ABSTRACT
The mechanisms responsible for the diminished EPO output by premature neonates are undefined. One mechanism of apparent importance is the belief that premature infants must rely on the liver as the primary site of EPO production, during the first several weeks of life, rather than on kidney (13). As established by animal studies, the sequence of EPO production in normal fetuses is liver followed by kidney. In lambs, EPO production by fetal liver begins to decrease after 120-130 days of gestation (term = 145-150 days), at which time renal EPO production increases (14). However, at term, 70-75% of EPO produced in response to anemia continues to be produced by the liver. This dependency on hepatic production of EPO is important because the liver is less sensitive to anemia and tissue hypoxia than is the kidney (14)—hence, the relatively poor EPO response in the fetus and neonate to the falling RBC mass. The switch to renal EPO production in lambs is complete by about 40 days after birth. Viewed from a teleological perspective, decreased EPO production under conditions of tissue hypoxemia in utero may offer an advantage to the fetus. If this were not the case, normal levels of fetal hypoxemia could stimulate high EPO output, with resulting polycythemia and hyperviscosity in utero. Following birth, however, diminished EPO responsiveness to tissue hypoxemia could result in ineffective erythropoietic compensation-not unlike that routinely observed as the physiologic anemia of infancy.
