Biomarkers for outcome at school age in preterm born children

Extremely preterm born infants (gestational age <28 weeks) are at increased
risk for cognitive and behavioural impairments at school age. We hypothesize
that early insults on brain maturation pervasively impact development, alter
essential neurodevelopmental sequences and thereby comprise building blocks for
higher cognitive functioning.

The objective of the study is to identify biomarkers that associate to brain
(physiological) status or mental (functional) health status and their
interaction. More specific, our first aim is to determine the association
between neuroinflammatory markers and mental health status. Our secondary aim
is to determine the association between EEG phenotypes and mental health
status.

Cohort study.

The burden of this study comprises of collection of a blood sample, faeces
sample, hair and buccal swab, an MRI scan of the brain and a quantitative
electroencephalography (EEG). These are study procedures on visit days for
routine clinical care. No extra visits are needed for study procedures. Routine
care and study procedures are specified in table 1 of the protocol (page 10).
On day 1, as part of the study procedure, a sample of 20 ml of blood will be
collected. A topical anaesthetic (EMLA) can be used to minimise pain sensation.
In addition, a faeces, hair and buccal swab sample will be collected and stored
in a biobank. In addition, the Vineland interview will be conducted with the
parents. Finally, an MRI scan will be made on this day and we will use a
Virtual Reality (VR) shopping task to assess cognitive skills.
If on day one, behavioral or developmental problems are present, or
parents/caregivers have concerns about behavior or development, the child will
be referred to the child psychiatrist for extra behavioral assessments and
treatment, if indicated. This is part of standard clinical care. We expect that
a subpopulation of ~ 50% ( i.e. n=64) of children will be referred.
On day 2, in addition to clinical care, the study procedure consists of a
resting state EEG, and EEG tests (a hearing test, mismatch negative paradigm
and a selective attention paradigm test).
Risks in participating in the study involve a small chance to develop a
hematoma after venepuncture. The faeces, hair, and buccal swab sample
collection and the MRI and EEG are non invasive procedures that pose no
specific burden to the participants. Overall, risks are expected negligible and
the burden is expected to be minimal. On the MRI scan, incidental findings may
be noticed. If medical treatment for these findings is indicated, the subjects
will be notified. If parents do not want to be informed about these findings,
children cannot participate. Clinically relevant abnormalities warrant routine
clinical care at the department of neonatology or psychiatry.