intraventricular hemorrhage (IVH) as a major cause of adverse outcome for very low birth weight (VLBW; birth weight <1501 grams) premature neonates. IVH most probably results from perturbations in cerebral blood flow to the immature germinal matrix microvasculature. The more severe grades of IVH (Grades 3 and 4) are characterized by acute distension of the cerebral ventricular system with blood (Grade 3) and intraventricular hemorrhage with parenchymal venous infarction (Grade 4).

Each year 12 ¿ 15% of VLBW infants born in the U.S. incur Grade 3 or 4 IVH; over three-quarters of affected infants develop mental retardation and/or CP. Based on data from the U.S. Census Bureau, the NICHD Neonatal Network and the Centers for Disease Control, there are over 3600 new cases of mental retardation attributable to Grade 3 or 4 IVH in the United States each year, and the lifetime care costs for these children exceeds 3.6 billion dollars.

Preterm birth represents a unique environment for the developing brain, and many important environmental factors such as inflammation, hypotension and hypoxemia that contribute to IVH have been identified.

Furthermore, both pharmacologic and care-oriented prevention strategies have been implemented. These studies have led to significant reductions in the incidence of less severe IVH (Grades 1 and 2) by changing practices in newborn resuscitation and perinatal care.

Nonetheless, the incidence of Grades 3 and 4 IVH has not changed over the last ten years. Until recently, there has been limited information on whether genetic factors play a role in the pathogenesis of Grades 3 and 4 IVH. However, new preliminary data show a familial susceptibility for IVH in VLBW twins, and several candidate gene studies have investigated the role of thrombophilia mutations, inflammatory factors and vascular genes in the genesis of this significant injury to developing brain. These data suggest that, for VLBW infants, IVH is attributable to combination of environmental and genetic factors. In order to further lower the incidence of IVH, and thus neurodevelopmental handicap in the preterm population, it is important to identify those alleles and haplotypes, which provide either susceptibility or protection for IVH.

The goals of this proposed research include the following:

1. To identify genetic factors (alleles and haplotypes of as yet unidentified genes) that render VLBW infants susceptible to IVH.

2.To assess the relative contribution of genetic and environmental factors to IVH.

The physical risks involved in this study are minimal. Buccal swabs will be used to obtain DNA. Standard collection techniques will be used, which include preparation by rinsing with water and rubbing the cheek with a soft cotton-tipped sterile swab for 10 to 20 strokes. The risk of injury due to buccal swabs is minimal with these procedures and is limited to mild abrasion of the buccal surface.

HUS screening is routinely performed as part of standard care of preterm infants in the NICU and pose no known risk to the infant. Scans will be performed on postnatal days 7 ¿ 10, and again on postnatal days 21 ¿ 28. All CD's containing copies of the patients' scans will be labeled only by patient study number; the actual electronic images, however, may contain some patient identifying information that may not be able to be removed after the scans are performed. These CD's containing the copies of the HUS's will be kept in a locked cabinet at the Core facility and destroyed at the end of the study period. Access to these scans will be limited to study personnel and Core radiologists who will be verifying patient eligibilty.

Risk of Discrimination:

It is possible that the study participant would be at risk for certain types of discrimination should his/her enrollment become known, or if personal genetic and/or medical data from the study were to become known. These include discrimination that may interfere with a subject¿s future ability to get insurance. It also includes stigmatization within the subject¿s family. We think, however, that the risks to the study participant will be remote due to the encoding protection and the restricted access to data files that could link a subject to a code number.