Meconium Ileus

Meconium ileus is rare, occurring in 1 in 25,000 neonates and accounts for 30-33% of small intestinal obstructions in neonates (1). It occurs in up to 20% of patients with cystic fibrosis with up to 80% of patients with meconium ileus having cystic fibrosis (1, 3-5).

Meconium ileus can be the earliest clinical sign of cystic fibrosis, however premature neonates and neonates exposed to medications that slow labor or intestinal motility have an increased risk of having meconium ileus (4, 6). Cystic fibrosis is a genetic condition characterized by the triad of chronic mucus obstruction and infection of the respiratory tract, exocrine pancreatic insufficiency, and elevated sweat chloride levels caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) encoding gene on chromosome 7.  It is an autosomal recessive condition with up to 1 in 25 non-Hispanic whites, 1 in 58 Hispanic whites, 1 in 61 African Americans, and 1 in 94 Asian Americans being carriers.  To date, over 1900 known mutations in this gene have been identified, the most common being the F508del mutation (3). The CFTR channel is responsible for Cl− and HCO3– excretion, which is important in creating normally formed stools and mucus (4). In the intestines, abnormal CFTR results in abnormal HCO3– secretion, making an acidic and dehydrating environment. Someone with two copies of the most common F508del mutation has a 24.9% risk of developing meconium ileus, someone with a F508del mutation and another mutation known to cause CF has a 16.9% risk of meconium ileus, and someone with two other CFTR mutations has a 12.5% risk of meconium ileus (4). 

Given the high incidence of cystic fibrosis in individuals with meconium ileus, all patients with meconium ileus, regardless of ethnicity, should be tested for cystic fibrosis. If there is concern for meconium ileus in a fetus, it is recommended that both parents have carrier screening. Targeted genotyping can be used to detect 500 genetic variants associated with CF, including 23 disease causing variants (7). If both have an identified mutation known to cause cystic fibrosis, genetic evaluation of the fetus can be done either with chorionic villus sampling or amniocentesis. Postnatal diagnosis can be made through various approaches, depending on age, genotype, and phenotype. The newborn screen for cystic fibrosis tests the immunoreactive trypsinogen (IRT) in the blood of the newborn (8). If an abnormal value is identified, the test is sent for genetic testing for CFTR gene mutations and should have approximately 90% to 95% sensitivity for the common ethnic groups in the region (9). In patients with meconium ileus, confirmatory testing should be carried out even if the newborn screen shows a normal immunoreactive trypsinogen level. The gold standard test for confirmatory testing is the sweat chloride test. A bilateral sweat chloride test should be performed on individuals who weigh at least 2 kg, are more than 36 weeks corrected gestation at birth, and at least 10 days old (8). If sweat chloride testing cannot be completed or is indeterminate, DNA analysis can be performed looking for all known mutations. While there are multiple panels to screen for CFTR gene mutations, even complete gene sequencing cannot identify all mutations (3).

Until recently, non-cystic fibrosis meconium ileus was not thought to have a genetic etiology. However, recent studies have found a mutation in the GUCY2C on chromosome 12 in some patients with meconium ileus (10). There may be utility of rapid whole exome sequencing to aid in diagnosis. Outside of this context, non-cystic fibrosis meconium ileus is thought to have a low recurrence risk. 
 

Normal fetal meconium appears hypoechoic or isoechoic to adjacent structures on ultrasound. Hyperechoic bowel is nonspecific and, in and of itself, is not diagnostic for meconium ileus. When a fetus is high risk for cystic fibrosis, the positive predictive value of the presence of hyperechoic bowel is just over 50%, but when the fetus is low risk for cystic fibrosis, the positive predictive value is less than 10% (3). Up to 65% of cases of isolated hyperechoic bowel resolve during the pregnancy and the majority of patients with hyperechoic bowel do not have meconium ileus. In cases of meconium ileus, the hyperechoic mass, representing meconium in the terminal ileum, may be seen along with non-visualization of the gallbladder (3, 5). Additional findings on ultrasound include enlarged, dilated bowel loops or a mass with proximal bowel distention. The bowel dilation is secondary to obstruction caused by the meconium but can also be seen with other diagnoses. Calcified meconium may be seen if meconium peritonitis has already occurred. If the fetus is unable to completely pass swallowed amniotic fluid due to the obstruction, polyhydramnios may also be seen. In cases of meconium peritonitis, the presence of meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of the need for neonatal surgery (11). A prenatal diagnosis of intestinal obstruction, seen in up to 25% of cases, is associated with adverse outcomes in one study (12).

While fetal ultrasound is helpful in identifying bowel dilation, there is variability and limits in determining the etiology and extent of bowel abnormalities (13-15). Fetal MRI allows for detailed imaging of the bowel contents and intraperitoneal space to better characterize the anatomy (14, 16). On MRI, meconium typically has a high signal intensity on T1 images due to the high protein, copper, iron, and manganese content (17, 18). It progresses throughout gestation, and a bright T1 signal is typically seen in the colon after 21 weeks. With meconium ileus, the signal stops at the level of the obstruction rather than progressing with increasing gestational age. Distal to the obstruction, the colon can appear collapsed without any meconium signal (19, 20). A recent study showed that common findings suggestive of complex meconium ileus are microcolon without the bright T1 meconium signal, fluid‐fluid and fluid‐solid contents in the small bowel, and an abnormally focal and localized meconium signal with abrupt truncation secondary to the obstruction (16). The additional details seen on MRI can aid in diagnosis, prognosis, and counseling about the expected neonatal course.

The differential diagnosis of suspected meconium ileus is largely dependent on imaging findings. In addition to meconium ileus, hyperechoic bowel has been reported with Down syndrome, intrauterine growth retardation, prematurity, in utero cytomegalovirus infection, intestinal atresia, placental abruption, swallowed blood in amniotic fluid, and fetal demise (3). Dilated bowel can also be seen with midgut volvulus, congenital bands, bowel atresia, intestinal duplication, internal hernia, meconium plug syndrome, or Hirschsprung disease (3). Nonvisualization of the fetal gallbladder can be seen in biliary atresia, omphalocele, diaphragmatic hernia, chromosomal abnormalities, as well as in normal pregnancy. Associated findings help to distinguish the diagnoses. When the diagnosis is suspected after delivery, the differential diagnosis includes meconium plug syndrome, Hirschsprung’s disease, small left colon syndrome, jejunoileal atresia, anorectal malformation, volvulus, and bowel perforation (5).

The American Academy of Obstetrics and Gynecology recommends that all individuals are offered prenatal cystic fibrosis carrier screening (21). When there are concerns for meconium ileus on prenatal ultrasound, the management depends on if the fetus is low or high risk for cystic fibrosis (3). If the pregnant individual has no cystic fibrosis causing mutations on a carrier screen, the fetus is considered low risk. An ultrasound can be repeated in 6 weeks and if there is continued concern for meconium ileus, the patient should be referred to a fetal care center for further counseling and management. When a mutation is identified on carrier screening, paternal carrier screening is recommended. If that is negative, the fetus is considered low risk and management would follow the low-risk algorithm. If the carrier screen is positive, and amniocentesis is recommended along with referral for multidisciplinary counseling and management options. Detailed ultrasound should be performed to assess for additional findings including the development of in-utero growth restriction, polyhydramnios, oligohydramnios, gastric distention, and bowel dilation. Patients typically have additional ultrasounds and non-stress tests later in pregnancy to monitor fetal wellbeing.

Vaginal delivery is considered to be safe in most cases of meconium ileus and cesarean delivery is reserved for the typical obstetric and fetal indications. If fetal growth, amniotic fluid volume, and antenatal testing are all otherwise normal, the risk of intrauterine fetal demise in meconium ileus is minimal, and delivery prior to 37 weeks is generally not recommended. 

Currently there are no standard fetal interventions for meconium ileus. One intervention under investigation for fetuses with cystic fibrosis-related meconium ileus is treating the pregnant individual with gene modifying therapy, CFTR correctors and potentiators that act on abnormal CFTR in the fetus (4, 5). Correctors are small molecules aimed at stabilizing the misfolded CFTR protein in the cytosol to prevent degradation and include lumacaftor (VX-809), tezacaftor (VX-661), ivacaftor, and elexacaftor (VX-445) from Vertex Pharmaceuticals and posenacaftor (PTI-801) from Proteostasis. Potentiators are small molecules that bind to the CFTR channel to facilitate its opening and include vacaftor (VX770) and dirocaftor (PTI-808) (22). Currently, there are several reported cases showing the potential benefit of Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor (23-25). If started early enough in the pregnancy, it may change the natural progression of meconium ileus.

Currently, fetal surgery to decompress the bowel is not being performed but in theory may prevent the development of microcolon or other complications of meconium ileus (5). If CFTR modulators prove to be an effective fetal intervention, those would be favored as fetal surgery poses risks to the pregnant individual and fetus.

Depending on the nature of the meconium ileus, neonates can be asymptomatic or present with abdominal distention, bilious emesis, delayed passage of stool, or signs of septic shock. Both simple and complex meconium ileus are initially managed similar to other types of neonatal bowel obstruction. The respiratory status of the baby is evaluated, and appropriate support ranging from no support up to need for mechanical ventilation is provided as clinically indicated. Antibiotics are usually given to decrease the chance of developing infection from translocation of gut bacteria into the bloodstream or peritoneal space.

When meconium ileus is suspected, a neonate is not fed by mouth. Instead, an intravenous catheter is placed to give fluids or nutrition and a nasogastric tube is placed to decompress the abdomen. Abdominal x-rays are obtained and often show air-filled loops of bowel. The Neuhauser sign, a soap-bubble appearance in the intestines in the right lower quadrant, due to a mixture of meconium and gas, is a characteristic finding (1, 5). The presence of calcifications, free air, or multiple air-fluid levels suggests intestinal perforation. When the diagnosis is suspected on x-ray, a contrast enema is helpful to distinguish meconium ileus from meconium plug syndrome, a more common and separate clinical entity not typically associated with systemic diseases such as cystic fibrosis. In meconium ileus, multiple filling defects—due to the meconium pellets—are seen on contrast enema in conjunction with a microcolon due to underuse of the colon. Once the diagnosis is confirmed, the ileus is managed either conservatively or with surgery (see below). During the process of relieving the obstruction, hydration and electrolyte management is important as neonates might have additional fluid losses and shifts related to the enemas or surgery. 

With simple meconium ileus, nonsurgical evacuation of the meconium with enemas has a 36-83% success rate (1). Historically, there were higher rates of success reported with this approach, but shifts in practice over time have favored proceeding with surgical intervention instead of aggressive nonsurgical management (26). While true, surgical interventions are associated with increased morbidity and mortality. With clear guidelines, nonsurgical evacuation is safe and effective. Resultantly, nonsurgical management is typically the first line treatment for most cases of simple meconium ileus.

The use of water-soluble enemas in the nonsurgical management of meconium ileus may be diagnostic and, at times, therapeutic. Hyperosmolar and water-soluble agents such as diatrizoate meglumine, Gastrografin (1940 mOsm/L), can be diluted to a 25-50% solution and administered to draw fluid into the intestinal lumen, hydrating and softening the meconium. Typically, 10 ml/kg is slowly infused under low hydrostatic pressure (3, 4). The enemas are carried out under fluoroscopic guidance. The contrast must pass through the ileocecal valve and reach the ileum in order to improve the bowel obstruction (6).  Due to the hyperosmolar nature of the contrast, it can lead to dehydration and if used, warrants careful attention to the neonate’s hydration status and fluid and electrolyte balance post-procedure. Potential complications associated with the Gastrografin enema procedure include perforation, hypovolemic shock, and ischemia. The risk of perforation during the procedure increases with repeated enemas. This can be due to perforation from the catheter itself, injury to the mucosa by the contrast, or severe distention of the bowel (3). Since nearly 50% of neonates also have microcolon, it is important to perform the enemas under fluoroscopic guidance and slowly instill the contrast (3, 27). Over distention of the microcolon can lead to ischemia. This can be worsened if the osmotic diuresis causes hypovolemia and hypoperfusion. Iso-osmolar or hypoosmolar agents, such as Hypaque and Omnipaque (240- 354 mOsm/L), have been used with success and less risk of dehydration or colitis. Occasionally, to help break down the meconium, mucolytic agents such as N-acetylcysteine can also be mixed with the contrast enema.

If the initial enema is successful, meconium is passed and continues to pass over the next 1-2 days. Abdominal x-rays are obtained immediately after the procedure and approximately 8-12 hours later to evaluate for a perforation and to confirm evacuation of the meconium (3). Additionally, 10% N-acetylcysteine solution can be given through a nasogastric tube to liquefy upper gastrointestinal secretions and warm saline enemas containing 1-4% N-acetylcysteine may be given to help complete the evacuation (1, 3). If the meconium is not completely evacuated or the contrast does not reflux to the dilated bowel, the enema can be repeated every 6-24 hours as long as there as there is progression of the contrast. Reflux of the enema into the terminal ileum is critical to relieve the bowel obstruction. 

With simple meconium ileus, surgical exploration is indicated when there is progressive abdominal distention, signs of clinical deterioration, or the contrast does not progress. In cases of complicated meconium ileus, surgery is always indicated. Premature neonates and ones with lower birthweights are at increased risk for needing surgical management (28). In general, indications for surgery include worsening abdominal distension, persistent bowel obstruction, enlarging abdominal mass, intestinal atresia, volvulus, perforation, meconium cyst formation with peritonitis, or bowel necrosis. The goal of surgery is to evacuate the meconium and preserve as much bowel as possible (1, 4). Successful reports of using saline through enterostomy for disimpaction of meconium ileus was first described in 1948 (29). Common procedures include enterotomy and decompression, enterostomy (with or without tube) with subsequent irrigation, resection and enterostomy, and resection and anastomosis (5, 30-36).

The type of surgery is tailored to the patient based on the entire clinical picture. With enterotomy and decompression, an incision is made on the antimesenteric border of the dilated ileum, and diluted N-acetylcysteine or saline solution are irrigated through the enterotomy to liquefy the meconium and evacuate it. After evacuation, the incision is closed. This is the most common procedure for simple meconium ileus, and rectal irrigations are often given afterwards for continued evacuation of the meconium. When irrigation does not evacuate the meconium, an indwelling catheter can be inserted into the  bowel for postoperative bowel irrigation and decompression. The irrigations are started on the first postoperative day and continued for 7-14 days. After successfully evacuating the inspissated meconium, the tube is removed and the hole closes spontaneously.

When there is nonviable bowel, bowel perforation, atresia, or volvulus, a bowel resection may be necessary. Rarely, a primary anastomosis can be done but may lead to an anastomotic leak or other complications in up to 31% of patients (37). More commonly, an ostomy is created. There are multiple surgical approaches and techniques described. Ostomies are typically reserved for situations where all other options have been considered because complications include potential postoperative fluid losses through high-volume stomas, bowel shortening by resection, and the need for a second procedure to reestablish intestinal continuity. Despite multiple studies, there is no clear best practice for the surgical management, and the intraoperative plans are largely tailored to the patient (5, 38).

Immediately after evacuation of the meconium ileus, management involves replacement of fluid losses from surgery or enemas, and the correction of ongoing losses. Adequate fluid resuscitation, at least 150 ml/kg/per day, is required to compensated for the anticipated fluid losses. The neonate remains on bowel rest and the nasogastric tube is maintained until bowel function returns. Commonly, 5 ml of 5-10% N-acetylcysteine or normal saline irrigations are given through this tube every 6-24 hours in conjunction with 10 ml/kg of normal saline or 4-10% N-acetylcysteine rectal irrigations (3, 4, 27, 29). Most patients will require central venous access and parenteral nutrition for a period of time. Once they have established a normal stooling pattern, oral feedings of breast milk or formula are introduced. With more complex cases, predigested formulas may be indicated. In severe cases, the bowel may be damaged and initial feeds may need to be continuous with diluted formula. For those with stomas, administering ostomy-drip feeds at low volumes enhances bowel growth, helps prevent bacterial translocation, and decreases injury to the liver related to total parenteral nutrition (40). When symptoms of meconium ileus resolve and the infant is gaining appropriate weight, the stoma can be taken down. This typically takes 4-12 weeks but may be longer (1, 3).

For neonates with cystic fibrosis, the care is more complex. If a diagnosis of cystic fibrosis has not been confirmed prenatally, the sweat chloride test should be done to confirm or rule it out (4). If a sweat chloride test cannot be done, the patient should have expanded genetic testing irrespective of the newborn screen results (8). The care of newborns and children with cystic fibrosis, in general, is complex and requires a multidisciplinary team including gastroenterology, genetics, neonatology, pulmonology, surgery, and others. Patient should receive care from a CF Center to optimize pulmonary and growth outcomes. Growth and nutrition are incredibly important to improve short-term and long term outcomes. Many neonates require additional calories to achieve appropriate growth and reach the recommended weight-for-length status of the 50th percentile by 2 years of age (9).

Once tolerating enteral feeds, the baby will need to be started on vitamins and Pancreatic Enzyme Replacement Therapy once they are taking a specific volume of enteral feeds (9). These enzymes are necessary to digest and absorb food appropriately as most patients with cystic fibrosis do not make enough of these enzymes on their own. Patients may need to start a proton pump inhibitor or histamine 2 receptor blocker to normalize the pH of the intestines so the pancreatic enzymes are not inactivated. They also have increased sodium losses and will need sodium supplementation. Neonates typically do not have significant lung disease. However, they should be started on albuterol and chest physical therapy early in life to decrease atelectasis or mucus plugging (9). CFTR modifiers, when indicated based on the specific genetic mutation, are started early in life to decrease morbidity and mortality. Ivacaftor is started around 6 months of age and Trikafta is started at 2 years (41). 

With improved management techniques, optimal nutritional support, and management of infections, the outcomes for patients with meconium ileus has improved (3). Survival is consistently reported at >8 0% and the majority do well long-term (4, 27, 38, 42). Patients are at risk for developing cholestasis, especially if they are on total parenteral nutrition. Infants who have had significant (> 33%) bowel resection may develop short bowel syndrome, especially if the ileocecal valve has been resected (1). Some infants, especially those who had meconium peritonitis, may present years later with bowel obstruction due to adhesions or segmental volvulus. Some older patients have developed bowel obstruction from inspissated stools in the ileum and colon referred to as meconium ileus equivalent or distal ileal obstruction syndrome (DIOS).

For cystic fibrosis related meconium ileus, there appears to be no difference in pulmonary outcomes, nutritional status, infection, or overall duration of survival for individuals with meconium ileus and cystic fibrosis compared to individuals with cystic fibrosis who did not have meconium ileus. The development of a comprehensive multidisciplinary approach to the care of infants with cystic fibrosis by pediatric surgeons, neonatologists, pulmonologists, respiratory therapists, gastroenterologists, and dieticians has led to improvements in short-term morbidity, and long-term differences in regards to nutritional status, pulmonary function, and infection status for cystic fibrosis patients with a history of both simple and complex meconium ileus (4). However, the risk of developing distal intestinal obstruction syndrome later in life is 50% in patients with cystic fibrosis who had meconium ileus compared to 15% in patients with cystic fibrosis who did not (4, 43). Patients may have delayed small bowel transit time due to a history of injured bowel or surgical intervention and adhesions, which puts them at increased risk for small bowel obstruction and small bowel bacterial overgrowth requiring antibiotics. 

1. Omogiade U. Meconium Ileus. In: Pediatric Surgery, Flowcharts, and Clinical Algorithms. Edited by: Shehata S. 2019.
2. Ziegler MM, Coran AG. Meconium Ileus. In: Seventh Edition. 2012. pp. 1073-1083.
3. Carlyle BE, Borowitz DS, Glick PL. A review of pathophysiology and management of fetuses and neonates with meconium ileus for the pediatric surgeon. J Pediatr Surg 2012; 47:772-781
4. Sathe M, Houwen R. Meconium ileus in Cystic Fibrosis. J Cyst Fibros 2017; 16 Suppl 2:S32-S39.
5. Donos MA, Ghiga G, Trandafir LM et al. Diagnosis and Management of Simple and Complicated Meconium Ileus in Cystic Fibrosis, a Systematic Review. Diagnostics (Basel) 2024; 14.
6. Shinohara T, Tsuda M, Koyama N. Management of meconium-related ileus in very low-birthweight infants. Pediatr Int 2007; 49:641-644.
7. Deignan JL, Astbury C, Cutting GR et al. CFTR variant testing: a technical standard of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2020; 22:1288-1295.
8. Farrell PM, White TB, Ren CL et al. Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation. J Pediatr 2017; 181S:S4-S15.e11.
9. Borowitz D, Robinson KA, Rosenfeld M et al. Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr 2009; 155:S73-93.
10. Woods JD, Payton KSE, Sanchez-Lara PA et al. Non-Cystic Fibrosis-Related Meconium Ileus: GUCY2C-Associated Disease Discovered through Rapid Neonatal Whole-Exome Sequencing. J Pediatr 2019; 211:207-210.
11. Shinar S, Agrawal S, Ryu M et al. Fetal Meconium Peritonitis - Prenatal Findings and Postnatal Outcome: A Case Series, Systematic Review, and Meta-Analysis. Ultraschall Med 2022; 43:194-203.
12. Padoan R, Cirilli N, Falchetti D et al. Risk factors for adverse outcome in infancy in meconium ileus cystic fibrosis infants: A multicentre Italian study. J Cyst Fibros 2019; 18:863-868.
13. Pugash D, Brugger PC, Bettelheim D, Prayer D. Prenatal ultrasound and fetal MRI: the comparative value of each modality in prenatal diagnosis. Eur J Radiol 2008; 68:214-226.
14. Gupta P, Sharma R, Kumar S et al. Role of MRI in fetal abdominal cystic masses detected on prenatal sonography. Arch Gynecol Obstet 2010; 281:519-526.
15. Benson CB, Doubilet PM. The history of imaging in obstetrics. Radiology 2014; 273:S92-110.
16. Gunderman PFR, Shea LAG, Gray BW, Brown BP. Fetal MRI in management of complicated meconium ileus: Prenatal and surgical imaging. Prenat Diagn 2018; 38:685-691.
17. Veyrac C, Couture A, Saguintaah M, Baud C. MRI of fetal GI tract abnormalities. Abdom Imaging 2004; 29:411-420.
18. Manganaro L, Saldari M, Bernardo S et al. Role of magnetic resonance imaging in the prenatal diagnosis of gastrointestinal fetal anomalies. Radiol Med 2015; 120:393-403.
19. Furey EA, Bailey AA, Twickler DM. Fetal MR Imaging of Gastrointestinal Abnormalities. Radiographics 2016; 36:904-917.
20. Farhataziz N, Engels JE, Ramus RM et al. Fetal MRI of urine and meconium by gestational age for the diagnosis of genitourinary and gastrointestinal abnormalities. AJR Am J Roentgenol 2005; 184:1891-1897.
21. ACOG Committee Opinion No. 486: Update on carrier screening for cystic fibrosis. Obstet Gynecol 2011; 117:1028-1031.
22. Lee JA, Cho A, Huang EN et al. Gene therapy for cystic fibrosis: new tools for precision medicine. J Transl Med 2021; 19:452.
23. Metcalf A, Martiniano SL, Sagel SD et al. Outcomes of prenatal use of elexacaftor/tezacaftor/ivacaftor in carrier mothers to treat meconium ileus in fetuses with cystic fibrosis. J Cyst Fibros 2024.
24. Szentpetery S, Foil K, Hendrix S et al. A case report of CFTR modulator administration via carrier mother to treat meconium ileus in a F508del homozygous fetus. J Cyst Fibros 2022; 21:721-724.
25. Blumenfeld YJ, Hintz SR, Aziz N et al. Treatment of Fetal Cystic Fibrosis With Cystic Fibrosis Transmembrane Conductance Regulator Modulation Therapy. Ann Intern Med 2023; 176:1015-1016.
26. Copeland DR, St Peter SD, Sharp SW et al. Diminishing role of contrast enema in simple meconium ileus. J Pediatr Surg 2009; 44:2130-2132.
27. Escobar MA, Grosfeld JL, Burdick JJ et al. Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes. Surgery 2005; 138:560-571; discussion 571-562.
28. Jessula S, Van Den Hof M, Mateos-Corral D et al. Predictors for surgical intervention and surgical outcomes in neonates with cystic fibrosis. J Pediatr Surg 2018; 53:2150-2154.
29. HIATT RB, WILSON PE. Celiac syndrome; therapy of meconium ileus, report of eight cases with a review of the literature. Surg Gynecol Obstet 1948; 87:317-327.
30. BISHOP HC, KOOP CE. Management of meconium ileus; resection, Roux-en-Y anastomosis and ileostomy irrigation with pancreatic enzymes. Ann Surg 1957; 145:410-414.
31. SANTULLI TV, BLANC WA. Congenital atresia of the intestine: pathogenesis and treatment. Ann Surg 1961; 154:939-948.
32. O'Neill JA, Grosfeld JL, Boles ET, Clatworthy HW. Surgical treatment of meconium ileus. Am J Surg 1970; 119:99-105.
33. Harberg FJ, Senekjian EK, Pokorny WJ. Treatment of uncomplicated meconium ileus via T-tube ileostomy. J Pediatr Surg 1981; 16:61-63.
34. Fitzgerald R, Conlon K. Use of the appendix stump in the treatment of meconium ileus. J Pediatr Surg 1989; 24:899-900.
35. Chappell JS. Management of meconium ileus by resection and end-to-end anastomosis. S Afr Med J 1977; 52:1093-1094.
36. Boczar M, Sawicka E, Zybert K. Meconium ileus in newborns with cystic fibrosis - results of treatment in the group of patients operated on in the years 2000-2014. Dev Period Med 2015; 19:32-40.
37. Jawaheer J, Khalil B, Plummer T et al. Primary resection and anastomosis for complicated meconium ileus: a safe procedure? Pediatr Surg Int 2007; 23:1091-1093.
38. Del Pin CA, Czyrko C, Ziegler MM et al. Management and survival of meconium ileus. A 30-year review. Ann Surg 1992; 215:179-185.
39. De Lisle RC, Roach E, Jansson K. Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine. Am J Physiol Gastrointest Liver Physiol 2007; 293:G577-584.
40. Wang Y, Tao YX, Cai W et al. Protective effect of parenteral glutamine supplementation on hepatic function in very low birth weight infants. Clin Nutr 2010; 29:307-311.
41. Collins MS, Mansilla-Rivera K. Diagnostic and Therapeutic Advances in Cystic Fibrosis: How Family Physicians Can Partner in Care. Am Fam Physician 2024; 109:388-390.
42. Caniano DA, Beaver BL. Meconium ileus: a fifteen-year experience with forty-two neonates. Surgery 1987; 102:699-703.
43. Waldhausen JHT, Richards M. Meconium Ileus. Clin Colon Rectal Surg 2018; 31:121-126.