Neonatal Small Left Colon Syndrome

Although the precise cause of this form of neonatal intestinal obstruction, which has a typical radiologic picture but is distinctly unusual, is unknown, numerous theories have been proposed, including neural, humoral, and drug-induced etiologic mechanisms.

In 1974, Davis et al reported the association of NSLCS with abnormalities of intestinal neurohistology.[5] Their initial report described increased numbers of immature small ganglion cells in the myenteric plexus (in both the narrowed and dilated portions of the colon) in four of 20 patients with NSLCS. They compared the histology from NSLCS patients with that from control subjects, including infants of diabetic mothers without colon changes, premature infants, and term infants.

Davis et al concluded that the hypercellularity observed in the specimens from patients with NSLCS most closely resembled the histology observed in the colons of premature infants.[5] Despite this conclusion, they did not provide gestational age data on the patients; therefore, at least some of them assumably were premature.

In 1991, Schofield et al reported an association in seven patients with clinical and radiographic NSLCS and suction rectal biopsy histology demonstrating intestinal neuronal dysplasia (IND).[6] In all seven cases, the biopsies, stained with hematoxylin and eosin (H&E) and acetylcholinesterase (AChE), demonstrated an increase in the number of AChE-stained fibers in the mucosa and increased submucosal ganglia or large ganglia. These changes are also observed with prematurity, and because most of the infants with NSLCS in this report were indeed premature, gestational age seems to have had a confounding effect on the biopsy results.

In a 1975 report, Philippart et al focused on humoral and autonomic nervous system changes, which occur in response to neonatal hypoglycemia, in developing a mechanistic explanation.[7]  Glucagon release and sympathoadrenal stimulation are typical responses to hypoglycemia in vivo, and both result in blood glucose stabilization through hepatic gluconeogenesis and glycogenolysis. Along with several effects on the gastrointestinal (GI) tract, glucagon release is known to decrease motility in the jejunum and left colon.

Hypoglycemia also stimulates sympathetic and parasympathetic arms of the autonomic nervous system. Maximal vagal (parasympathetic) stimulation results in increased motility in its area of distribution, which ends at the splenic flexure, whereas sympathetic stimulation results in diminished motility. Therefore, a composite effect of glucagon release with sympathetic and parasympathetic nervous system stimulation would hypothetically be an overall diminution in intestinal motility, with a functional block in the colon beyond the splenic flexure.

Philippart et al pointed out that precipitants other than hypoglycemia (eg, stress) may mediate the same changes through similar mechanisms, thereby explaining the phenomenon when it occurs in the absence of maternal diabetes mellitus.[7]

Other possible contributors to intestinal hypomotility include maternal drugs used during the third trimester that cross the placenta and affect the fetus. This concept is supported by the report of two cases of NSLCS in infants born to mothers using psychotropic drugs with known anticholinergic effects and the recognized association between hypermagnesemia (in infants born to eclamptic mothers treated with magnesium sulfate) and hypomotility conditions.

Although earlier reports of neonatal colonic obstruction undoubtedly included cases of NSLCS in the spectrum of obstructive conditions referred to as meconium plug syndrome, obstruction in NSLCS is not typically associated with the presence of a mucus or meconium plug in the distal constricted segment. No analytic abnormality has been reported in the meconium of infants with NSLCS, with the exception of a single case report of an infant with cystic fibrosis who presented with a meconium ileus–like obstruction at the splenic flexure with distal microcolon.

In contrast, the meconium in meconium plug syndrome is reported to have an elevated protein content with altered enzymatic activity, suggesting that the obstruction is caused by an immobile luminal obturator rather than mural constriction and diminished peristalsis.[8, 9]

A subsequent report illustrated the continued challenges of an accurate and etiologic diagnosis of the cause of neonatal meconium plug obstruction. This review of 21 neonates with meconium obstruction revealed eight patients (38%) with Hirschsprung disease, four (19%) with NSLCS, and nine (43%) with meconium plug syndrome.[10]

A specific relation has been identified between maternal diabetes and neonatal intestinal obstruction.[11] This was the subject of an analysis of an infant cohort born to diabetic mothers.[12] Of 105 offspring of diabetic mothers, six cases of intestinal obstruction (including a pair of twins) were reported with classic contrast enema findings of NSLCS. Of these, five responded to conservative treatment, and the sixth was found to have sigmoid Hirschsprung disease.

The frequency with which NSLCS occurs is difficult to estimate because the entire subject literature contains only case reports[13, 14] and a few case series.

In one institution's review of consecutive suction rectal biopsies performed in 456 pediatric patients (median age, 13 days) for symptoms of constipation, abdominal distention, and bloody stools, 61 cases of Hirschsprung disease (13%) were identified. The remaining cases included seven neonates who had a clinical and radiologic picture consistent with NSLCS. In this study cohort, the incidence of symptoms of distal intestinal obstruction, enterocolitis, or both was 1.5%.[6]

Most infants completely respond to contrast enema decompression and are able to progress quite rapidly to full enteral feedings. Numerous patients who have undergone follow-up examinations of their colon have demonstrated normalization of caliber within a few weeks. In a 1975 report, Philippart et al warned of the small number of patients who experience delayed complication, either recurrent or persistent obstruction or delayed perforation, mandating close surveillance during the first 1-2 weeks of life.[7]

The clinical features of infants described in seven English-language case series of neonatal small left colon syndrome (NSLCS) are summarized in Table 1 below.

Table 1. Clinical Features of Infants Described in English-Language Case Series of Neonatal Small Left Colon Syndrome (Open Table in a new window)

Most infants with NSLCS are born at or near term and are of normal birth weight. Approximately 50% have a history of maternal diabetes mellitus, and other maternal comorbidities (usually eclampsia), which contribute to neonatal stress, may also be present. All patients do not pass meconium within the first 24 hours of life, and they all develop abdominal distention with bilious vomiting or nasogastric aspirates. A small number of infants develop progressive distention leading to perforation, typically in the cecum, within the first 24-36 hours of life.

Basic laboratory investigations are indicated, including complete blood count (CBC) and differential, C-reactive protein (CRP), coagulation profiles, and blood cultures. Serum levels of glucose, calcium, and magnesium should be measured in infants of mothers with diabetes mellitus or eclampsia or in infants who otherwise appear stressed. Cross-matched blood should be available.

Two-view abdominal radiography should be promptly performed. Typically, distal intestinal obstruction with air-fluid levels is revealed (see the image below). Occasionally, infants (especially those in whom the recognition of intestinal obstruction has been delayed) have pneumoperitoneum on plain film radiography, which may be the result of a cecal perforation.

Supine shoot-through lateral abdominal radiograph of infant with abdominal distention, bilious nasogastric aspirates, and failure to pass meconium at 24 hours of life. Distended loops of bowel with air-fluid levels are evident.

If plain film radiography does not reveal perforation, the infant should undergo a contrast enema examination, usually with a water-soluble medium.[20] Because appropriate choice of contrast medium and sufficient experience with neonatal conditions are critical to the interpretive accuracy and safety of the examination, the contrast enema examination should be performed by a radiologist who has pediatric expertise.

The diagnosis of neonatal small left colon syndrome (NSLCS) on contrast enema examination is based on the following fluoroscopic findings (see the image below):

• Proximal dilation of the colon (and, to a lesser extent, the small bowel) with abundant intraluminal meconium
• Abrupt cone-shaped caliber transition at or just distal to the splenic flexure
• Constricted but smooth-contoured, and often foreshortened, descending and sigmoid colon devoid of meconium with a slightly larger-caliber rectum

Contrast enema of infant who presented with abdominal distention, bilious nasogastric aspirates, and failure to pass meconium at 24 hours of life demonstrates normal-caliber rectum and small-caliber sigmoid and descending colon, with abrupt caliber transition at splenic flexure. These findings are characteristic of neonatal small left colon syndrome (NSLCS). Supine shoot-through lateral abdominal radiograph had revealed distended loops of bowel with air-fluid levels.

Because Hirschsprung disease with a splenic flexure transition zone is clinically and radiologically indistinguishable from NSLCS, all infants must undergo a suction rectal biopsy to exclude aganglionosis. Cystic fibrosis that produces a colonic variant of meconium ileus should be considered, and the appropriate DNA testing should be performed, as well as a sweat chloride test when the infant is older, if appropriate.[21]

As discussed in subsequent sections, the indications for operation in neonatal small left colon syndrome (NSLCS) include intestinal perforation and failure of resolution of obstruction following contrast enema administration.

No absolute contraindications for surgical management of NSLCS are recognized. It must be kept in mind that the diagnosis is not definitive until Hirschsprung disease has been excluded by rectal biopsy findings; therefore, any surgical procedure must take into account this diagnostic similarity.

Apart from the need for a more definitive understanding of the pathophysiology of this condition, no real areas of controversy surround the treatment of NSLCS.

As for any newborn with intestinal obstruction, the first priority of treatment should include resuscitation, such as intravenous (IV) fluids, nasogastric decompression, and IV antibiotics (if clinically indicated). Once plain abdominal radiography has revealed a distal obstruction without pneumoperitoneum, the infant should undergo a contrast enema.

Fortunately, for most patients with NSLCS, the contrast enema is not only diagnostic of the condition but also therapeutic.[22] The vast majority of infants experience spontaneous passage of meconium after the examination, their abdominal distention resolves, and soon after, enteral feedings can be cautiously introduced and carefully advanced.

As noted above, it is important to exclude other diagnoses, even if the infant has the expected clinical response to a contrast enema; thus, a suction rectal biopsy and a workup for cystic fibrosis are always indicated.

Surgery is reserved for infants with intestinal perforation or for those in whom obstruction is refractory or recurrent despite appropriate conservative measures. Surgery in infants with intestinal perforation includes the following elements.

Following appropriate fluid, antibiotic, and, if necessary, blood product resuscitation, the infant is taken to the operating room and explored, usually through a transverse upper abdominal incision

Once the point of perforation has been identified, consideration should be given to determining the diagnosis because, in most cases, Hirschsprung disease still has not been excluded at this time

Provided that that the infant's condition is stable and a pathologist with the appropriate expertise is available, seromuscular biopsy samples from the distal colon, in what obviously would appear to be aganglionic bowel, should be obtained for frozen section examination. If a distal biopsy is aganglionic, biopsy samples should be obtained near the transition zone and proximally to localize the transition zone, and a stoma should be created in ganglionic bowel.

If the transition zone is at the splenic flexure, leaving the distal aganglionic bowel in place as a long Hartmann pouch is reasonable; however, if the transition zone is in the small bowel, a decompressive mucous fistula should be created. In cases of long segment disease, the aganglionic colon should be left undisturbed so as to preserve all subsequent reconstructive options.

In the rare case of intestinal perforation occurring after the diagnosis of Hirschsprung disease has been satisfactorily excluded, the safest operative strategy would involve a formal stoma or exteriorization of the perforation.

After the diagnosis of NSLCS has been adequately established, the need for surgical intervention seems unlikely. Historically, most operations have been performed because of a mistaken diagnosis of Hirschsprung disease. However, Philippart et al reported two patients who required delayed operations and did not have aganglionosis; one patient developed recurrent obstruction after initial successful enema decompression and required transition zone colostomy, and the other developed an obstruction with cecal perforation 6 days after institution of oral feedings.[7]