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Alan Leviton, MD
Professor
of Neurology
Harvard Medical School/Children's Hospital
MRRC Project(s)
1 U01 NS 40069-01A2
[9/30/01 - 11/30/06]
Molecular Antecedents of Brain Damage in Preterm Infants
Extremely low gestational
age newborns are at increased risk for a variety of cognitive disturbances
and other types of developmental disability. Much of this probably reflects
the consequences of neonatal white matter injury, or periventricular leukomalacia.
The ELGAN study (for
Extremely Low Gestational Age Newborns)
will seek the antecedents of cranial ultrasound abnormalities that predict
mental retardation as well as perceptual and motor disabilities that occur
commonly in very premature infants.
Designed to provide
scientific knowledge needed to justify clinical trials of ways to prevent
cerebral white matter damage, this study will measure fetal, placental,
and neonatal biomarkers that predict disabilities. Four sets of biomarkers
are included in this study: initiators of one set of processes
leading to brain damage (e.g., bacteria), damage promoters (e.g.,
pro-inflammatory cytokines), modulators of the inflammatory response
(e.g., anti-inflammatory cytokines, cytokine binding proteins, cytokine
receptor antagonists) and cerebral white matter protectors (e.g.,
hormones and growth promoters).
The ELGAN study is
expected to enroll 1,800 infants born before 28 weeks of gestation at
one of 14 participating institutions. It was designed to: a) identify
and measure in the placenta and umbilical cord: cellular morphology, infectious
organisms, and receptors for, and expression of endocrine hormones and
non-endocrine growth factors; b) measure in mother's blood, umbilical
cord and multiple postnatal blood samples: cytokines, hormones, and growth
and survival factors; c) measure and identify clinical predictors of cranial
ultrasound abnormalities and their developmental consequences; d) identify
early developmental problems by assessments at ages one and two years;
and, e) maintain contact with families so that at older ages (after the
termination of initial funding) school performance and neuropsychologic
function can be assessed; and g) maintain a "tissue bank" of placenta,
umbilical cord, and blood that will be available for analyses to be suggested
by future research findings.
By identifiying biomarkers
of processes that influence the risk of cerebral white matter damage and
its consequences in the most vulnerable, the ELGAN study should help provide
a rational and ethical basis for the design of clinical trials to reduce
the occurrence of early brain damage and later developmental disabilities.
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