Causes of intra-abdominal calcification include meconium peritonitis, enterolithiasis, cholelithiasis, and fetus in fetu.
Meconium peritonitis is the most common cause of intra-abdominal calcifications.
Cystic fibrosis is seen in only 8% to 13.5% of cases of fetal meconium peritonitis in contrast to 15% to 40% postnatally.
Enterolithiasis is often associated with rectourinary fistula as in imperforate anus or cloaca.
Enterolithiasis can be seen in bowel obstruction such as jejunoileal atresia or total colonic Hirschsprung’s disease.
Fetus in fetu is distinguished by the presence of well-formed long bones or vertebral bodies.
The most common causes of intra-abdominal calcifications include hepatic calcifications, meconium peritonitis, enterolithiasis, cholelithiasis, and fetus in fetu. The topic of hepatic calcification is fully covered in Chapter 69 and will not be covered further except to indicate how these can be distinguished from other causes of intra-abdominal calcifications.
Perforation of the bowel that occurs antenatally leads to a sterile chemical peritonitis referred to as meconium peritonitis, which is the most common cause of intra-abdominal calcifications. The peritonitis can be localized or diffuse and can lead to a fibrotic reaction with intraperitoneal calcifications. The clinical manifestations of meconium peritonitis depend on its underlying cause, timing, and whether or not the perforation heals spontaneously. The spectrum of disease ranges from asymptomatic intra-abdominal calcifications to giant cystic meconium peritonitis (Robertson et al., 1994; Dirkes et al., 1995; Kamata et al., 2000; Tseng et al., 2003; Zangheri et al., 2007). Meconium peritonitis has been associated with intestinal atresia or stenosis, meconium ileus, internal hernia, bowel ileus, intussusception, gastroschisis, Meckel diverticulum, and cytomegalovirus infection (Pletcher et al., 1991; Petrikovsky et al., 1993).
The presence of associated anomalies is unusual and depends on the underlying cause of meconium peritonitis. Up to 15% to 40% of neonates with meconium peritonitis have cystic fibrosis (Park and Grand, 1981; Payne and Nielsen, 1983). However, in prenatally diagnosed meconium peritonitis, cystic fibrosis is reported to be the cause in only 8% to 13.5% of cases (Foster et al., 1987; Dirkes et al., 1995; Casaccia et al., 2003). This apparent discrepancy may be due to the increased sensitivity of prenatal sonographic imaging in detecting abdominal calcification, as compared with postnatal plain films (Williams et al., 1984). It has also been suggested that sonographically detected calcifications could be due to fetal viral infection due to parvovirus B19, cytomegalovirus, herpes viruses, or even taxoplasmosis (Casaccia et al., 2003). It is also possible that cystic fibrosis is less likely to cause calcification due to the deficiency of pancreatic enzymes (Foster et al., 1987). The incidence of cystic fibrosis increases if there are other additional sonographic findings such as dilated bowel and hyperechoic bowel. The presence of calcifications alone suggests the risk of cystic fibrosis of 13% and if associated with evidence of obstruction at 24% (Casaccia et al., 2003). The risk of cystic fibrosis in meconium peritonitis is 330 times the risk in the general population, and the risk of cystic fibrosis in neonatal bowel obstruction is 600 times as high as the general population (1 in 2500) (Casaccia et al., 2003). Enterolithiasis, which is intraluminal calcification of meconium, is a more unusual course of intra-abdominal calcification (Lubusky et al., 2006). Enterolithiasis has been described in association with a number of conditions including imperforate anus, gastrointestinal atresias or stenosis, functional ileal obstruction, and total colonic Hirschsprung's disease (Rickham, 1957; Berdon et al., 1975; Felman et al., 1975; Martin et al., 1976; Cook, 1978; Fletcher and Yullish, 1978; Daneman and Martin, 1979; Berger and Bar-Maor, 1980; Bear and Gilsanz, 1981; Yousefzadeh et al., 1984; Pouillaude et al., 1987; Anderson et al., 1988). Perhaps the most commonly diagnosed setting is in patients with anorectal malformation and rectourinary fistula (Anderson et al., 1988). However, only 10 cases of prenatally diagnosed enterolithiasis associated with anorectal malformations have been reported (Mandell et al., 1992; Pohl-Schickinger et al., 2006; Pohl-Rolle et al., 2008).
The mechanism of calcification of intraluminal meconium has not been fully elucidated. It is assumed that meconium, urine, stasis, and low intraluminal pH may be pre-requisites (Shimotake et al., 2006). Most cases of anorectal malformation and rectourethral fistula, however, do not have enterolithiasis. Rolle et al. speculated that relative urinary outflow obstruction would cause reflux of more urine into the colon predisposing to calcification of meconium (Rolle et al., 2008). Shimotake et al., (2006) performed infrared spectrophotometry of intraluminal meconium calculi occurring in a case of anorectal malformation with associated rectourethral fistula. These stones were found to consist of ammonium hydrogen urate having the combined constituents of urine and meconium.
Enterolithiasis can occur in the absence of a rectourethral fistula presumably as a result of stasis and low intraluminal pH. Enterolithiasis has been observed in such cases because of intestinal atresia and total colonic Hirschsprung’s disease (Cook, 1978; Fletcher and Yullish, 1978; Yousefzadeh et al., 1984; Miller et al., 1988; Dirkes et al., 1995). It has been suggested that in these cases, the bowel proximal to the intestinal obstruction will have stasis of meconium and swallowed urine (amniotic fluid), in which case urate would become concentrated by fluid resorption by the bowel predisposing to stone formation.
Little is known about the natural history of fetal cholelithiasis. Analysis of a fetal gallstone has never been performed, and it is currently unknown if these stones are primarily made up of cholesterol or pigment or are of mixed type. Cholesterol stones occur as a result of numerous factors, present to varying degrees, acting in concert to promote hepatic secretion of bile saturated with cholesterol, gallbladder stasis, and altered gallbladder secretory function (Carey, 1989). Bile supersaturated with cholesterol is a prerequisite for cholesterol stone formation (Gilger, 1993). Pigment gallstone formation requires bile stasis and the enzymatic hydrolysis of bilirubin glucuronide into free bilirubin and glucuronic acid. Free unconjugated bilirubin, which is insoluble in water, then combines with calcium in the bile to produce the calcium bilirubinate matrix of pigment stones. Brown et al., (1992) observed a number of fetuses with echogenic material in the fetal gallbladder, which they presumed to be sludge. Allen et al. (1981) have demonstrated in adults that this echogenic sludge is composed of calcium bilirubinate crystals.
While numerous predisposing factors for gallstones have been identified in infants and children, with the exception of one case, no predisposing risk factors have been present in reported cases of fetal cholelithiasis (Beretsky and Lonkin, 1983; Heigne and Ednay, 1985; Klingensmith et al., 1988; Brown et al., 1992; Devonald et al., 1992; Suchet et al., 1993; Clarke and Roman, 1994; Munjuluri et al., 2005; Sheiner et al., 2006). One infant diagnosed prenatally with gallstones was found to have hereditary spherocytosis (Beretsky and Lonkin, 1983). Similarly, maternal predisposing factors, other than pregnancy, have been rare. Predisposing factors were present in only four mothers with hemolytic anemia, gallstones in one, and the presence or history of gallstones in three others. While six other mothers had sickle cell trait and one had hemoglobin A1C trait, neither condition is associated with hemolysis.
Fetus in fetu is a rare anomaly in which a fetus incorporates well-differentiated tissue of its monozygotic twin (Khadaroo et al., 2000). Fetus in fetu occurs most commonly in the retroperitoneum of the upper abdomen, although it has been reported to occur in the scrotum, skull, mediastinum, mouth, and adrenal gland (Aoki et al., 2004; Brand et al., 2004). Fetus in fetu may be confused with meconium pseudocyst or a teratoma. The feature that distinguishes fetus in fetu is the presence on histologic examination of well-differentiated tissues or organs (Gross and Clatworthy, 1951; Griscom, 1965)
Meconium peritonitis occurs in approximately 1 in every 35,000 livebirths (Olsen et al., 1982; Pan et al., 1983). No estimates are available for enterolithiasis. The incidence of fetal cholelithiasis is not known. Unlike cholelithiasis in children or adults, there is no apparent sex predominance for fetal cholelithiasis. Fetus in fetu is estimated to occur in fewer than 1 in 500,000 livebirths (Iyer et al., 2003).
A spectrum of findings may be observed with meconium on prenatal sonographic examination. The most consistent finding is extraluminal abdominal calcifications, which are present in 85% of cases (Figure 70-1A). Meconium peritonitis is the most common cause of fetal intra-abdominal calcifications. The sonographic criteria used for the diagnosis of meconium peritonitis include intra-abdominal calcifications often plaquelike or linear echogenicities that cause acoustic shadowing not caused by solid organ, intraluminal, intravascular, biliary, or tumor calcifications. Other associated findings include polyhydramnios, in 50% fetal ascites, and bowel dilatation in 27% of cases (Foster et al., 1987). The presence of dilated bowel, cysts, or ascites usually predicts complicated meconium peritonitis that will require postnatal surgical intervention. Dirkes et al., (1995) divided sonographically diagnosed cases of fetal intra-abdominal calcifications into simple and complex categories. Simple meconium peritonitis has isolated calcifications seen without any bowel dilatation, meconium pseudocysts, ascites, or polyhydramnios (see Figure 70-1A). Intra-abdominal calcifications in association with any of these features are classified as complex meconium peritonitis (see Figure 70-1B).
Prenatal sonographic image demonstrating isolated intraperitoneal calcifications with acoustic shadowing. This represents a case of simple meconium peritonitis. B. In contrast, this fetus has intraperitoneal calcifications with an associated meconium pseudocyst and ascites. This is an example of complex meconium peritonitis.
While not sufficient for a diagnosis, meconium peritonitis often starts as an echogenic bowel that goes on to perforate with subsequent formation of intraperitoneal calcifications. Serial sonography is indicated to follow this progression. Similarly, simple meconium peritonitis may evolve into complex meconium peritonitis with the development of bowel dilatation, meconium pseudocyst, ascites, or polyhydramnios (Dirkes et al., 1995). Conversely, complex meconium peritonitis with calcifications associated with ascites may see the perforation with resolution of ascites converting from complex to simple meconium peritonitis. The bowel in these cases may heal without atresia or stenosis. This is the presumed sequence of events in which the only evidence of meconium peritonitis is meconium periorchitis (Várkonyi et al., 2000).
Some have proposed classification schemes dividing meconium peritonitis into type I (large meconium ascites), type II (large pseudocyst), or type III (intra-abdominal calcifications and/or resolving ascites or shrinking pseudocyst) (Tseng et al., 2003).
Zangheri et al., (2007) suggest grade 0 for isolated intra-abdominal calcifications; grade 1 for intra-abdominal calcifications and ascites, pseudocyst, or bowel dilation; grade 2 for two associated findings; and grade 3 for all sonographic features present.
In contrast to meconium peritonitis, enterolithiases are calcifications within the bowel lumen. These are often multiple, small, stippled calcifications in contrast to linear, plaquelike calcifications seen in meconium peritonitis. Enterolithiasis often is seen in association with dilated bowel loops and evidence of urinary tract dilation. Calcifications with the bladder may also be observed in the setting of communication between bowel and bladder as in rectourinary fistula or cloaca.
Fetal gallstones are seen as echogenic foci within the lumen of the gallbladder, with associated distal shadowing (Figure 70-2). Brown et al., (1992) have also included echogenic foci within the gallbladder’s lumen with either no associated distal shadowing or “comet-tail” or V-shaped artifact. However, echogenic foci without associated distal shadowing more likely represent biliary sludge due to calcium bilirubinate. It is important to distinguish intraluminal calcifications because of fetal gallstones from intrahepatic calcifications, calcified hemangiomas or hamartomas in the liver, or intra-abdominal calcifications due to meconium peritonitis. The best sonographic confirmation is seeing the echogenic foci with associated distal shadowing clearly within the echolucent gallbladder lumen (see Figure 70-2). Sepulveda et al. (1995) reported 8 cases of cholecystomegaly, in which three were found to have aneuploidy (two trisomy 18 and one trisomy 13). While they suggested that cholecystomegaly may be a sonographic marker of aneuploidy, Petrikovsky and Klein (1995) challenged this view. They suggested that the cholecystomegaly may have been due to gallstones or sludge and did not represent a new marker for aneuploidy.
Ultrasound of a fetus at 24 weeks of gestation demonstrating dilated gallbladder and an echogenic gallstone with acoustic shadowing (arrow).
Fetus in fetu may be mistaken for meconium pseudocyst or teratoma. However, when well-formed vertebral bodies or long bones are seen, this allows a definitive diagnosis to be made.
MRI may be useful in distinguishing not only the cause of intra-abdominal calcifications but also associated findings such as bowel dilation due to atresia, stenosis, volvulus, or intussusception. The presence and definition of complex anorectal malformations with rectourethral fistula or cloaca may be diagnosed. Similarly, characteristic features of fetus in fetu may be more apparent when MRI is obtained as an adjunct to ultrasound.
The differential diagnosis of intra-abdominal calcification includes meconium peritonitis, fetal gallstones, hepatic calcifications, calcifications within hemangiomas, hematomas, and tumors such as dermoid, hepatoblastoma, neuroblastoma, or teratoma, and in fetus in fetu. Calcifications may also be observed in congenital infections such as cytomegalovirus and toxoplasmosis. Intra-abdominal calcifications also may be due to intraluminal calcification from reflux of urine into the colon in imperforate anus with retrourethral fistula or from stasis due to intestinal atresia or total colonic Hirschsprung’s disease.
Several lesions associated with calcifications may be mistaken for gallstones. Calcifications may be seen in the fetal liver within hematomas, hemangiomas, or hamartomas. Calcifications may also be seen in the right upper quadrant as the result of meconium peritonitis, calcified adrenal cyst, hematoma, or neuroblastoma (see Chapters 69 and 113). Calcifications may occur within the lumen of the colon in cases of imperforate anus with rectourethral fistula as a result of urine reflux into rectal lumen (Selke and Cowley, 1978; Miller et al., 1988). These calcifications may be seen proximal to the transverse colon. Hematomas and polyps within the wall of the gallbladder are echogenic but do not cause acoustic shadowing (Durrell et al., 1984).
ANTENATAL NATURAL HISTORY
The natural history of intra-abdominal calcifications depends on the underlying etiology. In meconium peritonitis diagnosed in utero, the natural history is markedly different from meconium peritonitis diagnosed in the newborn nursery. The overall mortality rate in antenatal reports is 11% to 15% (Foster et al., 1987; Chabulinski et al., 1992; Dirkes et al., 1995; Zangheri et al., 2007). This differs markedly from the mortality rates of 40% to 50% in postnatal series (Park and Grand, 1981; Payne and Nielsen, 1983; Tibboel et al., 1986).A major factor in the survival of patients with meconium peritonitis is the underlying cause. Tibboel et al., (1986) found that primary intestinal obstruction was present in 53% of 1084 neonatal cases of meconium peritonitis reviewed and reported a 54% mortality rate among their own 22 cases (Tibboel et al., 1986). Brugman et al. (1979) reported a 62% mortality rate in cases of meconium peritonitis that were associated with obstruction caused by atresia.
Prenatally diagnosed meconium peritonitis differs from postnatally diagnosed meconium peritonitis in reduced morbidity, lower incidence of cystic fibrosis, and an overall better prognosis (Dunne et al., 1983; Chabulinski et al., 1992; Dirkes et al., 1995; Tseng et al., 2003; Zangheri et al., 2007). It is clear that a prenatal ultrasound examination is more sensitive in detecting intra-abdominal calcifications than postnatal plain radiographs, and this may account for more cases with less severe meconium peritonitis being detected in utero (Dunne et al., 1983; Williams et al., 1984; Foster et al., 1987; Zangheri et al., 2007). Asymptomatic calcifications in hernia sacs, scrotal masses, and the abdomen are common incidental findings detected postnatally (Berdon et al., 1967; Thompson et al., 1973; Gunnn et al., 1978; Marchildon, 1978; Várkonyi et al., 2000). These asymptomatic patients may have had bowel perforations in utero that sealed spontaneously and represent the postnatal equivalent of simple meconium peritonitis. Estroff et al. (1992) reported a case of fetal ascites that resolved, leaving abdominal calcifications that were asymptomatic at birth. Because many cases are clinically silent, neonatal series of meconium peritonitis are skewed by sicker infants with more severe meconium peritonitis and a higher attendant morbidity and mortality rate (Dirkes et al., 1995). The natural history of meconium peritonitis diagnosed in utero more clearly reflects the entire spectrum of the disease (Dirkes et al., 1995).
The natural history of enterolithiasis will vary depending on the underlying cause ranging from isolated atresia to complex anorectal malformations with rectourinary fistula. Cases of small-bowel atresia without associated cystic fibrosis have an excellent prognosis. These cases may develop polyhydramnios in the third trimester if the level of obstruction is sufficiently proximal. A small-bowel atresia or obstruction due to intussusception may go on to perforation resulting in meconium peritonitis (see above). Enterolithiasis that occurs as a result of urine refluxing into the colon in cases of complex anorectal malformations has a variable prognosis. Polyhydramnios is unusual in these cases because of the low level of obstruction. At the most severe end of the spectrum would be anorectal septum malformation sequence consisting of the absence of the perineal and anal opening in association with ambiguous genitalia and urogenital, colonic, and lumbosacral anomalies. This is usually lethal in the newborn period because of pulmonary hypoplasia from oligohydramnios (Lubusky et al., 2006). But less severe forms such as cloaca or imperforate anus with rectourinary fistula can have a much more favorable outcome albeit with the need for complex reconstructive surgery.
Although fewer than 35 cases of fetal gallstones have been reported, some aspects of the antenatal natural history have been established. The diagnosis of fetal gallstones has no adverse consequences for the pregnancy. It requires no alteration in the delivery plan and is not associated with fetal loss. Despite recognized associations with gallstones postnatally, few prenatally diagnosed cases have had risk factors for gallstones, with the exception of a single case of hereditary spherocytosis (Beretsky and Lonkin, 1983; Brown et al., 1992). Similarly, predisposing factors, other than pregnancy, were identified rarely in mothers, the most common maternal risk factor being a history of gallstones (Brown et al., 1992). In one case there had been placental abruption with placental hematoma and it was suggested that a possible pigment load might predispose to fetal gallstones (Brown et al., 1992).
Stasis of bile within the gallbladder has been shown to be a critical factor in the pathogenesis of gallstones of any type. Bile stasis is thought to be an important causative factor in gallstone formation during pregnancy (Braverman et al., 1980). It is possible that the hormonal influences predisposing to maternal bile stasis and gallstone formation may affect their fetuses similarly.
Estrogen is a recognized risk factor for gallstones and its levels are known to increase in pregnancy from 14 to 40 weeks (Beischer and Brown, 1972). Estrogen is known to increase cholesterol secretion in bile and depress bile acid synthesis (Cotran et al., 1989). This progressive rise in estrogen levels during the later trimesters may account for fetal cholelithiasis being observed only in the third trimester.
Infants diagnosed prenatally with gallstones appear to have no clinical sequelae. If echogenic foci are associated with distal shadowing, 20% resolve postnatally, but 62% resolve if associated with comet-tail shadowing, and 75% resolve if associated with no distal shadowing (Brown et al., 1992). The remainder of infants with cholelithiasis appear to be asymptomatic. However, awareness of fetal cholelithiasis is important because symptoms referable to the biliary tract may be difficult to diagnose in infants and children. Only awareness of gallstones as a potential cause of symptoms will allow prompt recognition and treatment and minimal morbidity (Jacir et al., 1986).
The natural history of fetus in fetu is remarkably good, usually having no impact on the prenatal course of the pregnancy. It is important to distinguish fetus in fetu from teratoma as the latter has the risk of malignancy developing in up to 10% of patients (Coolen et al., 2007). There has been only a single case of malignant recurrence in fetus in fetu (Hopkins et al., 1997).
Fetal intra-abdominal calcifications detected by prenatal ultrasound examination should prompt an effort to determine whether these represent biliary, vascular, intraluminal, solid organ, or tumor calcifications; enterolithiasis; intraperitoneal calcification of meconium peritonitis; or fetus in fetu. Intrahepatic calcifications are discussed in Chapter 69. The presence of associated findings, such as dilated loops of bowel, meconium pseudocysts, ascites, and polyhydramnios should be excluded. Because these findings may develop later in gestation, serial sonography is advisable. In the absence of the findings that characterize complex meconium peritonitis, bowel obstruction, or severe complex anorectal anomalies such as urorectal septum malformation sequence, an excellent prognosis can be anticipated and delivery in a community setting can be safely recommended (Dirkes et al., 1995). In cases of enterolithiasis, atresia, or anorectal malformation, delivery in a setting in which these anomalies can be fully evaluated and treated postnatally should be considered. Even in simple meconium peritonitis, however, a postnatal abdominal radiographic examination should be obtained, and if normal, feedings can be initiated. The presence of other associated findings such as pseudocyst, ascites, bowel obstruction, enterolithiasis, anorectal malformation, or fetus in fetu will require additional diagnosis-specific evaluation using a combination of ultrasound, MRI, and voiding cystourethrogram (VCUG).
In cases of meconium peritonitis in which associated abnormalities such as bowel dilatation, meconium cysts, ascites, or polyhydramnios are prenatally diagnosed, there is up to a 52% chance that surgical intervention will be required during the newborn period (Dirkes et al., 1995; Tseng et al., 2003; Zangheri et al., 2007). Consideration should be given to delivery of the infant with complex meconium peritonitis in a tertiary care center.
Although the reported incidence of cystic fibrosis in neonatal meconium peritonitis ranges from 15% to 40%, three of the patients reported by Dirkes et al., (1995) had normal sweat tests and the remaining patients had no clinical manifestations of cystic fibrosis. Other prenatal series of meconium peritonitis have reported only an 8% incidence of cystic fibrosis (Boureau and Pat, 1974; Park and Grand, 1981; Finkel and Slovis, 1982; Foster et al., 1987; Chabulinski et al., 1992). Why the incidence of cystic fibrosis is lower in prenatally diagnosed meconium peritonitis is unknown. Finkel and Slovis, (1982) postulated that pancreatic enzymes, which are deficient in 80% of patients with cystic fibrosis, may be necessary for calcification to occur (Boureau and Pat, 1974). Conversely, Foster et al., (1987) speculated that the thick tenacious nature of meconium in cystic fibrosis precludes free spillage into the peritoneum.
Sonographic detection of meconium peritonitis can alert the obstetrician to a fetus potentially at risk for complications from obstruction, perforation, pseudocyst formation, ascites, and polyhydramnios that may precipitate preterm labor and premature delivery. Pediatric surgical consultation may be helpful in providing counseling about the overall favorable prognosis in cases of prenatally diagnosed meconium peritonitis. In cases of complex meconium peritonitis, the parents can be advised of a more guarded prognosis, with a 50% chance of surgical intervention during the neonatal period. Parental DNA testing to define the fetal risk for cystic fibrosis may be appropriate in cases of meconium peritonitis (Robertson et al., 1994). This can be performed by a referral laboratory on blood samples or mouth swabs from the parents. If both parents are carriers and the pregnancy is at less than 24 weeks of gestation, fetal testing for cystic fibrosis mutations may be indicated if termination of the pregnancy is an option for the parents. If an amniocentesis is being performed for other reasons, consideration should be given to testing amniocytes for mutations seen in cystic fibrosis.
A fetus with enterolithiasis should be followed closely for complications related to bowel obstruction, including polyhydramnios and preterm labor. Fetal MRI is indicated to help delineate the underlying etiology, the presence of rectourinary fistula, cloaca, imperforate anus, or intestinal atresia. Delivery should be planned in a setting with appropriate pediatric surgical expertise to manage any of the causes of enterolithiasis.
The diagnosis of fetal gallstones has no implications for the management of the pregnancy. A detailed history should be obtained for risk factors for maternal cholelithiasis. In addition, the mother should have an ultrasound examination to screen for the presence of gallstones.
The fetus diagnosed with fetus in fetu is not likely to develop complications but bowel compression and polyhydramnios can occur. Delivery should take place in a facility with pediatric surgical and radiologic expertise to manage this problem in the newborn.
There are no fetal interventions for any of the causes of intra-abdominal calcifications.
The infant should undergo abdominal examination immediately after delivery and an abdominal radiograph and ultrasound study of the abdomen should be obtained to confirm the prenatal findings (Figure 70-3). In the case of meconium peritonitis, an upper gastrointestinal study with small-bowel follow-through using water-soluble contrast may be necessary to confirm or exclude perforation, stenosis, atresia, or meconium pseudocysts (Figure 70-4). Postnatal treatment is directed by the underlying cause of meconium peritonitis. Abdominal radiography will confirm intra-abdominal calcification and demonstrate the presence or absence of cystic lesions or intestinal obstruction. Asymptomatic neonates with calcifications and otherwise normal plain abdominal radiographs and abdominal sonographic examinations may be cautiously observed and fed. If dilated bowel, meconium cysts, or ascites are present, nasogastric decompression and intravenous fluids should be administered. Associated anomalies should be evaluated and surgical correction performed when the infant is stable. A sweat chloride test or testing for DNA mutations should be performed during the postoperative period to exclude or definitively diagnose cystic fibrosis in all cases of meconium peritonitis. DNA analysis is preferable in newborns presenting with gastrointestinal symptoms. If DNA analysis reveals the presence of a mutation in the cystic fibrosis transmembrane regulator gene, sweat testing is unnecessary, as some mutations have been found in patients with normal sweat tests (Highsmith et al., 1994).
Plain abdominal radiograph in a newborn demonstrating intra-abdominal calcifications, particularly over the dome of the liver and in the scrotum.
Upper gastrointestinal contrast study with small-bowel follow-through demonstrating extra-abdominal contrast in a meconium pseudocyst in the right lower quadrant.
Physical examination in cases of prenatally diagnosed enterolithiasis is important to exclude imperforate anus or cloaca as an underlying cause. Plain radiographs and ultrasound may be helpful in making a diagnosis, but contrast studies and MRI scans may be necessary to define the anatomy.
The newborn with a prenatal diagnosis of fetal cholelithiasis should have a postnatal ultrasound examination performed during the newborn period. In healthy term infants, sonographic observation alone is indicated unless symptoms develop. The diagnosis of acute or chronic cholelithiasis may be difficult in an infant, but should be suspected with vomiting, irritability, or ileus. Gallstones associated with predisposing risk factors that are detected during the newborn period resolve spontaneously in 75% of cases with elimination of these risk factors–for example, by treatment with diuretics or total parenteral nutrition. It is unclear if gallstones with distal shadowing on an ultrasound examination performed in utero will spontaneously resolve during infancy. The only data on this came from Brown et al. (1992), who observed spontaneous resolution in 40% of cases of fetal gallstones when associated with acoustic shadowing. The higher rate of spontaneous resolution they observed, when echogenic foci were present without acoustic shadowing, may have been because they were “sludge” rather than true gallstones.
In cases of suspected fetus in fetu, ultrasound and plain radiographs may be adequate to confirm the diagnosis if a well-formed long bone or vertebral column is observed. CT or MRI may provide anatomic relations helpful in planning surgical resection.
The infant with complex meconium peritonitis will require surgical intervention in 50% of cases (Dirkes et al., 1995). The indications for surgery include intestinal perforation with ascites, meconium pseudocyst, intestinal atresia or stenosis, or volvulus. Surgical exploration for complications of meconium peritonitis may be extremely difficult because of the intense inflammatory reaction that occurs within the peritoneal cavity (Figure 70-5). Because of this and bacterial contamination of the peritoneal cavity, cases of meconium peritonitis complicated by perforation or meconium pseudocyst are best managed by resection and enterostomy. In cases of volvulus, the nonviable intestine is resected and proximal and distal stomas are created. In cases involving the proximal intestine, long-term venous access can be obtained to provide parenteral nutritional support until gastrointestinal continuity can be established.
Intraoperative appearance of meconium peritonitis in a newborn with a perforated colon. Note the adhesions, which are the results of an inflammatory reaction that occurred in utero.
Atresias most often will be amenable to resection and primary anastomoses but may require significant parenteral nutritional support if short gut or dysmotility are associated with the atresia. Anorectal malformations, particularly when associated with rectourinary fistula usually require initial diversion (see Chapter 76) as does a persistent cloaca (see Chapter 85).
The surgical management of fetus in fetu is usually straight forward with resection of the retroperitoneal mass causing few difficulties. Adjacent structures are usually displaced and there is a clear plane of dissection.
In asymptomatic infants diagnosed with fetal gallstones, we currently recommend observation only. If gallstones are radiopaque, periodic plain radiographs may be obtained to observe for spontaneous resolution. If stones are radiolucent, sonographic surveillance is recommended. We have a low threshold for performing cholecystectomy, as symptoms of acute or chronic cholecystitis in infants are often vague and nonspecific, and once it is symptomatic, acute cholecystitis is associated with a high rate of complications (Brill et al., 1982).
In infants undergoing abdominal surgery for other indications, such as pyloric stenosis or intestinal atresia, we recommend a cholecystectomy, as it can be performed with little additional morbidity.
The long-term outcome of infants with intra-abdominal calcification depends on the underlying cause. In fetuses with simple meconium peritonitis, the prognosis is excellent. In complex meconium peritonitis, the prognosis relates to the underlying cause of the perforation. In isolated meconium peritonitis, without cystic fibrosis, Hirschsprung’s disease, or intestinal pseudo-obstruction, the prognosis is excellent. In infants with cystic fibrosis or chronic pseudo-obstruction, however, the prognosis is more guarded. Enterolithiasis associated with urorectal septal malformations has a grim prognosis, but patients with anorectal malformation or cloaca have an excellent prognosis following reconstruction. The awareness of cholelithiasis in an infant leads to early intervention once symptoms referable to the gallbladder develop. Asymptomatic gallstones require no intervention. There are no long-term sequelae associated with a diagnosis of fetal cholelithiasis. Similarly, cases of fetus in fetu have an excellent outcome following resection.
GENETICS AND RECURRENCE RISK
There is no known risk of recurrence for intra-abdominal calcifications. However, the approximately 8% of antenatally diagnosed meconium peritonitis associated with cystic fibrosis are at a 25% risk for recurrence in subsequent pregnancies. Enterolithiasis has not been reported to recur in subsequent pregnancies.
There are no data on risk of recurrence of cholelithiasis in subsequent pregnancies. If maternal risk factors for cholelithiasis are present, such as a history of hemolytic anemia or of gallstones, a prenatal ultrasound examination during the third trimester is indicated to screen for an affected fetus. Hereditary spherocytosis is inherited as an autosomal dominant disorder. If the family history reveals that either parent is affected, the fetus has a 50% risk of inheriting this gene. Sickle cell anemia is inherited as an autosomal recessive disorder, with a 25% risk of recurrence. Other inherited enzyme abnormalities of the erythrocyte, such as pyruvate kinase deficiency, are associated with development of gallstones.
et al. Sludge is calciumbilirubinate associated with bile stasis. Am J Surg. 1981;141:51-–55.
et al. Enterolithiasis with imperforate anus. Report of two cases with sonographic demonstration and occurrence in a female. Pediatr Radiol. 1988;18:130-–133.
et al. MRI reveals fetus in fetu in the mediastinum. Pediatr Radiol. 2004;34:1017-–1019.
V Calcified meconium and persistent cloaca. AJR Am J Roentgenol. 1981;137:867-–868.
JB Current status of estrogen assays in obstetrics and gynecology. 2: Estrogen assays in late pregnancy. Obstet Gynecol Surv. 1972;27:303-–343.
et al. Scrotal masses in healed meconium peritonitis. N Engl J Med. 1967;277:585-–587.
et al. Calcified intraluminal meconium in newborn males with imperforate anus. Enterolithiasis in the newborn. Am J Roentgenol Radium Ther Nucl Med. 1975;125:449-–455.
DH Diagnosis of fetal cholelithiasis using real-time high-resolution imaging employing digital detection. J Ultrasound Med. 1983;2:381-–383.
JA Intraluminal intestinal calcifications in a newborn with atresia of the esophagus and imperforate anus. Clin Pediatr. 1980;19:770-–772.CrossRef
D Valeur diagnostique des calcifications intraperitoneales au cours de la peritonite meconiale. J Parisiennes Pediatr. 1974;9:149-–152.
et al. Fetus in fetu—diagnostic criteria and differential diagnosis—a case report and literature review. J Pediatr Surg. 2004;39:616-–618.
Jr Effects of pregnancy and contraceptive steroids on gallbladder function. N Engl J Med. 1980;302:362-–365.
et al. Echogenic material in the fetal gallbladder: sonographic and clinical observations. Radiology. 1992;182:73-–76.
et al. Sonographic findings with radiologic correlation in meconium peritonitis. J Clin Ultrasound. 1979;7:305-–306.
MC. Formation of cholesterol gallstones: the new paradigms. In: Baumgartner
W, eds. Trends in bile acid research. Dordrecht, the Netherlands: Kluwer; 1989:259-–281.
et al. The impact of cystic fibrosis on neonatal intestinal obstruction; the need for prenatal/neonatal screening. Pediatr Surg Int. 2003;19:75-–78.
G Meconium peritonitis: extrusion of meconium and different sonographical appearances in relation to the stage of the disease. Prenat Diagn. 1992;12:631-–636.
JD The outcome of two cases of fetal cholelithiasis. NZ Med J. 1994;107:270-–273.
et al. Fetus-in-fetu: confirmation of prenatal diagnosis with MRI. Prenat Diagn. 2007;27:73-–76.
SL Robblin’s Pathologic Basis of Disease. 4th ed. Philadelphia, PA: WB Saunders; 1989:966-–970.
DJ A syndrome of multiple gastrointestinal atresias with intraluminal calcification. Pediatr Radiol. 1979;8:227-–231.
PB The variable appearance of fetal gallstones. J Ultrasound Med. 1992;11:579-–585.
et al. Prenatal natural history of meconium peritonitis diagnosed in utero. J Pediatr Surg. 1995;30:979-–982.
CCJ Sonographic features of bowel perforation and calcific meconium peritonitis in utero. Pediatr Radiol. 1983;13:231-–233.
CA Gallbladder ultrasonography in clinical context. Semin Ultrasound CT MR. 1984;5:316-–317.
BR Fetal meconium peritonitis without sequelae. Pediatr Radiol. 1992;22:277-–278.
et al. Supralevator imperforate anus with unusual associated anomalies: colonic ureteral ectopy, intraluminal calcified meconium. Pediatr Radiol. 1975;3:78-–80.
TL Meconium peritonitis, intraperitoneal calcifications and cystic fibrosis. Pediatr Radiol. 1982;12:92-–93.
BS Intraluminal calcifications in the small bowel of newborn infants with total colonic aganglionosis. Radiology. 1978;126:451-–455.
et al. Meconium peritonitis: prenatal sonographic findings and their clinical significance. Radiology. 1987;165:661-–665.
MA. Cholelithiasis and cholecystitis. In: Wyllie
JS, eds. Pediatric gastrointestinal disease. Philadelphia: Saunders; 1993:931-–944.
NT The roentgenology of neonatal abdominal masses. AJR Am J Roentgenol. 1965;93:447-–463.
HG Healed meconium peritonitis presenting as a reducible scrotal mass. J Pediatr. 1978;92:847-–849.
D The development of fetal gallstones demonstrated by ultrasound. Radiography. 1985;51:155-–156.
et al. A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. N Engl J Med. 1994;331:974-–980.
et al. Fetus-in-fetu with malignant recurrence. J Pediatr Surg. 1997;32:1476-–1479.
F Multiple fetuses in fetu: imaging findings. Pediatr Radiol. 2003;33(1):53-–55.CrossRef
et al. Cholelithiasis in infancy: resolution of gallstones in three of four infants. J Pediatr Surg. 1986;21:567-–569.
et al. Meconium peritonitis in utero. Pediatr Surg Int. 2000;16:377-–379.
et al. Fetus-in-fetu presenting as cystic meconium peritonitis: diagnosis, pathology, and surgical management. J Pediatr Surg. 2000;35:721-–723.
et al. Fetal enterolithiasis: prenatal sonographic and MRI diagnosis in two cases of urorectal septum malformation (URSM) sequence. Prenat Diagn. 2006;26:345-–349.
et al. The prenatal diagnosis of imperforate anus with rectourinary fistula: dilated fetal colon with enterolithiasis. J Pediatr Surg. 1992;27:82-–84.
MB Meconium peritonitis and spontaneous gastric perforations. Clin Perinatol. 1978;5:79-–81.
RA Multiple gastrointestinal atresias, with intraluminal calcifications and cystic dilatation of bile ducts: a newly recognized entity resembling ‘a string of pearls’. Pediatrics. 1976;57:268-–271.
et al. Neonatal abdominal calcification: is it always meconium peritonitis? J Pediatr Surg. 1988;23:555-–556.
et al. Spectrum of meconium disease in infancy. J Pediatr Surg. 1982;17:479-–481.
et al. Radiographic diagnosis of meconium peritonitis: a report of 200 cases including 6 fetal cases. Pediatr Radiol. 1983;13:199-–205.
RJ Gastrointestinal manifestation of cystic fibrosis: a review. Gastroenterology. 1981;81:1143-–1161.
AM Meconium peritonitis. Am Surg. 1983;28:224-–231.
B Meconium peritonitis mimicking urinary ascites. Fetus. 1993;3:9-–12.
et al. Intrauterine cytomegalovirus infection presenting as fetal meconium peritonitis. Obstet Gynecol. 1991;78:903-–905.
et al. Echogenic foci in the dilated fetal colon may be associated with the presence of a rectourinary fistula. Ultrasound Obstet Gynecol. 2006;28:341-–344.
P, Tran Minh
et al. Enterolithiasis in two neonates with oesophageal and anorectal atresia. Pediatr Radiol. 1987;17:419-–421.
et al. Prenatal diagnosis and management of gastrointestinal anomalies. Semin Perinatol. 1994;18:182-–195.
et al. Bladder outlet obstruction causes fetal enterolithiasis in anorectal malformation with rectourinary fistula. J Pediatr Surg. 2008;43:e11-–e13.
CE Calcified intraluminal meconium in a female infant with imperforate anus. AJR Am J Roentgenol. 1978;130:786-–788.
NM Fetal cholecystomegaly: a prenatal mocker of aneuploidy. Prenat Diagn. 1995;15:193-–197.
R Fetal gallstones detected by routine third trimester ultrasound. Int J Gynaecol Obstet. 2006;92:255-–256.
et al. Infrared spectrophotometry of intraluminal meconium calculi in a neonate with imperforate anus and rectourethral fistula. J Pediatr Surg. 2006;41:1173-–1176.
et al. Fetal cholelithiasis: a case report and review of the literature. J Clin Ultrasound. 1993;21:198-–202.
DM Healed meconium peritonitis presenting as an inguinal mass. J Urol. 1973;110:364-–366.
JC The importance of mesenteric vascular insufficiency in meconium peritonitis. Hum Pathol. 1986;17:411-–416.
ES Meconium peritonitis in utero: prenatal sonographic findings and clinical implications. J Chin Med Assoc 2003;66:355-–359.
et al. Meconium periorchitis: case report and literature review. Eur J Pediatr Surg. 2000;10:404-–407.
et al. Sonographic demonstration of the progression of meconium peritonitis. Obstet Gynecol. 1984;64:822-–826.
et al. Intraluminal meconium calcification without distal obstruction. Pediatr Radiol. 1984;14:23-–27.
et al. Fetal intra-abdominal calcifications from meconium peritonitis: sonographic predictors of postnatal surgery. Prenat Diagn. 2007;27:960-–963.