Brain Injuries, Developmental Disabilities, Leukomalacia Periventricular, Premature Birth
Conditions
Keywords
Premature Birth, Brain Injuries, Leukomalacia Periventricular, S100B protein human, Glial Fibrillary Acidic Protein, Magnetic Resonance Imaging, Developmental Disabilities
Brief summary
The improvement of treatment of preterm neonates improved their survival, however there is still significant portion of preterm infants (specifically very preterm infants) that suffers from brain insults and as a result developmental deficits. The brain injury is a consequence of hypoxic ischemic events, intracranial hemorrhages, as well as, infections and metabolic crisis. The brain injury is a combination of abnormal myelination, axonal damage and neuronal death. Although there is reduction in focal brain injury, diffuse brain injury is still abundant. Several treatments has been suggested and tested in animal models to prevent the brain insults including glutamate receptor blockers, allopurinol, xenon and different types of stem cells. However, two main obstacles prevent the use of these medication, first the uncertainty of their effect on the developing brain and second the difficulty to time the brain insult. Unlike neonatal asphyxia, when the delivery time and clinical signs are used to time and grade the brain injury, in preterm infants there is no real time tool to indicate severity and timing of brain injury. The disability point out a beneficial therapeutic window is a major obstacle in the acute treatment of brain injury in preterm infants. The aim of this study is to try and delineate such therapeutic window by using brain injury biomarkers. S100b and GFAP are well recognized biomarkers of brain injury in adults, children and infants. Serial measurements of S100b in saliva (every 2 days) and GFAP in serum (weekly) will be sampled. A database of the clinical status of the infants will be collected, as well as, head ultra sound weekly and head MRI a term age. Development will be assessed by at 18 months. Two hypotheses are stated: One, increase in the levels of S100b and GFAP in their timing will be correlated with the severity of the clinical status, Two the duration of increased level of S100b and GFAP will be associated with abnormal MRI at term findings and abnormal developmental assessment.
Interventions
None listed
Sponsors
Sheba Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Days to 2 Days
Healthy volunteers
No
Inclusion criteria
\- Preterm delivery before 30 week gestational age
Exclusion criteria
* Dysmorphic features in initial neurological examination * Antenatal brain injury on fetal MRI or ultrasound * Brain malformation * Maternal drug abuse * Maternal use of teratogenic medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRI at term age | 2-3 month after recruitment | MRI description according to the protocol suggested by woodward et. al. (2006) |
| S100b and GFAP | 2-3 months after recruitment | The level of S100b in a sample of 0.5 cc saliva will collected every 2 days and GFAP every week from the day of birth to discharge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Developmental assessment at 18 month | 21 month after recruitment | Neurological examination Griffith mental developmental scales (GMD-2) Vineland adaptive behavioral scale (VinelandTM-II) Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale |
| Developmental assessment at 3 month corrected age | 5-6 months after recuitment | Neurological examination General Movements assessment Griffith mental developmental scales (GMD-2) Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale |
Countries
Israel
Contacts
Primary ContactOmer Bar Yosef, M.D. Ph.D.
Backup ContactLeah Leibovitch, M.D.
Outcome results
None listed