Congenital Megacolon

6 Interesting Facts of Congenital Megacolon 

1. Congenital megacolon is defined by the absence of enteric neurons in the distal colon
2. Age of presentation and the type of symptoms that occur vary dramatically among patients
   • Failure to pass meconium within 48 hours of delivery is the classic presentation of congenital megacolon in neonates
   • After newborn period, infants typically present with abdominal distention, vomiting, and constipation
3. Barium enema showing transition zone and anal manometry showing absence of rectosphincteric reflex strongly suggest diagnosis
4. Rectal biopsy is necessary to confirm diagnosis 
5. Surgical resection of aganglionic, denervated colon segment is definitive treatment (but not curative)
6. Main complication is enterocolitis (both preoperatively and postoperatively)
   • Following hospital admission, treat patients with Hirschsprung-associated enterocolitis with IV resuscitation, broad-spectrum IV antibiotics, and saline rectal washouts 

Pitfalls

• Failure to recognize enterocolitis in a child with congenital megacolon can lead to sepsis and death
• Rectal biopsy is not recommended during acute bowel obstruction or infection owing to high risk of perforation 

• Congenital megacolon is a disease of colonic dysmotility most commonly presenting with failure to pass meconium and symptoms and signs of large bowel obstruction 
  • Defining developmental birth defect in which the enteric nervous system is missing from the distal bowel 
• Also referred to as Hirschsprung disease or congenital aganglionic megacolon

Classification 

• Short-segment disease (most common; 85% of cases)
  • Confined to rectosigmoid region of colon
• Long-segment disease (10%)
  • Extends past rectosigmoid region to splenic flexure
• Total colonic aganglionosis (about 5%)
  • Affects entire colon

Clinical Presentation

History

• Age of presentation and accompanying symptoms are highly variable 
• Neonates
  • Failure to pass meconium in first 48 hours of life is a hallmark symptom
• Infants (most patients present at this age)
  • Constipation, poor feeding, and progressive abdominal distention
  • Other symptoms may include the following:
    • Bilious emesis
    • Diarrhea
    • Failure to thrive
  • Less commonly, enterocolitis in infants is the first presentation, marked by fever, vomiting, explosive bowel movements, and abdominal distention
• Older children
  • Chronic constipation (infrequency and difficulty)

Physical examination

• Abdominal distention and tenderness
• Tight anal sphincter
• Empty rectum
• Additional signs that occur with enterocolitis
  • Fever
  • Tachycardia
  • Hypotension

Causes

• Congenital absence of ganglion cells in submucosal (Meissner) and myenteric (Auerbach) plexuses in distal bowel, extending proximally for variable distances
  • Caused by failure of ganglion cells to migrate cephalocaudally through neural crest during weeks 4 to 12 of gestation
  • Absence of parasympathetic plexuses in the affected bowel causes incomplete distention and spasmodic contractions, leading to functional obstruction with upstream bowel dilation 
  • Length of aganglionic bowel is variable, but always extends proximally from the rectum in a contiguous manner 

Risk factors and/or associations

Age

• 80% of patients present in first few months of life 
• 15% of cases remain undiagnosed until age 5 years 
• Rarely, patients remain asymptomatic until adolescence

Sex

• More common in males than in females (2:1) 

Genetics

• Inheritance pattern is nonmendelian, multigenic, and partially penetrant 
• Germline inactivating mutations in RET gene (ret proto-oncogene) are associated with approximately 50% of familial cases and 20% of sporadic cases 
  • Very rarely (in approximately 2% of children), an activating mutation of RET will cause congenital megacolon and multiple endocrine neoplasia type 2 
• Germline mutations in genes EDNRB (endothelin receptor type B) and EDN3 (endothelin 3) account for 10% of cases 

Other risk factors/associations

• About 30% of children have serious medical problems as a manifestation of other genetic defects and could include: 
  • Down syndrome
  • Smith-Lemli-Opitz syndrome
  • Congenital deafness
  • Hydrocephalus
  • Meckel diverticulum
  • Imperforate anus
  • Ventricular septal defect
  • Congenital anomalies of kidney and urinary tract
  • Cryptorchidism
  • Waardenburg syndrome (pigment defects associated with deafness)
  • Neuroblastomas
  • Ondine curse (primary alveolar hypoventilation)
  • Congenital central hypoventilation syndrome
  • Mowat-Wilson syndrome
  • Bardet-Biedl syndrome

Diagnostic Procedures

Primary diagnostic tools

• Suggestive history, genetic risk factors, and signs on physical examination may prompt further evaluation 
  • In neonates, delayed meconium passage (no bowel movement for more than 48 hours after birth) or neonatal bowel perforation should raise suspicion of the disease
  • In older children, intractable constipation (ie, dependence on enemas or suppositories to pass stool) should raise suspicion
  • Combination of growth failure and abdominal distention should raise suspicion
  • Positive family history (parent, sibling) of congenital megacolon
  • Trisomy 21 plus any symptoms (threshold for evaluation lowered due to significantly elevated risk)
• Imaging studies are the second step, followed by rectal biopsy, which is required to confirm the diagnosis
• Begin diagnostic investigation with imaging when disease is suspected, as follows:
  • Plain radiography to determine if there is bowel obstruction; however, a negative finding does not rule out congenital megacolon
  • Barium enema or water-soluble contrast enema (perform in all suspected cases) to show dilated colon proximal to aganglionic region
  • Contrast enema can be interpreted as normal in approximately 20% of infants with the disease; false-positive contrast enema results also occur frequently, so imaging alone cannot be used to exclude or make a diagnosis 
• Anal manometry can be used as a diagnostic aid in stable patients, although it is not required
  • Most useful in neonates or patients with short-segment disease
  • Also useful to rule out the disease
• Rectal biopsy is gold standard to secure diagnosis in all patients 

Imaging

• Imaging starts with plain radiograph, followed by either barium or water-soluble contrast enema; imaging alone does not verify diagnosis, which requires rectal biopsy
• Plain radiography of abdomen
  • Widely dilated colon with multiple air-fluid levels and narrow distal segment may signify bowel obstruction; if this finding is absent, further testing is still indicated
• Barium enema
  • Standard imaging mode to evaluate for congenital megacolon
  • Identification of a transition zone (funnel-shaped region evident in the change from dilated colon proximally to narrowed aganglionic segment distally) is highly suggestive 
  • Identification of transition zone also aids in preoperative planning 
• Low-osmolality water-soluble contrast enema
  • Best study to evaluate for transition zone between normal and aganglionic bowel
  • Preferred study (compared with barium enema) when there is suspected perforation or a high risk for perforation
  • Accuracy similar to that of barium enema, but inferior to those of rectal suction biopsy or anal manometry 
    • Sensitivity about 70% 
    • Specificity about 83% 

Functional testing

• Anal manometry
  • Used as diagnostic aid in children when there is concern for congenital megacolon
    • Not necessary for diagnosis but can be useful to exclude the disease
  • Test records anal pressure changes during and after rectal distention with a balloon
  • Interpretation of results
    • Normal result: rectosphincteric reflex is elicited with distention
    • Positive result: absence of rectosphincteric reflex is indicative of congenital megacolon
  • Test is accurate but requires specialized expertise that may be available only in certain centers
    • Sensitivity is about 91% 
    • Specificity is about 94% 

Procedures

• General explanation
  • Tissue sample is acquired and submitted for histopathologic analysis with acetylcholinesterase staining
  • Gold standard for definitive diagnosis
  • High accuracy for diagnosis in infants aged 40 days or older
    • Sensitivity is about 93% 
    • Specificity is about 98% 
• Indication
  • Infant or child with suggestive clinical and/or radiologic findings
  • Done to confirm diagnosis in all patients 
• Contraindications
  • Active infection (eg, enterocolitis)
  • Acute bowel obstruction
  • Bleeding diathesis
• Interpretation of results
  • Absence of ganglion cells in Meissner and Auerbach plexuses confirms diagnosis

Other diagnostic tools

• Genetic testing for predicting associated medical problems
  • About 30% of children with Hirschsprung disease have other medical problems due to associated genetic defects 
  • Consider genetic evaluation as directed under the guidance of genetic counselors in children with apparent syndromic disease
  • Syndromic cases may be heralded by:
    • Sensorineural deafness and pigmentation defects
    • Central apnea
    • Short stature with alopecia and immunodeficiency
    • Kidney, heart, or immune system problems
    • Polydactyly, obesity, intellectual disability
    • Multiple organ malformations
    • Craniofacial defects

Differential Diagnosis

Most common

• Other causes of failure to pass meconium
  • Benign transient nonorganic ileus of neonates
    • Similar to congenital megacolon in that it presents in an infant aged 2 to 4 weeks with abdominal distention, emesis, and constipation
    • Difficult to distinguish from congenital megacolon on the basis of symptoms, examination, and even barium enema
    • Usually requires anal manometry and/or rectal biopsy to differentiate
      • Anal manometry shows normal rectoanal inhibitory reflex in benign transient nonorganic ileus of neonates
      • Rectal biopsy identifies ganglion cells in the distal rectum in benign transient nonorganic ileus of neonates
  • Meconium plug
    • Transient distal colonic or rectal obstruction caused by inspissated, immobile meconium
    • Different from congenital megacolon by virtue of resolution of symptoms and normalization of bowel movements after the plug is passed
    • Contrast enema is diagnostic and therapeutic
    • Differentiate from congenital megacolon by barium enema or water-soluble contrast enema
  • Meconium ileus
    • Impaction of thick, tenacious meconium in distal small bowel
    • Different from congenital megacolon by virtue of abdominal distention at birth, increasing within hours
    • On plain radiograph, in right lower abdomen, meconium is seen mixed with air, producing a ground-glass appearance
    • Differentiate from congenital megacolon by plain radiographs, barium enema, or water-soluble contrast enema
  • Anorectal malformation (anal stenosis, imperforate anus)
    • Anatomic anomalies of the lower intestinal tract, due to failure of embryologic development
    • Similar to congenital megacolon in that it presents with abdominal distention and inability to pass meconium
    • Different from congenital megacolon by virtue of anal anatomy
    • Differentiate from congenital megacolon by physical examination, which identifies external malformations in anorectal area
• Constipation
  • Similar to congenital megacolon in the difficulty or failure to pass stool
  • Different from congenital megacolon by virtue of onset after age 6 months, absence of lower intestinal obstruction, and no chronic abdominal distention or failure to thrive
  • Differentiate from congenital megacolon by presence of stool in rectum on examination and, if needed, by absence of signs of obstruction on plain abdominal radiograph

Treatment Goals

• Manage acute bowel obstruction
  • Correct volume deficits and restore electrolyte balance
  • Decompress gastrointestinal tract
• Recognize and eradicate any coexisting infections (eg, enterocolitis)
• Initial surgical goal is to eliminate functional obstruction caused by aganglionic bowel
• Ultimate surgical goal is to reconstruct the intestine, connecting normally innervated bowel to the anal opening

Disposition

Admission criteria

Admit infants and children with the following conditions, to stabilize before surgery:

• Suspicion for or evidence of enterocolitis, when the following occur:
  • Signs and symptoms of dehydration
  • Evidence of electrolyte imbalance
  • Evidence of bowel obstruction
• Failure to thrive and severe hypoproteinemia
• Urinary retention

Criteria for ICU admission

• Hemodynamic instability
• Sepsis due to enterocolitis

Recommendations for specialist referral

• Consult pediatric general or gastrointestinal surgeon for suspected congenital megacolon
• Consider referral to genetic counselor for risk assessment of disease in siblings 

Treatment Options

Surgery is required for definitive treatment

Antibiotics are given for any cases of suspected enterocolitis

Supportive care includes IV fluids and, if obstruction makes them necessary, total parenteral nutrition and gastrointestinal decompression

Drug therapy

• For empiric treatment of suspected enterocolitis (from Staphylococcus aureus, anaerobes, or coliforms) 
  • Mild episodes (hemodynamically stable)
    • Metronidazole
      • Metronidazole Solution for injection; Neonates 34 weeks postmenstrual age and younger†: 15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.
      • Metronidazole Solution for injection; Neonates 35 to 40 weeks postmenstrual age†: 15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Neonates older than 40 weeks postmenstrual age†: 15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Infants†, Children†, and Adolescents†: 22.5 to 40 mg/kg/day IV divided every 6 to 8 hours (Max: 4 g/day).
  • Severe episodes (those with hemodynamic instability or sepsis) require broad-spectrum regimens using multiple drugs, such as the following 3-drug regimen:
    • Ampicillin
      • Ampicillin Sodium Solution for injection; Neonates 34 weeks gestation and younger and 0 to 7 days: 50 mg/kg/dose IV every 12 hours for 7 to 10 days.
      • Ampicillin Sodium Solution for injection; Neonates 34 weeks gestation and younger and older than 7 days: 75 mg/kg/dose IV every 12 hours for 7 to 10 days.
      • Ampicillin Sodium Solution for injection; Neonates older than 34 weeks gestation: 50 mg/kg/dose IV every 8 hours for 7 to 10 days.
      • Ampicillin Sodium Solution for injection; Infants, Children, and Adolescents: 100 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 hours for 3 to 7 days.
    • Gentamicin
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV/IM every 18 to 24 hours. FDA-approved dosage is 2.5 mg/kg/dose IV/IM every 12 hours.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV/IM every 12 to 18 hours.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV/IM every 12 hours; extend interval to 18 to 24 hours for neonates on ECMO. Individualize subsequent dosing based on serum concentrations. Dosage adjustment needed after decannulation.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 8 to 29 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV/IM every 18 to 24 hours. FDA-approved dosage is 2.5 mg/kg/dose every 8 hours.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV/IM every 8 to 12 hours.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV/IM every 8 hours; extend interval to 18 to 24 hours for neonates on ECMO. Individualize subsequent dosing based on serum concentrations. Dosage adjustment needed after decannulation.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Infants: 2.5 mg/kg/dose IV/IM every 8 hours.
      • Gentamicin Sulfate, Sodium Chloride Solution for injection; Children and Adolescents: 2 to 2.5 mg/kg/dose IV/IM every 8 hours.
    • Metronidazole
      • Metronidazole Solution for injection; Neonates 34 weeks postmenstrual age and younger†: 15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.
      • Metronidazole Solution for injection; Neonates 35 to 40 weeks postmenstrual age†: 15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Neonates older than 40 weeks postmenstrual age†: 15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.
      • Metronidazole Solution for injection; Infants†, Children†, and Adolescents†: 22.5 to 40 mg/kg/day IV divided every 6 to 8 hours (Max: 4 g/day).

Nondrug and supportive care

IV fluids

Total parenteral nutrition for nutrient and calorie support if necessary

Gastrointestinal decompression if intestinal obstruction is present

Procedures

Pull-through surgery

General explanation

• Resects aganglionic colon segment and connects the normally innervated bowel with anastomosis to an area just above the anus, at a level that prevents further functional obstruction but preserves fecal continence
• Surgical approaches: 2 are common
  • Transanal (most widely used)
  • Laparoscopic abdominal: used in children with transition zones proximal to sigmoid colon
• Outcomes: Bowel function improves and obstruction is relieved for most patients with either approach 

Indication

• Hemodynamically stable infant with congenital megacolon

Contraindications

• Sepsis
• Severe malnutrition, as defined by the following:
  • Very low weight for height (below −3 standard deviation score from median growth standards)
  • Visible severe wasting
  • Presence of nutritional edema
• Intestinal perforation

Complications

• Persistent bowel symptoms, especially constipation (approximately 15% at age 3 years) 

Monitoring

• Children with congenital megacolon should receive regular follow-up to adulthood within the context of an interdisciplinary care team led by a pediatric surgeon 
  • Follow up more frequently during first year of life, and maintain regular contact every 1 to 2 years thereafter 

Complications

• Enterocolitis
  • Occurs preoperatively or at diagnosis in up to 26% of cases and as a postoperative complication in about 15%
  • Diagnosis is largely clinical, on the basis of history, physical examination, and radiographic findings 
  • Symptoms include fever, vomiting, and diarrhea with explosive, foul-smelling bowel movements 
  • Examination shows abdominal distention, with explosive discharge of gas and stool on rectal examination 
  • Features on plain abdominal radiography include 1 or more of the following: 
    • Multiple air-fluid levels
    • Dilated loops of bowel
    • Sawtooth appearance with irregular mucosal lining
    • Cutoff sign in rectosigmoid colon with absence of distal air
    • Pneumatosis
  • Suspect Hirschsprung-associated enterocolitis in patients with 4 or more points from the Pastor et al. Hirschsprung-associated enterocolitis score items 
  • Toxic megacolon (acute dilation of colon) can complicate enterocolitis
  • Following hospital admission, treat patients with Hirschsprung-associated enterocolitis with IV resuscitation, broad-spectrum IV antibiotics, and saline rectal washouts 
  • European Reference Network for rare inherited and congenital digestive anomalies recommends intersphincteric botulinum toxin injections for patients with recurrent or persistent symptoms of outlet obstruction and/or Hirschsprung-associated enterocolitis 
• Postoperative
  • Soiling or frank incontinence (about 25%; usually the former)
  • Enterocolitis (about 15%)
  • Constipation (about 10%)
  • Anastomotic stricture (about 7%)

Prognosis

• Untreated disease can cause death in childhood owing to bacteremia that occurs as a result of bowel inflammation (enterocolitis) or bowel perforation 
• Most patients attain satisfactory bowel function after surgery (85.7% in a large series) 
• Some achieve completely normal bowel function after surgery (21.4% in a large series) 

References

Kyrklund K et al: ERNICA guidelines for the management of rectosigmoid Hirschsprung’s disease. Orphanet J Rare Dis. 15(1):164, 2020