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.