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
03 August 2016
30 November 2016
06 January 2017 (eFirst)
Background 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.
Materials and Methods 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.
Results 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).
Conclusion 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.
- 1 Nassar N, Leoncini E, Amar E. , et al. Prevalence of esophageal atresia among 18 international birth defects surveillance programs. Birth Defects Res A Clin Mol Teratol 2012; 94 (11) 893-899
- 2 Pedersen RN, Calzolari E, Husby S, Garne E. ; EUROCAT Working group. Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions. Arch Dis Child 2012; 97 (03) 227-232
- 3 Gross RE. The Surgery of Infancy and Childhood. Philadelphia: WB Saunders; 1953
- 4 Vogt EC. Congenital esophageal atresia. Am J Roentgenol 1929; (22) 463-465
- 5 Spitz L. Oesophageal atresia. Orphanet J Rare Dis 2007; 2: 24
- 6 Geneviève D, de Pontual L, Amiel J, Sarnacki S, Lyonnet S. An overview of isolated and syndromic oesophageal atresia. Clin Genet 2007; 71 (05) 392-399
- 7 Brown AK, Roddam AW, Spitz L, Ward SJ. Oesophageal atresia, related malformations, and medical problems: a family study. Am J Med Genet 1999; 85 (01) 31-37
- 8 Chittmittrapap S, Spitz L, Kiely EM, Brereton RJ. Oesophageal atresia and associated anomalies. Arch Dis Child 1989; 64 (03) 364-368
- 9 Shaw-Smith C. Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association: review of genetics and epidemiology. J Med Genet 2006; 43 (07) 545-554
- 10 Bednarczyk D, Sasiadek MM, Smigiel R. Chromosome aberrations and gene mutations in patients with esophageal atresia. J Pediatr Gastroenterol Nutr 2013; 57 (06) 688-693
- 11 Brosens E, Ploeg M, van Bever Y. , et al. Clinical and etiological heterogeneity in patients with tracheo-esophageal malformations and associated anomalies. Eur J Med Genet 2014; 57 (08) 440-452
- 12 de Jong EM, Felix JF, Deurloo JA. , et al. Non-VACTERL-type anomalies are frequent in patients with esophageal atresia/tracheo-esophageal fistula and full or partial VACTERL association. Birth Defects Res A Clin Mol Teratol 2008; 82 (02) 92-97
- 13 de Jong EM, de Haan MA M, Gischler SJ. , et al. Pre- and postnatal diagnosis and outcome of fetuses and neonates with esophageal atresia and tracheoesophageal fistula. Prenat Diagn 2010; 30 (03) 274-279
- 14 Rasmussen SA, Olney RS, Holmes LB, Lin AE, Keppler-Noreuil KM, Moore CA. ; National Birth Defects Prevention Study. Guidelines for case classification for the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol 2003; 67 (03) 193-201
- 15 Zocchetti C, Consonni D, Bertazzi PA. Relationship between prevalence rate ratios and odds ratios in cross-sectional studies. Int J Epidemiol 1997; 26 (01) 220-223
- 16 Depaepe A, Dolk H, Lechat MF. ; EUROCAT Working Group. The epidemiology of tracheo-oesophageal fistula and oesophageal atresia in Europe. Arch Dis Child 1993; 68 (06) 743-748
- 17 Stoll C, Alembik Y, Dott B, Roth MP. Associated malformations in patients with esophageal atresia. Eur J Med Genet 2009; 52 (05) 287-290
- 18 Zwink N, Choinitzki V, Baudisch F. , et al. Comparison of environmental risk factors for esophageal atresia, anorectal malformations, and the combined phenotype in 263 German families. Dis Esophagus 2016; 29 (08) 1032-1042
- 19 Shaw-Smith C. Genetic factors in esophageal atresia, tracheo-esophageal fistula and the VACTERL association: roles for FOXF1 and the 16q24.1 FOX transcription factor gene cluster, and review of the literature. Eur J Med Genet 2010; 53 (01) 6-13
- 20 La Placa S, Giuffrè M, Gangemi A. , et al. Esophageal atresia in newborns: a wide spectrum from the isolated forms to a full VACTERL phenotype?. Ital J Pediatr 2013; 39 (01) 45
- 21 Carmi R, Sofer S, Karplus M. , et al. Aplasia cutis congenita in two sibs discordant for pyloric atresia. Am J Med Genet 1982; 11 (03) 319-328
- 22 Vivona G, Frontali M, Di Nunzio ML, Vendemiati A. Aplasia cutis congenita and/or epidermolysis bullosa. Am J Med Genet 1987; 26 (02) 497-502
- 23 Reutter H, Gurung N, Ludwig M. Evidence for annular pancreas as an associated anomaly in the VATER/VACTERL association and investigation of the gene encoding pancreas specific transcription factor 1A as a candidate gene. Am J Med Genet A 2014; 164A (06) 1611-1613
- 24 Källén KB, Castilla EE, da Graça Dutra M, Mastroiacovo P, Robert E, Källén BA. A modified method for the epidemiological analysis of registry data on infants with multiple malformations. Int J Epidemiol 1999; 28 (04) 701-710