What is the diagnostic workup and management for a newborn or infant suspected of having Hirschsprung (congenital aganglionic megacolon) disease?

Workup for Hirschsprung Disease

For any newborn or infant with suspected Hirschsprung disease, rectal suction biopsy is the definitive diagnostic test and should be performed to confirm the diagnosis, as it is the gold standard for demonstrating the absence of ganglion cells in the intestinal wall. 1, 2

Clinical Presentation Requiring Evaluation

The most common presentation is a neonate with:

• Delayed passage of first meconium beyond 24-48 hours of life 3, 2
• Abdominal distension 2
• Bilious vomiting 3, 4
• Signs of distal intestinal obstruction 3

Importantly, only 10% of Hirschsprung cases present with the classic late findings of chronic constipation and megacolon, making early neonatal diagnosis critical to prevent life-threatening complications such as enterocolitis or toxic megacolon. 5

Initial Diagnostic Algorithm

Step 1: Plain Abdominal Radiographs

Plain abdominal radiographs should be obtained first to evaluate for bowel obstruction patterns, demonstrating dilated bowel loops, air-fluid levels, and presence or absence of distal gas. 3, 6 This helps distinguish proximal from distal obstruction and guides further workup.

Step 2: Contrast Enema

For suspected distal obstruction, contrast enema is the diagnostic imaging procedure of choice. 3, 6 The contrast enema may demonstrate:

• A transition zone between dilated proximal bowel and narrowed distal aganglionic segment 2, 7
• Microcolon due to lack of intestinal contents passing through 3, 6
• Delayed evacuation of barium beyond 24 hours 7

Critical caveat: The barium enema has significant limitations—80% sensitivity for detecting a transition zone, with 20% of infants with confirmed aganglionosis showing no roentgenographic transition zone, and 29% of suspected transition zones proving false-positive. 7 Therefore, contrast enema should be considered a screening tool only, not definitive for excluding Hirschsprung disease. 7

Step 3: Rectal Suction Biopsy (Definitive Diagnosis)

Rectal suction biopsy is the gold standard and must be performed for definitive diagnosis. 8, 1, 2, 7 The biopsy demonstrates:

• Absence of ganglion cells in the myenteric and submucosal plexuses 2
• Hypertrophied nerve fibers 1

Timing consideration: Traditional teaching suggests waiting until after the first month of age for rectal suction biopsy, though anorectal manometry can be performed weekly during the neonatal period if initial testing is positive (showing absent rectoanal inhibitory reflex), with biopsy confirmation at the end of the neonatal period. 8

Ancillary Histopathological Tests

When conventional hematoxylin-and-eosin staining is equivocal, complementary tests include:

• Acetylcholinesterase histochemistry (shows increased acetylcholinesterase-positive nerve fibers in aganglionic bowel) 1, 5
• Calretinin immunohistochemistry (absent in aganglionic segments) 1, 5

Alternative Diagnostic Tool: Anorectal Manometry

Anorectal manometry can be used as an initial screening test in neonates suspected of having Hirschsprung disease, demonstrating absence of the rectoanal inhibitory reflex. 8 This test has 99% sensitivity with only 0.9% false-negative rate. 8 Sedation significantly improves test quality, reducing non-useful studies from 8% to 2.97%. 8

Critical Pitfalls to Avoid

• Never rely solely on contrast enema to exclude Hirschsprung disease in a constipated infant—the 20% false-negative rate makes rectal biopsy mandatory when clinical suspicion remains high. 7
• Never delay surgical consultation for imaging studies in a neonate with peritoneal signs (tenderness, absent bowel sounds), as this suggests bowel ischemia or perforation requiring immediate intervention. 3
• Do not perform rectal suction biopsy before surgical evaluation in a neonate with acute peritoneal signs, as this suggests a more urgent surgical emergency. 3

Associated Conditions Requiring Evaluation

Screen for associated syndromes in confirmed Hirschsprung disease:

• Trisomy 21 (most common association) 2
• Mowat-Wilson syndrome 2
• Congenital central hypoventilation syndrome (CCHS) - requires assessment for Hirschsprung disease in patients with PHOX2B mutations, particularly PARM 20/26 and higher 9, 2
• Shah-Waardenburg syndrome 2

Genetic Testing Considerations

Full RET mutation screening should be performed only in cases of total colonic aganglionosis (TCA), where mutation rate reaches 70%. 5 For all other Hirschsprung patients, testing should be limited to standard MEN2A and MTC mutations to identify those at risk for neuroendocrine tumors requiring surveillance. 5

Immediate Management Priorities

While pursuing diagnostic workup:

• Nil per os (NPO) status 3
• Intravenous fluid resuscitation to correct dehydration and electrolyte abnormalities 3
• Nasogastric tube decompression 3
• Immediate pediatric surgical consultation for any neonate with bilious vomiting, as 20% have midgut volvulus requiring urgent surgery 3