Comparison of school-age outcome in children with a history of perinatal asphyxia with and without hypothermia therapy with controls

Children who have suffered from cerebral injury, for instance after perinatal
asphyxia (PA), may show signs of impaired neurodevelopment, expressed in
behavioral, memory problems or learning disabilities. In children with PA these
deficits are also observed when in the neonatal period no significant
structural magnetic resonance imaging (MRI) abnormalities are found. Yet, from
clinical follow-up it appears that 20 to 25% of these infants without
hypothermia therapy encounter problems at school concerning behavior, memory or
learning. Therefore, rather than focusing on brain structure, studying
functional brain networks in these children by means of resting-state
functional MRI (rs-fMRI) may improve understanding why these children have
neurodevelopmental impairments and whether those children who have been cooled
are doing better, both with regard to their outcome as well as their rs-fMRI.
Hypothermia was first introduced in the netherlands in 2008. The technique was
implemented by dr F. Groenendaal (UMCU) and is performed in a standard way in
all 10 Dutch NICUs.It is hypothesized that different network configurations and
lower overall connectivity between resting-state networks in the areas for
executive functions are seen in the children that have cognitive and/or
behavioral problems.
Furthermore, it may in the near future also be possible to study functional
brain networks in these children by means of resting-state functional MRI
(rs-fMRI) already in the neonatal period, allowing early prediction of
concentration behavioral and memory problems at school age; this would allow
early recognition and intervention.

To study cognitive and behavioral outcome and resting-state dynamics in
children with a history of perinatal asphyxia before and after the introduction
of hyothermia and to compare these data with a group of controls.

This observational study will, after informed parental consent and child assent
has been obtained, use prospectively collected data of children with a history
of perinatal asphyxia. Standard clinical follow-up of the patients included
psychological and motor testing. Children with perinatal asphyxia have been
seen in the follow-up clinic as standard clinical care until the age of 5
years. When participating in the study, children will have a neuropsychological
assessment and an MRI including resting-state functional MRI. Resting-state
dynamics of these children with perinatal asphyxia, with and without
hypothermia, will be compared to data of age-matched, otherwise healthy
controls derived from the Youth study (http://youthonderzoek.nl/)

In this observational study participants are subject to standard clinical care
and follow-up, in which MRI has become standard clinical care in children with
perinatal asphyxia and problems at school. In this study, neuropsychological
assessment and resting-state sequence will be additional and children who are
doing well at school will also be invited to particpate. Risks associated with
participation are limited, if not negligible, as MRI has been performed for
clinical purposes in almost all follow-up centres for many years. Therefore,
considerable collective expertise has been gained in MRI techniques and
associated practical issues in teenaged children. Moreover, it has been shown
that physical and psychological risks are negligible in this type of MR imaging
that does not require administration of sedatives or contrast agents.
Performing brain imaging in children this age with this condition is important
to understand why children with these conditions have neurocognitive problems,
in which the lack of structural abnormalities fails to explain the deficits. In
addition, we will be able to see the potential benfit of hypothermia on
neuropsychological outcome and networks. Results of the study may aid patients
to understand some of the limitations in behaviour or learning they may
experience, in turn offering possibilities for intervention. Additionally, this
study may contribute to the identification of prognostic parameters for outcome
in similar patient populations.