Human fetal metabolism is largely unexplored. Understanding how a healthy fetus achieves its fast growth rates could eventually play a pivotal role in improving future nutritional strategies for premature infants. To quantify specific fetal amino acid kinetics, eight healthy pregnant women received before elective cesarean section at term, continuous stable isotope infusions of the essential amino acids [1-13 C, 15 N]leucine, [U-13 C 5 ]valine, and [1-13 C]methionine. Umbilical blood was collected after birth and analyzed for enrichments and concentrations using mass spectrometry techniques. Fetuses showed considerable leucine, valine, and methionine uptake and high turnover rates. ␣-Ketoisocaproate, but not ␣-ketoisovalerate (the leucine and valine ketoacids, respectively), was transported at net rate from the fetus to the placenta. Especially, leucine and valine data suggested high oxidation rates, up to half of net uptake. This was supported by relatively low ␣-ketoisocaproate reamination rates to leucine. Our data suggest high protein breakdown and synthesis rates, comparable with, or even slightly higher than in premature infants. The relatively large uptakes of total leucine and valine carbon also suggest high fetal oxidation rates of these essential branched chain amino acids. (Pediatr Res 70: 566-571, 2011) H istorical wise, the fact that the design of current nutrition for premature neonates is merely step-by-step alterations of the original composition of breast milk (1) is not surprising. Years ago, gestational viability was closer to term than it is currently, and the analysis of normal neonatal nutrition was easier than the study of fetal nutrition. But with increased survival of less mature infants, metabolic demands of these young individuals probably deviate much more from those who receive breast milk or regular formula after term birth. Besides, we know from several decades of animal fetal research that intrauterine nutrient supply delivers more amino acids and less fat than is supplied during breast feeding (2). Today, however, the exact composition of human fetal nutrient supply still remains unknown.With the availability of harmless tracer studies, human fetal metabolism can be unraveled (3-7). To add to the very scarce knowledge bank, our aim was to investigate several aspects of human fetal essential amino acid metabolism. In this study, we were interested in fetal kinetics of the branched chain amino acids (leucine and valine) and of another essential amino acid, methionine. Previously, fetal kinetics of phenylalanine and tyrosine were described. These two amino acids together with those studied here were chosen both scientifically as well as practically. First, they are often subject of debate when it comes to (parenteral) neonatal nutrition. Second, their stable isotopomers are affordable, and our laboratory has much experience analyzing them accurately. Metabolism was determined after the infusion of stable isotopically labeled amino acids into pregnant women undergoing ele...