Address correspondence to: Luc De Catte, MD, Academic Hospital, Dept. of Obstetrics and Gynecology, Free University of Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium. Ph: 32-2-477-6531; Fax: 32-2-477-6505

Introduction

Meconium peritonitis is a sterile inflammatory reaction in the fetal abdomen resulting from in utero bowel perforation that nearly always involves the small bowel. Its prevalence is 0.29 in 10,000 live-births [2,3]. In the neonatal period, meconium peritonitis presents as an intestinal obstruction and requires surgical exploration. This form was first described by Morgagni in 1761 [3]. On rare occasions, this chemical peritonitis heals spontaneously without clinical manifestation. Attention to this type of pathology was drawn by the finding of intraperitoneal, inguinal or scrotal masses or calcifications [4]. However, differential diagnosis with other intraperitoneal tumors or testicular neoplasm caused some unnecessary surgeries. Since the introduction of ultrasound, 40 cases of meconium peritonitis with associated findings, investigation and outcome have been reported. Recently, the natural history of meconium peritonitis and, even more exceptional, the extrusion of the meconium plug has been depicted [2].

The prenatal diagnosis process should include: testing for cystic fibrosis, chromosomal abnormalities and congenital anatomical or structural anomalies as well as the chemical and histologic analysis of the peritoneal fluid obtained by fetal paracentesis [5,6]. The resulting diagnosis is of paramount importance in formulating a management plan for the obstetrical and perinatal management of the patient.

We present a patient with spontaneous in utero regression of meconium peritonitis. Neonatal surgery was required to treat ileal atresia.

Case report

A G₁P₀ woman was referred to our unit for a detailed ultrasound scan after diagnosis of fetal ascites at 29 weeks of gestation. This 30-year-old woman became pregnant only after several attempts of intrauterine insemination. The first trimester of pregnancy evolved uneventfully. However, at 16 weeks of gestation, the patient was admitted for an acute appendicitis. Recovery was complete after appendectomy. A detailed sonogram at 21 weeks showed a normal developing fetus. At 29 weeks of gestation, abundant ascites with debris, a clustering of hyperechogenic intestines with no peristalsis and an echogenic spot was observed on the diaphragmatic aspect of the liver were observed (Image 1-2).

The differential diagnosis included a chromosomal malformation, congenital viral infection, meconium peritonitis secondary to bowel perforation due to cystic fibrosis or mechanical bowel obstruction.

Fetal blood and ascitic fluid were obtained for chromosomal, microbiological, DNA, liver enzymes and hematologic analysis. These analysis revealed a normal female karyotype. Fetal hematological values and fetal liver enzymes were normal. Fetal DNA analysis to exclude cystic fibrosis was negative for the most common deletions. Light microscopic analysis of fetal ascites, however, revealed intra- and extrahistiocystic dark-stained amorphous sediments and numerous inflammatory cells (Image 3). The diagnosis of meconium peritonitis secondary to mechanical bowel obstruction and perforation was made.

A remarkable recovery was sonographically observed over the next 4 weeks. Fetal ascites regressed spontaneously and bowel peristalsis reappeared. However, intestinal contents remained echogenic (Image 4). At 38 weeks of gestation, labor was induced and a girl of 3000g was born.

Physical examination revealed a healthy newborn. The abdomen was not distended, and a plain X-ray failed to show dilated bowel loops. However, small nonparenchymal calcified areas in the left hypochondrium were observed. A few hours after the first feeding, the baby started vomiting meconial fluid. Abdominal radiography revealed distension of the small bowel loops without intraperitoneal air. Surgical exploration of the neonatal abdomen demonstrated multiple small atretic ileal segments. A 25cm bowel fragment including the proximal dilated part was removed, followed by an end-to-end anastomosis (Image 5).

Postoperative evolution was uncomplicated, and the baby is thriving well. Serial sweat chloride tests performed in the neonatal period were negative. On histological examination, the submucosal layer of bowel wall showed various degrees of inflammatory reaction. Distal to the atretic area, a meconium plug was found. The ileal atretic segment was characterized by an intraluminal septum, causing a type 1 ileal atresia (Image 6). A small bowel perforation was surrounded by subserosal calcifications (Image 7).

Discussion

Definition

Meconium peritonitis is a sterile chemical peritonitis which is most frequently the result of intrauterine small bowel perforations.

Prevalence

Meconium peritonitis is a rare condition occurring in 1/35,000 live births [1]. This figure is probably underestimated because of spontaneous regression of the inflammatory process and sealing of the perforated intestinal area, without neonatal clinical manifestations.

Etiology

Any condition causing bowel obstruction may be responsible for bowel distension and perforation, leading to a sterile chemical peritonitis. Meconium ileus, which related to cystic fibrosis in 90% of cases, accounts for less than 25%. More frequently, mechanical bowel obstruction is provoked by intestinal atresia, volvulus, intussusception or herniation. Exceptionally colonic aganglionosis, resulting in an aperistalsis and a microcolon, is responsible for a meconium ileus and perforation of the intestinal wall [1,3,5].

Analysis of 40 cases of prenatally detected meconium peritonitis (Table 1) revealed an etiologic factor in only 20 of them; intestinal obstruction due to volvulus or atresia; accounted for 75% (15/20); cystic fibrosis for 20% and congenital infection for 5% (1/20). The large majority of cases, however, lacked information about perinatal analysis for cystic fibrosis.

Pathology - pathogenesis

Meconium formation starts in the third month of gestation. Some components -lipases, bile acids and salts - are particularly irritating.

Dilatation of the bowel loops leads to local vascular impairment of the intestinal wall, necrosis and subsequent perforation. Some authors suggest that an intestinal hypoperfusion, as a result of fetal hypoxia, is the primary cause of bowel atresia and perforation. Bowel peristalsis forces meconium and digestive enzymes into the peritoneal cavity, resulting in an intense chemical inflammatory process. Within days, giant cells and histiocytes surround the extruded meconium to form foreign body granulomas and calcifications. Depending on the spread of the inflammatory response, three pathological types are distinguished. In the generalized type, characterized by diffuse peritoneal fibrotic thickening and calcium deposits, the meconium spread throughout the peritoneal cavity. The fibroadhesive variant, which is the most common, produces obstruction by adhesive bands sealing the perforated site. If the perforated site is not effectively sealed, a thick-walled cyst is formed by adhesion of the proximal bowel loops to the perforated site. So the perforated intestinal area communicates only with the newly formed pseudocyst, which is lined by a calcified wall.

Associated malformations

Cystic fibrosis is associated with meconium ileus and subsequent meconium peritonitis in about 15% of the cases [3]. Newer data that analyze the Cystic Fibrosis Transconductance Receptor gene suggest that the association is higher. Characteristic findings in the second and early third trimester include highly echogenic intra-abdominal masses. In the third trimester, often enlarged bowel loops are observed [7]. Parental carrier detection and prenatal diagnosis by DNA analysis is possible in about 70% of cases related to the mutation in DF₅₀₈ allele on chromosome 7⁸. Neonatal investigation should include repetitive sweat chloride tests.

Polyhydramnios is present in 10-64% of cases and has been attributed to difficulty in swallowing as the result of deficient bowel peristalsis [2,9]. On rare occasions, fetal hydrops may be present.

Diagnosis and differential diagnosis

Prenatal diagnosis is suspected when fetal intra-abdominal calcifications are observed, especially in association with fetal ascites and polyhydramnios [5]. Fetal bowel obstruction associated with fast developing fetal ascites or hydrops should alert the sonographer. On rare occasions, however, fetal ascites regresses, intestinal dilatation disappears and peristalsis reappears. Only hyperechoic area remains [2,9]. Sometimes, intra-abdominal meconium pseudocysts are the sole remnants of the meconium peritonitis. Fetal abdominal hyperechoic masses or pseudocysts have recently been associated with congenital infections [11], chromosomal abnormalities and cystic fibrosis [12,13]. Differential diagnosis further includes hematometrocolpos, ovarian, urachal, mesenteric and retroperitoneal cysts, and rare intra-abdominal tumors [8].

Prenatal investigation by fetal blood sampling should detect chromosomal abnormalities, rule out cystic fibrosis by DNA analysis and exclude congenital infection through fetal hematological, immunological and hepatic investigation. More precise information about fetal ascites and bowel perforation can be obtained by fetal paracentesis and histological analysis of the aspirated fluid. As observed in our case and as previously reported by Baxi6 an intense inflammatory reaction is present together with intra- and extracellular amorphous material.

Prognosis

Prenatal detected cases of meconium peritonitis most frequently have a fair prognosis, as proven by a rather low perinatal mortality rate (6/40). Exclusion of chromosomal or rare infectious etiologies results in a perinatal survival rate of more than 80% (Table 1). In about 35% of cases no surgical exploration was needed. The intense chemical peritonitis may seal the intestinal perforation permanently. Fifty percent of the newborns had a laparotomy and intestinal exploration, with resection of atretic or perforated segments in most cases.

Long-term prognosis is strongly affected by the presence of cystic fibrosis resulting in pancreatic insufficiency and digestive disturbances, multiple respiratory infections and chronic lung disease. Therefore, prenatal investigation should include DNA analysis of the DF₅₀₈ mutation on chromosome 7, or repetitive sweat-chloride tests in the neonatal period. However, the association of cystic fibrosis and meconium peritonitis has been made only in 15/40 reported cases: 4 neonates were found positive for cystic fibrosis.

Table 1: Review of the literature (Gray background cells represent fatal outcome)

Management

Frequent sonographic observation permits the evaluation the amount of fetal ascites, the evolution of intra-abdominal calcification and the restoration of bowel peristalsis. Exclusion of chromosomal malformations, congenital infections and cystic fibrosis is an essential element in the further management. Early diagnosis may change the couple's attitude towards termination of pregnancy [5].

If meconium peritonitis resolves spontaneously, there is no need for induction of labor. Postnatal observation of bowel peristalsis and a plain radiography of the neonatal abdomen should alert the pediatrician. Surgical exploration might be necessary.

In case of progressive deterioration of fetal condition with increasing amount of ascites, preterm delivery can be considered in a tertiary care center. Postnatal surgery will be required immediately. Cesarean section has not been proven to improve neonatal outcome [5].

References

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