* Department of Gynecology, Félix Guyon’Hospital ** Gynecologist, Jeanne D’Arc clinic *** Radiologist, 6th, Savannah street,  Réunion Island, France

Definition: The fetal gallstones are mobile echogenic foci in the fetal gallbladder.  Gallstones have been ignored so far and the ultrasound screening in search of fetal anomalies have failed to refer to it as a possible issue of malformation (1).

Synonyms: Fetal gallstones; cholelithiasis; calculi; mobile echogenic foci in the fetal gallbladder (2).

Case report: This is a 36-year-old woman, G5P4, referred at 36 weeks due to a hyperechoic lesion on the fetal gallbladder. There were no associated anomalies. There was no evidence of ascites or hydrops.

The infant was born vaginally at 38 weeks (3500g). The baby was in good health (Apgar 10/10). There was no evidence of hematological incompatibility, sepsis and jaundice. All tests including cystic fibrosis gene, hemoglobinopathy and liver function were normal. At day 5, a scan was performed and a normal size gallbladder with different gallstones was diagnosed. Weekly ultrasound examinations were performed and the gallstones disappeared at one month of age.

Transverse section of the abdome showing the gallstones

History: The prenatal diagnosis of fetal gallstones or cholelithiasis was first described by Beretsky and Lankin in 1992 (3). The first series of fetal gallstones was described by Bronshtein.

Prevalence: The prevalence of fetal gallstones is unknown and very few cases have been described. Neonatal gallstones have an incidence of 1.5% (1). According to Bronshtein, the incidence of fetal gallstones is 0.15% but this incidence was based in a selected private population in their study (4). Some authors described that fetal gallstones are more common in boys.  Brown et al reported the largest series of fetal gallstones (including 26 fetuses) and no predisposing factor for developing fetal gallstones were identified.

Etiology: Although cholelithiasis is uncommon in the first year of life, in the pediatric patient it is a well-established disorder, frequently associated with pathological conditions as hemolytic disease; cholestasis; intestinal malabsorption; family history of gallstones; obesity and idiopathic condition (5). Gallstones are also found more frequently in infants who develop ileum pathologies; biliary tract congenital; anomalies and/or cholestatasia related to septic states, furosemide use, phototherapy, overfeeding and Down syndrome (6). The hypotheses (unproved) advanced to explain the formation of echogenic material in the fetal gallbladder are:

In some cases of hemorrhage (as placenta hemorrhage), there is a subsequent breakdown of hemoglobin that transforms into bilirubin, crosses the placenta and increases the fetal levels of indirect bilirubin.
Another theory describes that an increased level of oestrogen might predispose to the formation of pigment stones by increasing the secretion of cholesterol and reducing the synthesis of biliary acids.

The use of narcotics during the pregnancy is another hypothesis to explain gallstone formation in fetal life.

Hemolytica anemia, RHD incompatibility and anomalies such as choledochal cyst are considered as risk factors (5).

The only common factor in some series on the literature is that the echogenic foci in the fetal gallbladder are a third trimester phenomenon with no apparent explication predominance (7-8). Kiserud et al, in their study (1.656 obstetric scans) described that no echogenic gallbladder contents were found before 28 weeks. In the subgroup of 523 fetuses examined during 28–42 weeks, only six fetuses were found to have echogenic material in the gallbladder. The echogenicities were found in patients who had the following:

• extra-amniotic hematoma with IUGR and oligohydramnios
• tetralogy of Fallot
• trisomy 21 with atrioventricular septal defect and transient
• ascites
• early abnormally distended fetal gallbladder
• chromosomal aberration (translocation 10; 11) with bilateral clubfoot, and  gastroschisis (9).

In our case, the fetal gallstones were an incidental finding. We did not find any risk factor or associated malformation. After birth, the baby was in good health.

Pathogenesis: The natural history of fetal gallstones is different in children from the adults. Gallstones in adults and children grow at about 1 to 2 mm per year, occurring many years before clinical symptom appear. During fetal life, the gallbladder forms at about 7 weeks and bile formation starts at 14 weeks. Anomalies of fetal biliary tree that have been detected sonographically incudes choledochal cyst and fetal cholelithiasis (4). Gallstones have a tendency to form in the third trimester of pregnancy. Disappearance occurs in the majority of cases (dissolution or spontaneous passage of the gallstones during early neonatal period? dilution of cholesterol crystals with postnatal hydratation ?). The natural history and clinical significance of echogenic foci in the fetal gallbladder are unknown. The sludge is made up of a precipitation of calcium, pigment and cholesterol element (calcium bilirubinate granules and cholesterol crystals) and is the precursor of gallstones (8).

Sonographic findings: Fetal cholelithiasis has been an extremely uncommon ultrasound finding. The fetal gallbladder appeared on the basis of the lack of acoustic shadowing, to contain sludges and no stones. The sludge is made up of a precipitation of calcium, pigment and certainly cholesterol element. The different developmental stages during which sludges can be found within the fetal gallbladder may explain the variable sonographic appearance. The lack of acoustic shadowing in some cases of sludge or small echogenic foci may be explained by the fact that very small stones may not cause shadowing if they do not lie in the center of the beam. Single or multiple hyperechoic structures with a posterior acoustic shadow inside the fetal gallbladder, with or without regular flat borders and no posterior echogenic shadows can be seen.

Differential diagnosis: The differential diagnosis includes:

• Infection: CMV, Herpes, Parvovirus B19
• Meconium peritonitis
• Subphrenic sequestration of the lung
• Hemangioendothelioma
• Intrahepatic calcifications: they should be differentiated from gallstones, because the intrahepatic calcifications can be associated with an adverse perinatal outcome.

Associated anomalies: there are no associated anomalies.

Prognosis: The outcome of fetuses with gallstones is very good. In the majority of the cases there is a complete spontaneous resolution after birth but postnatal follow-up until resolution is recommended. Nevertheless when the fetal echogenic foci persist and when the child is asymptomatic, treatment must be conservative.

Management: The management involves a postnatal scan to confirm the number and appearances of the stones as well as to exclude biliary tract abnormality. In our case, no biliary tract abnormality was seen. Most fetal gallstones resolve spontaneously. The presence of echogenic material within the gallbladder is probably a rare finding in the fetus and the list of predisposing factors known for postnatal life seems not to be applicable to prenatal diagnosis. Nevertheless the presence of fetal gallstones does not alter the obstetrical scrupulous management. The value of neonatal follow up has not been established.

References:
Akute O.O., Marinho A.O., Kalejaiye A.O., Sogo K.- Prevalence of gallstone in a group of antenatal women in Ibadan, Nigeria. Afr J Med  Med Sci 1999; 28: 159-61.
Jeanty P., Shah S., jeanty C.- 2004-10-06-12 gallstones, video clip @ jeanty www.thefetus.net/
Beretsky I., Lankin D.H.- Diagnosis of fetal cholelithiasis using real-time high resolution imagin employing digital detection. J Ultrasound med 1983 ; 2 : 381-3.
Bronshtein M., Weiner Z., Abramavici H., H., Filmar S., Erlik Y., Blumenfeld Z.- Prenatal diagnosis of gall bladder anomalies-report of 17 cases.
Munjuluri N.,Elgharaby N., Acolet D., Abdul Kadir R.- fetal gallstones. Fetal Diagn Therapy 2005 ; 20 : 241-3.
 Devonald KJ, Ellwood DA, Colditz PB. The variable appearances of fetal gallstones.J Ultrasound Med. 1992 Nov;11(11):579-85.
Klingensmith WC 3rd, Cioffi-Ragan DT..Radiology. 1988 Apr;167(1):143-4. Fetal gallstones.
Suma V., Marini A., Buci N., Toffolutti T., Talenti E.- Fetal gallstones : sonographic and clinical observations. Ultrasound Obstet Gynecol 1998; 12 : 439-441.
Kiserud T., Gjelland K., Bognø H., Waardal M., Reigallstonestad H., Rosendahl K.- Echogenic material in the fetal gallbladder and fetal disease. Ultrasound Obstet Gynecol 1997; 10: 1469-71.