Esophageal Atresia With Or Without Tracheoesophageal Fistula Research Articles

Esophageal Atresia With or Without Tracheoesophageal Fistula: Comorbidities, Genetic Evaluations, and Neonatal Outcomes.

Objective Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) has a reported incidence of 1 in 3500 live births and requires intensive care and surgery. To evaluate the prevalence of a molecularly confirmed genetic etiology ofEA/TEFin a level IV neonatal intensive care unit (NICU), focusing on genetic evaluation, diagnostic yield, and clinical outcomes of these neonates. Study design A retrospective cohort study over a period of seven years was performed for all patients admitted with a diagnosis of EA/TEF. Automated data was extracted for demographic information and manual extraction was done to evaluate the frequency of associated anomalies, type of genetic evaluations and diagnoses, and outcomes at NICU discharge. Results Sixty-eight infants met the inclusion criteria. The majority were male (n=42; 62%), born at >37 weeks'gestation (n=36; 53%), and had EA with distal TEF (n=54; 79%). Most (n=53; 78%) had additional associated congenital anomalies, but only 47 (69%) patients had a genetics evaluation performed and genetic testing was sent for 44 (65%) of those patients. The most common genetic testing performed was chromosomal microarray analysis (n=40; 59%), followed by chromosome analysis (n=11; 16%), and whole exome/genome sequencing (n=7; 10%). Five unique genetic diagnoses including CHARGE Syndrome, Fanconi Syndrome, EFTUD2-related mandibulofacial dysostosis, and two different chromosomal deletion syndromes were made for a total of nine (13%) patients in our cohort. The cohort suffered a high rate of morbidity and mortality during their NICU stay with important differences noted in isolated vs non-isolated EA/TEF. Twelve infants (18%) died prior to NICU discharge. Of those surviving, 40 (71%) infants had a primary repair, 37 (66%) infants required G or GJ feedings at NICU discharge, and eight (14%) patients were discharged on some type of respiratory support. Conclusion In this high-risk cohort of EA/TEF patients cared for at a quaternary NICU, a majority were non-isolated and had some form of a genetic evaluation, but a minority underwent exome or genome sequencing. Given the high prevalence of associated anomalies, high mortality, and genetic disease prevalence in this cohort, we recommend standardization of phenotyping and genetic evaluation to allow for precision care and appropriate risk stratification.

Surgical management of acute life-threatening events affecting esophageal atresia and/or tracheoesophageal fistula patients

BackgroundFollowing surgical correction, many patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) present to the emergency department (ED) with acute airway complications. We sought to determine the incidence and risk factors for severe acute life-threatening events (ALTEs) in pediatric patients with repaired congenital EA/TEF and the outcomes of operative interventions. MethodsA retrospective cohort chart review was performed on patients with EA/TEF with surgical repair and follow-up at a single centre from 2000 to 2018. Primary outcomes included 5-year ED visits and/or hospitalizations for ALTEs. Demographic, operative, and outcome data were collected. Chi-square tests and univariate analyses were performed. ResultsIn total, 266 EA/TEF patients met inclusion criteria. Of these, 59 (22.2%) had experienced ALTEs. Patients with low birth weight, low gestational age, documented tracheomalacia, and clinically significant esophageal strictures were more likely to experience ALTEs (p < 0.05). ALTEs occurred prior to 1 year of age in 76.3% (45/59) of patients with a median age at presentation of 8 months (range 0–51 months). Recurrence of ALTEs after esophageal dilatation was 45.5% (10/22), mostly due to stricture recurrence. Patients experiencing ALTEs received anti-reflux procedures (8/59, 13.6%), airway pexy procedures (7/59, 11.9%), or both (5/59, 8.5%) within a median age of 6 months of life. The resolution and recurrence of ALTEs after operative interventions are described. ConclusionSignificant respiratory morbidity is common among patients with EA/TEF. Understanding the multifactorial etiology and operative management of ALTEs have an important role in their resolution. Type of StudyOriginal Research, Clinical Research. Level of EvidenceLevel III Retrospective Comparative Study.

Human exome and mouse embryonic expression data implicate ZFHX3, TRPS1, and CHD7 in human esophageal atresia.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development. To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal. In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants. Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.

Gastrointestinal diseases among relatives of patients with esophageal atresia with or without tracheoesophageal fistula.

Several studies have identified genetic factors that are associated with the formation of isolated and non-isolated esophageal atresia with or without tracheoesophageal fistula (EA/TEF) in human and mice. Some of these genetic factors like FOXF1/Foxf1 are associated with Barrett syndrome, esophageal carcinoma or tumors of the gastrointestinal tract. Here, we investigated the prevalence of common gastrointestinal diseases among EA/TEF patients and their first- and second-degree relatives (parents and grandparents). We send out a questionnaire to 280 EA/TEF families asking for the presence of Barrett syndrome, Achalasia and carcinoma of the esophagus, the stomach, the small and large intestine among first- and second-degree relatives. In 32 of 124 families we found at least one affected family member with a possible association of colon carcinoma and the occurrence of EA/TEF within the same family. Further studies are needed to evaluate a possible association.

Outcomes of multi-gestational pregnancies affected by esophageal atresia – tracheoesophageal fistula

BackgroundContemporary outcomes of infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) from multi-gestational pregnancies compared to those of singleton pregnancies have not been reported. MethodsA single-center retrospective review of EA/TEF patients born from 1999 to 2013 was performed. Patient demographics, gestational age (GA), birth weight, associated anomalies, requirement for gastrostomy tube and mortality were reviewed. ResultsSingleton EA/TEF patients outnumbered those from multi-gestational pregnancies nearly 10:1 (214 vs 22 patients). EA/TEF patients from multi-gestational pregnancies were more likely to be premature (77% vs. 32%), have lower birth weight (mean 1766 g vs. 2695 g), have associated duodenal atresia (18% vs. 6%) and require gastrostomy tube (41% vs. 33%) for feeding challenges compared to EA/TEF singletons. Mortality was also significantly greater for multi-gestational EA/TEF patients compared to singleton EA/TEF patients (18% vs. 6%). Conclusion: EA/TEF infants from multi-gestational pregnancies have greater clinical complexity and mortality than singleton EA/TEF patients. Parents of EA/TEF multi-gestational infants should be appropriately counseled and supported.

Prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for esophageal atresia with or without tracheoesophageal fistula

BackgroundScoliosis has been reported after repair of esophageal atresia with or without tracheoesophageal fistula (EA-TEF). This study aims to investigate the prevalence and natural history of scoliosis and associated congenital vertebral anomalies in patients operated for EATEF. MethodsA retrospective review of patients operated for EA-TEF with radiological examination for the presence of scoliosis or associated spine congenital anomalies was done on 106 patients (ages 5–19 years). ResultsScoliosis was found in 53 patients (49%) for which 46 of these were in the thoracic region and 33 were right-thoracic curves. After a follow-up ranging from 5 to 14 years, four patients (3.7%) out of 106 were operated for scoliosis. Right-sided thoracotomy (RST) was the identifiable risk factor for scoliosis development; all patients with scoliosis had their EA repaired through RST. Congenital vertebral anomalies were found in 8 of those patients (7.5%). After a median follow-up of 6.5 years, no patients progressed enough to require operation. ConclusionScoliosis affects one of every two patients operated for EA; it may progress to the indication of surgery. RST was the identifiable risk factor for scoliosis development.

Infants with esophageal atresia and right aortic arch: Characteristics and outcomes from the Midwest Pediatric Surgery Consortium

PurposeRight sided aortic arch (RAA) is a rare anatomic finding in infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF). In the presence of RAA, significant controversy exists regarding optimal side for thoracotomy in repair of the EA/TEF. The purpose of this study was to characterize the incidence, demographics, surgical approach, and outcomes of patients with RAA and EA/TEF. MethodsA multi-institutional, IRB approved, retrospective cohort study of infants with EA/TEF treated at 11 children's hospitals in the United States over a 5-year period (2009 to 2014) was performed. All patients had a minimum of one-year follow-up. ResultsIn a cohort of 396 infants with esophageal atresia, 20 (5%) had RAA, with 18 having EA with a distal TEF and 2 with pure EA. Compared to infants with left sided arch (LAA), RAA infants had a lower median birth weight, (1.96 kg (IQR 1.54–2.65) vs. 2.57 kg (2.00–3.03), p = 0.01), earlier gestational age (34.5 weeks (IQR 32–37) vs. 37 weeks (35–39), p = 0.01), and a higher incidence of congenital heart disease (90% vs. 32%, p < 0.0001). The most common cardiac lesions in the RAA group were ventricular septal defect (7), tetralogy of Fallot (7) and vascular ring (5). Seventeen infants with RAA underwent successful EA repair, 12 (71%) via right thoracotomy and 5 (29%) through left thoracotomy. Anastomotic strictures trended toward a difference in RAA patients undergoing right thoracotomy for primary repair of their EA/TEF compared to left thoracotomy (50% vs. 0%, p = 0.1). Side of thoracotomy in RAA patients undergoing EA/TEF repair was not significantly associated with mortality, anastomotic leak, recurrent laryngeal nerve injury, recurrent fistula, or esophageal dehiscence (all p > 0.29). ConclusionRAA in infants with EA/TEF is rare with an incidence of 5%. Compared to infants with EA/TEF and LAA, infants with EA/TEF and RAA are more severely ill with lower birth weight and higher rates of prematurity and complex congenital heart disease. In neonates with RAA, surgical repair of the EA/TEF is technically feasible via thoracotomy from either chest. A higher incidence of anastomotic strictures may occur with a right-sided approach. Level of evidenceLevel III.

Utilizing stricture indices to predict dilation of strictures after esophageal atresia repair

BackgroundAnastomotic stricture is the most common postoperative complication in infants undergoing repair of esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Stricture indices (SIs) are used to predict infants at risk for stricture requiring dilation. We sought to determine the most accurate SI and optimal timing for predicting anastomotic dilation. Materials and methodsA retrospective study of infants undergoing repair of EA/TEF between 2008 and 2013 was performed. Esophagrams were used to calculate four SIs (upper pouch esophageal anastomotic stricture index [U-EASI], lower pouch esophageal anastomotic stricture index [L-EASI], lateral SI, and anterior/posterior SI). The best performing SI was identified. Logistic regression analysis was performed to determine if a first or second esophagram SI threshold was associated with dilation. A receiver operating characteristic curve measured the accuracy of the model using SIs to predict dilation. ResultsOf 45 EA/TEF infants included, 20 (44%) had postoperative strictures requiring dilation. As the best performing SI, logistic regression analysis showed that U-EASI as a continuous variable was predictive of dilation (P = 0.03) but was not significant at U-EASI ≤ 0.37. However, U-EASI ≤ 0.37 was associated with needing earlier dilation. On second esophagram (median, 38 days), U-EASI of ≤0.39 was significantly associated with dilation (OR: 7.8, 95% CI: 1.05-57.58, P = 0.04). The area under the receiver operating characteristic curve of the U-EASI model controlling for days to esophagram demonstrated improved predictive ability from first (AUC 0.73) to second esophagram (AUC 0.81). ConclusionsCalculation of the SI utilizing a U-EASI ≤ 0.39 on the delayed esophagram is associated with future anastomotic dilation. A multi-institutional study is necessary to confirm the predictive ability of the U-EASI.

Esophageal Atresia with or without Tracheoesophageal Fistula (EA/TEF): Association of Different EA/TEF Subtypes with Specific Co-occurring Congenital Anomalies and Implications for Diagnostic Workup.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) represents the most common developmental malformation of the upper digestive tract. It is classified into six subtypes according to the classification of Vogt, depending on anatomical variation of this malformation. Around 50% of the patients with EA/TEF present additional anomalies, which often influence, next to the EA/TEF subtype, the overall prognosis of EA/TEF newborns. Here, we investigated the association of the different EA/TEF subtypes with co-occurring congenital anomalies in EA/TEF patients and demonstrate their implications for postnatal diagnostic workup. We investigated 333 patients of a large German multicenter study born between 1980 and 2012. After evaluation of all available clinical records, 235 patients were included in our analysis. We compared our results with existing data. The highest risk for co-occurring anomalies was seen in patients with most common Vogt 3b (p = 0.024), especially for additional gastrointestinal anomalies (p = 0.04). Co-occurring anomalies of the skin were significantly more common in patients with subtype Vogt 2 (p = 0.024). A significant correlation was observed for an impaired neurodevelopmental outcome and EA/TEF Vogt 3a (p = 0.041). Patients with EA/TEF showed a higher risk to present with any additional congenital anomaly compared with the general population (p < 0.001). Our results warrant thorough clinical workup for gastrointestinal anomalies especially in patients with Vogt 3b. Moreover, it might be necessary to focus on a thorough aftercare for neurocognitive development in patients with Vogt 3a. The here presented observations need to be confirmed by future studies.

Long-term esophageal and respiratory outcomes in children with esophageal atresia and tracheoesophageal fistula.

Objectives: Few studies have evaluated the long-term complications and outcomes of esophageal atresia with or without tracheoesophageal fistula (EA/TEF) beyond childhood. The aim of our study was to characterize the esophageal and respiratory morbidity of EA/TEF through evaluation of clinical symptoms, diagnostic testing and therapeutic intervention at a tertiary care center.Methods: Patients with congenital EA/TEF evaluated from 2011 to 2014 were included. Demographic characteristics, type and mode of repair of EA/TEF, clinical symptoms, radiographic, endoscopic, bronchoscopic and medication use data were obtained.Results: A total of 43 patients were identified. The median age of this predominantly Caucasian population was 8 years (interquartile range: 3, 20). Twenty (62.5%) had type C (EA with distal TEF) abnormality. Twenty-one (48.8%) patients had heartburn, 19 (44.1%) had acid regurgitation, and 31 (72.1%) had dysphagia to solids. Barium swallow in 26 patients revealed strictures in 17 (65.4%), dysmotility in 20 (76.9%) and recurrent fistulas in four patients (15.4%). Thirty patients underwent upper endoscopy, of which 21 (70.0%) had a stricture, and six (20.0%) had recurrent fistula requiring surgical intervention. Eight (18.6%) patients underwent fundoplication. Pulmonary evaluation showed cough and choking in 31 (72.1%) patients and dyspnea and wheezing in 32 (53.4%) patients. Recurrent respiratory infections were reported in 19 (44.2%).patients. Other findings included tracheomalacia in 86.7% and restrictive lung disease in 54.5% of patients.Conclusion: There is a high burden of residual esophageal and pulmonary pathology in patients with EA/TEF. Ongoing follow-up is required to monitor both the clinical symptoms and treatment responses.

Long-term burden of care and radiation exposure in survivors of esophageal atresia

BackgroundPatients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) historically have had a high risk of neonatal mortality but the majority of patients are now expected to live into adulthood. However, the long-term burden of care among recent EA/TEF survivors has not been documented. MethodsA single-institution retrospective review of newborns with EA/TEF treated from 2001-2005 was conducted, including initial and total hospitalization length of stay, and number of clinic visits and procedures requiring general anesthesia in the first three years of life. Exposure to and number of radiological studies involving ionizing radiation (IR) were recorded. ResultsSeventy-one of 78 (91%) patients survived to discharge and 69 were included for analysis. Mean length of initial hospital stay was 51.3 (range 9-390) days. By age 3 years, patients required 4.5 (mean, range 1-23) procedures performed under general anesthesia, attended 13.5 (mean, range 3-40) outpatient visits and were exposed to 17.4 mSv (mean, range 3.0-59.9) of IR from 40 (mean, range 5-165) radiological studies. ConclusionPatients with EA/TEF need complex and frequent hospital-based care from infancy to early childhood. Opportunities to critically review clinical services and imaging needs should be explored to improve the experience of patients and their families.

Morbidity and mortality in patients with esophageal atresia

This study reports national estimates of population characteristics and outcomes for patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and evaluates the relationships between hospital volume and outcomes. Patients admitted within 30 days of life who had International Classification of Diseases, 9th Edition, Clinical Modification diagnosis and procedure codes relevant to EA/TEF during 1999-2012 were identified with the Pediatric Health Information System database. Baseline demographics, comorbidities, and postoperative outcomes, including predictors of in-hospital mortality, were examined up to 2 years after EA/TEF repair. We identified 3,479 patients with EA/TEF treated at 43 children's hospitals; 37% were premature and 83.5% had ≥1 additional congenital anomaly, with cardiac anomalies (69.6%) being the most prevalent. Within 2 years of discharge, 54.7% were readmitted, 5.2% had a repeat TEF ligation, 11.4% had a repeat operation for their esophageal reconstruction, and 11.7% underwent fundoplication. In-hospital mortality was 5.4%. Independent predictors of mortality included lower birth weight, congenital heart disease, other congenital anomalies, and preoperative mechanical ventilation. There was no relationship between hospital volume and mortality or repeat TEF ligation. This study describes population characteristics and outcomes, including predictors of in-hospital mortality, in EA/TEF patients treated at children's hospitals across the United States. Across these hospitals, rates of mortality or repeat TEF ligation were not dependent on hospital volume.

Structural and numerical changes of chromosome X in patients with esophageal atresia

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is a relatively common birth defect often associated with additional congenital anomalies such as vertebral, anal, cardiovascular, renal and limb defects, the so-called VACTERL association. Yet, little is known about the causal genetic factors. Rare case reports of gastrointestinal anomalies in children with triple X syndrome prompted us to survey the incidence of structural and numerical changes of chromosome X in patients with EA/TEF. All available (n=269) karyotypes of our large (321) EA/TEF patient cohort were evaluated for X-chromosome anomalies. If sufficient DNA material was available, we determined genome-wide copy number profiles with SNP array and identified subtelomeric aberrations on the difficult to profile PAR1 region using telomere-multiplex ligation-dependent probe amplification. In addition, we investigated X-chromosome inactivation (XCI) patterns and mode of inheritance of detected aberrations in selected patients. Three EA/TEF patients had an additional maternally inherited X chromosome. These three female patients had normal random XCI patterns. Two male EA/TEF patients had small inherited duplications of the XY-linked SHOX (Short stature HOmeoboX-containing) locus. Patients were small for gestational age at birth (<P5) and had additional, mostly VACTERL associated, anomalies. Triple X syndrome is rarely described in patients with EA/TEF and no duplications of the SHOX gene were reported so far in these patients. As normal patterns of XCI were seen, overexpression of X-linked genes that escape XCI, such as the SHOX gene, could be pathogenic by disturbing developmental pathways.

Genetic and cellular mechanisms regulating anterior foregut and esophageal development

Separation of the single anterior foregut tube into the esophagus and trachea involves cell proliferation and differentiation, as well as dynamic changes in cell–cell adhesion and migration. These biological processes are regulated and coordinated at multiple levels through the interplay of the epithelium and mesenchyme. Genetic studies and in vitro modeling have shed light on relevant regulatory networks that include a number of transcription factors and signaling pathways. These signaling molecules exhibit unique expression patterns and play specific functions in their respective territories before the separation process occurs. Disruption of regulatory networks inevitably leads to defective separation and malformation of the trachea and esophagus and results in the formation of a relatively common birth defect, esophageal atresia with or without tracheoesophageal fistula (EA/TEF). Significantly, some of the signaling pathways and transcription factors involved in anterior foregut separation continue to play important roles in the morphogenesis of the individual organs. In this review, we will focus on new findings related to these different developmental processes and discuss them in the context of developmental disorders or birth defects commonly seen in clinics.

348: The accuracy of prenatal ultrasound in the diagnosis of true microcephaly

in the diagnosis of true microcephaly Jennifer Wong, Casey Howe, Angela Bianco, Robert Green, Joanne Stone Mount Sinai School of Medicine, Maternal Fetal Medicine, New York, NY, Mount Sinai School of Medicine, Department of Obstetrics and Gynecology, New York, NY, Department of Pediatrics, New York, NY OBJECTIVE: To determine the accuracy of prenatal ultrasound in detection of microcephaly, defined as birth head circumference (HCbirth) 10%ile. STUDY DESIGN: This was a retrospective chart review of fetuses identified prenatally with a head circumference (HCfetal) of 3%ile. HCbirth were abstracted from the newborn medical chart, and Z-scores calculated for both. Sensitivity, specificity, false positive (FP) and false negative (FN) rates were calculated for HCfetal. An ROC curve was calculated to determine the accuracy of HCfetal in the detection of microcephaly. RESULTS: An ultrasound database search from Jan 2005 to July 2011 for HC 3% identified 730 ultrasounds of 455 fetuses in 433 patients. There were 375 live births in this group. Median Z-scores were similar between fetal and neonatal groups ( 1.16 [ 1.6, 0.9] and 1.2 [ 1.8, 0.7], respectively). The overall prevalence of microcephaly was similar in both groups using an HCfetal Z-score cutoff of 1.3 (40.1% and 49.6% respectively). A Z-score of 1.3 had 44.6% sensitivity, 35.1% specificity, 44.9% FP rate, and 45.9% FN rate for detection of microcephaly (p 0.08). Using a HCfetal Z-score cutoff of 1.7 yielded 28.8% sensitivity, 21% specificity, 62.6% FP and 28.2% FN rate (p 0.09). The area under the ROC curve was 0.6, indicating that HCfetal is an inaccurate test for microcephaly. Gestational age at time of ultrasound was not significantly associated with microcephaly (95% CI 0.27-0.01). CONCLUSION: Prenatal ultrasound was able to detect a population at risk for microcephaly as evidenced by the high prevalence in this group at birth; however, the ability of prenatal ultrasound to predict a specific HCbirth for an individual is poor. Sensitivity and specificity for prenatal ultrasound are low, and FP and FN rates are high. Factors which contribute to the inaccuracy of prenatal ultrasound include the variability of the microcephaly phenotype, heterogeneous etiologies, lack of consensus regarding the definition of microcephaly, high rate of concurrent growth restriction, and lack of genderor race-specific fetal growth curves. 349 Antenatal ultrasonographic findings to predict esophageal atresia in cases with visible stomach bubble Jeong Woo Park, Yeo rang Kim, Seung Mi Lee, Chan-Wook Park, Joong Shin Park, Jong Kwan Jun, Hee Chul Shin Seoul National University College of Medicine, Deptartment of Obstetrics and Gynecology, Seoul, Korea, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Obstetrics and Gynecology, Seoul, Korea, Seoul National University College of Medicine, Department of Obstetrics and Gynecology, Seoul, Korea OBJECTIVE: Becauses fetuses with esophageal atresia need an early postnatal surgery, they should be delivered in a tertiary center. However, prenatal diagnosis of esophageal atresia sometimes challenging. The aim of this study was to determine the antenatal ultrasonographic findings which offer the best diagnostic accuracy in fetal esophageal atresia with or without tracheoesophageal fistula (EA/TEF) with moderate to severe polyhydramnios and visible stomach bubble. STUDY DESIGN: We performed a retrospective analysis of 121 pregnant women who presented polyhydramnios (AFI 24) between March 1996 and April 2011. Of these, 3 cases in whom EA was suspicious but delivered stillbirth without autopsy, and those who were diagnosed as having other fetal gastrointestinal obstructions (e.g. duodenal atresia, jejunal atresia, or ileal atresia), hydrops fetalis, or congenital diaphragmatic hernia were excluded. A total of 87 cases were enrolled. Ultrasonographic findings evaluated were (1) small abdominal circumference (AC) less than 10 percentile for gestational age, (2) upper pouch sign, and (3) tiny stomach bubble. Predictive value of an individual sonographic marker was calculated. RESULTS: Of a total of 87 cases with polyhydramnios, 2 cases had upper neck pouch sign. Of these 85 cases, 8 cases showed absent stomach bubble. The remaining 77 cases were analysed. In the setting of polyhydramnios and visible stomach bubble (77 cases), the prevalence of EA/TEF was 6.5% (5/77). Small AC had higher sensitivity compared to tiny stomach bubble. Small AC and tiny stomach bubble were statistically significant sonographic findings for diagnosing esophageal atresia antenatally. After adjusting possible confounders, only small AC was remained significant (P 0.05). CONCLUSION: In polyhydramnios and visible fetal stomach bubble, small AC as an antenatal sonographic finding suggests that the fetus has EA/TEF. Clinicians should measure AC in this setting. Poster Session II Diabetes, Labor, Medical-Surgical-Disease, Obstetric Quality & Safety, Prematurity, Ultrasound-Imaging www.AJOG.org

Current status of prenatal diagnosis, operative management and outcome of esophageal atresia/tracheo‐esophageal fistula

Ultrasonographic features suggestive of esophageal atresia with or without tracheo-esophageal fistula (EA/TEF) are only in a small minority of fetuses with EA/TEF (<10%) identifiable on prenatal scans.The prenatal diagnosis of EA/TEF relies in principle, on two nonspecific signs: polyhydramnios and absent or small stomach bubble. Polyhydramnios is associated with a wide range of fetal abnormalities, but most commonly it pursues a benign course. Similarly the sonographic absence of a stomach bubble may point to a variety of fetal anomalies.The combination of polyhydramnios and absent stomach bubble in two small series offers a modest positive predictive value of 44 and 56% respectively. Prenatal scanning for EA/TEF identifies a larger proportion of fetuses with Edwards syndrome; there is also a higher proportion of isolated EA in comparison to postnatal studies.Current ultrasound technology does not allow for a definite diagnosis of EA/TEF and therefore, counseling of parents should be guarded.Postnatal diagnosis of EA is confirmed by the failure to pass a firm nasogastric tube into the stomach; on chest X-ray, the tube is seen curling in the upper esophageal pouch. Corrective surgery for EA/TEF is well established and survival rates of over 90% can be expected.

Environmental factors in the etiology of esophageal atresia and congenital diaphragmatic hernia: Results of a case‐control study

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH) are severe congenital anomalies. Their etiologies are mostly unknown and are thought to be multifactorial. No specific environmental factors have consistently been described as risk factors. In a study conducted during the years 2000 to 2004 in a pediatric surgical referral center in the Netherlands, parents of children with EA/TEF or with CDH of the Bochdalek type and parents of a group of children without major birth defects filled out a questionnaire about possible exposure to environmental risk factors during the period from 1 month before conception to the end of the first trimester of pregnancy. Children with chromosomal anomalies were excluded. Questionnaires were returned for 47 out of 64 cases (73%) with EA/TEF, for 63 out of 77 cases (82%) with CDH, and for 202 out of 243 controls (83%). In EA/TEF, maternal age was borderline significantly higher than in controls (32.2 vs. 30.6 years, p = .05). Contact with herbicides or insecticides was associated with EA/TEF in univariate analysis (OR 2.0; 95% CI: 1.0-4.1) and in multivariate analysis, although of borderline significance. In univariate analysis, CDH was significantly associated with maternal use of alcohol (OR 2.9; 95% CI: 1.6-5.2). We found a significant association between maternal alcohol use around the time of conception and CDH. A possible explanation might be the effect of alcohol on the retinoic acid pathway. An association was found between contact with herbicides or insecticides and EA/TEF.

Manometric evaluation of the intrathoracic stomach after gastric transposition in children.

Gastric transposition (GT) is one of the options for the esophageal replacement in children with esophageal atresia with or without tracheoesophageal fistula (EATEF). To date, no manometric studies have been conducted on the intrathoracic stomach after GT in EATEF patients; hence, this study was designed. Babies ( n=18) of EATEF who underwent esophageal replacement by GT were studied and manometry was correlated with the clinical outcome, age at surgery, and route of GT. The mean age at evaluation was 30.5 months (range 4-84 months). These cases were sub-stratified into group I (GT during neonatal period) and group II (GT during post-neonatal period). Mean age at surgery was 6 days and 7.8 months in groups I and II, respectively. There was no propulsive antegrade propagated peristaltic waves in any of the patients. Mean resting pressure and mean peak pressures were 19.5 and 50.4 mm Hg in groups I and II, respectively. Mass contractions to liquid swallow was noted in 77 and 55% of patients in groups I and II, respectively. There was no significant difference in the pressure parameters or appearance of mass contractions between group-I and group-II patients. Similarly, there was no significant difference in pressure parameters or appearance of mass contractions between the children who had transhiatal vs retrosternal GT. It needs to be determined whether the mass contractions noted in GT ever progress to a coordinated propulsive rhythmic contractions and whether this has a final bearing on the long-term functional outcome of GT patients.

Azygos vein anomaly: the best predictor of a long gap in esophageal atresia and tracheoesophageal fistula.

The gap between the pouches has a direct bearing on the tension at the anastomosis that ultimately determines the anastomotic leak in esophageal atresia with or without tracheoesophageal fistula (EA-TEF). Long-gap EA has been reported to be associated with aortic-arch anomalies and 13 pairs of ribs. Our observation that EA-TEF with an azygos-vein anomaly (AVA) invariably had a long gap led us to retrospectively analyze our data. The mean gaps (+/- SD) in the groups with 13 pairs of ribs (n = 6), right-sided aortic arch (n = 16), and AVA (n = 9) were 1.25 +/- 0.27, 2.18 +/- 0.98, and 3.16 +/- 0.16 cm, respectively. There was no statistically significant difference in the gap in patients who had 13 pairs of ribs compared with controls who had 12 pairs of ribs. The gap was highest in the AVA group and was statistically significant (P < 0.001) compared with patients with a normal azygos vein. In addition, the AVA group had a significant increase in mortality (P < 0.05) compared to the groups with a normal azygos vein; although there was no statistically significant difference in other factors: birth weight, time between delivery and surgery, cardiac anomalies, anorectal malformations, renal malformations, and chest infection in the AVA group and controls. An extra pair of ribs is not associated with a long gap, and an AVA per se is an independent predictor of a long gap and mortality in EA-TEF.