Address correspondence to: Boris Petrikovsky, MD, PhD, Division of Maternal Fetal Medicine and Department of Radiology, North Shore University Hospital, Cornell University Medical College, 300 Community Drive, Manhasset, NY 11030-3876. Ph: 516-562-2892 Fax: 516-562-3624.

Synonyms: Cholelithiasis, calculi.

Definition: Mobile echogenic foci in the fetal gallbladder.

Prevalence: Unknown.

Etiology: A possible association with maternal sickle cell anemia, hemolytic anemia, and abruptio placenta has been discussed in the literature. Placental estrogens may also contribute to the formation of fetal gallstones. Gallstones in the maternal gallbladder have been detected in some cases^l .

Associated anomalies: None.

Differential diagnosis: Liver calcifications.

Prognosis: Favorable. Most fetal gallstones resolve spontaneously.

Recurrence risk: Unknown.

Management: The presence of fetal gallstones does not alter the obstetrical management. Fetal gallstones should not serve as an indication for repeat sonographic assessment. The value of neonatal follow-up has not been established.

MESH Cholelithiasis CDC 751.6 ICD9 751.645

Introduction

Fetal gallstones are rare findings on prenatal sonograms. Most resolve spontaneously prior to delivery. Brown et al.^l reported the largest series of fetal gallstones which included 26 fetuses. We present the sonographic and neonatal outcome in fetuses with echogenic material in the gallbladder and bile ducts.

Case reports

Case #1

A 36-year-old G₁P₀ patient underwent her first prenatal ultrasound at 14 ½ weeks of pregnancy during an amniocentesis performed because of advanced maternal age. Fetal intracranial, thoracic and abdominal (including gallbladder) anatomy appeared normal. A repeat ultrasound examination was performed at 34 weeks of gestation to rule out liver calcifications felt to be present on a follow-up sonographic examination performed by the obstetrician to assess fetal growth. The interval growth was normal. Multiple echogenic structures were visualized within the gallbladder (fig. 1). The gallbladder was somewhat prominent, but the liver appeared normal.

Figure 1: Gallstones in the gallbladder neck.

The patient had a normal vaginal delivery of a 3600g infant, with Apgar scores of 8 and 10 at 1 and 5 minutes, respectively. An abdominal ultrasound performed at 24 hours of life revealed a 5 mm echogenic structure in the gallbladder and a 2 mm structure in the cystic duct. A follow-up abdominal ultrasound at 30 days of age demonstrated total resolution of echogenic structures within the gallbladder. At 6 months, the infant has been developing normally.

Case #2

A 24-year-old white G₃P₂ patient was referred to the Fetal Diagnosis and Treatment Unit at 28 weeks of gestation to assess intra-abdominal calcifications seen during routine ultrasound examination and presumed to be within the fetal liver. The repeat ultrasound examination demonstrated normal intracranial and intrathoracic anatomy. Gallstones were identified within the gallbladder (fig. 2). The liver had a normal ultrasound appearance. A follow-up ultrasound examination showed no change in the echogenic structures within the gallbladder at 32, 36, and 40 weeks of gestation. A follow-up neonatal abdominal ultrasound examination revealed a normal gallbladder without gallstones.

Figure 2: Gallstones in the gallbladder neck.

Case #3

A 28-year-old G₁P₀ patientwas referred to North Shore University Hospital Fetal Diagnosis and Treatment Unit for a targeted ultrasound. Fetal intracranial and thoracic anatomy appeared unremarkable. Fetal biometry was consistent with 37 weeks of gestation. Two echogenic structures were identified within the fetal gallbladder and one within the projection of the cystic duct in the close proximity to the gallbladder neck (fig. 3).

Figure 3: Small and large gallstones.

A follow-up neonatal ultrasound performed within 24 hours of neonatal life revealed a normal appearing gallbladder with no trace of stones or sludge.

Discussion

Incidence

Fetal gallstones are a very rare finding on prenatal ultrasound^2,3,4. Brown et al.¹ reported the largest series of fetal gallstones in 26 patients. Echogenic material in the gallbladder was observed only in third trimester fetuses and resolved spontaneously postnatally in the majority of infants. No predisposing risk factors for developing fetal gallstones were identified in any of these series. Twelve percent of fetuses had a single echogenic focus, 73% had multiple foci, and the remaining 15% had a diffuse filling of the lumen of the gallbladder. In seven of these cases, the authors provided information on the maternal gallbladder: gallstones were present in four cases and absent in three. Total resolution of prenatal findings occurred within 30 days of life in our series.

Differential diagnosis

The differential diagnosis of fetal gallstones includes singular or multiple calcifications within the fetal liver. In our series, two out of three cases were referred for the targeted ultrasound because of suspected echogenic foci within the fetal liver. Careful assessment allowed us to localize the echogenic foci within fetal gallbladder. Correct identification of fetal gallstones allows for adequate counseling and avoids unnecessary work-up and maternal anxiety.

Pathogenesis

Two major theories in the formation of fetal gallstones have been proposed:

• the presence of a placental hematoma with subsequent breakdown of hemoglobin to bilirubin.

• increased cholesterol secretions and depressed bile acid synthesis caused by estrogens².

None of our patients, as well as the ones reported by other investigators^1,3,4, had signs of retroplacental hematoma.

Etiology and natural history

The natural history of fetal gallstones seems to be very different from that of children and adults. Gallstones in adults and children grow at about 1 to 2 mm per year, occurring many years before clinical symptoms appear. Gallstones do not continually form in the gallbladder but probably nucleate as crops of stones that then grow at the same rate⁵. However, even in adults, the precipitation of cholesterol is a reversible process: crystals can be eliminated either by spontaneous dissolution or passage into the small intestine^6,7. Most gallstones are clinically silent. Sixty-six to 80 percent of adults with gallstones detected on epidemiological screening surveys are asymptomatic and remain so on long-term follow-ups. Gallbladder motility decreases once stones develop. Some, but not all, patients with cholelithiasis have impaired gallbladder emptying⁵.

Fetal gallstones have a tendency to form in the third trimester of pregnancy. We observed gallstones in a 26 week fetus, which represents the earliest reported case in the literature. In the series of Brown et al¹, the mean gestational age at the time of diagnosis was 36.2 weeks, with a range of 28 to 42 weeks.

Natural history of fetal gallstones

Disappearance of fetal gallstones which occurs in the majority of cases has two possible explanations:

• spontaneous passage of the gallstones during early neonatal period or

• the dilution of cholesterol crystals with postnatal hydration.

The fact that we were able to detect gallstones in the bile ducts may favor the first hypothesis in which fetal gallstones are passed. Regardless of the mechanism, total resolution of fetal gallstones is not universal. Some gallstones diagnosed in utero may persist for several months and years¹.

Fetal gallstones, including those in the bile ducts, are rare but benign findings which should be differentiated from intrahepatic calcifications which can be associated with an adverse perinatal outcome.

References

1. Brown DL, Teele RL, Doubilet PM, et al. Echogenic material in the fetal gallbladder: sonographic and clinical observations. Radiology 1992; 182:73-76.

2. Beretsky I, Lankin DH. Diagnosis of fetal cholelithiasis using real-time high-resolution imaging employing digital detection. J Ultrasound Med 1983; 2:381-383.

3. Heijne L, Ednay D. The development of fetal gallstones demonstrated by ultrasound. Radiographics 1985; 51:155-15.

4. Klingensmith WC, Cioffi-Ragan DT. Fetal gallstones. Radiology 1988; 167:143-144.

5. Shaffer EA. Gallbladder disease. In Walker WA, Durie PR, Hamilton JR, Walker-Smith JA, Watkins JB (eds). Pediatric gastrointestinal disease. Philadelphia, BC Decker Inc.1993; 11:152-60.

6. Ren PL, Liu CD, Lee TL, et al. Ultrasonographic assessment of intraluminal gallbladder masses. J CU 1994; 22:401-4.

7. Lee SP, Meher K, Nichills J. Origin and fate of biliary sludges. Gastroenterology 1989; 94:172-6.

Originally published in The Fetus in 1994, posted 6/1999