Brazilian Multicenter Study on Esophageal Atresia

Official title

Evolution of Neonates With Esophageal Atresia in Brazil - A Multicenter Study

Overview

Esophageal atresia is a congenital malformation where the esophagus does not form properly, often associated with a tracheoesophageal fistula. This condition requires complex surgical treatment and intensive neonatal care. Survival has improved worldwide, but results from other countries cannot be directly applied to Brazil due to differences in health resources. This study will gather data from 72 neonatal centers across Brazil to better understand the characteristics, treatments, complications, and outcomes of newborns with esophageal atresia. The goal is to identify factors associated with complications and mortality, and to generate national evidence that can guide better care and improve survival and quality of life.

Detailed description

Esophageal atresia is a congenital malformation characterized by an interruption of the esophageal lumen, frequently associated with a tracheoesophageal fistula. Although survival has significantly improved over the past decades in high-income countries, outcomes remain heterogeneous, and the results from international registries cannot be directly extrapolated to the Brazilian context due to regional differences in health system resources, neonatal intensive care, and surgical practice. At present, Brazil lacks a comprehensive national study evaluating the epidemiology, management, and outcomes of neonates with esophageal atresia.

The present multicenter project represents the first nationwide collaboration dedicated to this condition. Seventy-two neonatal centers across Brazil will contribute data, creating a large national cohort that encompasses both retrospective and prospective cases.

Data collection will be standardized and managed using the REDCap platform (Research Electronic Data Capture), with local entry validated centrally at the coordinating center. Variables collected will include prenatal and perinatal information, associated anomalies, anatomical classification of the atresia, diagnostic procedures performed, intraoperative surgical details, postoperative course, complications, and mortality. Particular attention will be given to factors such as prematurity, congenital heart disease, VACTERL association, and "long-gap" esophageal atresia, as these conditions are expected to have significant impact on outcomes.

The study aims to describe the current Brazilian panorama of esophageal atresia, focusing on short- and mid-term outcomes, including mortality within the first year of life, early complications such as anastomotic leakage and sepsis, and late complications including strictures and recurrent fistulas. A multivariate statistical analysis will be performed to identify predictors of adverse outcomes and to compare the results of different treatment strategies adopted across participating centers.

This initiative is expected to provide unprecedented epidemiological and clinical insights into esophageal atresia in Brazil. By combining the expertise and data of multiple neonatal units across diverse regions, the study will generate robust evidence to guide best practices, inform clinical guidelines, and support improvements in neonatal surgical care. Ultimately, the findings have the potential to improve survival and quality of life for Brazilian neonates affected by this challenging congenital condition.

Primary outcome measures

• All-cause mortality within the first year of life [Time frame: From birth until 12 months of age]

Secondary outcome measures (8)

• Surgical complications after primary repair of distal fistula [Time frame: From surgery until 12 months of age]
• Incidence of postoperative complications among premature vs. term neonates with esophageal atresia [Time frame: From birth until 12 months of age]
• Mortality rate among premature vs. term neonates with esophageal atresia [Time frame: From birth until 12 months of age]
• Incidence of postoperative sepsis among neonates with esophageal atresia [Time frame: From surgery until 12 months of age]
• Incidence of postoperative complications among neonates with long-gap esophageal atresia [Time frame: From surgery until 12 months of age]
• Incidence of mortality among neonates with long-gap esophageal atresia [Time frame: From surgery until 12 months of age]
• Incidence of complications among neonates with vs. without associated congenital anomalies (cardiac or VACTERL components) [Time frame: From birth until 12 months of age]
• Mortality rate among neonates with vs. without associated congenital anomalies (cardiac or VACTERL components) [Time frame: From birth until 12 months of age]

Eligibility criteria

Inclusion criteria

• Neonates with a confirmed diagnosis of esophageal atresia of any anatomical type (with or without tracheoesophageal fistula).
• Birth in, or transfer to, one of the participating neonatal centers within the first 15 days of life.

Exclusion criteria

\- Patients lost to follow-up before reaching 12 months of age.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Brazil · 1 center

• Instituto da Crianca e do Adolescente, Hospital das Clinicas, Faculdade de Medicina, Unive — São Paulo

Publications

• Ishimaru T, Fujiogi M, Michihata N, Matsui H, Fushimi K, Kawashima H, Fujishiro J, Yasunaga H. Impact of congenital heart disease on outcomes after primary repair of esophageal atresia: a retrospective observational study using a nationwide database in Japan. Pediatr Surg Int. 2019 Oct;35(10):1077-1083. doi: 10.1007/s00383-019-04542-w. Epub 2019 Aug 8. PMID 31396739
• Lal DR, Gadepalli SK, Downard CD, Ostlie DJ, Minneci PC, Swedler RM, Chelius TH, Cassidy L, Rapp CT, Billmire D, Bruch S, Burns RC, Deans KJ, Fallat ME, Fraser JD, Grabowski J, Hebel F, Helmrath MA, Hirschl RB, Kabre R, Kohler J, Landman MP, Leys CM, Mak GZ, Raque J, Rymeski B, Saito JM, St Peter SD, von Allmen D, Warner BW, Sato TT; Midwest Pediatric Surgery Consortium. Challenging surgical dogma PMID 28599967
• Tannuri U, Maksoud-Filho JG, Tannuri AC, Andrade W, Maksoud JG. Which is better for esophageal substitution in children, esophagocoloplasty or gastric transposition? A 27-year experience of a single center. J Pediatr Surg. 2007 Mar;42(3):500-4. doi: 10.1016/j.jpedsurg.2006.10.042. PMID 17336187
• Foker JE, Kendall TC, Catton K, Khan KM. A flexible approach to achieve a true primary repair for all infants with esophageal atresia. Semin Pediatr Surg. 2005 Feb;14(1):8-15. doi: 10.1053/j.sempedsurg.2004.10.021. PMID 15770584
• Tobia A, Luque CG, Leitmeyer K, Dorling M, Chadha NK. Endoscopic treatment in pediatric patients with recurrent and H-type tracheoesophageal fistulas - A systematic review and meta-analysis. Int J Pediatr Otorhinolaryngol. 2023 May;168:111541. doi: 10.1016/j.ijporl.2023.111541. Epub 2023 Mar 31. PMID 37043961
• Koivusalo A, Pakarinen MP, Rintala RJ. Anastomotic dilatation after repair of esophageal atresia with distal fistula. Comparison of results after routine versus selective dilatation. Dis Esophagus. 2009;22(2):190-4. doi: 10.1111/j.1442-2050.2008.00902.x. Epub 2008 Dec 22. PMID 19207547
• Aslanabadi S, Jamshidi M, Tubbs RS, Shoja MM. The role of prophylactic chest drainage in the operative management of esophageal atresia with tracheoesophageal fistula. Pediatr Surg Int. 2009 Apr;25(4):365-8. doi: 10.1007/s00383-009-2345-7. Epub 2009 Mar 17. PMID 19290533
• Davenport M, Rothenberg SS, Crabbe DC, Wulkan ML. The great debate: open or thoracoscopic repair for oesophageal atresia or diaphragmatic hernia. J Pediatr Surg. 2015 Feb;50(2):240-6. doi: 10.1016/j.jpedsurg.2014.11.008. Epub 2014 Nov 7. PMID 25638610

Identifiers

NCT: NCT07210736 · 85624924.8.1001.0068

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗