More recent data
E32 confirm that survival may be enabled by means of EXIT [12]. To our knowledge, only one case survived for a long time without EXIT procedure, undergoing several corrective surgeries [13]. An ideal surgical approach to repair TA is not definite, and ethical framework should also be considered when TA is associated with other congenital malformations. We describe this case as a reminder for critical care physicians managing unexpected emergencies in the delivery room. Our case demonstrates that ventilating a TA baby can be completely impossible without a tracheotomy; therefore, a prenatal diagnosis is mandatory to manage these cases and ensure the best survival chances.
Acknowledgment This work was partially supported by grants from Università Cattolica del Sacro Cuore, Milan, Italy. The authors thanks Mr Egidio Stigliano and Ms Chiara Campana for their precious technical support.
References [1] van Veenendaal MB, Liem KD, Marres HAM. Congenital absence of the trachea. Eur J Pediatr 2000;159:8-13.
D. De Luca et al. [2] International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: neonatal resuscitation. Pediatrics 2006;117:e978-88. [3] Saleeby MG, Vustar M, Algren J. Tracheal agenesis: a rare disease with unique airway considerations. Anesth Analg 2003;97:50-2. [4] Heimann K, Bartz C, Naami A, et al. Three new cases of congenital agenesis of the trachea. Eur J Pediatr 2007;166:79-82, doi:10.1007/ s00431-006-0210-4. [5] De José Maria B, Drudis R, Monclus E, et al. Management of tracheal agenesis. Paediatr Anaesth 2000;10:441-4. [6] Que J, Choi M, Ziel JW, et al. Morphogenesis of the trachea and oesophagus: current players and new roles for noggin and Bmps. Differentiation 2006;74:422-37. [7] Floyd J, Campbell DCJ, Dominy DE. Agenesis of the trachea. Am Rev Respir Dis 1962;86:557-60. [8] Faro RS, Goodwin CD, Organ Jr CH, et al. Tracheal agenesis. Ann Thorac Surg 1979;28:295-9. [9] Hedrick MH, Ferro MM, Filly RA, et al. Congenital high airway obstruction syndrome (CHAOS): a potential for perinatal intervention. J Pediatr Surg 1994;29:271-4. [10] Kassanos D, Christodoulou CN, Agapitos E, et al. Prenatal ultrasonographic detection of the tracheal atresia sequence. Ultrasound Obstet Gynecol 1997;10:133-6. [11] Lim F, Crombleholme T, Hedrick HL, et al. Congenital high airway obstruction syndrome: natural history and management. J Pediatr Surg 2003;38:940-5. [12] Shimabukuro F, Sakumoto K, Masamoto H, et al. A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature. Am J Perinatol 2007;24:197-201. [13] Baroncini-Cornea S, Fae F, Gargiulo G, et al. Tracheal agenesis: management of the first 10 months of age. Paediatr Anaesth 2004;14: 774-7.