Splanchnic aspartate metabolism in preterm infants

Most premature infants (gestational age < 37 weeks) are in the first postnatal
days or weeks fed with parenteral nutrition. Enteral feeding is, depending on
the infants clinical condition, commenced after a few days and gradually
advanced over time. This is because in the premature newborn the gastro
intestinal tract is not fully developed and digestion of nutrients is
suboptimal. This increases chances of developing necrotizing enterocolitis
(NEC). NEC is an inflammatory bowel disease with a high morbidity/mortality and
high incidence in the premature.
However, in these infants we try to establish a growth rate that resembles the
intra-uterine growth rate (14-20 gr/kg/day). The intestine plays a key role in
this growth because only a well developed gut can absorp the required amount of
nutrients. It is known that the portal drained viscera (PDV) (spleen, stomach,
intestine and pancreas) although accounting for only 5% of the body weight, are
responsible for 35% of energy expenditure. Which substrates are used for this
high demand is largely unknown.

To quantify splanchnic and whole body aspartate metabolism in premature
neonates.

The design is a single-center intervention non-therapeutic study design. Eight
hours before the start of the study infants will be maintained on regular
infant formula, Nenatal. This formula is given in our NICU to infants not
receiving mothers milk. Infants usually fed with breastmilk will receive
breastmilk again after the study.
At the start of the study infants are infused (IV) for two hours with
[13C]natriumbicarbonate (Nabic). This is to determine whole body oxidation.
Directly here after [U-13C]aspartate and [2,3,3-D3] aspartate will be infused
for 5 hours, one tracer will be given IV and the other IG. On study day 2 the
route of administration of the two tracers will be reversed. The simoultaneous
infusion of different labeled aspartate will allow us to determine first pass
uptake by the splanchnic tissues. Infusion of [U-13C] aspartate on 2 separate
days will allow us to calculate the difference in whole body and splanchnic
oxidation rate.

Blood samples:
3 samples will be collected:
One sample before to infusion of aspartate (to determine baseline enrichment)
One sample after 4,5 hours of aspartate infusion and one sample at the end of
aspartate infusion (after 5 hours)
Expired air collection:
Breath samples will be taken every half hour. During the last hour of Nabic and
aspartate infusion samples will be taken every 15 minutes.

The Ethical Committee Rotterdam and the CCMO decided that this study should be
examined by the CCMO as a non-therapeutical intervention study because the
neonate receives formula instead of mother milk during the period of 2 days.

The labelled amino acid is not a substance that will cause a reaction in the
body for research purposes. It is a standard part of the enteral feeding,
except that it is enriched with a stable isotope 13C, which increases the total
enrichment of the C-atoms in the body with 0,001%. The labelled amino acid is
not the purpose of the study; the metabolism of nutritional parts is the
purpose of this study.

On two separate days, three blood samples of 200 ul are requested for this
study. This is in total 1,2 ml, which is less than 2% of the blood volume of an
infant weighing 1000 grams. If infants have no arterial catheter to withdraw
blood samples from the first sample will be combined with the regular morning
blood sample collection for clinical purposes. The blood samples at the end of
the tracer protocol will then be collected by heel stick. No arterial catheter
will be placed for research purposes.
In total 18 breath samples are collected through a 6 Fr gastric tube placed 1
to 1.5 cm into the nasopharynx. This takes approximately a minute per sample
and carries no burden to the infant.
Stable isotope techniques have been used for over 20 years in our department
for metabolism studies and to the best of our knowledge no adverse effects have
ever occurred.