The hepatocyte performs a multitude of essential physiologic tasks. These include production of plasma proteins, gluconeogenesis and glycogenolysis, biotransformation of toxins and chemicals, bile acid metabolism and cholesterol regulation, and bilirubin excretion. During gestation, many of these functions are performed for the fetus through placental transport and maternal hepatic function. Many of the excretory functions of the fetal liver mature only after birth. The physiologic immaturity of the newborn liver undoubtedly contributes to the pathophysiology of several neonatal diseases characterized by abnormal bile composition or flow.

Bile acids are formed in the liver by stereospecific additions and modifications of cholesterol. Bile acid metabolism is a critical determinant of cholesterol regulation and intestinal absorption of dietary fat.

The enterohepatic circulation maintains the bile acid pool by recycling excreted bile acids. This occurs through a sodium–bile acid cotransport system present on the ileal brush border. The bile acids then return to the liver through the portal circulation, where they are actively secreted by a second sodium–bile acid cotransporter across the hepatocyte canalicular membrane. Bacteria present in the jejunum and ileum metabolize a portion of the primary bile acids to secondary bile acids (deoxycholic acid, ursodeoxycholic acid, and lithocholic acid), which are passively absorbed in the colon and reenter the hepatic circulation. Lithocholate can be hepatotoxic and may contribute to
the liver damage associated with various types of cholestasis.

Bile acids are first detected in human fetuses at about 14 weeks’ gestation. The bile acid pool increases in late gestation, but remains relatively smaller in children than adults. Despite decreased bile acid pool size and diminished intestinal absorption, serum bile acids remain elevated in human infants younger than 6 months of age, implying ineffective hepatic clearance. Thus, the newborn infant is relatively predisposed to cholestasis.

Most bilirubin is the product of heme degradation derived from effete erythrocytes. Erythrocyte half-life is shorter in the fetus and neonate; therefore, production of unconjugated bilirubin is relatively greater than in the adult. Most pigment is transferred unaltered across the placenta to the maternal circulation. Bilirubin uridine 5′-diphosphate (UDP)-glucuronyltransferase, which conjugates bilirubin, is first detected at about 20 weeks’ gestation, but its activity remains low until after birth. The serum bilirubin concentration normally peaks on the third to fifth day of life in full-term newborns and gradually declines to adult levels thereafter. Bacterial flora responsible for the conversion of conjugated bilirubin to urobilin are absent or reduced in the newborn gut, which allows the enzyme β-glucuronidase to deconjugate the accumulated bilirubin. This results in the absorption of a significant load of unconjugated bilirubin from the newborn intestine and accounts for the increased jaundice seen when there is delayed passage of meconium or intestinal obstruction.

Various morphologic abnormalities of the number, shape, position, and mucosal lining of the gallbladder have been recorded. Most cases of agenesis of the gallbladder are incidental findings at autopsy or laparotomy. Estimated incidence is about 1 in 3,000 to 6,000 (1). Agenesis may be an isolated finding or it may be associated with multiple congenital malformations. An intrahepatic gallbladder can be excluded by ultrasound scan. Duplications may occur. Variations include bilobed and completely duplicated gallbladders (2). The latter have either a Y-shaped cystic duct or two separate cystic ducts, and they may be surrounded by a common serosal coat or lie in separate but adjacent fossae. It is uncertain whether duplication predisposes to cholelithiasis (3).

The gallbladder may lie to the left of the falciform ligament, and the cystic duct either enters the hepatic duct from the left or, more commonly, the common duct from the right (2,4). The condition is usually without clinical sequelae.

Gallbladder septa can be congenital or acquired, longitudinal or transverse, and single or multiple. Some are composed of fibrous tissue whereas others contain smooth muscle fibers (3). Incomplete septa predispose to cholelithiasis (5).

Ectopic gastric mucosa within the extrahepatic biliary tree is well described. The gallbladder is affected more often than the bile ducts (6). Most cases are incidental findings, but abdominal pain, cholecystitis, hemobilia, and/or obstructive jaundice have been reported.

The prevalence of gallstones in children varies according to geography and age. Ultrasound studies provide the following estimates: 0.5% of neonates in Germany (7), 0.13% to 0.2% of infants and children in Italy (8), and less than 0.13% of children in Japan (9). Most studies show a bimodal distribution with a small peak in infancy and a steadily rising incidence from early adolescence onward (10). In early childhood, boys are affected at least as often as girls, but a clear female predisposition emerges during adolescence. In Western children, there has been a consistent increase in both the prevalence of gallstones and the frequency of cholecystectomy for cholelithiasis since the mid-1970s (11,12,13,14,15). This may reflect improved detection from the widespread use of diagnostic ultrasonography and/or a genuine increase in the incidence of cholelithiasis.