Cerebrospinal fluid metabolites as marker for the severity of progressive post-hemorrhagic ventricular dilatation in preterm infants

Post-hemorrhagic ventricular dilatation (PHVD) as complication of
intraventricular hemorrhage in preterm infants may result in impaired cerebral
perfusion, resulting in ischemic brain lesion and impaired neurodevelopmental
outcome. As treatment reduction of ventricular dilatation can be achieved by
intermittent removal of cerebrospinal fluid (CSF) through a puncture of
subcutaneous ventricular catheter reservoir (SVCR). Increased brain specific
proteins in CSF are related to brain tissue damage. It can be expected that
there is a relationship between the concentration of brain specific proteins
and glucose in CSF on the one side and the severity of PHVD and
neurodevelopmental outcome on the other side. This relationship has not been
investigated yet. When there is a strong relationship, the concentration of
these CSF metabolites can be used as marker in the decision process of the
timing of therapeutic CSF removal and for predicting the outcome. This
relationship will be investigated from the CSF obtained from the study
"Randomised PHVD treatment study: a multicentre randomised controlled trial of
low versus high threshold treatment in preterm infants with progressive
posthemorrhagic ventricular dilatation", which has been started in the
Netherlands since april 2006. Preterm infants with progressive PHVD will be
randomised in low or high threshold group. In low threshold group the therapy
will be started at moderate PHVD; in high threshold at severe PHVD. Both the
therapy and the end-point of the therapy (desired ventricular size) are the
same for both groups.

1. Is the concentration of brain specific proteins in CSF higher in newborn who
are treated after high threshold as compared to newborns who are treated after
low threshold?
2. Is there any relationship between the concentration of brain specific
proteins in CSF, glucose and lactate on the one hand and the severity of
ventricular dilatation, VP drain insertion and neurodevelopmental outcome at
the age of 2 year on the other hand?

CSF will be collected at day 1 and thereafter twice a week in the first 2 weeks
and once in the third week after start of serial intermittent CSF removal from
SCVR. Cell count, total protein, glucose, and lactate will be determined at own
hospital. Brain specific proteins (S100, NSE, GFAP, NFL, MBP, Tau) will be
determined in Radboud University Nijmegen Medical Centre. Simultaneously, the
severity of ventricular dilatation will be assessed by cerebral ultrasound.
Placement of ventriculoperitoneal drain will be registered.. Neurodevelopmental
outcome at the age of 2 year will be assessed by Bayley Scales of Infant
Development. The relationship between the concentration of brain specific
proteins, glucose and lactate in CSF on the one hand and the therapy threshold,
the severity of ventricular dilatation, VP drain insertion and
neurodevelopmental outcome at the age of 2 year on the other hand will be
investigated using correlation analysis.

There is no risk or burden. The CSF and the data of cerebral ultrasound and
Bayley Scales of Infant Development are already available from the *Randomised
PHVD treatment study*.