A 12-hour-old term infant has an episode of bilious emesis after feeding. He has voided but has not passed meconium. On exam, he appears uncomfortable with abdominal distension and tenderness, hyperactive bowel sounds, and a patent anus. An abdominal radiograph shows dilated bowel suggestive of a distal obstruction. A contrast enema is also obtained (Figure 1). He develops fulminant peritonitis with Escherichia coli sepsis and is emergently taken to the operating room for an exploratory laparotomy.
Figure 1: Contrast enema in the infant from the question vignette. From: Anders A, Vachharajani A, Ramachandran V. Term newborn with abdominal distention and bilious emesis. Neoreviews. 2022;23(7):e497. 10.1542/neo.23-6-e3631
Which of the following diagnoses is most likely associated with this finding?
- Congenital hypothyroidism
- Cystic fibrosis
- Heterotaxy syndrome
- Trisomy 21
Answer: B. Cystic fibrosis
The contrast enema shown in Figure 1 reveals a diffuse microcolon with filling defects secondary to inspissated meconium, which is most consistent with a meconium ileus.1 Additional imaging demonstrated a normal rectosigmoid ratio of 1.2. The infant developed peritonitis and septic shock with subsequent bowel perforation requiring double-barrel ostomy formation. He was diagnosed with cystic fibrosis (Option B) after genetic testing revealed a pathogenic mutation in the cystic fibrosis transmembrane regulator (CFTR) gene.1
Cystic fibrosis (Option B) is an autosomal recessive multi-organ disease caused by a genetic mutation that results in an abnormal CFTR protein and subsequent dysregulated chloride and bicarbonate transport.2,3 In the intestinal tract, abnormal bicarbonate secretion creates an acidic and dehydrated intestinal lumen, resulting in thick, tenacious meconium that causes a small bowel obstruction typically involving the terminal ileus, known as meconium ileus.4 Meconium ileus develops in utero and represents one of the earliest clinical manifestations of cystic fibrosis.2 Infants present with symptoms within the first 48 hours after birth with variable manifestations ranging from bilious emesis, abdominal distension, and failure to pass meconium to fulminant segmental volvulus, ischemic necrosis, and meconium peritonitis.2,3 Radiographic findings include diffuse dilation of the small bowel proximal to the obstruction and peritoneal calcifications if the perforation occurs in utero.
In patients with meconium ileus, a contrast enema will demonstrate a diffuse microcolon with filling defects representing inspissated meconium within the lumen (Figure 2).3 In mild cases, a contrast enema can be both diagnostic and therapeutic, whereas in more complex cases, surgical exploration with enterotomy or small bowel resection with ostomy formation may be needed.3 Importantly, up to 90% of neonates presenting with meconium ileus are ultimately diagnosed with cystic fibrosis. As such, this clinical presentation warrants further evaluation, including serum immunoreactive trypsinogen levels that are measured on the newborn screen, followed by confirmatory whole CFTR gene sequencing and/or a sweat chloride test.4
Figure 2: Contrast enema demonstrating a diffuse microcolon with small filling defects (white arrow) in the proximal colon due to inspissated meconium. From: Ngo A, Phillips G. Radiologic approach to the diagnosis of bowel emergencies in neonates. Neoreviews. 2018;19(10):e594
Congenital hypothyroidism (Option A) represents a group of disorders caused by decreased levels of biologically active thyroid hormone that can lead to severe developmental delay and irreversible brain damage if left untreated.5 Signs and symptoms are often nonspecific, including coarse facial features with a widened anterior fontanelle, macroglossia, umbilical hernia, poor feeding, prolonged jaundice, and goiter.5 Affected patients can present with transient colonic obstruction of the newborn (TCON), often referred to as small left colon syndrome or meconium plug syndrome.3 TCON is secondary to functional immaturity of the ganglion cells in the descending colon, mimicking a distal bowel obstruction. In addition to congenital hypothyroidism, TCON may be associated with maternal diabetes and hypermagnesemia, which is often seen in infants born to mothers treated for pre-eclampsia.3
Infants with small left colon syndrome present with abdominal distension, bilious emesis, failure to pass meconium with nonspecific radiographic findings of dilated bowel loops with or without air-fluid levels, and no rectal gas.3 A contrast enema would reveal a small left colon with a normal rectosigmoid diameter (Figure 3).3,6 Infants with a small left colon should be evaluated for congenital hypothyroidism if no other risk factors are present. The infant in this question had evidence of a diffuse microcolon, which is more consistent with meconium ileus, instead of an isolated small descending colon, which is seen in patients with TCON.
Figure 3: Contrast enema demonstrating a small left colon with multiple intraluminal defects (white arrow) suggestive of meconium plugs and a normal rectosigmoid ratio in an infant with transient colonic obstruction. From: Lyle A, Byrne B. Abdominal distension in a term infant with unilateral ventriculomegaly. Neoreviews. 2019;20(10):e594
Galactosemia (Option C) is an autosomal recessive disorder of galactose metabolism, leading to an accumulation of galactose levels in the blood that is most often due to deficient galactose-1-phosphate uridyltransferase (GALT) enzyme activity.7 Following ingestion of human milk or cow milk-based formulas (both contain lactose), infants can present with liver failure secondary to galactitol toxicity, resulting in hepatomegaly, hypoglycemia, hyperbilirubinemia, coagulopathy, feeding intolerance, and cataracts.7 About 10% of infants develop Escherichia coli (E. coli) sepsis, which can be fatal.7 Radiographic findings are nonspecific and may include liver enlargement or ileus. Newborn screening in the United States includes measurement of GALT enzyme activity in erythrocytes, which are reduced in patients with galactosemia. Elevated serum galactose concentrations and positive urine reducing substances for galactose and galactitol support the diagnosis of galactosemia.7 Although our infant presented with E. coli sepsis, this infection was secondary to bowel ischemia and perforation in the setting of meconium ileus.
Heterotaxy syndrome (Option D) is comprised of a group of congenital disorders in which the normal left and right orientation of the internal thoraco-abdominal organs is reversed. Cardiac anomalies occur in 20% of patients and include septal lesions, outflow tract anomalies, anomalous pulmonary venous return, or complete heart block.8 Intestinal rotation abnormalities, including malrotation, are present in more than 70% of infants with heterotaxy; thus, an upper gastrointestinal series is recommended to evaluate for malrotation and midgut volvulus. Malrotation occurs secondary to incomplete rotation and abnormal bowel fixation, placing the infant at risk for midgut volvulus and bowel obstruction secondary to mesenteric bands extending from the cecum to the duodenum.3 Infants with malrotation may be asymptomatic or present with bilious emesis and abdominal distension, while infants with midgut volvulus are systemically ill with peritonitis and bowel ischemia. Midgut volvulus is a surgical emergency. An upper gastrointestinal series is the preferred imaging modality to diagnose malrotation with or without volvulus (Figure 4).3 In up to 80% of patients with malrotation, a contrast enema may demonstrate malposition of the cecum and appendix in the left lower quadrant. In contrast, patients who have findings suggestive of meconium ileus, as noted in our infant in this vignette, have a normally positioned cecum in the right lower quadrant.9
Figure 4: Upper gastrointestinal series demonstrating an abnormally low position of the ligament of Treitz (white arrow) and twisted proximal jejunum (black arrow) in an infant diagnosed with malrotation with volvulus. From: Westfal M, Goldstein A. Diagnosing and managing Hirschsprung disease in the newborn. Neoreviews. 2018;19(10):e593
Trisomy 21 (Option E) is the most commonly inherited chromosomal abnormality. It is associated with an increased risk of congenital heart disease and gastrointestinal malformations, including duodenal atresia and Hirschsprung disease.10 Infants with Hirschsprung disease present with large bowel obstruction secondary to the absence of ganglion cells in the rectum and various lengths of the large bowel, including the whole colon in rare cases.10,11 An unusual exam finding shown in Video 1 demonstrates “stepladder peristalsis,” which can be seen in patients with small bowel obstruction such as total colonic aganglionosis.11 Infants with Hirschsprung disease present with failure to pass meconium in the first 48 hours after birth. Radiography demonstrates nonspecific dilated bowel loops. A contrast enema would reveal a narrow rectum with a rectosigmoid ratio less than one and a “transition zone” marking the distinction between the dilated proximal colon with ganglion cells and the narrower distal colon with an absence of ganglion cells (Figure 5).3,10 A suction biopsy of the rectum demonstrating the absence of ganglion cells is the gold standard for diagnosis.10 Although most cases occur sporadically, genetic testing should be offered to families; 20% of cases are familial, and 30% are associated with genetic syndromes, with Trisomy 21 as the most common genetic finding. The infant in our case does not have findings consistent with Hirschsprung disease because he has a microcolon and a normal rectosigmoid ratio greater than one.
Video 1: Physical exam finding of a “stepladder pattern of peristalsis” noted in an infant with small bowel obstruction who had total colonic aganglionosis. From: Arumugam S, Natarajan S, Ramalingam R, Kandasamy P. Recurrent episodes of abdominal distension. Neoreviews. 2021;22(7):e493
Figure 5: Contrast enema demonstrating an abnormal rectosigmoid ratio with transition zone (white arrow) in the distal sigmoid colon in an infant ultimately diagnosed with Hirschsprung disease. From: Westfal M, Goldstein A. Diagnosing and managing Hirschsprung disease in the newborn. Neoreviews. 2018;19(10):e580
Did you know?
Infants with cystic fibrosis and concurrent meconium ileus are at much higher risk for distal intestinal obstruction syndrome later in life, occurring in up to 50% of patients.4
What is the primary cause of gastrointestinal-related deaths in infants with Cornelia de Lange syndrome?
To find the answer, please refer to the following article: Richardson T, Ransom M, Crane G, Plosa E, Sucre J. Emesis in a term infant with dysmorphic features. Neoreviews.2020;21(2):e127–e130
NeoQuest June Authors
Faith Kim, MD, Department of Pediatrics, Columbia University Medical Center/NewYork-Presbyterian Children’s Hospital
Anisha Bhatia, MD, Department of Pediatrics, Northeast Ohio Medical University, Rootstown, OH
- Anders A, Vachharajani A, Ramachandran V. Term newborn with abdominal distention and bilious emesis. Neoreviews. 2022;23(7):e497. 10.1542/neo.23-6-e363
- Galante G, Freeman J. Gastrointestinal, pancreatic, and hepatic manifestations of cystic fibrosis in the newborn. Neoreviews. 2019;20(1):e12–e24
- Ngo A, Phillips G. Radiologic approach to the diagnosis of bowel emergencies in neonates. Neoreviews. 2018;19(10):e589–e600
- Sathe M, Houwen R. Meconium ileus in cystic fibrosis. J Cyst Fibros. 2017;16(2):S32–S39
- Weiner A, Oberfield S, Vuguin P. The laboratory features of congenital hypothyroidism and approach to therapy. Neoreviews. 2020;21(1):e37–e44
- Lyle A, Byrne B. Abdominal distension in a term infant with unilateral ventriculomegaly. Neoreviews. 2019;20(10):e594–e596
- Grade N, Millard D. Congenital galactosemia. Neoreviews. 2017;18(4):e228–e233
- Geddes G, Samudrala S, Earing M. Neonatal assessment of infants with heterotaxy. Clin Perinatol. 2020;47(1):171–182
- Graziano K, Islam S, Dasgupta R, Lopez M, Austin A, Chen L, Goldin A, Downard C, Renaud E, Abdullah F. Asymptomatic malrotation: diagnosis and surgical management: An American Pediatric Surgical Association outcomes and evidence based practice committee systematic review. J Pediatr Surg. 2015;50(10):1783–1790
- Westfal M, Goldstein A. Diagnosing and managing Hirschsprung disease in the newborn. Neoreviews. 2018;19(10):e577–e588
- Arumugam S, Natarajan S, Ramalingam R, Kandasamy P. Recurrent episodes of abdominal distension. Neoreviews. 2021;22(7):e492–e495