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Human fetal amino acid metabolism at term gestation^1,2,3

¹ From the Department of Pediatrics, Division of Neonatology, Erasmus MC–Sophia Children's Hospital, Rotterdam, Netherlands (CHPvdA, HS, KYD, and JBvG); the Department of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, Rotterdam, Netherlands (EMS, JJD, and EAPS); and the Hospital Pharmacy, Erasmus MC, Rotterdam, Netherlands (AV).

² Supported by Sophia Children's Hospital Fund (grant 459), institutional grant 2006-10 (Erasmus MC–Sophia Children's Hospital, Rotterdam, Netherlands), and Nutricia Research Foundation (independent charity; Nutricia, Wageningen, Netherlands). Both grant suppliers had no involvement whatsoever in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the report for publication.

³ Reprints not available. Address correspondence to JB van Goudoever, Erasmus MC–Sophia Children's Hospital, Room sp-3433, PO Box 2060, 3000 CB Rotterdam, Netherlands. E-mail: j.vangoudoever{at}erasmusmc.nl.

Background: Knowledge on human fetal amino acid (AA) metabolism, largely lacking thus far, is pivotal in improving nutritional strategies for prematurely born infants. Phenylalanine kinetics is of special interest as is debate as to whether neonates will adequately hydroxylate phenylalanine to the semiessential AA tyrosine.

Objective: Our aim was to quantify human fetal phenylalanine and tyrosine metabolism.

Design: Eight fasted, healthy, pregnant women undergoing elective cesarean delivery at term received primed continuous stable-isotope infusions of [1-¹³C]phenylalanine and [ring-D₄]tyrosine starting before surgery. Umbilical blood flow was measured by ultrasound. Maternal and umbilical cord blood was collected and analyzed by gas chromatography–mass spectrometry for phenylalanine and tyrosine enrichments and concentrations. Data are expressed as medians (25th–75th percentile).

Results: Women were in a catabolic state for which net fetal AA uptake was responsible for 25%. Maternal and fetal hydroxylation rates were 2.6 (2.2–2.9) and 7.5 (6.2–15.5) µmol phenylalanine/(kg · h), respectively. Fetal protein synthesis rates were higher than breakdown rates: 92 (84–116) and 73 (68–87) µmol phenylalanine/(kg · h), respectively, which indicated an anabolic state. The median metabolized fraction of available phenylalanine and tyrosine in the fetus was <20% for both AAs.

Conclusions: At term gestation, fetuses still show considerable net AA uptake and AA accretion [converted to tissue 12 g/(kg · d)]. The low metabolic uptake (AA usage) implies a very large nutritional reserve capacity of nutrients delivered through the umbilical cord. Fetuses at term are quite capable of hydroxylating phenylalanine to tyrosine.