*Associate Director of Meternal-Fetal Medicine, Mary Birch Hospital for Women at Sharp Memorial Hospital, 8010 Frost Street, Suite M, San Diego, CA 92123-2786 Ph: 619-541-6880; Fax: 619-541-6899.

Synonyms:  Meconium peritonitis, meconium pseudocyst.

Definition: Meconium peritonitis and pseudocyst associated with intraperitoneal calcification, ascites, and cystic fibrosis.

Prevalence:  Rare. Cystic fibrosis occurs in 0.25:10,000 live births among whites and 0.6:10,000 live births among Blacks in North America; meconium ileus is present in approximately 15% of babies with cystic fibrosis at birth. Meconium peritonitis with pseudo­cyst formation is less common.

Pathogenesis:  Bowel perforation in utero results in meconium peritonitis and ascites. Bowel obstruction due to atresia, volvulus, intus­susception, or bands, and cystic fibrosis are the most common causes of meconium peritonitis. Factors favoring meconium pseudocyst formation in meconium peritonitis are not known.

Differential diagnosis: Ascites and intraperitoneal calcification may be caused by a wide range of conditions, including viral infections. Meconium pseudocyst has a rather characteristic appearance on ultrasound but may be confused with other intra-abdominal cysts and tumors.

Prognosis:  Depends upon the underlying pathology.

Management:  Delivery may be indicated if the ascites increases rapidly. Postnatal surgical intervention may be required.

MESH: Cystic fibrosis BDE 0237 MIM 219700 POS 3792 ICD9 277.0 CDC 277.010, 777.600

Introduction

Meconium peritonitis results from perforation of the bowel in utero. Any cause of bowel obstruction may result in meconium peritonitis; these include atresia of the bowel, volvulus, intussusception, bands, and meconium plug syndrome in cystic fibrosis. A sterile inflammatory reaction and ascites accompany bowel perforation. Depending upon the cause of the perforation, the peritonitis and ascites may resolve in utero or may persist after delivery. Meconium pseudocyst results when the meconium, rather than distributing throughout the peritoneal cavity, persists in a localized collection and is walled off; calcification of the cyst often occurs. In this report, we describe antepartum sonographic findings, postpartum radiographic studies, and prenatal DNA testing in a fetus homozygous for the D-F-508 cystic fibrosis mutation, with ascites, meconium peritonitis, and meconium pseudocyst.

Case report

The patient is a 20-year-old G₂P₂ white female, who was referred at 33 weeks" gestation for hydramnios and ascites.

The patient and her husband are natives of the United States. Both are of Northern European ancestry. They are not related. There was no family history of birth defects, and the pregnancy had been uncomplicated until a size / dates discrepancy was noted at a routine antepartum visit, one week prior to referral. Sonography showed fetal ascites.

On sonography at Sharp Perinatal Center, mild polyhydramnios, bilateral hydroceles, and ascites were noted. A large calcified cyst containing both fluid and an inhomogeneous solid component was seen in the left upper quadrant of the fetal abdomen (fig. 1). A smaller calcified mass, filled with inhomogeneous solid material, was seen closer to midline in the upper abdomen. Scattered calcification of the peritoneal surfaces of the bowel was noted (fig. 2). The remainder of a comprehensive anatomic survey was normal.

Figure 1: Transverse view of the abdomen. A large, thick-walled pseudocyst partly filled with meconium is seen in the dependent (left) side of the fetal abdomen. A smaller, thick-walled pseudocyst, filled with meconium, is seen just superior to the larger one and just anterior to the fetal spine.

Figure 2: Longitudinal view of the fetal abdomen. The larger pseudocyst

The patient was in preterm labor and was hospitalized for control of uterine activity. After tocolytic therapy, an amniocentesis was performed for lung maturity studies, karyotype determination, and testing for the most common cystic fibrosis gene (D-F-508 mutation). The L:S ratio was 2.4, with a negative PG. The patient was weaned to oral terbutaline and discharged.

Ten days later, ultrasound showed increased ascites and an increase in the size of the left upper quadrant mass. The decision was made to discontinue tocolytic therapy. The patient delivered a 2385g male infant with Apgars of 7 at 1 minute and 8 at five minutes. Radiographic studies, including a plain film of the abdomen, abdominal ultrasound, and upper gastrointestinal contrast studies, showed the neonate to have ascites, normal stomach and bowel, and two cystic masses, one adjacent to the inferior margin of the stomach, and a smaller one posterior to the liver, in the midline (fig. 3).

Figure 3:

The prenatal DNA studies returned while the patient was in labor, showing the fetus to be homozygous for the D-F-508 mutation, diagnostic of cystic fibrosis (fig. 4).

Figure 4:  Polyacrylamide electrophoresis of polymerase

The neonatal course was marked by necrotizing enterocolitis, which was medically treated. The infant progressed to oral feedings and was discharged home in stable condition, but the child was subsequently lost to follow-up.

Discussion

Frequency

Meconium peritonitis is a rare condition. Among neonates, the frequency is given as 1 in 35,000. Since some cases occurring in utero may resolve or may be clinically inapparent at delivery, the actual frequency may be higher¹. The diagnosis was reported by radiography in 1944². Prenatal sonographic diagnosis was first described in 1980, and subsequently, a number of additional cases have been described, including several in which meconium pseudocysts were identified^3-7. All of the cases were diagnosed after 24 weeks" gestation.

Pathogenesis

Meconium peritonitis occurs when in utero bowel perforation from any cause results in leakage of meconium into the peritoneal cavity. A remarkable case in which leakage was actually observed during an ultrasound examination was recently reported⁴; these authors described the flowing meconium to have "a high affinity to the surface of the liver and to the part of the umbilical vein which passed freely through the ascitesâ€. A sterile inflammatory reaction follows meconium contamination of the peritoneal cavity. In some cases, calcification results; in others, pseudocyst formation follows.

The causes of meconium peritonitis include bowel obstruction due to stricture, atresia, volvulus, intussusception, and meconium plug syndrome from cystic fibrosis⁸. In cases diagnosed after delivery, cystic fibrosis is the most frequent cause and is present in 40% of cases¹.

Cystic fibrosis is an autosomal recessive disorder that affects multiple organs. The molecular defect is still not well understood, but it produces a dysfunction of the exocrine glands, resulting in excessive sodium and chloride excretion in sweat glands and from other epithelial surfaces⁹. In cystic fibrosis, the viscosity of mucus secreted by the intestinal tract is markedly increased. It clings to the intestinal wall and is difficult to move. Inspissated and impacted meconium can fill the intestine, particularly the distal ileum. This produces intestinal obstruction - "meconium ileusâ€.

Perforation of the intestine in utero is uncommon even in cystic fibrosis. Ninety percent of babies with meconium ileus have cystic fibrosis; 10-15% of babies with cystic fibrosis present with meconium ileus¹⁰.

Differential diagnosis

The differential diagnosis at the time of prenatal sonographic evaluation includes other causes of ascites. Acites with intra-abdominal calcification also raises the possibility of congenital infection with cytomegalovirus or toxoplasmosis. Meconium pseudo­cyst must be differentiated from other intra-abdominal cysts and masses, including ovarian, urachal, mesenteric, omental, and retroperitoneal cysts, hematometrocolpos, and the extremely rare intra-abdominal tumors¹¹.

Association with cystic fibrosis

In their review of 19 cases reported between 1980 and 1987, and seven newly diagnosed cases, Foster and associates⁷ noted that the rate of cystic fibrosis in cases diagnosed in utero was lower than that in postnatal series. They also made the observation that cases with calcification were unlikely to be of cystic fibrosis: "To date, no infant with sonographically detectable peritoneal calcification has proved to have cystic fibrosis, although such cases will undoubtedly be reported in future†⁷.

Prenatal evaluation

The first step in evaluation of the fetus with ascites and suspected meconium peritonitis is a careful survey of other aspects of fetal anatomy. If no other anomalies are identified, and the fetus is not hydropic, testing of maternal blood for antibodies to red cell determinants, cytomegalovirus, and toxoplasmosis is indicated. DNA testing now affords the possibility of making the rapid and firm diagnosis of cystic fibrosis in utero in the majority of patients of Northern European ancestry.

Cystic fibrosis trait is localized on the long arm of chromosome 7. The cystic fibrosis gene codes for a protein called cystic fibrosis transmembrane regulator (CFTR). It inserts into the cell membrane and is believed to function as an anion pump regulator. The most common gene mutation results in a deletion of phenylalanine amino acid 508, within one of the ATP binding sites. This mutation, D-F-508, accounts for approximately 70% of all cystic fibrosis genes in Caucasians in North America. There are more than 50 less common mutations of the gene which account for the remainder of cystic fibrosis cases. D-F-508 allele testing can be performed from specimens obtained by chorionic villus sampling, amniocentesis, or fetal or neonatal blood^12-15.

Management

There is a paucity of information regarding the natural history of meconium peritonitis, with or without pseudocyst formation, diagnosed in utero. Therapy is empiric. Since some cases improve and may even resolve in utero, most authors recommend expectant management, unless the fetus develops rapidly progressive ascites or other signs of compromise⁸.

In the neonate with meconium peritonitis, the perforation may either have sealed off completely in utero, may seal off in the neonatal period, or may require surgical repair. Prior to labor, meconium is sterile, so that perforation does not translate into bacterial contamination. However, this can occur after delivery. Treatment consists of elimination of the obstructing meconium and evaluation of the gastrointestinal tract for continued leakage; continued leakage would be an indication for surgical repair.

Necrotizing enterocolitis, to our knowledge, has not been previously reported in meconium ileus, perforation in meconium ileus or in perforation in cystic fibrosis. The occurrence of necrotizing enterocolitis, however, is consistent with the risk factors of compromised intestinal function and prematurity.

References

1. Foster M, Nyberg D, Mahony B, et al: Meconium peritonitis: prenatal sonographic findings and their clinical significance. Radiology 165:661-5, 1987.

2. Neuhauser EBD: The roentgen diagnosis of fetal meconium peritonitis. AJR 51:421, 1944.

3. Fleischer A, Davis R, Campbell L: Sonographic detection of a meconium-containing mass in a fetus: a case report. JCU 11:103-5, 1983.

4. Chalubinski K., Deutinger J., Bernaschek G. Meconium peritonitis: extrusion of meconium and different sonographical appearances in relation to the stage of the disease. Prenat Diagn 12:631-6, 1992.

5. Lauler J, Cradock T. Meconium pseudocyst: prenatal sonographic and antenatal radiologic correlation. J Ultrasound Med 1:333-5, 1982.

6. McGahan J, Hanson F. Meconium peritonitis with accompanying pseudocyst: prenatal sonographic diagnosis. Radiology 148:125-6, 1983.

7. Fleischer A, David R, Campbell L. Sonographic detection of a meconium-containing mass in a fetus: a case report. JCU 11:103-5, 1983.

8. Romero R, Pilu G, Jeanty P, et al: Prenatal diagnosis of congenital anomalies. Norwalk: Appleton & Lange pp 243-245 1986

9. Behrman RE, ed. Cystic fibrosis. Nelson Textbook of Pediatrics, 14th Edition. Philadelphia: W.B. Saunders Co. 1992 pp 1106-1116.

10. Behrman RE, ed. Meconium ileus in cystic fibrosis. Nelson Textbook of Pediatrics, 14th Edition Philadelphia: W.B. Saunders Co, 1992 pp 475-6.

11. Nyberg DA. Intra-abdominal abnormalities. In:Nyberg DA, Mahony BS, Pretorius DH; eds. Diagnostic ultrasound of fetal anomalies: text and atlas. Chicago: Yearbook Medical Publishers, 342394, 1990.

12. Karem BS, Rommens JM, Buchanan JA, et al: Identification of the cystic fibrosis gene: genetic analysis. Science 245:1073-80, 1989.

13. Rommens JM, Kerem BS, Greer W, et al: Rapid non-radioactive detection of the major CF mutation. Am J Hum Genet 46:395-6, 1990.

14. Karem E, Lynch A. Screening for cystic fibrosis: Ethical and social issues. Am Rev Respir Dis 143:457-6, 1991.

15. Tizzano EF, Buchwald M. Cystic fibrosis: Beyond the gene to therapy. J Pediatr 120:337-49, 1992.