Intake and growth in late preterms

Moderately preterm infants (late preterms, gestational age 32-36 wks) show
impaired growth and increased morbidities such as behavioural problems and
developmental delays compared to term infants. They have not been routinely
followed and it has been thought that they were at a relatively low risk of
developing neurological abnormalities. There are no prospective studies
performed in these infants to determine whether suboptimal intakes in feeding
and impaired growth might play a role in these morbidities.
It might be possible, as shown in extremely preterm infants by Lucas and al.
(Lancet 1990) that optimalizing protein and caloric intakes might result in
better growth and outcome in these moderately preterm infants. No studies have
been performed analyzing prospective protein and caloric intake and growth
parameters in the 32-36 weeks preterms. Thereby, no study combined these
prospective growth and intake data with a developmental scale at 2 years of
age. Combining the intake and growth data with a body composition measurement
could also determine whether these moderately preterms are at risk to develop
long term morbidities like metabolic syndrome as has been suggested in
extremely preterms by Singhal et al. (Lancet 2004). This could lead to new
insights and might result in new strategies to decrease morbities in this
"relatively forgotten" group of late preterm infants.

Primary Objective:
To prospectively obtain the (parenteral/enteral) intake of protein, fat,
carbohydrates and calories in moderately preterm infants (32-36 weeks) and
obtain prospectively growth data in the first 2 years of life.

Secondary Objective(s):
- To determine whether intake and/or growth in the first 2 years influences
motor and/or mental development at the age of 24 months. The intake and growth
data will be compared with a Bayley Scales of Infant Development (BSID-III)
test at the age of 24 months to determine whether intake or growth in the first
2 years of life is a risk factor for an impaired motor or mental development.

- To determine whether intake and/or growth in the first 2 years of life
influences body composition at the age of 2 years. This could indicate whether
these infants are at risk for long term morbidities like the metabolic syndrome
as described in extremely preterm infants (<32 weeks).

The study will be an open, non-therapeutic exploratory study. The intake of
fat, protein, carbohydrates and calories will be collected in all infants born
32-36 weeks or transferred to the neonatology ward of the Medical Center
Alkmaar (MCA). Subjects will be weighted weekly at the Neonatology Ward of the
MCA, their head circumference and length will me measured weekly until they are
discharged. The data of the protein, fat, carbohydrates and calories intake
will be daily observed (e.g. actual intakes instead of prescribed intakes) by
the research nurse by using the day lists of the children filled in by the
nurses. The growth will be weekly determined in the Growth Round that is held
as standard care every Wednesday morning. After discharge, the infant will be
followed at the Outpatient Ward at the age of 6 weeks, 3 months, 6 months, 1
year and 2 years as standard care. At these moments the intakes will be
collected by using a diet list and the growth will be determined by the use of
the weight, length and head circumference that is measured by the research
nurse or the doctor. At 2 years, the growth data are collected by measuring the
weight, length and head circumference as standard care. In the infants of which
parents consented for the study procedures, a BSID III will be performed by a
specialist physiologist of the MCA together with a specialised children*s
physiotherapist of the MCA at the age of 2 years. Secondly, a body
composition measurement will be performed at the age of 2 years by using the
double labelled water techniques. Total body composition (TBW) can be measured
by using a single dose of deuterium (D2O). The use of deuterium dilution is
save and non-invasive. Stable isotopes are non-radioactive, not detrimental and
are already naturally present in the human body in small amounts. An small
amount (3 ml per kilogram body weight) of 2H2O will be administered. Saliva
samples can be easily collected by swabbing a dry cotton rod in the child*s
mouth for 2-5 minutes. Both methods are non-painful. No extra blood samples are
needed.

The study is a non-therapeutic, exploratory cohort study. It concerns preterm
infants born between 32 and 36 weeks of gestation that are followed untill the
age of 2 years. They are minors and thereby incapacitated subjects. The study
will be non-therapeutic in which the infants have no benefits. It will not be
an intervention study which makes the risks for SAE*s neglectable. Regarding
the CCMO guidelines in minors the risk must be neglectable and the objections
must be minimal. In our study, the use of the BSID III will take 2.5 hours of
time. It is a developmental tool that is performed in all preterm infants born
< 32 weeks as routine assessment in the Netherlands at the age of 2 years. In
these children it is experienced as minimally objective .
The use of deuterium dilution is save and non-invasive. Stable isotopes are
non-radioactive, not detrimental and are already naturally present in the human
body in small amounts. An small amount (3 ml per kilogram body weight) of 2H2O
will be administered. Saliva samples can be easily collected by swabbing a dry
cotton rod in the child*s mouth for 2-5 minutes. In previous studies that are
performed in children using deuterium dilution the procedure is minimally
objective and safe.

Benefits and group relatedness:
In these moderately preterm infants a benefit could be that by standardising
the feeding regimen at the ward and performing the weekly Growth round, the
growth and intake in these late preterms will improve. In different studies in
extremely (<32 wks) preterm infants it has been shown that standardisation of
feeding protocol and weekly feeding rounds can result in less growth
retardation and might influence later outcome (ref toevoegen). If we can show
that by monitoring intake and growth as standard care as is performed in our
Neonatology department can result in a normal neurodevelopment and not result
in abnormal body composition, all moderately preterm infants in the world can
benefit in the future.
No study has been performed analyzing prospective protein and caloric intake
and growth parameters in the 32-36 weeks preterms. Thereby, no study combined
these prospective growth and intake data with a developmental scale at 2 years
of age. Combining the intake and growth data with a body composition
measurement could also determine whether these moderately preterms are at risk
to develop long term morbidities like metabolic syndrome as has been suggested
in extremely preterms (32). This could lead to new insights and might result in
new strategies to decrease morbities in this "relatively forgotten" group of
late preterm infants.
Concluding, the risks are neglectable, the burden is minimal and it this study
could result in answers or new research questions why this late preterm group
shows morbidities in growth and development in retrospective studies. This
implicates that the research-question is group-related and can only be
performed in this group of infants.