A new rat model of prenatal bowel obstruction: development and early assessment

Purpose

Although intestinal motility disorders often complicate the postoperative surgical management of newborns with congenital intestinal atresia, their pathogenesis remains unclear. Animal models of prenatal intestinal obstruction have been mainly developed in the lamb and the chicken. Despite new insights brought by these models, they have one or more limitations, such as high fetal mortality rates, high costs, long gestation periods, and an insufficient number of fetuses per litter. Moreover, some species are phylogenetically distant from mammals.

Methods

We developed a reproducible model of prenatal intestinal obstruction in the rat to study the histologic changes induced by the obstruction. We report, the technical devices and the first assessment of this atresia model in a didactic way to allow other researchers to easily reproduce the model.

Results

Prenatal intestinal obstructions in this study fulfilled all the macroscopic and histologic criteria usually listed by other models of prenatal intestinal obstruction that have been developed in other species. Furthermore with our model, we obtained a high success rate at a low cost.

Conclusions

We presented in this study a reproducible model of prenatal intestinal obstruction in the rat with the macroscopical and histologic features of prenatal intestinal obstruction.     

In utero repair of gastroschisis in the sheep (Ovis aries) model

Objective

Gastroschisis is associated with inflammatory changes in the exposed bowel which leads to intestinal dysmotility after postnatal repair. The insult is a combined effect of amniotic fluid exposure and mechanical constriction. We hypothesized that in utero anatomic repair is possible in a sheep model, and that it may halt the inflammatory damage caused by both mechanisms.

Methods

Gastroschisis was surgically created in mid-gestation (day 75) in 8 sheep fetuses. On gestational day 100, 2 fetuses underwent open fetal gastroschisis repair, where the eviscerated bowel was returned to the peritoneal cavity, and the abdominal wall was primarily closed. All fetuses were harvested at 135 days of gestation.

Results

Six fetuses survived the initial operation, and both fetuses that underwent gastroschisis repair survived to term. At 100 and 135 days of gestation, the eviscerated bowel showed progressive signs of inflammation and peel development. The gross and microscopic inflammatory changes in the gastroschisis bowel at 100 days of gestation were completely resolved at term following in utero repair.

Conclusion

In utero anatomic repair of gastroschisis is possible in mid-gestation in the fetal lamb model, and it appears to ameliorate the inflammatory process.     

The etiologic role of intrauterine volvulus and intussusception in jejunoileal atresia

Purpose

Although intussusception has been reported as quite a rare cause of jejunoileal atresia (JIA), pediatric surgeons have noted the frequent presence of intussusception as well as volvulus at surgery. The aim of this study was to investigate the contribution of intrauterine intussusception and volvulus to the development of JIA.

Methods

In 48 newborns (24 boys and 24 girls) treated for JIA at our hospital between 1978 and 2004, the operative and pathologic findings were reviewed.

Results

Intussusception was responsible for gap and cord type atresia in 12 cases (25%). The cord showed an atrophic intestinal lumen in 2 cases. Volvulus was observed in 13 cases. Volvulus and intussusception were simultaneously noted in 1 case. This suggested that intussusception was the cause of the atresia, whereas volvulus was a secondary event. Neither intussusception nor volvulus was observed in high jejunal, apple peel, or multiple atresia.

Conclusions

Intrauterine volvulus and intussusception were commonly observed in single mid- and low JIA. Thus, intrauterine intussusception may be a common cause of gap and cord type JIA. Volvulus may not only cause JIA but also result from anatomic changes after the development of JIA in some cases.     

Intestinal atresia with segmental musculature and neural defect

Background/Purpose

The aim of this study was to investigate the possible etiologic factors of small bowel atresia and to detect the prognostic role of adequate resection and tapering in postoperative morbidity and mortality.

Methods

Intestinal resection specimens were obtained from 10 patients with jejunoileal atresia and 3 control subjects without any gastrointestinal disease. Intestinal specimens taken from 2-cm and 4-cm proximal sides of atresia, atretic segment, and 1-cm and 2-cm distal sides of atresia were stained with Masson trichrome and H&E. Immunohistochemical staining of the biopsy specimens with synaptophysin was also performed to ascertain the number, the intensity, and the morphology of ganglia.

Results

At the blind proximal end, there was segmental absence of muscular layers, presence of neural defects, and replacement of the muscular layers with fibrous tissue beside the relatively intact mucosa.

Conclusions

Segmental defects in muscular and neural structures of the intestinal wall observed in both the antimesenteric and mesenteric sides of the atretic small bowel were considered to support the vascular insult theory as an etiologic factor. Adequate resection rather than tapering the dilated proximal atretic intestinal segment should be included in the surgical treatment of this pathology to avoid the intestinal dysmotility, which may result in gut-related sepsis and death in the postoperative period.     

Placental vascular compromise in jejunoileal atresia

Background/Purpose

The mechanisms of intrauterine vascular disruptions that result in the development of jejunoileal atresia (JIA) are not fully understood. Monochorionic twinning with fetal death of a cotwin is known to be correlated with the development of JIA in the survivor through placental communication. The aim of this study was to evaluate whether other placental vascular compromises might contribute to the development of JIA.

Methods

Forty-five newborns (23 boys and 22 girls) who were treated for JIA at Tsukuba University Hospital from 1978 to 2003 were reviewed. Placental findings were informative in 23 cases.

Results

No or slight abnormality of the placenta was found in 19 cases. Significant placental abnormalities were found in 4 patients who also had a low birth weight. One patient with apple peel atresia (APA) had excessive torsion of the umbilical cord (UC), which was inserted at the margin of the placenta, and there was an adjacent area of infarction. One patent with multiple atresia (MA) was a surviving monochorionic twin with intrauterine fetal death of the other. Another case of MA showed marginal insertion of the UC. Severe placental abnormalities including wide infarction, cyst formation, and marginal insertion of the UC were found in 1 case of MA. These 3 cases of MA were complicated with other anomalies including brain anomaly.

Conclusions

Placental vascular compromises were involved infrequently in JIA but might possibly be responsible for the development of JIA as well as associated anomalies and a low birth weight as chronic insults since an early stage of gestation in some cases.     

Impact of corticosteroid on intestinal injury in a gastroschisis rat model: morphometric analysis

Background/Purpose

The goal in the treatment of gastroschisis is to prevent intestinal injury. Corticosteroids are known by their effects at the inflammatory response and by the improvement on the intestinal maturity. The authors evaluated the effects of maternal corticosteroid administration on the intestines of rats that underwent fetal gastroschisis.

Methods

A Correia-Pinto-modified gastroschisis rat model was used. Two groups were assessed: the control group (group 1) and the dexamethasone group (group 2). Each group was composed of control and sham fetuses, and fetuses with gastroschisis. Fetal body weight, intestinal weight, intestinal length, and protein were assessed. Histologic analysis involved measures of intestinal loop diameter, total intestinal wall, mucosa and submucosa, both circular and longitudinal muscle layers, and serosal thicknesses. Differences between groups and subgroups were tested by the analysis of variance method with a significant P value less than .05.

Results

Dexamethasone decreased in all the morphometric data except in the intestinal length. Dexamethasone increased the intestinal protein content in fetuses with gastroschisis, and control and sham fetuses. In both groups, all histologic parameters were increased in fetuses with gastroschisis (P < .0001).

Conclusions

Dexamethasone caused a substantial decrease in intestinal weight in GFs, increased the intestinal protein content, and it may be useful in decreasing the intestinal damage of gastroschisis.     

A randomized controlled trial of elective preterm delivery of fetuses with gastroschisis

Background

Elective preterm delivery of the fetus with gastroschisis may help to limit injury to the extruded fetal gut and thus promote faster recovery of neonatal gut function and earlier hospital discharge. This hypothesis has not previously been tested in a prospective randomized controlled trial.

Methods

Between May 1995 and September 1999, all women referred to a single tertiary center before 34 weeks' gestation with a sonographically diagnosed fetal gastroschisis were invited to participate in a randomized controlled trial. Eligible patients were randomized to elective delivery at 36 weeks or to await the onset of spontaneous labor. The method of delivery was not prescribed by the trial. Primary outcome measures in the neonate were the time taken to tolerate full enteral feeding (150 mL/kg per day) and duration of hospital stay.

Results

Of 44 eligible women, 42 were randomized, 21 to elective delivery and 21 to await spontaneous labor. There were 20 liveborn infants in each group. Four babies in the elective group and 4 in the spontaneous group delivered before 36 weeks' gestation but were included in the analysis on an intention-to-treat basis. Mean gestational age at delivery was 35.8 weeks in the elective group and 36.7 weeks in the spontaneous group. Primary closure of the gastroschisis was achieved in a similar proportion (80%-85%) of infants in both groups. Two babies in the elective group died from short gut complications. In the survivors, there was a trend in favor of a shorter median time to achieve full enteral feeding (30.5 vs 37.5 days) and a shorter median duration of hospital stay (47.5 vs 53 days) in the elective group, but this was not statistically significant. These findings remained unaltered when the data were reanalyzed after (a) excluding infants with intestinal atresia or (b) excluding infants born before 36 weeks' gestation.

Conclusions

Although limited by the small number of patients, this randomized controlled trial demonstrates no significant benefit from elective preterm delivery of fetuses with gastroschisis.     

Neonatal outcomes associated with intestinal abnormalities diagnosed by fetal ultrasound

Purpose

Intestinal abnormalities are sometimes seen during antenatal testing; however, the postnatal importance of these findings has not been well established. We evaluated whether abnormal intestinal appearance on fetal ultrasound (US) was ultimately related to neonatal outcome.

Methods

Fetal US examinations from 2003 to 2006 were evaluated. Hyperechogenic bowel was defined as having the echogenicity comparable to bone, and dilated bowel was identified based on the sonographer's assessment. Persistence or resolution of US findings on subsequent US examinations and eventual outcomes were assessed. Cases were categorized as hyperechogenic or dilated and then subgrouped based on whether the US finding resolved.

Results

Sixty-eight fetuses had either hyperechogenic (n = 48) or dilated bowel (n = 20) on antenatal US. In 56 cases, complete data were available for analysis. Of 44 liveborn infants, 11 (25.0%) had an abdominal abnormality, and 33 (75.0%) were normal at birth. Compared to those with dilated bowel, fetuses with hyperechogenic bowel had a higher rate of prenatal demise (20.8% vs 10%) but a lower rate of abnormality at birth (10.3% vs 53.3%). Hyperechogenic bowel resolved on subsequent US more frequently than dilated bowel (65.5% vs 20.0%). In both groups, all fetuses with sonographic resolution were normal at birth. Of 9 fetuses that had persistently hyperechogenic bowel, 3 (33.3%) were born with an abnormality, and all were found to have meconium peritonitis or meconium ileus. In the 12 cases where dilated bowel did not resolve, 8 (66.7%) were eventually born with an abnormality, most commonly intestinal atresia.

Conclusions

Hyperechogenic and dilated bowel are associated with a significant rate of fetal demise. Hyperechogenicity is more common than dilation and is more likely to be transient. Dilated bowel is more often associated with neonatal abnormality than hyperechogenic bowel. Persistence of fetal US findings predicts a higher likelihood of abnormality in the neonate.     

Hepatolithiasis after hepatic portoenterostomy for biliary atresia

Background

Hepatolithiasis after hepatic portoenterostomy for biliary atresia has been paid little attention, with only 22 reported cases.

Patients and Methods

Fifteen patients underwent living-related liver transplantation for biliary atresia after hepatic portoenterostomy in our hospital between 1998 and 2004. The resected livers were examined for the existence and location of hepatolithiasis, composition of the calculi, and bacterial infection of bile. The relation between a history of cholangitis and the presence of hepatolithiasis was analyzed.

Results

Intrahepatic calculi were found in 8 (53%) of 15 patients. The calculi consisted of almost 100% calcium bilirubinate. Calculi were found in bile lakes in 8 patients. Bacteria were present in the bile in 8 (53%) of the 15 patients. Of the 8 patients, 7 (88%) had a history of ascending cholangitis.

Conclusions

Hepatolithiasis occurs after hepatic portoenterostomy for biliary atresia more frequently than previously thought. Bile stasis and possibly bile infection are the main causes of calculi formation.     

Transumbilical laparotomy in infants: a novel approach for a wide variety of surgical disease

Background/purpose

Laparoscopy has kindled an interest in minimally invasive surgery in infants. To combine improved cosmesis with the advantages of open exposure, we adopted the transumbilical approach for laparotomy in babies up to 26 months of age.

Methods

Only hemodynamically stable babies were considered candidates. The umbilicus was incised nearly circumferentially, and the peritoneum was entered in the midline. The procedure was completed in the standard, open fashion by positioning the incision over the area of interest, and the periumbilical wound was closed subcuticularly.

Results

Since 1998, 42 infants have undergone 44 transumbilical laparotomies, with only one conversion to a traditional incision (operating time, 35 to 202 minutes). Twenty-nine newborns were treated transumbilically for duodenal atresia/stenosis/web (n = 11), malrotation (n = 7), intestinal atresia/stricture (n = 5), and other pathology (n = 7). Thirteen older infants (1 to 9 months) were treated transumbilically for intussusception (n = 4), malrotation (n = 4), and other pathology (n = 5). Three toddlers (13 to 24 months) also underwent successful transumbilical laparotomy. There were 2 wound infections and one anastomotic leak.

Conclusions

These results suggest that a transumbilical approach is feasible, safe, and cosmetically superior to the open operation for a broad spectrum of surgical procedures in infants, and it may also be useful in older children.     

Lentiviral vector-mediated, in vivo gene transfer to the tracheobronchial tree in fetal rabbits

Background/Purpose

Fetal gene replacement is a novel, potential therapy for antenatally diagnosed monogenic disorders. The purpose of this study was to evaluate in vivo techniques of lentiviral (LV) vector-mediated gene transfer to the tracheobronchial tree in a rabbit model of fetal gene therapy.

Methods

Via triple plasmid transfection, vesicular stomatitis virus-G-pseudotyped LV vector containing green fluorescent protein (GFP) reporter gene under the control of a cytomegalovirus promoter was constructed.In vivo gene transfer of 5 × 10⁶ LV particles to fetuses of time-mated NZW rabbits (term = 31 days) was attempted using 2 techniques: (1) direct amniotic injection (gestation = 24-26 days) and (2) direct tracheal injection (gestation = 26 days). Injected fetuses and saline-injected littermate controls were delivered and killed on gestational day 30. Fetal and maternal tissues were analyzed.

Results

Both in vivo techniques produced gene transfer to fetal tissues (trachea, lung, liver, intestine), including those of some controls. In one prep, GFP DNA was identified in maternal lung.

Conclusions

Lentiviral vector-mediated GFP gene transfer to fetal rabbit tracheobronchial epithelium occurs within 4 days of transfection by both amniotic injection or direct fetal tracheal injection. This in vivo model confirms bioavailability of vector through amniotic fluid with some cross-infection of adjacent fetuses. Vector access to fetal tissues appears to be by both luminal and hematogenous routes. Transplacental gene transfer from fetus to mother may occur in this model.     

Congenital high airway obstruction syndrome: natural history and management

Background

Congenital high airway obstruction syndrome (CHAOS) is a life-threatening condition with a poorly understood natural history.

Methods

A retrospective review of five patients with CHAOS between 1997 and 2002 was performed.

Results

All fetuses had large echogenic lungs, dilated airways, inverted diaphragms, and massive ascites. One fetus with a laryngeal cyst was terminated at 22 weeks. A twin fetus with findings suggestive of a tracheal web had progressive hydrops, which led to fetal demise. The remaining 3 patients delivered via the ex utero intrapartum treatment (EXIT) procedure survived. The first patient tolerated progressive hydrops for 12 weeks in utero. He had tracheal atresia but underwent laryngotracheoplasty successfully. He is the first long-term CHAOS survivor and is speaking at 5 years of age. The 2 patients with relatively stable lung volumes prenatally have laryngeal atresia with a pinpoint posterior laryngeal fistula. Their postnatal clinical courses were much more benign than the first survivor.

Conclusions

The prenatal natural history and postnatal course of CHAOS depends on whether the airway obstruction is complete. The EXIT procedure offers the potential for salvage of this otherwise lethal condition. Hydrops may be well tolerated prenatally for weeks with potential resolution if airway fistulization is present.     

Congenital intestinal anomalies, neonatal short bowel syndrome, and prenatal/neonatal counseling

Background

Short bowel syndrome (SBS) is a severe malabsorption caused by bowel loss. Congenital intestinal anomalies (CIA) detectable by prenatal ultrasound as jejunoileal atresia, meconium peritonitis, complicated meconium ileus, and fetal volvulus can be responsible for SBS.

Aims

This study aims to investigate either frequency of SBS or the morbidity in CIA population during the first admission.

Material and methods

Records of CIA treated from 1997 to 2003 were reviewed. The prenatal ultrasound findings were correlated with SBS. Student's t and χ² tests were performed to analyze epidemiological data, growth at discharge, sepsis, liver disease, catheter-related complications, motor developmental delay, and hospital stay in CIA with and without SBS.

Results

Forty-four CIA: SBS developed in 43%, ranging from 83% in volvulus to 0% in complicated meconium ileus. Thirty-six prenatal diagnoses: a strong correlation with SBS was observed in isolated dilated bowel (58%). In SBS neonates, birth weight, gestational age, and growth at discharge were statistically lower, whereas sepsis, motor delay, and hospital stay were statistically higher.

Conclusions

Many neonates with CIA detectable by prenatal ultrasound develop SBS. Short bowel syndrome presents a significant higher morbidity. The counseling should stress the frequent association between CIA and SBS as well as the significant morbidity in SBS.     

Large fetal congenital cystic adenomatoid malformations: growth trends and patient survival

Purpose

The prognosis for fetuses with large congenital cystic adenomatoid malformations (CCAMs) remains uncertain. This study examined the natural history of large fetal CCAMs managed expectantly at a major referral center.

Methods

A 5-year retrospective review was conducted on fetuses diagnosed with a thoracic lesion (n = 59). Large CCAMs were identified on prenatal imaging and followed longitudinally. Perinatal outcomes were assessed.

Results

Twelve (20.3%) fetuses had large CCAMs in the absence of other congenital anomalies. Peak CCAM size occurred at 25.3 ± 3.6 weeks' gestation. Serial magnetic resonance volumetry demonstrated a trend toward decreasing CCAM mass volume relative to thoracic cavity volume over time. Overall, 6 patients, including 3 with signs of early hydrops, showed a marked regression of their lesions relative to estimated fetal weight. Five fetuses required an emergent intervention postnatally, including extracorporeal membrane oxygenation support (n = 1), cyst aspiration (n = 1), and lung resection (n = 5). Overall survival was 75%, with severe hydrops before 30 weeks seen in all 3 deaths.

Conclusion

Large fetal CCAMs tend to peak in size at 25 weeks' gestation and are characterized by in utero diminution relative to overall fetal growth. The prognosis for most fetuses with large CCAMs remains quite favorable under careful perinatal management.     

Severe pulmonary hypoplasia associated with giant cervical teratomas

Background

The use of the ex utero intrapartum treatment (EXIT) procedure has salvaged many fetuses with giant neck masses. Despite an adequate airway, a subset of these patients die from an inability to achieve adequate gas exchange.

Methods

We reviewed our experience with the EXIT procedure from 1996 to 2004. The EXIT was used to deliver 23 fetuses with giant neck masses.

Results

Three fetuses with giant cervical teratomas died of severe pulmonary hypoplasia. On postmortem, these patients had severe airway distortion by the mass. The carina was retracted superiorly to the first or second rib resulting in compression of the lungs in the apices of the chest and pulmonary hypoplasia. Hypoplasia was reflected in the lung weights of 24 vs 38 g and 17 vs 34 g for age-matched normal lung.

Conclusions

Unsuspected obstructive fetal neck masses can be fatal because of an inability to secure an airway. Prenatal ultrasonography can identify fetuses at risk, allowing the fetus to be salvaged using the EXIT procedure. Despite obtaining airway control, a subset of these patients will die because of pulmonary hypoplasia. When counseling patients with large cervical masses it is important to discuss potential pulmonary hypoplasia in these patients.     

Cholestasis associated with small bowel atresia: do we always need to investigate?

Background/Purpose

Cholestasis occurs frequently in patients with small bowel atresia (SBA) and is often attributed to prolonged parental nutrition. When severe or prolonged, patients may undergo unnecessary intensive or invasive investigation. We characterized cholestasis and analyzed the pertinence of investigating this patient population.

Methods

With Research Ethics Board approval, patients with SBA between 1996 and 2005 were retrospectively reviewed. Demographics, location of atresia, operative findings, complications, investigations, resumption of feeding, duration of prolonged parental nutrition, and follow-up information were examined. Cholestasis was evaluated for incidence, severity, and evolution.

Results

Fifty-five patients (29 male, 26 female), with a median gestational age and birth weight of 36 weeks and 2025 g, respectively, were reviewed. Care was withdrawn for 2 patients before repair. For the remaining 53 patients, SBA were duodenal atresia in 18, jejunoileal atresia in 32, and multiple atresia in 3. Of 53, 24 (45%) patients developed cholestasis postoperatively (direct/total bilirubin >20%). All patients with short bowel (4) and 60% (6/10) of patients with a delay of enteral feeding more than 14 days postoperatively had cholestasis. Ten patients (36%) proceeded with in-depth evaluations for cholestasis, with 8 (28%) undergoing liver biopsy. No patient had biliary atresia. No deaths were related to isolated cholestasis/cirrhosis. Cholestasis resolved spontaneously in all the survivors.

Conclusions

Small bowel atresia is frequently associated with postoperative cholestasis that will resolve with time. We recommend a more selective and expectant approach to SBA-associated cholestasis to minimize unnecessary investigations.     

Antenatal diagnosis of bowel dilatation in gastroschisis is predictive of poor postnatal outcome

Purpose

Although gastroschisis infants usually have a good outcome, there remains a cohort of babies who fare poorly. We inquired whether the presence of bowel dilatation in utero is predictive of postnatal course in infants with gastroschisis.

Methods

We compared the clinical course of infants who had bowel dilatation with those who did not. Bowel dilatation was defined as more than 20 mm in cross-sectional diameter on ultrasound at any gestational age. Outcome measures used were length of time of parenteral nutrition, death, and surgery for intestinal failure.

Results

A review of 170 infants with gastroschisis identified 74 who had dilatation of more than 20 mm (43.5%). There was no significant difference in the incidence of intestinal atresia in those with bowel dilatation and those without (P = .07). Those with bowel dilatation spent a longer period on parenteral nutrition. There were significantly more deaths in the group with bowel dilatation (P = .01). There was no significant difference in the number of infants requiring surgery for intestinal failure between the 2 groups (P = .47).

Conclusions

We found that sonographically detected bowel dilatation more than 20 mm in utero in fetuses with gastroschisis may have value in predicting clinically significant adverse postnatal outcomes.     

Cost-benefit estimation of cadaveric kidney transplantation: the case of a developing country

Background

In this paper we have estimated the cost savings for the health care system and quality-of-life improvement for patients from an increased number of kidney transplants in Chile. We compared the present value of dialysis and transplantation costs and quality of life over a 20-year horizon.

Methods

We used Markov models and introduced some degree of uncertainty in the value of some of the parameters that built the model. Using Monte Carlo simulations, we estimated the confidence intervals for our results.

Results

Our estimates suggested that a kidney transplant showed an expected savings value of US$28,000 for the health care system. If the quality-of-life improvement was also considered, the expected savings rise to US$ 102,000. These results imply that increasing donation rate by 1 donor per million population would achieve an estimated cost saving of US$827,000 per year, or near US$3 million per year considering the effect on the quality of life.

Conclusion

These results demonstrated that kidney transplantation along with a better quality of life for patients are a cost-saving decision for developing countries.     

A prospective comparative evaluation of persistent respiratory morbidity in esophageal atresia and congenital diaphragmatic hernia survivors

Purpose

The aim of the study was to compare long-term respiratory morbidity in children after repair of esophageal atresia (EA) or congenital diaphragmatic hernia (CDH).

Patients and Methods

Children were seen at 6, 12, and 24 months and 5 years within a prospective longitudinal follow-up program in a tertiary children's hospital. Respiratory morbidity and physical condition were evaluated at all moments. At age 5 years, pulmonary function and maximal exercise performance were tested.

Results

In 3 of 23 atresia patients and 10 of 20 hernia patients, bronchopulmonary dysplasia was developed. Seventeen atresia and 11 hernia patients had recurrent respiratory tract infections mainly in the first years of life. At age 5, 25% of EA and CDH patients measured showed reduced forced expiratory volume in 1 second (z-score < −2). Both atresia and hernia patients showed impaired growth, with catch-up growth at 5 years in patients with EA but not in those with hernia. Maximal exercise performance was significantly below normal for both groups.

Conclusions

Esophageal atresia and CDH are associated with equal risk of long-term respiratory morbidity, growth impairment, and disturbed maximal exercise performance. Prospective follow-up of EA patients aimed at identifying respiratory problems other than tracheomalacia should be an integral part of interdisciplinary follow-up programs.