Body composition and neurodevelopment in preterm infants

Preterm infants are born in a critical period for both growth and brain
development. It is well known that they are at increased risk for long-term
growth failure and neurologic, developmental and cognitive impairment. Many
preterm infants are growth restricted at hospital discharge, often caused by
inadequate nutrional intake. This insufficient intake leads to protein and
energy deficits early in life. Preterm infants are also known to have altered
body composition. Both catch-up growth and (intra- or extra-uterine) growth
restriction increase the risk of metabolic syndrome later in life, while only
catch-up growth diminishes the risk of neurodevelopmental impairment. Recently,
it has been shown that the amount of subcutaneous fat accretion is positively
related to the quality of motor development. However, in contrast to these
findings, a negative relationship has shown between visceral fat and brain
volume.
Thus, it seems likely that nutrition and nutritional status are of great
importance in growth, body composition and brain development of preterm
infants. However, the relationship between body composition and development of
the brain in preterm infants has not been investigated yet. While we think this
is of great importance for feeding practices and development of the infant. We
hypothesize that growth restricted infants have altered brain development
compared to non-growth restricted infants, which is (partly) related to
differences in body composition. Furthermore, very little is known about the
dental- and bone development of children born preterm.
Taking all this above into account, it seems clear that preterm born children
are at risk for multiple long-term complications, which can alter the quality
of life. Value-based healthcare, focused on (not necessarily medical) outcomes
that are relevant for the patients and their families is trending. Therefore,
we will assess the quality of life of preterm born children aged 8 years
(according to themselves and their parents). Furthermore, parents will be asked
to evaluate the items of the standard ex-NICU follow-up protocol and the BOND
study for transition to value-based healthcare for the neonatal follow-up
protocol, since it is important and needed taking parents* perceptions into
account.

Our main objective is to explore the relationship between nutritional intake,
growth, body composition and brain development. Hereby we want to improve our
knowledge about how to feed the preterm infant in a way that contributes to a
better cognitive development and a decrease in the risk of developing metabolic
syndrome.

Observational, cohort study

The burden and risk of this study is expected to be minimal. During hospital
stay in the neonatal period no assessments will be performed. Data will be
obtained about growth, nutritional intake and neonatal course. Brain
development will be assessed using standard care MRI scans and cranial
ultrasound. Both parents will be asked to fill out a short questionnaire (10
minutes) during hospital stay about lifestyle and pregnancy. Parents will be
asked to keep record of changes in feeding practices and to note the exact
intake 3 days twice until the corrected age of 6 months.

Preterm infants are routinely assessed at the outpatient clinic and nearly all
of our study measurements will be done at those visits. Only the assessments at
the age of 3 (and possibly 8) years old requires an extra hospital visit; if
parents agree to this extra visit, their travel expenses will be compensated.

At these routine follow-up visits, body composition will be measured repeatedly
in the PEAPOD and BODPOD. The PEAPOD and BODPOD are non-invasive and quick
methods for measuring body composition. The PEAPOD proved to be safe for
measuring preterm infants.
Once a cranial ultrasound will be performed, which will be done while the
infant is comfortable/asleep, lying with his parents. This measurement will
take less than 5 minutes.
The other assessments at 2, 3, 5 and 8 years corrected age are all
non-invasive, safe, most of them are performed at home, at a time convenient
for the parents and are little burden to the parents and the child. At 8 years
of age, the children fill in 1 short questionnaire themselves. At 5.5 and 8
years corrected age ca, dental health status will be examined through a
pediatric dentist.

The assessments will be performed by dedicated people who are familiar with
this specific patient population. The infants included in this study will not
directly benefit from participation in this study. However, if we are able to
identify the influence of growth pattern, and thereby nutritional requirements,
on body composition and brain development, it will help us to provide the most
optimal outcome for preterm infants in the future.