Congenital Megacolon

History

• Age of presentation and accompanying symptoms are highly variable ^r4
  • Neonates
    • Failure to pass meconium in first 48 hours of life is a hallmark symptom ^c1
  • Infants (most patients present at this age)
    • Constipation, poor feeding, and progressive abdominal distention ^c2c3c4
    • Other symptoms may include the following:
      • Bilious emesis ^c5
      • Diarrhea ^c6
      • Failure to thrive ^c7
    • Less commonly, enterocolitis in infants is the first presentation, marked by fever, vomiting, explosive bowel movements, and abdominal distention ^c8c9c10c11
  • Older children
    • Chronic constipation (infrequency and difficulty) ^c12

Physical examination

• Abdominal distention and tenderness ^c13c14
• Tight anal sphincter ^c15
• Empty rectum ^c16
• Additional signs that occur with enterocolitis
  • Fever ^c17
  • Tachycardia ^c18
  • Hypotension ^c19

Causes

• Congenital absence of ganglion cells in submucosal (Meissner) and myenteric (Auerbach) plexuses in distal bowel, extending proximally for variable distances ^c20
  • 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 ^r6
  • Length of aganglionic bowel is variable, but always extends proximally from the rectum in a contiguous manner ^r6

Risk factors and/or associations

Primary diagnostic tools

• Suggestive history, genetic risk factors, and signs on physical examination may prompt further evaluation ^r4c47
  • 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 ^r4
• 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 ^r1r11

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 ^c48
  • 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 ^c49
  • 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 ^r12
  • Identification of transition zone also aids in preoperative planning ^r13
• Low-osmolality water-soluble contrast enema ^c50
  • 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 ^r14
    • Sensitivity approximately 70% ^r15r16
    • Specificity approximately 83% ^r15r16

Functional testing

• Anal manometry ^c51c52c53
  • 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 approximately 91% ^r16
    • Specificity is approximately 94% ^r16

Procedures

Other diagnostic tools

• Genetic testing for predicting associated medical problems ^r4c55
  • Approximately 30% of children with Hirschsprung disease have other medical problems due to associated genetic defects ^r4
  • Consider genetic evaluation as directed under the guidance of genetic counselors in children with apparent syndromic disease
  • Syndromic cases may be heralded by: ^r4
    • 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

Most common

• Other causes of failure to pass meconium
  • Benign transient nonorganic ileus of neonates ^r18c56
    • 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 ^r19c57
    • 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 ^r19
    • 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) ^r19c58c59c60
    • 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 ^r20c61
  • 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

Admission criteria

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

• Suspicion for or evidence of enterocolitis^r1, 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

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 ^r4

Drug therapy

• For empiric treatment of suspected enterocolitis (from Staphylococcus aureus, anaerobes, or coliforms) ^r2
  • Mild episodes (hemodynamically stable)
    • Metronidazole ^c62
      • Metronidazole Solution for injection; Neonates 34 weeks postmenstrual age and younger†: 7.5 mg/kg/dose IV every 12 hours for 7 to 10 days.
      • Metronidazole Solution for injection; Neonates 35 to 40 weeks postmenstrual age†: 7.5 mg/kg/dose IV every 8 hours 7 to 10 days.
      • Metronidazole Solution for injection; Neonates older than 40 weeks postmenstrual age†: 7.5 mg/kg/dose IV every 8 hours for 7 to 10 days.
      • Metronidazole Solution for injection; Infants†, Children†, and Adolescents†: 22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided 8 hours for 3 to 7 days.
  • Severe episodes (those with hemodynamic instability or sepsis) require broad-spectrum regimens using multiple drugs, such as the following 3-drug regimen:
    • Ampicillin ^c63c64c65
      • 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 ^c66c67c68c69
      • Gentamicin Sulfate 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 in combination with other appropriate antimicrobial agents.
      • Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV/IM every 18 hours in combination with other appropriate antimicrobial agents.
      • Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV/IM every 12 hours in combination with other appropriate antimicrobial agents; extend interval to 18 to 24 hours for neonates on ECMO with subsequent dosing based on serum concentrations.
      • Gentamicin Sulfate 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 in combination with other appropriate antimicrobial agents.
      • Gentamicin Sulfate Solution for injection; Neonates 8 to 29 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV/IM every 12 hours in combination with other appropriate antimicrobial agents.
      • Gentamicin Sulfate Solution for injection; Neonates 8 to 29 days weighing more than 2 kg: 2.5 mg/kg/dose IV/IM every 8 hours in combination with other appropriate antimicrobial agents; extend interval to 18 to 24 hours for neonates on ECMO with subsequent dosing based on serum concentrations.
      • Gentamicin Sulfate Solution for injection; Premature infants 30 days and older weighing less than 1.2 kg: 2.5 mg/kg/dose IV/IM every 18 hours in combination with other appropriate antimicrobial agents.
      • Gentamicin Sulfate Solution for injection; Infants: 2.5 mg/kg/dose IV/IM every 8 hours in combination with other appropriate antimicrobial agents for 4 to 7 days.
      • Gentamicin Sulfate Solution for injection; Children and Adolescents: 2 to 2.5 mg/kg/dose IV/IM every 8 hours in combination with other appropriate antimicrobial agents for 4 to 7 days.
    • Metronidazole ^c70c71c72c73
      • Metronidazole Solution for injection; Neonates 34 weeks postmenstrual age and younger†: 7.5 mg/kg/dose IV every 12 hours for 7 to 10 days.
      • Metronidazole Solution for injection; Neonates 35 to 40 weeks postmenstrual age†: 7.5 mg/kg/dose IV every 8 hours 7 to 10 days.
      • Metronidazole Solution for injection; Neonates older than 40 weeks postmenstrual age†: 7.5 mg/kg/dose IV every 8 hours for 7 to 10 days.
      • Metronidazole Solution for injection; Infants†, Children†, and Adolescents†: 22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided 8 hours for 3 to 7 days.

Nondrug and supportive care

IV fluids ^c74

Total parenteral nutrition for nutrient and calorie support if necessary ^c75

Gastrointestinal decompression if intestinal obstruction is present ^c76