Threonine requirement in preterm neonates

The exact requirement of essential amino acids for term and preterm neonates is
not known. So far, requirements have been estimated either from the composition
of human milk or are derived using nitrogen balance studies which are known to
be imprecise. By using a new method, the indicator amino acid oxidation (IAAO),
we are able to determine the exact individual requirement for all essential
amino acids in both term and preterm infants. This will improve our knowledge
on how to feed infants and might improve functional outcome in these vulnerable
patient groups. We recently determined the requirement of the branched chain
amino acids valine, isoleucine and leucine in Asian term neonates. The
requirement of valine and isoleucine showed to be two fold higher than current
recommendations.

The aim of the study is to quantify the requirement of threonine in preterm
infants. We hypothesize that the current estimations for preterms are too high.

This will be a randomized, unblinded, non-therapeutic intervention study. It
will be a multicenter trial performed in the Erasmus MC-Sophia, the Sint
Francisus Hospital, the Maasstad Hospital (all Rotterdam), the Albert
Schweitzer Hospital Dordrecht, the Amphia Hospital Breda and the Haga Hospital
in The Hague.The study will start September 2011 and will last for 2 years.

The subjects will adapt for 24 hours to the study formula. At the study day,
subjects will receive a primed (15 µmol/(kg) continuous (10 µmol/(kg•h))
enteral infusion of [13C]bicarbonate for 2.5 h to quantify individual CO2
production. An elemental diet (Neocate®, Numico) will be used to provide the
infants with different amino acid intakes. The labeled sodium bicarbonate
infusion will be directly followed by a primed (40 µmol/(kg)) continuous (30
µmol/(kg•h)) enteral infusion of [1-13C]-Lysine for four hours. 30 minutes
before start of the oxidation study the feeding regimen will be changed into
continuous drip-feeding. Enterally infused tracer will be mixed with the study
formula and infused continuously by an infusion pump via the nasogastric tube.
Breath samples will be obtained using the direct sampling method described by
Van der Schoor et al. (1). Briefly, a 6 Fr gastric tube (6 Ch Argyle; Cherwood
Medical, Tullamore, Ireland) will be placed 1 to 1.5 cm into the nasopharynx
and end-tidal breath will be taken slowly with a syringe connected at the end.
Baseline samples will be obtained 15 and 5 minutes before starting tracer
infusion. During the experiment duplicate 13C-enriched breath samples will be
collected every 10 minutes during the last 45 minutes of the [13C]bicarbonate
infusion and the last hour of the [1-13C]-lysine infusion

The children eligible for our study are already warded at the Department of
Neonatology of the participating centers. All preterm babies already have a
nasogastric tube as a standard procedure.We will insert a tube 1-1.5 cm. in the
nasopharynx to obtain the air samples. Although the insertion might give some
discomfort since the tube will be fixed, we did not notice any discomfort in
our ample experience. We have already performed this procedure in more than 300
infants. In all studies done with stable isotopes in premature neonates, no
side-effects were seen. We expect there are no risks and no benefits for the
included children.