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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 231-236

Hirschsprung's disease and neonatal intestinal obstruction: Where does it lie in the spectrum?


1 Department of Pediatric Surgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of General Surgery, RNT Medical College, Udaipur, Rajasthan, India

Date of Web Publication15-Oct-2018

Correspondence Address:
Dr. Manish Pathak
Department of Pediatric Surgery, All India Institute of Medical Sciences, Jodhpur - 342 005, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcn.JCN_48_18

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  Abstract 


Introduction: Neonatal intestinal obstruction may be caused by varied etiologies. These different etiologies differ in presentation, management, and outcome. Hirschsprung's disease (HD) is an important differential diagnosis in such patients and differs in presentation, management, and outcome. Objective: The objective of the study was to compare the clinical presentation and outcome of HD with other causes of neonatal intestinal obstruction. Methods: The medical record of all the patients, presented at our institute with intestinal obstruction in the neonatal period during 2014–2015, was reviewed retrospectively for etiology, clinical features, investigations, management, and outcome. The cases diagnosed with HD (Cohort A) were compared with the cohort containing patients with all other causes of neonatal intestinal obstruction (Cohort B). Results: A total of 53 cases with congenital neonatal intestinal obstruction were identified. Among them, 17 had HD and 36 had other causes of intestinal obstruction (27 intestinal atresia, 7 malrotation, and 2 Meckel's diverticulum). The male:female ratio in Cohort A and B was 4.66:1 and 2.6:1, respectively. The median age of presentation in Cohort A and B was 7 days and 4 days, respectively. All patients in Cohort A presented with abdominal distension and delayed passage of meconium. In Cohort B, bilious vomiting was the chief complaint. There were no associated congenital anomalies in Cohort A, whereas 22% of the patients in Cohort B had associated anomalies. There was no mortality in Cohort A, while there was 27% mortality in Cohort B. Conclusion: HD is an important cause of neonatal intestinal obstruction. HD is not usually associated with other congenital anomalies. It has excellent survival in comparison to other causes of neonatal intestinal obstruction.

Keywords: Hirschsprung's disease, intestinal obstruction, neonate


How to cite this article:
Pathak M, Saxena R, Sinha A, Singh V. Hirschsprung's disease and neonatal intestinal obstruction: Where does it lie in the spectrum?. J Clin Neonatol 2018;7:231-6

How to cite this URL:
Pathak M, Saxena R, Sinha A, Singh V. Hirschsprung's disease and neonatal intestinal obstruction: Where does it lie in the spectrum?. J Clin Neonatol [serial online] 2018 [cited 2018 Dec 16];7:231-6. Available from: http://www.jcnonweb.com/text.asp?2018/7/4/231/243336




  Introduction Top


Neonatal intestinal obstruction is one of the most common causes of neonatal surgical emergencies. Neonatal intestinal obstruction may be caused by varied etiologies. These different etiologies differ in presentation, management, and outcome. Hirschsprung's disease (HD) is an important differential diagnosis in such patients and differs in presentation, management, and outcome.[1] The purpose of this study is to retrospectively compare clinical presentation and outcome of HD with other causes of neonatal intestinal obstruction.


  Methods Top


The medical record of all the patients, presented at our institute with intestinal obstruction in the neonatal period during 2014 and 2015, was reviewed retrospectively for etiology, clinical features, investigations, management, and outcome. Patients of anorectal malformation and esophageal atresia were excluded from the study. Medical causes of neonatal intestinal obstruction such as neonatal sepsis, conservatively managed necrotizing enterocolitis, and the cases of meconium ileus which were managed conservatively, also excluded. The cases diagnosed with HD (Cohort A) were compared with the cohort containing patients with all other causes of neonatal intestinal obstruction (Cohort B).


  Results Top


A total of 53 cases with congenital neonatal intestinal obstruction were identified. Among them, 17 had HD and 36 had other causes of intestinal obstruction (27 intestinal atresia, 7 malrotation, and 2 Meckel's diverticulum).

Among the 53 cases of neonatal intestinal obstruction, 28 patients (53%) presented with bilious vomiting and 25 (47%) presented with abdominal distension and delayed passage of meconium. None of the patients in Cohort A was premature, while in Cohort B, 15/36 (42%) patients were premature. The mean follow-up was 30 months (27–39 months) [Table 1].
Table 1: Comparison between Hirschsprung's disease and other causes of neonatal intestinal obstruction. (n=53)

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All patients in Cohort A presented with abdominal distension and delayed passage of meconium. In Cohort B, bilious vomiting was the chief complaint in 28/36 patients (78%), while abdominal distension was the chief complaint in 8/36 patients (22%).

An upright abdominal X-ray was either normal looking (5/53) or showed features of upper intestinal obstruction (19/53) and distal intestinal obstruction (29/53). All the patients having normal looking upper abdominal X-ray were later diagnosed as malrotation on upper G.I study or on exploration. All patients with features of upper intestinal obstruction on upright abdominal X-ray fell in Cohort B (duodenal atresia n = 9, jejunal atresia n = 8, and malrotation n = 2). All patients in Cohort A had features of distal intestinal obstruction such as distended bowel loops all over the abdomen. Air–fluid levels were seen in 7/17 patients only in the initial X-ray film at the time of presentation. Five more patients developed air-fluid levels in the course of the next 1–2 days during the evaluation of abdominal distension. All patients in Cohort A showed the absence of gas in the pelvis on initial X-ray at the time of presentation. In Cohort B, features of distal intestinal obstruction such as multiple air-fluid levels and distended bowel loops were present in 12/36 (33%) patients.

All the patients with distal intestinal obstruction underwent contrast enema examination. Contrast enema revealed transition zone in only 7/17 (41%) patients in Cohort A. Ten of the 12 patients who underwent contrast enema examination in Cohort B had evidence of microcolon. Remaining two patients with normal contrast enema were diagnosed as Meckel's diverticulum on exploration.

There were no associated congenital anomalies in Cohort A, whereas 22% of the patients in Cohort B had associated anomalies. Associated anomalies in Cohort B included anorectal malformation (n = 2), tracheoesophageal fistula (n = 1), other gastrointestinal anomalies, for example, malrotation with or without volvulus and other atresia (n = 4), and meconium ileus (n = 1).

In Cohort A, all patients underwent right transverse colostomy and multiple seromuscular biopsies as the initial procedure in neonatal age. Right transverse colostomy was preferred so as to be able to do the definitive procedure under the cover of colostomy in the most common variant of HD (rectosigmoid HD). Intraoperatively, gross transition zone was seen in only 8/17 (47%) [Figure 1]. Radiological and intraoperative gross transition zone matched in four patients only; others had intraoperatively seen gross transition zone more proximally than the radiological transition zone. In Cohort A, 15/17 (88%) had classic or rectosigmoid HD, whereas 2/17 (12%) had long segment HD. Two patients needed rectal biopsy later, to confirm the diagnosis because multiple seromuscular biopsies at the time of colostomy revealed the presence of ganglion cells even in the distal most biopsy. Sixteen patients underwent modified Duhamel pull-through, and one patient underwent transanal Swenson pull-through procedure as definitive procedure. Following the definitive pull-through, 3/17 (18%) patients had a postoperative wound infection. Four out of 17 (23%) patients had constipation. The postoperative constipation was managed by dietary modification and laxatives in two patients, while the other two patients required bowel washes for about 1 year. The constipation improved gradually in both of these two patients and they are on laxatives now.
Figure 1: Gross transition zone in Hirschsprung's disease

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In Cohort B, all patients underwent their respective operations depending on the diagnosis.

There was no mortality in Cohort A, while there were 27% mortalities in Cohort B. In Cohort A, none of the patients developed any surgical or nonsurgical postoperative complication after the initial colostomy at neonatal age. In Cohort B, Sepsis (12 patients [22.6%]) and pneumonitis (4 patients [7.5%]) were the postoperative nonsurgical complications. Anastomotic leak (1 patient [1.9%]) and wound infection (1 patient [1.9%]) were surgical complications seen in this cohort. There were 10 deaths (27%). The mortality was attributed to only septicemia in seven patients, pneumonitis in two patients, anastomotic leak in one patient, and wound infection leading to septicemia in one patient. All the ten deaths reported in this study had birth weights <2.5 kg and 9 of these ten mortality cases were premature. Five out of these ten patients had associated anomalies. Hypothermia, metabolic acidosis, and septic shock were main mortality events.


  Discussion Top


Intestinal obstruction in the newborn contributes a significant proportion of neonatal admissions in a pediatric surgical unit. The obstruction may be due to a variety of conditions including atresia and stenosis, HD, malrotation, meconium ileus, neoplasia, trauma, and other rare causes.

While most of the etiologies cause mechanical/anatomical obstruction, HD causes functional obstruction. Detailed history, thorough physical examination, and well-directed investigation will ensure early diagnosis and prompt treatment.

HD is a common cause of neonatal intestinal obstruction.[1] It is a developmental disorder of intrinsic enteric nervous system characterized by the absence of ganglion cells in submucosal and myenteric plexus of distal intestine. Ganglion cells are derived from the neural crest. By 13 weeks of gestation, cranial to caudal migration of neural crest cells occurs followed by maturation into ganglion cells. The disruption of either of these, i.e., migration or maturation leads to HD.[1] Various animal models have been studied to understand the embryologic basis of the HD, and there is some evidence to support both the theories of migration and maturation.[2],[3] HD is actually a heterogeneous condition with multiple etiologic mechanisms. Mutations in a variety of genes have been identified, and these include RET proto-oncogene, glial cell line-derived neurotrophic factor, endothelin, and SOX-10 gene.[4],[5],[6] As HD is due to abnormal development of neural crest-derived cells, it may be associated with other neurocristopathies, for example, central hypoventilation syndrome, sensorineural hearing deafness, Waardenburg's syndrome, and MEN Type II B syndrome.[1] Down's syndrome is the most common chromosomal abnormality associated with HD (up to 16%). The basic pathophysiologic characteristic in HD is a functional obstruction caused by spastic distal aganglionic bowel preventing the propagation of peristaltic waves. There are lots of discrepancy between the length of nonfunctioning bowel and the degree of obstruction. It makes it unlikely that the aganglionosis is the only cause of the spasticity of involved segment; there are other histopathologic findings both in the aganglionic segments and in the proximal ganglionic segment in HD, and these may explain the varied presentation. Kubota et al. have studied the electrophysiological and pharmacological characteristics of the different bowel segments in HD and concluded that the aganglionic segment receives two nervous flows of different origins; one is the intrinsic inhibitory flow from the ganglionic segment through the transition zone, while the other is the excitatory nervous flow from the lower end of the aganglionic segment.[7] Since the stagnation occurs at the transition zone, they infer that a decrease in the intrinsic inhibitory nervous flow might be the cause of the intestinal obstruction.

In contrast to HD, most of the other causes of neonatal intestinal obstruction are mechanical or anatomical obstructions. Intestinal atresia is the most common cause of mechanical intestinal obstruction. Atresia may affect any segment of intestine starting from esophagus to rectum. The presentation of esophagus is not as intestinal obstruction, while rectal atresia is part of the anorectal malformation. To keep the comparison more specific, we have excluded esophageal atresia and rectal atresia cases from our study. The duodenal atresia occurs due to failure of recanalization of duodenum after epithelial plugging of intestinal lumen at 6 weeks of gestation.[8],[9] Failure of recanalization is an early developmental defect and can affect the other organs developing at the same time. This can explain the high incidence of associated anomalies in duodenal atresia. In comparison to it, the jejunoileal atresia (JIA) is due to vascular disruption at later age of gestation.[10] Associated anomalies are uncommon in JIA because the other organs have already developed by the time this event occurs. In our series also, 4 out of 9 (44%) patients with duodenal atresia had associated anomaly, while only 3 out of 12 (25%) patients with JIA had associated anomalies. Apple peel atresia is a type of JIA characterized by spiraling of small bowel around vessel like the peel of apple. One of our patients had duodenal atresia associated with apple peel atresia. There was no other associated anomaly in this patient. This rare association raises the question on embryogenesis of duodenal atresia and suggests that late gestational vascular disruption may be responsible for the embryogenesis of at least some of the duodenal atresia. The incidence of associated anomalies in duodenal atresia and JIA in our series is in agreement with reported world literature. Although the antenatal diagnosis of HD is rare, up to 31% cases of small bowel atresia can be diagnosed antenatally.[11] In our series, none of our patients was diagnosed antenatally; this discrepancy may be explained by the fact that the most of our patients were referred from periphery where many of the pregnancies are not supervised, and there is unavailability of expert ultrasonologist.

The early detection of HD can reduce the morbidity and mortality associated with disease.[12] In developed countries, most of the patients get diagnosed in neonatal age group, while in developing countries, most of children are diagnosed later.[13] The common clinical features of neonatal HD are abdominal distension, abnormality of bowel habit, vomiting, and reluctance to feed.

All patients of HD in our study (100%) had abdominal distension and history of delayed passage of meconium. Bilious vomiting was not the presenting feature in any of our patients. In the study conducted by Duess et al., abdominal distension was present in 80% of preterm infants, delayed passage of meconium in 57%, and only 37% of premature infants presented with bile-stained vomiting.[14] There are other studies, which report the presence of delayed passage of stools in 40%–90% and bilious vomiting and abdominal distension in two-third of their patients.[13],[15] This presentation resembling intestinal obstruction was noticed in other studies also.[16]

In a neonate with suspected HD, the absence of gas from the pelvis especially on an erect lateral X-ray is helpful in diagnosis.[17] All of our patients with HD had this feature. In our patients, the contrast enema was suggestive of transition zone in 7/17 (41%) patients. The diagnostic efficacy of contrast enema in neonates is doubtful, but some authors have suggested accuracy up to 90% in newborn.[15] Rectal biopsy in newborn is difficult and may provide too little tissue to give a confirmatory diagnosis. A suction rectal biopsy is still feasible in young neonates. Rectal biopsy is considered to be gold standard to confirm the diagnosis of HD. Calretinin, a calcium-binding protein, is an important new marker in HD. It has been found to be especially useful in the context of total colonic aganglionosis, superficial biopsies, and prematurity.[18] We retrospectively analyzed our data and tried to find the HD in the wide spectrum of varied etiologies of neonatal intestinal obstruction. HD usually presents as distal intestinal obstruction, while other etiologies can present either as proximal or distal intestinal obstruction depending on the involved anatomical site. In our series also, delayed passage of meconium and abdominal distension was the most common presentation of HD, while bilious vomiting was the chief complaint in other causes of intestinal obstruction.

The features such as delayed passage of meconium, tight anus, abdominal distension, and vomiting are helpful in the diagnosis of HD in newborns. In study of Guo et al., delayed meconium, tight anus, contrast enema, and rectal manometry were statistically significant for the diagnosis of HD in comparison to other parameters. The predictive value of delayed passage of meconium, tight anus, transition zone on contrast enema is 0.77, 0.68, and 0.84, respectively. They also developed a HD scoring system in which delayed meconium, tight anus, contrast enema, and rectal manometry were diagnostic factors. The score >3 was present in 84% patients of HD and score <3 was seen in 75% of non-HD patients. The patients with score ≤3 were selected for rectal biopsy on clinical suspicion of HD.[19] In our series, all patients with HD had delayed passage of meconium and 41% had transition zone on contrast enema.

HD may also present as enterocolitis or perforation peritonitis. One study showed that the incidence of Hirschsprung-associated enterocolitis was 24% for infants diagnosed with HD after the 1st week of life compared to 11% if diagnosed within the 1st week.[20] None of our patients presented with enterocolitis or perforation.

Anatomical causes of obstruction more frequently lead to acute obstruction and present early while HD can present either as acute, subacute, or chronic intestinal obstruction. In our series, median age of presentation of patients with HD was 7 days, while it was 4 days in Cohort B.

The median weight of our patients with HD was 2.1 kg and none of them was premature. The trend of increasing ratio of patients with a low birth weight, associated anomalies, or a family history was noticed by Suita et al.[16] Due to an increase in premature deliveries, the delayed passage of meconium, especially within 48 h may not always mean HD.

Management of HD has progressed from three-stage procedure to single-stage procedure and now increasingly being done as a single-stage procedure. Three-stage procedure involves transverse colostomy followed by pull-through. Colostomy closure is done in the last stage. In two-stage procedure leveling colostomy is done after confirming the distal most ganglionic bowel by intraoperative frozen section with the increasing popularity of laparoscopic surgery, minimal access techniques are being applied in various pediatric surgical diseases. In 1995, Georgeson first described the laparoscopic pull-through procedure for HD.[21] In 1998, De La Torre Mondragon and Ortega-Salgado described the transanal pull-through.[22] This operation provides the advantages of a minimal access approach with a shorter hospital stay, shorter time to full feeding, less pain, and improved cosmesis with excellent outcome. It is mandatory to have frozen section facility to confirm the presence of ganglion cells in the pull-through bowel. Single-stage transanal pull-through is not feasible when diagnosis is not confirmed, acute intestinal obstruction not responding to rectal stimulation, patient with severe enterocolitis or perforation, or when the proximal bowel is grossly distended. The absence of frozen section facility and presentation with refractory acute intestinal obstruction made our patients unsuitable for single-stage transanal pull-through. There are few series comparing the transanal pull-through to a control group undergoing an open approach. Short-term results are encouraging but long-term outcome data after transanal pull-through is not available.[23]

There was no mortality in Cohort A and mortality is 27% in Cohort B. Prematurity, low birth weight, presence of other anomalies, postoperative septicemia, pneumonitis, anastomotic leakage, and wound sepsis have been found to be various causes for mortality in our series. In Cohort A, there were no associated significant anomalies, relatively simple surgery of neonate with no risk of anastomotic leak. These factors led to decreased risk of postoperative septicemia and wound sepsis culminating into better survival in Cohort A.


  Conclusion Top


HD is an important cause of neonatal intestinal obstruction. HD is usually not associated with other congenital anomalies. It has excellent survival in comparison to other causes of neonatal intestinal obstruction.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Duess JW, Hofmann AD, Puri P. Prevalence of Hirschsprung's disease in premature infants: A systematic review. Pediatr Surg Int 2014;30:791-5.  Back to cited text no. 14
    
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Suita S, Taguchi T, Ieiri S, Nakatsuji T. Hirschsprung's disease in Japan: Analysis of 3852 patients based on a nationwide survey in 30 years. J Pediatr Surg 2005;40:197-201.  Back to cited text no. 16
    
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22.
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23.
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