TABLE 1.

Developmental Changes in Hepatic Metabolism, Biotransformation, and Enterohepatic Circulation

Low rates of gluconeogenesis and glucose use by the fetal liver
Amino acids are an important energy source for fetal liver (transamination and oxidative degradation)
Decreased capacity of the neonatal liver to metabolize, detoxify, and excrete xenobiotics
Decreased levels of many enzymes involved in oxidation, reduction, and conjugation reactions
Early expression of many CYP enzymes in the embryo and fetus (eg, CYP3A7, involved in steroid metabolism)
Delayed expression of other CYP enzymes important for xenobiotic metabolism (eg, CYP1A2, important in drug metabolism)
Reduced activity of phase II enzymes (eg, UGT, NAT2) in the fetus and neonate
Decreased hepatocyte bile acid uptake, binding, and transport in the fetus and newborn
Altered conjugation and sulfation of bile acids
Decreased bile acid pool size (mostly in the premature infant)
Decreased bile flow rates and intraluminal bile acid concentration
  • UGT indicates uridine diphosphate glucuronyl transferase; NAT2, N-acetyltransferase 2.