The liver attains its highest relative size at about 10% of fetal weight at the ninth week of gestation. Early in gestation the liver is the primary site for hematopoiesis. At 7 weeks of gestation, hematopoietic cells outnumber hepatocytes. Primitive hepatocytes are smaller than mature cells and are deficient in glycogen. As the fetus nears term, hepatocytes predominate and enlarge with expansion of the endoplasmic reticulum and accumulation of glycogen. Hepatic blood flow, plasma protein binding, and intrinsic clearance by the liver (reflected in the maximal enzymatic and transport capacity of the liver) also undergo significant postnatal maturation [1]. These changes correlate with an increased capacity for hepatic metabolism and detoxification. At birth the liver constitutes about 4% of body weight compared with 2% in the adult. Liver weight doubles by 12 months of age and increases threefold by 3 years of age.

The functional development of the liver that occurs in concert with growth requires a complicated orchestration of changes in hepatic enzymes and metabolic pathways that result in the mature capacity of the liver to undertake metabolism, biotransformation, and vectorial transport. Greengard [2] has established a paradigm for hepatic development based on a group of several hepatic enzymes studied in the rat and, less extensively, in humans. In one pattern of hepatic development, enzymatic activity is high in a fetus and falls during postnatal development. Examples would include thymidine kinase and ornithine decarboxylase [3].