Clinical Characteristics and Management of Benign Transient Non-Organic Ileus of Neonates: A Single-Center Experience

First described in 1886, Hirschsprung's disease is generally suspected in neonates and infants with abdominal distension and constipation.1 Pediatricians or pediatric surgeons often encounter patients whose symptoms are similar to Hirschsprung's disease, however, ganglion cells are present in their rectal biopsies and their clinical course are different form the Hirschsprung's disease. These patients are variously labeled with pseudo-Hirschsprung's disease, neonatal intestinal pseudo-obstruction, intestinal neuronal dysplasia, hypoganglionosis, and internal anal sphincter achalasia. Most of these terms are now considered variants of Hirschsprung's disease.2

Interestingly, however, some patients could not be classified as the variants of Hirschsprung's disease because their symptoms disappear spontaneously without any specific treatment, even though their symptoms and radiologic findings are not distinguishable from the Hirschsprung's disease. Yamauchi, et al.3 first coined the term benign transient non-organic ileus of neonates (BTNIN) in 2002. This entity is likely more common than originally thought, but the detailed characteristics are not fully understood. The aim of this study is to describe our experiences with BTNIN and evaluate the clinical characteristics and proper treatment of BTNIN.

A retrospective review was made on the clinical data from patients who were treated for BTNIN at Severance Children's Hospital in Seoul, Korea between January 2008 and December 2011. A diagnosis of BTNIN was established based on previously published criteria: presence of a non-organic ileus of the neonate excluding Hirschsprung's disease, Hirschsprung's disease-allied disorders, and functional ileus associated with meconium obstruction.3 Nineteen patients were treated during the study period, and no patients were excluded from the study. Patients' demographics, symptoms, diagnostic studies, and clinical courses were analyzed.

This study was approved by the Institutional Review Board of Severance Children's Hospital.

Although the term of 'benign transient non-organic ileus of neonate' is not well established yet, it should be considered in the differential diagnosis of Hirschsprung's disease. First reported in 2002,3 BTNIN did not receive much attention from pediatric surgeons because of its favorable clinical course, and very few supportive articles have been published.4, 5 However, the age at the definitive surgery of Hirschsprung's disease is far younger than previous decade and one-stage procedure has been popular.6-8 These new treatment strategies require early and reliable diagnosis.9-11 Consequently, it is more important than ever to differentiate Hirschsprung's disease from other nonsurgical conditions.9-11

The most important characteristics of BTNIN are its similarity to Hirschsprung's disease. In our present study, the initial symptoms in order of frequency were abdominal distension, emesis, explosive defecation, and constipation. Unfortunately, however, these symptoms alone are not distinguishable from those of Hirschsprung's disease. In addition, plain radiographs of the abdomen are also very similar to Hirschsprung's disease. One-third of our patients showed the typical transition zone in barium studies. However, the presence of ganglion cells in rectal biopsies and the presence of the rectoanal inhibitory reflex in anorectal manometry were excellent discriminators in favor of BTNIN.

BTNIN responds well to conservative treatment and demonstrates an excellent prognosis. The average duration of treatment was only 4.4 months in our study and has been reported to be 5 months in a previous study.3 Conservative treatment should be periodic or intermittent glycerin enema. Prokinetic medication has not shown any remarkable effect.3

The etiology of BTNIN has not been fully understood, but it could not be classified as the variants of Hirschsprung's disease or meconium related disorders. BTNIN occurs in the neonatal period with no association with birth weight or complications during pregnancy.3 Our results identified only one patient born at less than 35 weeks gestational age with a birth weight of 2.5 kg. Most patients with BTNIN showed normal appearance of ganglion cells without hyper- or hypoganglionosis. In addition, the clinical outcome of BTNIN in this study was more favorable than the other variants of Hirschsprung's disease.

The one possible cause of BTNIN was allergy-related disorder.4, 5 Kubota, et al.4 suggest that cow's milk allergy is the main cause of BTNIN. In their study, patients who were diagnosed with BTNIN showed a positive drug-induced lymphocyte stimulation test for cow's milk. The majority of these patients had symptom relief after conversion to formula. Allergic proctitis, a specific form of cow's milk allergy, could induce symptoms mimicking Hirschsprung's disease.5 Eosinophilic infiltration and inflammatory cell infiltration in the lamina propria of rectum have been identified, and rectal suction biopsy is very useful to differentiate this from other disorders.

However, our results did not support the aforementioned etiology. Although we had the limitation that allergy test for cow's milk was not performed, most patients in our study were breast-fed and improved without a formula change. Although cow's milk allergy could happen in breast-fed infants, the proportion of breast feeding in our study was too high to consider cow's milk allergy as the sole etiology of BTNIN.12 Allergic proctitis could not be considered as the possible cause of BTNIN because no patients showed eosinophilic infiltration in the rectal biopsies in our study. Considering that BTNIN occurs in the neonatal period and disappears with age, immaturity of the ganglion cells is suspected as the likely pathophysiology.13

In this retrospective study, we could not perform advanced histopathologic evaluations. Furthermore, the number of patients was not sufficient to generate any statistical results. These are also the limitations of this study. Nevertheless, we think that our results showed important clinical characteristics and management of BTNIN.

In summary, our data suggest that BTNIN has symptoms very similar to but should be differentiated from Hirschsprung's disease. Rectal biopsy and anorectal manometry were useful diagnostic tools. Patients with BTNIN had excellent outcomes with conservative treatment, and symptoms disappeared by 5 months of age. The pathophysiology of this disease is not fully understood, and further studies are required.