OVERVIEW: What every practitioner needs to know
Are you sure your patient has delayed passage of meconium? What are the typical findings for this disease?
Delayed passage of meconium, defined as failure of the newborn to pass meconium within 24-48 hours, is an important symptom in the neonate and warrants evaluation for disorders that lead to neonatal intestinal obstruction. In neonates, Hirschsprung disease is the most commonly considered among diseases that cause lower intestinal obstruction and delayed passage of meconium.
Meconium passage is expected within the first 24-48 hours of life in the term newborn. Premature neonates may have more delayed meconium passage, but this is still expected to occur within the first several days of life.
Any infant with delayed passage of meconium accompanied by vomiting, poor feeding, or abdominal distention should be evaluated urgently with a high index of suspicion for neonatal bowel obstruction. Availability of pediatric surgical expertise is highly recommended in this setting.
The most common presenting symptoms in Hirschsprung disease include delayed passage of meconium and abdominal distention. Other symptoms may include poor feeding, lethargy, vomiting, diarrhea, bloody stools, and constipation.
What physical examination findings are important in the evaluation of the neonate with delayed passage of meconium?
It is important that the practitioner carefully examine the baby for any evidence of a congenital anorectal malformation, which may also present with delayed passage of meconium. Examination findings may include imperforate anus with or without fistulous communication to the perineum, anal stenosis, or displacement of the anal sphincter (Figure 1, Figure 2, Figure 3). Evaluation and management of a neonate with congenital anorectal malformation requires pediatric surgical expertise.
What other disease/condition shares some of these symptoms?
Differential diagnosis of the neonate with delayed passage of meconium
Meconium plug syndrome
Cystic fibrosis with meconium ileus
Small left colon syndrome
Rare motility disorders
Neuronal intestinal dysplasia
Megacystis-microcolon intestinal hypoperistalsis syndrome
What caused this disease to develop at this time?
In Hirschsprung disease, congenital absence of ganglion cells leads to a functional obstruction of the affected intestine. Hirschsprung disease most commonly involves the rectosigmoid colon, but aganglionosis may extend proximally to the small intestine (long segment) in 10% of patients.
Motility failure in the affected segment leads to symptoms and findings of obstruction proximal to the aganglionotic bowel.
The classic neonatal presentation is delayed passage of meconium with abdominal distention or neonatal-onset constipation.
Hirschsprung-associated enterocolitis may present with vomiting, diarrhea (occasionally with microscopic or visible blood), abdominal distention, or lethargy/shock.
Physical examination reveals a rectum that is empty of stool, and there may be narrowing of the anorectal canal. An explosive release of stool and gas often follows digital rectal examination.
What laboratory or clinical studies should you request to help confirm the diagnosis? How should you interpret the results?
Hirschprung disease should be suspected based on clinical presentation and physical examination. Imaging studies may be helpful.
Anorectal manometry reveals failure of anal sphincter relaxation despite rectal distention in patients with Hirschsprung disease.
The diagnosis of Hirschsprung disease is confirmed by rectal biopsy. Histologic diagnosis confirms the absence of ganglion cells within the submucosal layers of the rectum. Associated findings may include hypertrophic nerve fibers.
If Hirschsprung disease is excluded in a neonate with delayed meconium passage, a sweat chloride test may be helpful to evaluate for cystic fibrosis (CF) if clinically suspected. In some centers, CF genotyping may be preferred to evaluate for CF in infants.
Would imaging studies be helpful? If so, which ones?
Plain abdominal radiography may demonstrate diffusely dilated loops of bowel. There may be a paucity of gas in the rectum. These findings are suggestive of lower intestine obstruction (Figure 4). Contrast enema is an important evaluation in the neonate with suspected lower intestine obstruction. The classic finding in Hirschsprung disease is a transition zone. Twenty-five percent of neonates with Hirschprung disease may have normal barium enema findings, as the proximal bowel has not distended enough to demonstrate a transition zone (Figure 5).
In meconium plug syndrome, contrast enema reveals a filling defect (meconium plug) in the lumen. Contrast enema may facilitate evacuation of the meconium plug, thus the study may be therapeutic as well as diagnostic (Figure 6).
In meconium ileus and ileal atresia, contrast enema reveals a microcolon (Figure 7 and Figure 8).
Confirming the diagnosis
Rectal biopsy is the gold standard for diagnosis of Hirschsprung disease. If this disease is suspected in a neonate with delayed passage of meconium, even in the setting of normal imaging studies, rectal biopsy should be considered.
If you are able to confirm that the patient has Hirschsprung disease, what treatment should be initiated?
Surgical treatment is the definitive therapy for Hirschsprung disease. Historically, this surgery typically involved diversion by colostomy until the proximal bowel had decompressed, followed by definitive resection. In the current era, surgical management is typically performed through a one- or two-stage pull-through, which may be performed transabdominally (by laparotomy or with laparoscopic assistance) or transanally by the endorectal approach.
Preoperative management involves stabilization of the patient. If enterocolitis is suspected, management involves rectal irrigation using a catheter for colonic decompression, initiation of broad spectrum antibiotics, and fluid resuscitation.
What are the adverse effects associated with each treatment option?
Long-term complications after pull-through surgery include risks of recurrent enterocolitis, stenosis, malabsorption, dysmotility, and a spectrum of stooling abnormalities.
Enterocolitis may occur in 10-40% of patients after pull-through surgery. Presentation includes diarrhea with or without blood, and may be accompanied by abdominal distention or lethargy.
Some patients acquire anorectal stenosis, which may require anal dilation, myectomy, or myotomy.
Diarrhea and malabsorption may occur in the initial period after surgery, but this typically improves over time as colonic caliber and function normalizes. Patients with long-segment aganglionosis may have chronic malabsorption associated with short bowel syndrome.
Abnormal stooling patterns, including constipation, delayed toilet training, and incontinence are frequent outcomes after surgical therapy for Hirschsprung disease.
What are the possible outcomes of delayed passage of meconium?
Ninety-nine percent of healthy term newborns should pass meconium within 24 hours, and all term newborns should pass meconium within 48 hours. If delayed passage of meconium (beyond 48 hours) is encountered, the practitioner should aggressively consider important causes, including Hirschsprung disease.
Earlier recognition of Hirschsprung disease has improved morbidity and mortality. Most children have a good outcome immediately after surgical repair. Long-term morbidity and mortality after surgical repair of Hirschsprung disease is higher when enterocolitis develops, sometimes in the setting of a retained aganglionotic segment or stricture.
Constipation or abnormal stooling may persist in up to 85% of patients less than 5 years old. Longer term outcome data are supportive of normalization of bowel habits in the majority of patients. Fecal soiling may occur in some patients (caused by either constipation with fecal overflow or incontinence). Fecal soiling is an important negative impact on both patient and caregiver quality of life.
What causes this disease and how frequent is it?
Hirschprung disease affects 1/5000 live births, affecting males more than females (4:1 ratio). There is not a single genetic defect associated with Hirschsprung disease. However, several genetic syndromes (including Down syndrome) are known to have an association. Twelve percent of patients with Hirschsprung disease have an associated chromosomal anomaly, and approximately 5% of all patients with Hirschsprung disease have Down syndrome.
In normal embryologic development, ganglion cells migrate caudally along the gastrointestinal tract between the 5th and 12th weeks of gestation. Incomplete migration of ganglion cells leads to failure of the enteric nervous system in the affected area.
Mutations in the RET gene have been detected in cases of familial or long-segment Hirschsprung disease. These mutations may affect migration of neural crest cells.
How can Hirschsprung disease be prevented?
At present, no preventive treatment is available for Hirschsprung disease. Earlier recognition of Hirschsprung disease and its complications, including enterocolitis, is associated with improved outcomes.
What is the evidence?
Clark, DA. “Times of first void and first stool in 500 newborns”. Pediatrics. vol. 60. 1977. pp. 457-9.
Aboagye, J, Goldstein, SD, Salazar, JH, Papandria, D. “Age at presentation of common pediatric surgical conditions: Reexamining dogma”. J Pediatr Surg. vol. 49. 2014. pp. 995-9. (This "big data" review re-examines the typical age of recognition/presentation for Hirschsprung’s disease and suggests a somewhat later presentation during the first year of life.)
Garcia, R, Arcement, C, Hormaza, L. “Use of the recto-sigmoid index to diagnose Hirschsprung’s disease”. Clin Pediatr (Phila). vol. 46. 2007. pp. 59-63.
Lewis, NA, Levitt, MA, Zallen, GS. “Diagnosing Hirschsprung’s disease: increasing the odds of a positive rectal biopsy result”. J Pediatr Surg. vol. 38. 2003. pp. 412-6.
Schäppi, MG, Staiano, A, Milla, PJ, Smith, VV. “A practical guide for the diagnosis of primary enteric nervous system disorders”. J Pediatr Gastroenterol Nutr. vol. 57. 2013. pp. 677-86. (This clinical review offers a concise and current summary of the pathophysiology of Hirshsprung’s disease and associated disorders, and it focuses on clinical evaluation, including radiographic and histopathological diagnostic tools.)
Langer, JC. “Laparoscopic and transanal pull-through for Hirschsprung disease”. Semin Pediatr Surg. vol. 21. 2012. pp. 283-90. (Excellent and timely summary of current surgical techniques.)
Rintala, RJ, Pakarinen, MP. “Long-term outcomes of Hirschsprung’s disease”. Semin Pediatr Surg. vol. 21. 2012. pp. 336-43. (This review offers a current summary of long-term surgical outcomes.)
Levitt, MA, Dickie, B, Peña, A. “The Hirschsprungs patient who is soiling after what was considered a "successful" pull-through”. Semin Pediatr Surg. vol. 21. 2012. pp. 344-53. (Updated clinical approach to post-pull-through incontinence.)
More, K, Rao, S, McMichael, J, Minutillo, C. “Growth and developmental outcomes of infants with hirschsprung disease presenting in the neonatal period: a retrospective study”. J Pediatr. vol. 165. 2014. pp. 73-77. (A novel look at short term outcomes (12 months) in infants with typical presentation and surgical management, confirming the clinical observation that the majority of these infants have ongoing gastrointestinal symptoms despite normal growth and development.)
Langer, JC. “Hirschsprung disease”. Curr Opin Pediatr. vol. 25. 2013. pp. 368-74. (Excellent review tailored towards the general pediatrician, with a focus on surgical management and outcomes.)
Kenny, SE, Tam, PK, Garcia-Barcelo, M. “Hirschsprung’s disease”. Semin Pediatr Surg. vol. 19. 2010. pp. 194-200.
Amiel, J, Lyonnet, S. “Hirschsprung disease, associated syndromes, and genetics”. J Med Genet. vol. 38. 2001. pp. 729-39.
Bergeron, KF, Silversides, DW, Pilon, N. “The developmental genetics of Hirschsprung’s disease”. Clin Genet. vol. 83. 2013. pp. 15-22.
Kim, JH, Cheong, HS, Sul, JH, Seo, JM. “A genome-wide association study identifies potential susceptibility loci for Hirschsprung disease”. PLoS One. vol. 9. 2014. (Utilizing GWAS, this study confirms and expands the current understanding of RET mutation and Hirschsprung’s pathogenesis.)
Ongoing controversies regarding etiology, diagnosis, treatment
The majority of outcome data in pediatric Hirschsprung disease is based on single-center experience. Evaluation of which surgical approaches are associated with improved short- and long-term outcomes has not clearly identified one approach versus another. Therefore, clinical decision making is largely guided by surgical expertise and preferences. As longer term outcomes—including bowel function, continence, and quality of life—are better assessed, a decidedly more optimal surgical procedure may be identified.
Further translation research regarding the molecular genetics of Hirschsprung disease may help in understanding the development of the enteric nervous system and may further provide a new direction of management of patients with Hirschsprung disease through gut neural crest cell transplantation.
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- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has delayed passage of meconium? What are the typical findings for this disease?
- What other disease/condition shares some of these symptoms?
- What caused this disease to develop at this time?
- What laboratory or clinical studies should you request to help confirm the diagnosis? How should you interpret the results?
- Would imaging studies be helpful? If so, which ones?
- Confirming the diagnosis
- If you are able to confirm that the patient has Hirschsprung disease, what treatment should be initiated?
- What are the adverse effects associated with each treatment option?
- What are the possible outcomes of delayed passage of meconium?
- What causes this disease and how frequent is it?
- How can Hirschsprung disease be prevented?
- What is the evidence?
- Ongoing controversies regarding etiology, diagnosis, treatment