Anorectal malformations occur approximately in 1/1,500 to 1/5,000 live births [1,2]. They may occur alone, but they can commonly have other associated anomalies or occur as a part of the combined anomaly. The treatment involved may be complicated by a need to address the associated anomalies, in addition to the anorectal malformations. Furthermore, the problems of these associated anomalies could have more of an impact on the morbidity and mortality before and after surgical treatment.

The frequency of associated anomalies in other organs is known to be approximately 40-70% in the decreasing order of urogenital system, musculoskeletal system, and cardiovascular system [3,4]. In addition, anomaly in other parts of the gastrointestinal system can occur concomitantly, and a prompt treatment is required in such situations when the neonate's life is threatened. In particular, when an esophageal atresia accompanies the anorectal malformations, the complex of surgical procedure and the difficulty of situational postoperative management must be considered.

Thus, we conducted the present study to analyze the characteristics of and treatment results in neonates with anorectal malformations associated with esophageal atresia.

In patients with anorectal malformations, associated anomalies in other organs are not uncommon. These associated anomalies may sometimes cause a high rate of morbidity and mortality.

Although it is difficult to directly compare the types of associated anomalies because of their varied natures, cases of associated with esophageal atresia are known to some extent because of their clinical importance. Associated esophageal atresia in patients with anorectal malformations may occur alone or as a part of complex anomaly, and its incidence is reported approximately in 8-11% [3,5]. The incidence rate in the present study was 7.1%, which was not largely different from that in other reports. Moreover, associated anomalies other than anorectal malformations and esophageal atresia were observed in all patient subjects. The majority of these anomalies were problems of the cardiovascular or urogenital systems, and they were not largely different from those reported in previous studies [6]. However, a relatively higher frequency of anomalies was observed in the subjects with esophageal atresia than in those without esophageal atresia. Thus, given that additional associated anomalies were observed in all patients, it is suggested that the management of anorectal malformations associated with esophageal atresia will require more caution and efforts than the management of patients presenting with anorectal malformations alone.

Although many factors may be involved in the occurrence of these anomalies, it may be thought that anorectal malformations and esophageal atresia are types of midline defects, which present along the body. These defects occur as results of the combination of deficits in mesodermal migration and endodermal defects [7,8]. On the other hand, in VACTERL association, there are two different explanations involving it; genetic factors and external environmental factors. First, the genetic factor model has been supported through animal experiments, and it proposes the formation of anomalies due to genetic mutations that induce signaling pathway abnormalities [9-11]. Second, it is thought that external environmental factors such as maternal diabetes, hormonal exposure during infertility treatments, and exposure to toxic factors negatively influence the morphological development of the fetus, leading to malformations in the fetus [12-15]. In our study, we could not identify any factors, such as chromosomal defects, which may induce this anomaly, but it is necessary to be supposed to think about an adequate investigation of these factors. However, since the incidence of the disease itself is not very high, there are still many limitations to investigate directly.

Generally, associated anomalies occur more frequently in high-type of anorectal malformations than in low-type malformations; the frequency is also higher in males than in females [2-4,16,17]. In our study, for anorectal malformations associated with esophageal atresia, the gender distribution was relatively equal, with a 1.3 : 1 male to female ratio. In the case of male, most of anorectal malformations were intermediate- or high-type with rectourethral fistula (7/8, 87.5%), and mainly low-type or cloacal malformations in female. This findings showed a different distribution in cases of anorectal malformations without esophageal atresia. A relatively high frequency, 28.6%, of the cases occurred as a part of the VACTERL association, which may be considered as result of multiple congenital malformations. In addition, considering the report that the frequency of concomitant gastrointestinal atresia is 4 times as high in VACTERL association than in the cases with a single anomaly of anorectal malformation, this can also be inferred as a result of simple primary malformation due to deficits in the organ formation process, in addition to the previously mentioned disease occurrence process [18-20].

In the management of a complex anomaly, the correlation with life support must be considered primarily in the neonatal period, and it is essential to do appropriately a staged procedure. Ultimately, when considering it's clinical results, the complicated nature of the surgical procedure and appropriate surgical approaches must be considered in managing a case of anorectal malformations associated with esophageal atresia. In this study, the majority of the surgical treatments administered in the neonatal period were a staged procedure with good results, and there were no major differences compared to other reports [21-23]. Although the mortality rates after appropriate treatments are relatively low in the cases of simple anorectal malformations and esophageal atresia, the total mortality rate observed in the present study was 21.4%, a very high frequency compared to that in other gastrointestinal anomalies. In particular, when compared to anorectal malformations without esophageal atresia, it can be concluded that this high mortality rate is attributable to complications associated with other anomalies, rather than the disease itself. Two of the 3 deaths in our study were caused by heart problems during observation after the primary surgery in the neonatal period, and 1 death in VACTERL associations without surgical intervention. Thus, it could be inferred that the influence of other associated anomalies was greater than that of anorectal malformations and esophageal atresia. Meanwhile, diverting colostomy was performed initially in 2 patients. Each case involved a delayed diagnosis of esophageal atresia or concomitant gastrointestinal perforation. Because of these complications, complex surgical procedures were unavoidable, and one case involved with gastrointestinal perforation resulted in a death during the postoperative recovery period. This indicates that a more careful and timely diagnosis based on clinical and radiological findings is necessary before the primary operation.

In conclusion, anorectal malformations associated with esophageal atresia, whether alone or as a part of a complex syndrome, had a relatively high frequency of associated anomalies in other organs, as well as a high mortality rate. It may be suggested that a staged and multidisciplinary approach is essential in the management of neonates with this anomaly. In addition, reasonable treatments considering these possibilities may lead to improved outcomes by preventing delays in the diagnosis of anorectal malformations associated with esophageal atresia, as well as the development of serious complications.