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 A_1C 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).

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.

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).