Risk factors for adverse outcomes following surgical repair of esophageal atresia. A retrospective cohort study

Summary

Esophageal atresia (EA) is a life-threatening congenital malformation of the esophagus. Despite considerable recent advances in perinatal resuscitation and neonatal care, EA remains an important cause of mortality and morbidity, especially in low-income countries. The aim of this study was to assess risk factors for adverse outcomes following surgical repair of EA at a single center in Tunisia. We performed a retrospective analysis using medical records of neonates with surgical management of EA at our institution from 1 January 2007 to 31 December 2021. In total, 88 neonates were included with a mortality rate of 25%. There were 29 girls and 59 boys. The diagnosis of EA was suspected prenatally in 19 patients. The most common associated anomalies were congenital heart diseases. Prematurity, low birth weight, outborn birth, age at admission >12 hours, congenital heart disease, postoperative sepsis, and anastomotic leak were risk factors for mortality following surgical repair of EA. Anastomotic tension was the only factor associated with short-term complications and the occurrence of short-term complications was predictive of mid-term complications. This study provides physicians and families with contemporary information regarding risk factors for adverse outcomes following surgical repair of EA. Thus, any effort to reduce these risk factors would be critical to improving patient outcomes and reducing cost. Future multi-institutional studies are needed to identify, investigate, and establish best practices and clinical care guidelines for neonates with EA.

INTRODUCTION

Congenital anomalies are a major public health burden. Over 95% of deaths from congenital malformations occur in low-income and middle-income countries.^1,2 Esophageal atresia (EA) is a life-threatening congenital malformation of the esophagus. The true incidence of EA is still unknown due to the lack of robust epidemiologic data. Several authors estimate that EA affects 1/2500 to 1/4500 live births.^3–6 Despite considerable recent advances in perinatal resuscitation and neonatal care, EA remains an important cause of mortality and morbidity, especially in low-income countries.^7–14 The aim of this study was to assess risk factors for adverse outcomes following surgical repair of EA at a single center in Tunisia.

METHODS

Subjects

We conducted a retrospective data collection through a review of the patients’ medical records. Ninety-five neonates with a surgical management of EA between 1 January 2007 and 31 December 2021 were included. Incomplete medical records represented the exclusion criteria from this study. The Ethical Committee of the Hedi Chaker University Hospital, Sfax, Tunisia, approved the study (HCH/022/0239).

Patients’ management

Preoperative management

The confirmation of the diagnosis of EA was made using a simple chest X-ray with a gastric tube inserted on the upper esophageal pouch. Once the diagnosis of EA has been established, continuous salivary suction from the upper pouch was done. In our institution, all patients with EA underwent echocardiography. However, preoperative tracheobronchoscopy was not performed because of the nonavailability, in our country, of the necessary equipment to carry out this investigation. Patients with severe respiratory distress underwent intubation and mechanical ventilation. Gap length was measured based on preoperative chest X-ray or at the time of surgical exploration. An anatomic distance of three or more vertebral bodies between the ends of the upper and distal esophageal pouches defined long-gap EA.

Surgical management

Surgical repair of EA depended on the anatomical type. Ladd classification was used to specify the type of EA. Open thoracotomy with extrapleural approach was done in all the patients.

In our patients with type III, IV, or V EA, the procedure begins with the closure of the fistula. Then we accomplished esophageal continuity using a single-layer, end-to-end anastomosis with monofilament absorbable sutures. A transanastomotic tube was inserted and a chest drain was placed near the anastomosis for an early diagnosis of anastomotic leak. The chest drain is usually removed at the seventh postoperative day after performing contrast esophagography.

In our patients with type I and II EA, we performed esophagostomy and gastrostomy. After 6 months to 1 year, these patients will be candidates for esophageal replacement.

Postoperative management

Postoperatively, tracheal intubation was maintained for a minimum of 24 hours. Empiric postoperative antibiotics were prescribed for all patients. We defined anastomotic leak as the presence of saliva in the chest tube or a recorded diagnosis of anastomotic leak on the contrast esophagography report. The absence of an anastomotic leak on the contrast esophagography performed on the seventh postoperative day allowed the start of oral feeding. Before discharge, all patients underwent spinal X-ray and renal ultrasound. Thereafter, we will try to identify postoperative complications while ensuring a regular and prolonged follow-up of these patients. The need for dilatation within 1 year of establishing esophageal continuity defined esophageal anastomotic stricture.

Risk factors for adverse outcomes

We evaluated the following predictive factors for adverse outcomes in neonates with in EA: sex, gestational age, birth weight, inborn/outborn status, age at admission, congenital heart disease, VACTERL association (Vertebral, Anorectal, Cardiac, Tracheo-Esophageal, Renal, Limb), twin birth, preoperative mechanical ventilation, age at surgery, anastomotic tension, long gap, postoperative sepsis, anastomotic leak, and occurrence of short-term complications (STC). Adverse outcomes included postoperative mortality and morbidity. We defined STC as complications occurring during the first postoperative year. Mid-term complications (MTC) were defined as complications occurring during the second and the third postoperative years.

Statistical analysis

We performed statistical analyses using IBM SPSS Statistics, version 20.0. Significance was assumed with P-values <0.05. We used chi-square tests to compare categorical variables including preoperative, surgical, and postoperative variables between nonsurvivor versus survivor groups, STC versus non-STC groups, and MTC versus non-MTC groups. For continuous variables, we used Student’s t-tests.

RESULTS

Baseline information

In total, 95 neonates were included during the study period. Seven patients with incomplete medical records were excluded leaving 88 neonates for final analysis. There were 29 girls and 59 boys (sex ratio = 2). The diagnosis of EA was suspected prenatally in 19 (21.6%) patients based on fetal ultrasound results, including absent or small stomach (n = 4) and polyhydramnios (n = 18). Eight neonates were born from a twin pregnancy. The median gestational age was 38 weeks, (interquartile range [IQR], 36–39 weeks). Eighteen (20.4%) patients were premature. Twenty-five (28.4%) newborns weighed <2500 g. Forty-nine (55.7%) patients had associated malformations. The most common associated anomalies were congenital heart diseases (Table 1). The types of EA included types I (7.9%; n = 7), II (1.1%; n = 1), III (77.3%; n = 68), IV (4.5%; n = 4), and V (9.1%; n = 8). A primary anastomosis of the esophageal ends was done in all patients with short gap EA (n = 10; 11.4%). Seventy patients had an intermediate gap EA; of these patients, 15 (17%) patients had a low-tension anastomosis, and 55 (62.5%) had a nontension primary anastomosis. Eight (9.1%) neonates with long-gap EA underwent esophagostomy and gastrostomy.

The main postoperative short-term complications included anastomotic leak (n = 17, 19.3%), pneumothorax (n = 12, 13.6%), and nosocomial infection (n = 10, 11.4%). The most common MTCs included recurrent pulmonary infections (n = 22, 33.3%), anastomotic stricture (n = 21, 31.8%), and gastroesophageal reflux (n = 8, 12.1%) (Table 2). The mortality rate in our series was 25%. The median follow-up in survivors was 7 years (IQR, 3–11 years).

Multivariate analysis of non-survivor versus survivor groups

Firstly, we performed univariate analysis to select significant variables. Then, the significant risk factors were put in mulitvariate analysis by stepwise selection of variables. Table 3 shows that prematurity, low birth weight, outborn birth, age at admission >12 hours, congenital heart disease, postoperative sepsis, and anastomotic leak were risk factors for mortality following surgical repair of EA.

Multivariate analysis of STC versus non-STC groups

Multivariate logistic analyses demonstrated that anastomotic tension was the only factor associated with STC following surgical repair of EA (Table 4).

Multivariate analysis of MTC versus non-MTC groups

The comparison of MTC and non-MTC groups revealed that the occurrence of a postoperative short-term complication was the only predictive factor of MTCs (Table 5).

DISCUSSION

In this study, the diagnosis of EA was suspected prenatally in 21.6% of cases. This was in accordance with previous studies that reported a 20–30% rate of prenatal diagnosis of EA.¹⁵

Most of our patients (77.3%) had type III EA, whereas only one neonate (1.1%) had type II EA. The distribution of anatomical types of EA was similar to previous studies.^16–18

We identified associated anomalies in 55.7% of our patients with 39.8% having congenital heart diseases. These results are similar to those reported by other studies.^5,7,13,19,20 In accordance with our results, many authors demonstrated that these malformations are a strong predictive factor of mortality following surgical repair of EA.^5,7,21,22 However, based on a nationwide analysis of clinical outcomes among neonates with EA, Wang et al.²³ suggested that only major cardiac malformations should be considered as predictive factors of death in EA. In addition to the known VACTERL association including vertebral, anorectal, cardiac, tracheoesophageal, renal, and limb abnormalities, we found intracranial/cranial facial anomalies in nine (10.2%) patients and chromosomal abnormalities in 9.1% of patients. These rates are higher than those reported by Keckler et al.,²⁴ which were 5% and 4%, respectively. Therefore, we suggest that a comprehensive work-up is critical to identify the associated anomalies in neonates with EA.

In our series, 22 (25%) patients died following surgical management of EA. While the survival rate after surgical treatment of EA is greater than 90% in high-income countries, the mortality rate is still high in low-income countries, ranging from 25 to 40%.^{3,7,13,21,25–30} Recent advances in perinatal resuscitation and neonatal care have led to significant improvements in survival in developed countries.^21,23,31,32 However, EA remains an important cause of mortality in low-income countries.^13,32,33 The main cause that could explain the high mortality rate in our study is the absence of neonatal intensive care and pediatric surgery units in the vast majority of hospitals in southern Tunisia. In accordance with this idea, we found that neonates born outside our institution had a significantly higher mortality rate. This could be explained by the delayed diagnosis in these patients. Our institution, as an academic referral hospital, is the only institution in southern Tunisia that provides neonatal intensive care and pediatric surgery services. It covers an area of 100,000 km² and a population of 3 million inhabitants. Surgical care in low-income countries has many challenges including delayed presentation, poor infrastructure, and lack of trained personnel. Ekenze et al.³⁴ confirmed these difficulties based on a literature review including all publications on neonatal surgery in Africa over 20 years. The authors recommended some strategies to overcome these challenges. These strategies include improving health-care funding, implementing policies that facilitate interprofessional collaboration, making neonatal intensive care cost effective, and promoting focused international collaboration.

Our study revealed that prematurity, low birth weight, outborn birth, age at admission >12 hours, congenital heart disease, postoperative sepsis, and anastomotic leak were associated with mortality following surgical repair of EA. These results were similar to other studies.^22,33,35,36

Interestingly, postoperative sepsis was the strongest risk factor for mortality following surgical repair of EA. Neonatal sepsis is the third most common cause of mortality in neonates and a growing public health problem, especially in low-income countries.³⁷ Several factors including prematurity, delayed diagnosis, and anastomotic leak contribute to sepsis-related death following surgical repair of EA.^{13,31–33,35}

This study found that nosocomial infections were the most common infectious postoperative complication. Nosocomial infections are common in neonatal intensive care units. According to many authors, vascular catheters, high-calorie hyperalimentation infusions, assisted ventilation, and prior use of antibiotics are significant risk factors for neonatal nosocomial infections. Therefore, strategies including hand hygiene before and after patient contact, use of maternal breast milk, and implementation of quality improvement programs are critical to preventing neonatal nosocomial infections and improving the prognosis of these patients.^38,39

This study pointed out the role of anastomotic tension as the only risk factor for STC following surgical repair of EA. This is in accordance with most studies suggesting that the presence of a long gap between the two esophageal ends, with consequent anastomotic tension is an important risk factor for postoperative complications, including anastomotic leak and infectious complications.^12,13,21,27

The occurrence of STC was the only predictor of MTC in our study. This is in agreement with published literature data. Anastomotic leak and long gap, particularly, has been identified by many authors as important risk factors for anastomotic stricture.^40,41

Our study is one of the few studies conducted in low-income countries that focused on risk factors for mortality and morbidity following surgical repair of EA. The identification of these factors may help develop diagnostic, therapeutic, and preventive strategies for early detection and management of adverse outcomes in neonates with EA. This could significantly improve the prognosis of these patients. However, the findings of this study should be considered in light of some limitations. Firstly, it was a retrospective observational study. Therefore, bias and errors in data extraction were possible. Moreover, the retrospective design of our study and the limited follow-up for some patients made it difficult to assess long-term complications following surgical repair of EA. Secondly, the present study was monocentric; so, our results are not necessarily representative of all patients with EA in Tunisia. We believe that further prospective multicenter cohort studies are needed to validate the identified risk factors. The final limitation of our study was the relatively small sample size.

CONCLUSION

This study provides physicians and families with contemporary information regarding risk factors for adverse outcomes following surgical repair of EA. Our study demonstrated that prematurity, low birth weight, outborn birth, age at admission >12 hours, congenital heart disease, postoperative sepsis, and anastomotic leak were risk factors for mortality. Anastomotic tension was predictive of STC and the occurrence of STC was predictive of MTC. Thus, any effort to reduce these risk factors would be critical to improving patient outcomes and reducing cost. Future multi-institutional studies are needed to identify, investigate, and establish best practices and clinical care guidelines for neonates with EA.

Conflicts of interest: The authors declare that they have no conflict of interest

References