Article Text

  1. C H P van den Akker1,
  2. H Schierbeek1,
  3. K Y Dorst1,
  4. E M Schoonderwaldt2,
  5. A Vermes3,
  6. J J Duvekot2,
  7. E A P Steegers2,
  8. J B van Goudoever1
  1. 1Pediatrics-Neonatology, Erasmus MC, Sophia Children’s Hospital, Rotterdam, The Netherlands
  2. 2Obstetrics and Prenatal Medicine, Erasmus MC, Rotterdam, The Netherlands
  3. 3Hospital Pharmacy, Erasmus MC, Rotterdam, The Netherlands


Background Human fetal metabolism is a largely unknown area. However, this knowledge might play a pivotal role in improving nutritional strategies for prematurely born infants to ameliorate long-term outcome. Phenylalanine kinetics are of special interest because there is debate as to whether neonates are able to hydroxylate phenylalanine adequately to the semi-essential amino acid (AA) tyrosine.

Objective To quantify human fetal phenylalanine and tyrosine metabolism.

Methods Eight fasted healthy pregnant women undergoing elective Caesarean section at term received continuous stable isotope infusions of [1-13C]phenylalanine and [ring-D4]tyrosine starting before surgery. Umbilical blood flow was measured using ultrasound. Maternal and umbilical cord blood was collected and analysed for phenylalanine and tyrosine enrichments and concentrations using gas–chromatography mass–spectrometry. Data are expressed as median (25th–75th percentile).

Results Women were in a catabolic state for which net fetal AA uptake was responsible for at least one quarter. 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) vs 73 (68–87) μmol phenylalanine/(kg/h), respectively. The median metabolised fraction of available phenylalanine and tyrosine in the fetus was less than 20% for both AA.

Conclusion Although all fetuses were born at term, on average they still showed considerable net AA uptake and growth (converted to tissue ∼11 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.

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