Background: Neonatal and infantile cholelithiasis is an uncommon condition, increasingly recognized due to widespread use of ultrasonography. Although most cases are asymptomatic and self-limiting, gallstones in neonates may present with feeding intolerance, cholestasis, or hyperbilirubinemia.
Case Presentation: We report a preterm male twin born at 31 weeks and 2 days of gestation via lower segment cesarean section (LSCS), admitted to the neonatal intensive care unit (NICU) for respiratory distress. On day 3 of life, twin 2 developed feeding intolerance, abdominal distension, and neonatal hyperbilirubinemia. Abdominal ultrasonography revealed cholelithiasis with gallbladder sludge. Hyperbilirubinemia was managed with one day of phototherapy, resulting in normalization of serum bilirubin levels appropriate for gestational age and day of life. Conservative management was adopted, and the infant showed clinical improvement without surgical intervention.
Conclusion: Neonatal cholelithiasis in preterm infants may be associated with prematurity and phototherapy exposure. Most cases resolve spontaneously with conservative management. Awareness of this entity is important to avoid unnecessary invasive interventions.
Cholelithiasis in neonates and infants is rare, accounting for a small proportion of gallstone disease in childhood.1 Fetal and neonatal gallstones are increasingly diagnosed due to advances in ultrasonography.2,3
Predisposing factors in neonates include:1,3,4
Phototherapy has been identified as a potential contributing factor in some cases.1,4 However, up to 30–40% of infants have no identifiable risk factors.4
Most neonatal gallstones are asymptomatic and resolve spontaneously within the first year of life.2,5
We present a case of transient cholelithiasis in a preterm twin presenting with feeding intolerance and hyperbilirubinemia.
CASE PRESENTATION
A male preterm twin (Twin 2) was delivered at 31 weeks and 2 days of gestation via LSCS. Birth weight and Apgar scores were appropriate for gestational age (details available in NICU records). He was admitted to the NICU for respiratory distress, managed as per standard preterm protocol.
Day 3 of Life
The infant developed:
There was no documented hemolytic disease, congenital anomaly, or exposure to TPN.
Investigations
Fig. 1: Ultrasound images of the gallbladder showing few shadowing echogenicities of approximately 2 to 3 mm with sludge.
Ultrasound findings were consistent with descriptions in prior neonatal reports.3,4
Management
Following phototherapy, bilirubin levels normalized appropriately for gestational age and postnatal age.
The infant improved clinically, feeding intolerance resolved, and abdominal distension subsided. Surgical intervention was not required.
DISCUSSION
Neonatal and infantile cholelithiasis is an uncommon but increasingly recognized clinical entity, largely due to the widespread use of high-resolution ultrasonography in both prenatal and postnatal care. Historically considered rare, recent literature suggests that its detection has risen significantly over the past two decades.2,3 Although pediatric gallstone disease remains far less common than adult cholelithiasis, infants represent a distinct clinical subgroup with unique etiopathogenic mechanisms and a markedly different natural history.
Epidemiology and Clinical Context
The reported incidence of fetal cholelithiasis ranges from 0.07% to 1.15% in third-trimester ultrasonographic evaluations.2 Postnatally, cholelithiasis accounts for a small fraction of pediatric gallstone disease, with approximately 15% of pediatric gallstone cases occurring in infants under one year of age.4 However, true incidence may be underestimated, as many cases remain asymptomatic and are detected incidentally.
In our case, cholelithiasis was identified in a preterm infant on day 3 of life during evaluation for feeding intolerance and hyperbilirubinemia. The early presentation aligns with previous reports describing gallstones in both neonatal and early infancy periods.1,3
Pathophysiology
The mechanisms underlying neonatal cholelithiasis differ substantially from those observed in adults. In adults, cholesterol supersaturation, gallbladder hypomotility, and mucin hypersecretion are primary drivers of stone formation. In neonates, however, pigment stones predominate.
More than 70% of pediatric gallstones are pigment stones, particularly calcium bilirubinate stones.1,4 These result from:
Neonates naturally have higher bilirubin production due to increased red blood cell mass and shorter erythrocyte lifespan. In preterm infants, hepatic immaturity further compromises bilirubin conjugation and excretion, increasing biliary bilirubin concentration. Supersaturation of bile with unconjugated bilirubin may precipitate pigment stone formation.
In addition, bile stasis plays a critical role. Reduced enteral feeding, fasting, and immaturity of gallbladder contractility decrease bile flow, promoting sludge formation. This mechanism is well described in association with total parenteral nutrition.2,6 Although our patient did not receive TPN, prematurity and early feeding intolerance may have transiently impaired gallbladder emptying.
Risk Factors in the Present Case
Multiple risk factors for neonatal cholelithiasis have been described in the literature, including:1,2,4,7
Prematurity is consistently cited as a risk factor. Preterm infants have:1,4
Our patient, born at 31 weeks and 2 days, likely had transient physiological cholestasis contributing to sludge and stone formation.
Phototherapy has been implicated as a potential contributing factor.1,4 Although the mechanism is not fully established, proposed explanations include:
While causality remains unproven, several case reports note phototherapy exposure as the only identifiable risk factor. In our case, hyperbilirubinemia requiring phototherapy may have contributed to transient pigment stone formation.
Twin gestations are associated with elevated maternal estrogen and progesterone levels, which may influence fetal bile composition.2 Although fetal cholelithiasis has been described in monochorionic twins,2,7the precise contribution of twin gestation remains unclear.
Clinical Presentation
Neonatal cholelithiasis is often asymptomatic. When symptomatic, presentations may include:1,3
Our patient presented with feeding intolerance and abdominal distension, but without evidence of biliary obstruction or cholecystitis. The absence of bile duct dilation on ultrasound suggested non-obstructive disease.
It is important to distinguish gallstone-related cholestasis from more serious causes of neonatal conjugated hyperbilirubinemia such as:3
In our case, normal ductal caliber and spontaneous improvement supported a benign etiology.
Imaging Considerations
Ultrasonography remains the gold standard for diagnosis.
Typical findings include:2,3,4
Ultrasound sensitivity for gallbladder stones approaches 95%, though lower for common bile duct stones.4 In neonates, distinguishing sludge from tumefactive sludge or masses requires careful Doppler assessment.
In our case, ultrasonography demonstrated gallbladder sludge and calculi without ductal dilation, consistent with uncomplicated cholelithiasis.
Natural History and Prognosis
A striking difference between neonatal and adult gallstone disease is the high rate of spontaneous resolution in infants.
Hurni et al. (2017)2, reviewing 133 fetal cases, reported:
Similarly, Marathum Palli (2023)4 reported spontaneous resolution in most infants managed conservatively. Jeanty et al. (2015)5 concluded that invasive intervention is rarely required in infancy.
Resolution is thought to occur due to:2
Our patient demonstrated rapid clinical improvement and normalization of bilirubin following phototherapy, supporting a transient and self-limiting process.
Management Strategy
Management of neonatal cholelithiasis depends on symptomatology.
Conservative Management (Preferred in Asymptomatic Cases)
Most authors recommend conservative management in asymptomatic or mildly symptomatic infants.4,5
Medical Therapy
Ursodeoxycholic acid has been used in select cases, though evidence does not demonstrate clear superiority over observation.2
Surgical Intervention
Indications include:
Surgery is rarely required in neonates.5
Our patient required only supportive care and phototherapy, with no need for pharmacologic bile acid therapy or surgical consultation.
Clinical Implications
This case reinforces several important clinical principles:
Given the increasing use of abdominal ultrasonography in NICUs, clinicians should be aware that incidental gallstones in neonates often represent a transient physiological phenomenon rather than a surgical disease.
Summary of Key Learning Points
REFERENCES:
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