eMedicine Specialties > Pediatrics: Surgery > General Surgery

Surgical Aspects of Cystic Fibrosis and Meconium Ileus

Author: Michael S Irish, MD, Adjunct Clinical Assistant Professor, Department of Surgery, University of Iowa; Consulting Pediatric Surgeon, Department of Pediatric Surgery, Blank Children's Hospital and Children's Hospital Physicians Group
Coauthor(s): Philip M Bovet, DO, MPH, Resident Physician in Family Medicine, University of Wisconsin Health Clinic
Contributor Information and Disclosures

Updated: Jan 12, 2010

Introduction

Meconium ileus (MI) is among the most common causes of intestinal obstruction in the newborn, accounting for 9%-33% of neonatal intestinal obstructions. Meconium ileus is the earliest clinical manifestation of cystic fibrosis (CF) and occurs as either simple or complicated in approximately 16%-20% of patients who have CF, although meconium ileus also occurs in patients who do not have CF. Clinically, CF is characterized by the following triad:

  1. Chronic obstruction and infection of the respiratory tract
  2. Exocrine pancreatic insufficiency
  3. Elevated sweat chloride levels

In 1905, Landsteiner described the association between inspissated meconium in a newborn and pathologic changes in the pancreas. He speculated that an enzyme deficiency causing pancreatic fibrosis also led to abnormally thick meconium.1 In 1936, Fanconi et al were the first to use the term cystic fibrosis to describe the combination of pancreatic insufficiency and chronic pulmonary disease in childhood.2 Anderson associated meconium ileus with CF 2 years later, noting that the histologic lesions in the pancreas were identical in both conditions.3

In 1946, Glanzmann was the first to suggest that abnormal intestinal mucus causes inspissation of meconium.4 In 1952, Buchanan and Rapoport chemically analyzed inspissated meconium from infants with meconium ileus.5 A year later, Bodian attributed the abnormally viscid nature of meconium in meconium ileus to abnormal mucus secreted by the intestines of patients with CF.6

A possible meconium ileus diagnosis should raise the suspicion of CF in the fetus. Antenatal diagnosis of meconium ileus can be confirmed in 2 groups. In the low-risk group, the diagnosis is suspected when routine prenatal ultrasonography reveals the sonographic appearances of meconium ileus. The high-risk group consists of all pregnancies subsequent to the birth of a child with CF. Parents of a child with CF are obligate carriers of a CF mutation.

History of the Procedure

Before 1948, the prognosis for infants with meconium ileus was uniformly poor despite surgical treatment. In that year, Hiatt and Wilson of Babies & Children's Hospital of New York reported the first successful surgical management of 5 infants with meconium ileus, using intraoperative disimpaction of meconium with saline instilled into the bowel via a tube enterostomy.7 In 1989, Fitzgerald and Conlon proposed a similar technique in which an appendectomy is performed and a cecostomy catheter is placed through the appendiceal stump to insert irrigant and to evacuate impacted meconium.8

Problem

In the simple form, thickened meconium begins to form in utero. It obstructs the mid ileum, causing proximal dilatation, bowel wall thickening, and congestion.

Frequency

  • Meconium ileus is among of the most common causes of intestinal obstruction in newborns, accounting for 9%-33% of neonatal intestinal obstructions.
  • Meconium ileus is the earliest clinical manifestation of CF, occurring in approximately 16%-20% of patients with the condition.
  • Of all operative cases of CF, 38% are due to meconium ileus.
  • CF is an autosomal-recessive disease; its estimated heterozygote frequency in white people is up to 1 in 20. Each offspring of 2 heterozygote parents has a 25% chance of developing CF. A family history of CF has been noted in 10%-40% of new patients with meconium ileus. Allan et al, in a 1981 review of 488 families with at least one child with CF, reported a meconium ileus recurrence rate of 39% in families with a previously affected sibling.9

Etiology

Genetic causes of cystic fibrosis

  • In 1989, the CF locus was localized through linkage analysis to the long arm of human chromosome 7, band q31. The disease is caused by mutations in the gene that codes for the cell membrane protein CF transmembrane (conductance) regulator (CFTR). This protein is an adenosine 3',5'-cyclic adenosine monophosphate (cAMP)–induced chloride channel, which also regulates the flow of other ions across the apical surface of epithelial cells. The alteration in CFTR causes abnormal electrolyte content in the environment external to the apical surface of epithelial membranes. This leads to desiccation and reduced secretion clearance from tubular structures lined by affected epithelia.
  • The most common mutation of the CFTR gene is a 3 base pair deletion that removes a phenylalanine residue at amino acid position 508 of CFTR. This is called the DF508 mutation. More than 1568 CFTR mutations had been reported to the CF Genetic Consortium as of March 2007. About 42% (654) of these mutations are missense, and approximately 50% of individuals with CF are homozygous for DF508; another 25%-30% have one copy of DF508 plus another mutation.10
  • Certain alleles cluster with increased frequency in specific populations. For example, W1282X is common in Ashkenazi Jewish people, and A455E is common both in Dutch people and in individuals from northern Quebec. D1152H is the third most prevalent in Ashkenazi and other ethnic Jewish groups. Past tests were only for F508del, G542X, N1303K, and 3849+10KbC>T. The prevalence of D1152 mutation in Jewish population comprises 5.2% of all CFTR mutations.
  • Genotype-phenotype correlation demonstrates that DF508 homozygosity nearly always confers a pancreatic exocrine insufficiency. Individuals with 1 or 2 copies of missense mutations (eg, R117H) tend to be pancreatic sufficient and have milder disease. The incidence of meconium ileus is higher in patients who are homozygous for DF508 or who have DF508 plus G542X. Conversely, not all patients with these genotypes have meconium ileus, so other non -CFTR factors, either genetic and/or environmental, must be involved in meconium ileus pathogenesis.
  • Regarding meconium ileus, no specific haplotype variant is available to determine its presence; however, 79% of the patients who have DF508 mutations presented initially with abdominal pain instead of lung problems.
  • Because of the significant variability in disease presentation, evidence supports the role of modifier genes. Supporting this is the finding that the CFTR gene most commonly has 2 or more modifiers in neonates with CF who have intestinal obstruction. This neonatal genetic finding is contrasted by evidence showing that older children develop obstruction due mostly to environmental factors, such as introduction of pancreatic enzymes causing a stricture.11,12
  • Studies in murine CF models have shown an increase in mast cells and neutrophils as part of the immune response. For example, the KITL gene plays a vital role in the differentiation of mast cells, as demonstrated by a decreased expression of MCPT2. Another focus includes the proteins selectin and ICAM-1, which facilitate neutrophil extravasation. Neutrophils and mast cells release proteases, prostaglandins, and histamine, influencing mucus production.
  • A research model found in CFTR- knockout gene mice highlighted the importance of MCLCA3 expression in goblet cells. This gene influences mucus production, among other activities, and its expression was noted to be diminished in these CF mice. Correction of this deficiency was found to increase survival and to decrease intestinal disease. In humans, this finding may translate to applications such as correcting modifier genes (eg, HCLCA1) in order to improve outcomes in patients with CF.13
  • Additional genetic modifiers include a 129/Sv allelic contribution in mice that yields a milder inflammatory response in CF and was potentially linked to chromosomes 1, 9, and 10.
  • The regulation of these genes and processes helps explain the range of phenotypic variability in similar genetic mutations.

Pathophysiology

  • Meconium in patients with meconium ileus has higher protein and lower carbohydrate concentration than that in control populations. In 1958, Green et al found that albumin was the major protein present in the meconium of infants with meconium ileus.14 The concentration of albumin is 5-10 times higher, along with a significant increase in the liver's production of intraluminal glutamyltranspeptidase (GGTP) and 5'-nucleotidase in the meconium that causes meconium ileus. The addition of albumin to normal meconium makes it viscid; the addition of pancreatic protease liquefies the viscid mass. This led to the belief that pancreatic insufficiency played a central role in meconium ileus pathogenesis, although pancreatic insufficiency is not the sole cause of abnormal meconium in meconium ileus. In 1988, Lands et al reported 2 infants with CF and meconium ileus, aged 9 and 11 months, who displayed no clinical evidence of pancreatic insufficiency.15
  • Abnormal intestinal motility may also contribute to meconium ileus development. Some patients with CF have prolonged small intestinal transit times. Non-CF diseases associated with abnormal gut motility (eg, Hirschsprung disease, chronic intestinal pseudo-obstruction) have been associated with meconium ileus–like disease, suggesting that decreased peristalsis may allow increased resorption of water, thus favoring meconium ileus development.
  • In the murine model of CF, developed in 1992, newborn mice had severe intestinal obstruction at birth with minimal pulmonary or pancreatic involvement. These animal studies support the concept that meconium ileus may occur in patients with sufficient pancreatic activity. The lack of concordance between meconium ileus and severity of pancreatic disease suggests that intraluminal intestinal factors contribute to meconium ileus development.
  • Postnatally, intestinal disease is characterized by a glandular abnormality that produces hyperviscous mucus. It is not fully understood how mutations of the CF gene generate abnormal mucins, nor is the developmental sequence of mucin secretion in the fetal intestine, although the CFTR ion channel defect possibly leads to dehydration of intraluminal contents. The meconium of fetuses with CF and meconium ileus has increased viscosity and decreased water content compared with those of healthy controls.

Presentation

  • Patients with simple meconium ileus usually present with abdominal distension at birth, eventually progressing to failure to pass meconium, bilious vomiting, and progressive abdominal distension. Often, examination reveals dilated loops of bowel with a doughy character that indent on palpation. The rectum and anus are usually narrow, a finding possibly misinterpreted as anal stenosis.
  • Patients with complicated meconium ileus present more dramatically at birth with severe abdominal distension, sometimes accompanied by abdominal wall erythema and edema. Abdominal distension may be severe enough to cause respiratory distress. Signs of peritonitis include tenderness, abdominal wall edema, distension, and clinical evidence of sepsis. A palpable mass may indicate pseudocyst formation. Often, the neonate is in extremis and needs urgent resuscitation and surgical exploration.
  • CF is characterized clinically by the following triad:
    • Chronic obstruction and infection of the respiratory tract
    • Exocrine pancreatic insufficiency
    • Elevated sweat chloride levels
  • Approximately 10% of patients with CF remain pancreatic sufficient and tend to have a milder course.
  • Clinical variants have recently been described, such as adult males with bilateral absence of the vas deferens who have little other clinical involvement. Absence of the vas deferens is considered an atypical presentation of CF, and 80% of men with this presentation have at least one CFTR gene mutation. In 1995, Zielenski et al reported that the most common of these mutations is the IVS8/5T mutation.16
  • Another atypical manifestation of CF was polyuria and polyphagia in an infant. Despite not having any initial intestinal symptoms, such as diarrhea, an infant in Belgium with failure to thrive was initially treated for diabetes insipidus before being diagnosed with CF.17 Although a sweat test result may be abnormal in diabetes insipidus, CF must be excluded upon any positive sweat test result.

Indications

Surgical exploration is indicated for patients with progressive distension, signs of peritonitis, or clinical deterioration.

Surgery is always indicated for complicated meconium ileus (MI). Complicated meconium ileus requires resection more often than simple meconium ileus and always requires temporary stomas.

The following complications require surgical management:

Relevant Anatomy

Fetuses with cystic fibrosis (CF) have abnormal development of the pancreas and intestinal tract. CFTR expression can be detected in the pancreatic ductules at 18 weeks' gestation. In patients with CF, abnormal pancreatic secretions obstruct the duct system, leading to autodigestion of the acinar cells, fatty replacement, and ultimately, fibrosis. Beginning in utero, this progressive process occurs variably over time. Approximately two thirds of infants later diagnosed with CF by neonatal screening have pancreatic insufficiency at birth. Approximately 10% of patients with CF remain pancreatic sufficient and tend to have a milder course.

Contraindications

See Treatment.

More on Surgical Aspects of Cystic Fibrosis and Meconium Ileus

Overview: Surgical Aspects of Cystic Fibrosis and Meconium Ileus
Workup: Surgical Aspects of Cystic Fibrosis and Meconium Ileus
Treatment: Surgical Aspects of Cystic Fibrosis and Meconium Ileus
Follow-up: Surgical Aspects of Cystic Fibrosis and Meconium Ileus
References
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References

  1. Landsteiner K. Darmverschluss durch eingedicktes Meconium: Pancreatitis. Zentralbl Allg Pathol. 1905;16:903-7.

  2. Fanconi G, Uehlinger E, Knauer C. Das Coeliakiesyndrom bei angeborener zystischer pancreas fibromatose und bronchiektasien. Wien Med Wochenschr. 1936;27/28:753-6.

  3. Anderson D. Cystic fibrosis of the pancreas and its relationship to celiac disease. Am J Dis Child. 1938;56:344-99.

  4. Glanzmann E. Dysporia entero-bronco-pancreatica congenita familiaris. Ann Paediat. 1946;166:289.

  5. Buchanan D, Rapoport S. Chemical comparison of normal meconium and meconium from patients with meconium ileus. Pediatrics. 1952;9:304-10.

  6. Bodian M. Congenital disorder of mucous production-mucosis. Fibrocystic Disease of the Pancrease. 1953.

  7. Hiatt RB, Wilson PE. Celiac syndrome; therapy of meconium ileus, report of eight cases with a review of the literature. Surg Gynecol Obstet. Sep 1948;87(3):317-27. [Medline].

  8. Fitzgerald R, Conlon K. Use of the appendix stump in the treatment of meconium ileus. J Pediatr Surg. Sep 1989;24(9):899-900. [Medline].

  9. Allan JL, Robbie M, Phelan PD, Danks DM. Familial occurrence of meconium ileus. Eur J Pediatr. Feb 1981;135(3):291-2. [Medline].

  10. Julian Zielenski, Anluan O'Brien and Lap-Chee Tsui. Cystis Fibrosis Mutation Database. Cystic Fibrosis Genetic Analysis Consortium. Available at http://www.genet.sickkids.on.ca/cftr/StatisticsPage.html. Accessed June 24, 2008.

  11. Chaudry G, Navarro OM, Levine DS, Oudjhane K. Abdominal manifestations of cystic fibrosis in children. Pediatr Radiol. Mar 2006;36(3):233-40. [Medline].

  12. Blackman SM, Deering-Brose R, McWilliams R, Naughton K, Coleman B, Lai T, et al. Relative contribution of genetic and nongenetic modifiers to intestinal obstruction in cystic fibrosis. Gastroenterology. Oct 2006;131(4):1030-9. [Medline].

  13. Young FD, Newbigging S, Choi C, Keet M, Kent G, Rozmahel RF. Amelioration of cystic fibrosis intestinal mucous disease in mice by restoration of mCLCA3. Gastroenterology. Dec 2007;133(6):1928-37. [Medline].

  14. Green MN, Clarke JT, Shwachman H. Studies in cystic fibrosis of the pancreas; protein pattern in meconium ileus. Pediatrics. Apr 1958;21(4):635-41. [Medline].

  15. Gross R. Intestinal Obstruction in the Newborn Arising from Meconium Ileus. The surgery of infants and childhood. 1953;175-191.

  16. Zielenski J, Patrizio P, Corey M, et al. CFTR gene variant for patients with congenital absence of vas deferens. Am J Hum Genet. Oct 1995;57(4):958-60. [Medline].

  17. Vande Velde S, Van Biervliet S, Robberecht E. Cystic fibrosis presenting as diabetes insipidus unresponsive to desmopressin. Acta Gastroenterol Belg. Jul-Sep 2007;70(3):300-1. [Medline].

  18. Steven LC, Gavel G, Young D, Carachi R. Immunoreactive trypsin levels in neonates with meconium ileus. Pediatr Surg Int. Mar 2006;22(3):236-9. [Medline].

  19. Santulli TV, Blanc WA. Congenital atresia of the intestine: pathogenesis and treatment. Ann Surg. Dec 1961;154:939-48. [Medline].

  20. Dicke JM, Crane JP. Sonographically detected hyperechoic fetal bowel: significance and implications for pregnancy management. Obstet Gynecol. Nov 1992;80(5):778-82. [Medline].

  21. Leonidas JC, Berdon WE, Baker DH, Santulli TV. Meconium ileus and its complications. A reappraisal of plain film roentgen diagnostic criteria. Am J Roentgenol Radium Ther Nucl Med. Mar 1970;108(3):598-609. [Medline].

  22. Shinohara T, Tsuda M, Koyama N. Management of meconium-related ileus in very low-birthweight infants. Pediatr Int. Oct 2007;49(5):641-4. [Medline].

  23. Noblett HR. Treatment of uncomplicated meconium ileus by Gastrografin enema: a preliminary report. J Pediatr Surg. Apr 1969;4(2):190-7. [Medline].

  24. Escobar MA, Grosfeld JL, Burdick JJ, et al. Surgical considerations in cystic fibrosis: a 32-year evaluation of outcomes. Surgery. Oct 2005;138(4):560-71; discussion 571-2. [Medline].

  25. Ein SH, Shandling B, Reilly BJ, Stephens CA. Bowel perforation with nonoperative treatment of meconium ileus. J Pediatr Surg. Feb 1987;22(2):146-7. [Medline].

  26. O'Neill JA Jr, Grosfeld JL, Boles ET Jr, Clatworthy HW Jr. Surgical treatment of meconium ileus. Am J Surg. Jan 1970;119(1):99-105. [Medline].

  27. Harberg FJ, Senekjian EK, Pokorny WJ. Treatment of uncomplicated meconium ileus via T-tube ileostomy. J Pediatr Surg. Feb 1981;16(1):61-3. [Medline].

  28. Bishop HC, Koop CE. Management of meconium ileus; resection, Roux-en-Y anastomosis and ileostomy irrigation with pancreatic enzymes. Ann Surg. Mar 1957;145(3):410-4. [Medline].

  29. Swenson O. Pediatric Surgery. 2nd ed. 1962.

  30. Chappell JS. Management of meconium ileus by resection and end-to-end anastomosis. S Afr Med J. Dec 24 1977;52(27):1093-4. [Medline].

  31. Mabogunje OA, Wang CI, Mahour H. Improved survival of neonates with meconium ileus. Arch Surg. Jan 1982;117(1):37-40. [Medline].

  32. Molmenti EP, Squires RH, Nagata D, et al. Liver transplantation for cholestasis associated with cystic fibrosis in the pediatric population. Pediatr Transplant. Apr 2003;7(2):93-7. [Medline].

  33. Fridell JA, Mazariegos GV, Orenstein D, et al. Liver and intestinal transplantation in a child with cystic fibrosis: a case report. Pediatr Transplant. Jun 2003;7(3):240-2. [Medline].

  34. Lai HJ, Cheng Y, Cho H, et al. Association between initial disease presentation, lung disease outcomes, and survival in patients with cystic fibrosis. Am J Epidemiol. Mar 15 2004;159(6):537-46. [Medline].

  35. David AL, Peebles DM, Gregory L, Waddington SN, Themis M, Weisz B, et al. Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases. Hum Gene Ther. Jul 2006;17(7):767-79. [Medline].

  36. Andrassy R, Nirgiotis J. Meconium disease of infancy: meconium ileus, meconium plug syndrome, and meconium peritonitis. Pediatric Surgery. 1990;331-40.

  37. Anguiano A, Oates RD, Amos JA, et al. Congenital bilateral absence of the vas deferens. A primarily genital form of cystic fibrosis. JAMA. Apr 1 1992;267(13):1794-7. [Medline].

  38. Bahado-Singh R, Morotti R, Copel JA, Mahoney MJ. Hyperechoic fetal bowel: the perinatal consequences. Prenat Diagn. Oct 1994;14(10):981-7. [Medline].

  39. Bali A, Stableforth DE, Asquith P. Prolonged small-intestinal transit time in cystic fibrosis. Br Med J (Clin Res Ed). Oct 8 1983;287(6398):1011-3. [Medline].

  40. Bear CE, Li CH, Kartner N, et al. Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR). Cell. Feb 21 1992;68(4):809-18. [Medline].

  41. Benacerraf BR, Chaudhury AK. Echogenic fetal bowel in the third trimester associated with meconium ileus secondary to cystic fibrosis. A case report. J Reprod Med. Apr 1989;34(4):299-300. [Medline].

  42. Boat T, Welsh M, Beaudet A. Cystic Fibrosis. In: The Metabolic Basis of Inherited Disease. New York, NY: McGraw-Hill; 1989:2649-80.

  43. Borowitz D, Scheig R. Recurrent abdominal pain in a patient with cystic fibrosis and type IV hyperlipidemia. J Pediatr Gastroenterol Nutr. May 1995;20(4):440-2. [Medline].

  44. Borowitz D, Wegman T, Harris M. Preventive care for patients with chronic illness. Multivitamin use in patients with cystic fibrosis. Clin Pediatr (Phila). Dec 1994;33(12):720-5. [Medline].

  45. Boue A, Muller F, Nezelof C, et al. Prenatal diagnosis in 200 pregnancies with a 1-in-4 risk of cystic fibrosis. Hum Genet. Nov 1986;74(3):288-97. [Medline].

  46. Bower TR, Pringle KC, Soper RT. Sodium deficit causing decreased weight gain and metabolic acidosis in infants with ileostomy. J Pediatr Surg. Jun 1988;23(6):567-72. [Medline].

  47. Bromley B, Doubilet P, Frigoletto FD Jr, et al. Is fetal hyperechoic bowel on second-trimester sonogram an indication for amniocentesis?. Obstet Gynecol. May 1994;83(5 Pt 1):647-51. [Medline].

  48. Bronstein MN, Sokol RJ, Abman SH, et al. Pancreatic insufficiency, growth, and nutrition in infants identified by newborn screening as having cystic fibrosis. J Pediatr. Apr 1992;120(4 Pt 1):533-40. [Medline].

  49. Burke MS, Ragi JM, Karamanoukian HL, et al. New strategies in nonoperative management of meconium ileus. J Pediatr Surg. May 2002;37(5):760-4. [Medline].

  50. Caniano DA, Beaver BL. Meconium ileus: a fifteen-year experience with forty-two neonates. Surgery. Oct 1987;102(4):699-703. [Medline].

  51. Caspi B, Elchalal U, Lancet M, Chemke J. Prenatal diagnosis of cystic fibrosis: ultrasonographic appearance of meconium ileus in the fetus. Prenat Diagn. Jun 1988;8(5):379-82. [Medline].

  52. Clarke LL, Grubb BR, Yankaskas JR, et al. Relationship of a non-cystic fibrosis transmembrane conductance regulator-mediated chloride conductance to organ-level disease in Cftr(-/-) mice. Proc Natl Acad Sci U S A. Jan 18 1994;91(2):479-83. [Medline]. [Full Text].

  53. Colledge WH, Abella BS, Southern KW, et al. Generation and characterization of a delta F508 cystic fibrosis mouse model. Nat Genet. Aug 1995;10(4):445-52. [Medline].

  54. Dalzell AM, Freestone NS, Billington D, Heaf DP. Small intestinal permeability and orocaecal transit time in cystic fibrosis. Arch Dis Child. Jun 1990;65(6):585-8. [Medline].

  55. Dechelotte PJ, Mulliez NM, Bouvier RJ, et al. Pseudo-meconium ileus due to cytomegalovirus infection: a report of three cases. Pediatr Pathol. Jan-Feb 1992;12(1):73-82. [Medline].

  56. DeLorimier AA, Fonkalsrud EW, Hays DM. Congenital atresia and stenosis of the jejunum and ileum. Surgery. May 1969;65(5):819-27. [Medline].

  57. Denholm TA, Crow HC, Edwards WH, et al. Prenatal sonographic appearance of meconium ileus in twins. AJR Am J Roentgenol. Aug 1984;143(2):371-2. [Medline].

  58. Dolan TF Jr, Touloukian RJ. Familial meconium ileus not associated with cystic fibrosis. J Pediatr Surg. Dec 1974;9(6):821-24. [Medline].

  59. Donnison AB, Shwachman H, Gross RE. A review of 164 children with meconium ileus seen at the Children's Hospital Medical Center, Boston. Pediatrics. May 1966;37(5):833-50. [Medline].

  60. Duchatel F, Muller F, Oury JF, et al. Prenatal diagnosis of cystic fibrosis: ultrasonography of the gallbladder at 17-19 weeks of gestation. Fetal Diagn Ther. Jan-Feb 1993;8(1):28-36. [Medline].

  61. Durie PR, Newth CJ, Forstner GG, Gall DG. Malabsorption of medium-chain triglycerides in infants with cystic fibrosis: correction with pancreatic enzyme supplement. J Pediatr. May 1980;96(5):862-4. [Medline].

  62. Estroff JA, Parad RB, Benacerraf BR. Prevalence of cystic fibrosis in fetuses with dilated bowel. Radiology. Jun 1992;183(3):677-80. [Medline].

  63. Fakhry J, Reiser M, Shapiro LR, et al. Increased echogenicity in the lower fetal abdomen: a common normal variant in the second trimester. J Ultrasound Med. Sep 1986;5(9):489-92. [Medline].

  64. Farber S. The relation of pancreatic achylia to meconium ileus. J Pediatr. 1944;24:387-92.

  65. FitzSimmons SC. The changing epidemiology of cystic fibrosis. J Pediatr. Jan 1993;122(1):1-9. [Medline].

  66. FitzSimmons SC, Burkhart GA, Borowitz D, et al. High-dose pancreatic-enzyme supplements and fibrosing colonopathy in children with cystic fibrosis. N Engl J Med. May 1 1997;336(18):1283-9. [Medline].

  67. Forouzan I. Fetal abdominal echogenic mass: an early sign of intrauterine cytomegalovirus infection. Obstet Gynecol. Sep 1992;80(3 Pt 2):535-7. [Medline].

  68. Foulkes AG, Harris A. Localization of expression of the cystic fibrosis gene in human pancreatic development. Pancreas. Jan 1993;8(1):3-6. [Medline].

  69. Genzyme Corporation. Genzyme launches new cystic fibrosis gene sequence test. Medical News Today. Available at http://www.medicalnewstoday.com/articles/55498.php. Accessed June 24, 2008.

  70. Gillis DA, Grantmyre EB. The meconium-plug syndrome and Hirschsprung's disease. Can Med Assoc J. Jan 30 1965;92:225-7. [Medline].

  71. Goldstein RB, Filly RA, Callen PW. Sonographic diagnosis of meconium ileus in utero. J Ultrasound Med. Nov 1987;6(11):663-6. [Medline].

  72. Gollin Y, Shaffer W, Gollin G. Increased abdominal echogenicity in utero a marker for intestinal obstruction. Am J Obstet Gynecol (Abstract No. 181). 1993;168:349.

  73. Grantmyre EB, Butler GJ, Gillis DA. Necrotizing enterocolitis after Renografin-76 treatment of meconium ileus. AJR Am J Roentgenol. May 1981;136(5):990-1. [Medline].

  74. Hasty P, O'Neal WK, Liu KQ, Morris AP, Bebok Z, Shumyatsky GB, et al. Severe phenotype in mice with termination mutation in exon 2 of cystic fibrosis gene. Somat Cell Mol Genet. May 1995;21(3):177-87. [Medline].

  75. Hendeles L. Use bioequivalency rating to select generics. Am Pharm. Oct 1989;NS29(10):6. [Medline].

  76. Hendeles L, Dorf A, Stecenko A. Treatment failure after substitution of generic pancrelipase capsules. Correlation with in vitro lipase activity. JAMA. May 9 1990;263(18):2459-61. [Medline].

  77. Herson RE. Meconium ileus. Radiology. Apr 1957;68(4):568-71. [Medline].

  78. Hurwitt E. Meconium ileus associated with stenosis of the pancreatic ducts. Am J Dis Child. 1942;64:443-54.

  79. Hyman PE, Everett SL, Harada T. Gastric acid hypersecretion in short bowel syndrome in infants: association with extent of resection and enteral feeding. J Pediatr Gastroenterol Nutr. Mar-Apr 1986;5(2):191-7. [Medline].

  80. Irish MS, Glick PL, Borowitz DS, Kantos M. An asfaliogenic complication arising from profit-motivated decision-making. Pediatrics. Mar 1997;99(3):503-4. [Medline]. [Full Text].

  81. Irish MS, Gollin Y, Borowitz DS. Meconium Ileus antenatal diagnosis and perinatal care. 1996;8:79-83.

  82. Irish MS, Ragi JM, Karamanoukian H, et al. Prenatal diagnosis of the fetus with cystic fibrosis and meconium ileus. Pediatr Surg Int. Jul 1997;12(5-6):434-6. [Medline].

  83. Jarvi K, McCallum S, Zielenski J, et al. Heterogeneity of reproductive tract abnormalities in men with absence of the vas deferens: role of cystic fibrosis transmembrane conductance regulator gene mutations. Fertil Steril. Oct 1998;70(4):724-8. [Medline].

  84. Kent G, Oliver M, Foskett JK, et al. Phenotypic abnormalities in long-term surviving cystic fibrosis mice. Pediatr Res. Aug 1996;40(2):233-41. [Medline].

  85. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis. Science. Sep 8 1989;245(4922):1073-80. [Medline].

  86. Kerem E, Corey M, Kerem B, et al. Clinical and genetic comparisons of patients with cystic fibrosis, with or without meconium ileus. J Pediatr. May 1989;114(5):767-73. [Medline].

  87. Kerem E, Corey M, Kerem BS, et al. The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med. Nov 29 1990;323(22):1517-22. [Medline].

  88. Kristidis P, Bozon D, Corey M, et al. Genetic determination of exocrine pancreatic function in cystic fibrosis. Am J Hum Genet. Jun 1992;50(6):1178-84. [Medline].

  89. Lands L, Zinman R, Wise M, Kopelman H. Pancreatic function testing in meconium disease in CF: two case reports. J Pediatr Gastroenterol Nutr. Mar-Apr 1988;7(2):276-9. [Medline].

  90. Leonidas JC, Burry VF, Fellows RA, Beatty EC. Possible adverse effect of methylglucamine diatrizoate compounds on the bowel of newborn infants with meconium ileus. Radiology. Dec 1976;121(3 Pt. 1):693-6. [Medline].

  91. Li Z, Lai HJ, Kosorok MR, et al. Longitudinal pulmonary status of cystic fibrosis children with meconium ileus. Pediatr Pulmonol. Oct 2004;38(4):277-84. [Medline].

  92. Lince DM, Pretorius DH, Manco-Johnson ML, et al. The clinical significance of increased echogenicity in the fetal abdomen. AJR Am J Roentgenol. Oct 1985;145(4):683-6. [Medline].

  93. Lutzger LG, Factor SM. Effects of some water-soluble contrast media on the colonic mucosa. Radiology. Mar 1976;118(3):545-8. [Medline].

  94. Makowski GS, Nadeau FL, Hopfer SM. Single tube multiplex PCR detection of 27 cystic fibrosis mutations and 4 polymorphisms using neonatal blood samples collected on Guthrie cards. Ann Clin Lab Sci. 2003;33(3):243-50. [Medline].

  95. McPartlin JF, Dickson JA, Swain VA. Meconium ileus. Immediate and long-term survival. Arch Dis Child. Apr 1972;47(252):207-10. [Medline].

  96. [Best Evidence] Moran F, Bradley JM, Piper AJ. Non-invasive ventilation for cystic fibrosis. Cochrane Database Syst Rev. Jan 21 2009;CD002769. [Medline].

  97. Noblett H. Meconium Ileus. Pediatric Surgery. 1979;3rd ed:943-51.

  98. Norkina O, De Lisle RC. Potential genetic modifiers of the cystic fibrosis intestinal inflammatory phenotype on mouse chromosomes 1, 9, and 10. BMC Genet. 2005;6(1):29. [Medline]. [Full Text].

  99. Nyberg DA, Dubinsky T, Resta RG, et al. Echogenic fetal bowel during the second trimester: clinical importance. Radiology. Aug 1993;188(2):527-31. [Medline].

  100. Nyberg DA, Hastrup W, Watts H, Mack LA. Dilated fetal bowel. A sonographic sign of cystic fibrosis. J Ultrasound Med. May 1987;6(5):257-60. [Medline].

  101. Nyberg DA, Resta RG, Luthy DA, et al. Prenatal sonographic findings of Down syndrome: review of 94 cases. Obstet Gynecol. Sep 1990;76(3 Pt 1):370-7. [Medline].

  102. Olsen MM, Luck SR, Lloyd-Still J, Raffensperger JG. The spectrum of meconium disease in infancy. J Pediatr Surg. Oct 1982;17(5):479-81. [Medline].

  103. Orgad S, Berkenstadt M, Achiron R, et al. Hyperechogenic bowel loops and meconium ileus in a fetus carrying the D1152H and G542X cystic fibrosis CFTR mutations. Prenat Diagn. Jul 2002;22(7):636-7. [Medline].

  104. Paulson EK, Hertzberg BS. Hyperechoic meconium in the third trimester fetus: an uncommon normal variant. J Ultrasound Med. Dec 1991;10(12):677-80. [Medline].

  105. Rescorla FJ, Grosfeld JL, West KJ, Vane DW. Changing patterns of treatment and survival in neonates with meconium ileus. Arch Surg. Jul 1989;124(7):837-40. [Medline].

  106. Reyes J, Mazariegos GV, Bond GM, et al. Pediatric intestinal transplantation: historical notes, principles and controversies. Pediatr Transplant. Jun 2002;6(3):193-207. [Medline].

  107. Rickham PP, Boeckman CR. Neonatal meconium obstruction in the absence of mucoviscidosis. Am J Surg. Feb 1965;109:173-7. [Medline].

  108. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. Sep 8 1989;245(4922):1066-73. [Medline].

  109. Rommens JM, Iannuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. Sep 8 1989;245(4922):1059-65. [Medline].

  110. Rowe MI, Furst AJ, Altman DH, Poole CA. The neonatal response to gastrografin enema. Pediatrics. Jul 1971;48(1):29-35. [Medline].

  111. Rowe MI, Seagram G, Weinberger M. Gastrografin-induced hypertonicity. The pathogenesis of a neonatal hazard. Am J Surg. Feb 1973;125(2):185-8. [Medline].

  112. Rozmahel R, Wilschanski M, Matin A, et al. Modulation of disease severity in cystic fibrosis transmembrane conductance regulator deficient mice by a secondary genetic factor. Nat Genet. Mar 1996;12(3):280-7. [Medline].

  113. Santulli T. Meconium ileus. Pediatric Surgery. 1980.

  114. Shalev J, Navon R, Urbach D, et al. Intestinal obstruction and cystic fibrosis: antenatal ultrasound appearance. J Med Genet. Jun 1983;20(3):229-30. [Medline].

  115. Snouwaert JN, Brigman KK, Latour AM, et al. A murine model of cystic fibrosis. Am J Respir Crit Care Med. Mar 1995;151(3 Pt 2):S59-64. [Medline].

  116. Sontag MK, Corey M, Hokanson JE, Marshall JA, Sommer SS, Zerbe GO, et al. Genetic and physiologic correlates of longitudinal immunoreactive trypsinogen decline in infants with cystic fibrosis identified through newborn screening. J Pediatr. Nov 2006;149(5):650-657. [Medline].

  117. Stephan U, Busch EW, Kollberg H, Hellsing K. Cystic fibrosis detection by means of a test-strip. Pediatrics. Jan 1975;55(1):35-8. [Medline].

  118. Sung V, Hutson J. A novel way to diagnose cystic fibrosis in the neonate with a bowel obstruction and possible meconium ileus. J Paediatr Child Health. Dec 2003;39(9):720. [Medline].

  119. Tsui LC. Cystic Fibrosis Mutation Database. 2005;[Full Text].

  120. van Doorninck JH, French PJ, Verbeek E, et al. A mouse model for the cystic fibrosis delta F508 mutation. EMBO J. Sep 15 1995;14(18):4403-11. [Medline]. [Full Text].

  121. Vinograd I, Mogle P, Peleg O, et al. Meconium disease in premature infants with very low birth weight. J Pediatr. Dec 1983;103(6):963-6. [Medline].

  122. Welsh MJ, Anderson MP, Rich DP, et al. Cystic fibrosis transmembrane conductance regulator: a chloride channel with novel regulation. Neuron. May 1992;8(5):821-9. [Medline].

  123. White H. Meconium ileus: a new roentgen sign. Radiology. Apr 1956;66(4):567-71. [Medline].

  124. Wilcox DT, Borowitz DS, Stovroff MC, Glick PL. Chronic intestinal pseudo-obstruction with meconium ileus at onset. J Pediatr. Nov 1993;123(5):751-2. [Medline].

  125. Wilschanski MA, Rozmahel R, Beharry S, et al. In vivo measurements of ion transport in long-living CF mice. Biochem Biophys Res Commun. Feb 27 1996;219(3):753-9. [Medline].

  126. Wood BP, Katzberg RW, Ryan DH, Karch FE. Diatrizoate enemas: facts and fallacies of colonic toxicity. Radiology. Feb 1978;126(2):441-4. [Medline].

  127. Wrobleski D, Wesselhoeft C. Ultrasonic diagnosis of prenatal intestinal obstruction. J Pediatr Surg. Oct 1979;14(5):598-600. [Medline].

  128. Yamashita T, Asano K, Takahashi N, Akatsu T, Udagawa N, Sasaki T, et al. Cloning of an osteoblastic cell line involved in the formation of osteoclast-like cells. J Cell Physiol. Dec 1990;145(3):587-95. [Medline].

  129. Zeiher BG, Eichwald E, Zabner J, et al. A mouse model for the delta F508 allele of cystic fibrosis. J Clin Invest. Oct 1995;96(4):2051-64. [Medline]. [Full Text].

  130. Ziegler MM. Meconium ileus. Curr Probl Surg. Sep 1994;31(9):731-77. [Medline].

  131. Zinner MJ, Schwartz SI, Ellis H. Section XV: Pediatrics -Meconium Ileus. Maingot's Abdominal Operations 10th ed. 1997;2088-90.

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Further Reading

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Keywords

cystic fibrosis, CF, meconium ileus, MI, simple meconium ileus, complicated meconium ileus

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Contributor Information and Disclosures

Author

Michael S Irish, MD, Adjunct Clinical Assistant Professor, Department of Surgery, University of Iowa; Consulting Pediatric Surgeon, Department of Pediatric Surgery, Blank Children's Hospital and Children's Hospital Physicians Group
Michael S Irish, MD is a member of the following medical societies: International Pediatric Endosurgery Group and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Philip M Bovet, DO, MPH, Resident Physician in Family Medicine, University of Wisconsin Health Clinic
Philip M Bovet, DO, MPH is a member of the following medical societies: American Academy of Family Physicians, American Medical Association, American Osteopathic Association, and Wisconsin Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Denis Bensard, MD, Director, Pediatric Trauma, Division of Pediatric Surgery, Children's Hospital of Denver; Associate Professor, University of Colorado Health Sciences Center
Denis Bensard, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Surgeons, American Pediatric Surgical Association, Association for Academic Surgery, and Society of University Surgeons
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Gail E Besner, MD, John E Wilson Endowed Professor of Neonatal Research, Nationwide Children's Hospital; Professor of Surgery and Pediatrics, Department of Surgery, Ohio State University College of Medicine; Director, Pediatric Surgical Research, Department of Surgery, Nationwide Children's Hospital
Gail E Besner, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Burn Association, American College of Surgeons, American Gastroenterological Association, American Medical Association, American Medical Women's Association, American Pediatric Surgical Association, Association for Academic Surgery, Federation of American Societies for Experimental Biology, Society of Critical Care Medicine, Society of Surgical Oncology, and Society of University Surgeons
Disclosure: Nothing to disclose.

CME Editor

H Biemann Othersen Jr, MD, Professor of Surgery and Pediatrics, Emeritus Head, Division of Pediatric Surgery, Medical University of South Carolina
H Biemann Othersen Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association for the Surgery of Trauma, American Burn Association, American Cancer Society, American College of Surgeons, American Medical Association, American Pediatric Surgical Association, American Society for Parenteral and Enteral Nutrition, American Surgical Association, American Thoracic Society, British Association of Paediatric Surgeons, Society for Surgery of the Alimentary Tract, Society of Critical Care Medicine, South Carolina Medical Association, Southeastern Surgical Congress, Southern Medical Association, Southern Society for Pediatric Research, and Southern Thoracic Surgical Association
Disclosure: Nothing to disclose.

Chief Editor

Marleta Reynolds, MD, Professor of Surgery, Feinberg School of Medicine, Northwestern University; Interim Head, Department of Surgery and Surgeon in Chief, Head, Division of Pediatric Surgery, Children's Memorial Hospital of Chicago
Marleta Reynolds, MD is a member of the following medical societies: American Pediatric Surgical Association
Disclosure: Nothing to disclose.

 
 
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