This study, an outgrowth of a previous multicenter study of white matter injury in the preterm infant, aims to provide understanding of the molecular antecedents of white matter damage, and to lay the foundation for clinical trials designed to prevent cerebral white matter damage. To achieve these goals, we will identify and measure four sets of fetal, placental, and neonatal biomarkers, which, in animal and in vitro studies, have been associated with an altered risk of cerebral white matter damage. These include: (1) initiators of the fetal inflammatory response (e.g., bacteria), (2) damage promoters (e.g., pro-inflammatory cytokines), (3) modulators of the inflammatory response (e.g., anti-inflammatory cytokines, cytokine binding proteins, cytokine receptor antagonists), and (4) cerebral white matter protectors (e.g., hormones and growth promoters). Colleagues at 14 neonatal intensive care units are expected to enroll 1,800 infants born before 28 weeks of gestation in a multi-center study, and with the help of our laboratory colleagues will:
a) identify and measure clinical characteristics and experiences of mother and her newborn;
b) identify and measure in the placenta and umbilical cord: cellular morphology, infectious organisms, and receptors for and expression of endocrine hormones, non-endocrine growth factors and selected integrins;
c) measure in one or more specimens of mother’s blood, one of which will be obtained close to the time of delivery: cytokines, chemokines, adhesion molecules, hormones, and growth and survival factors;
d) measure in umbilical cord blood and multiple postnatal blood samples: cytokines, chemokines, adhesion molecules, hormones, and growth and survival factors;
e) from a, b c and d, identify the clinical, morphologic, and biochemical characteristics that predict white matter damage as indicated by an echolucency on cranial ultrasound scan;
f) using neurologic examinations and neuropsychologic tests, examine the babies at 12 months and at 24 months corrected age to test for neurodevelopmental delays and abnormalities;
g) maintain a "tissue bank" of placenta, umbilical cord, and blood that will be available for analyses to be suggested by future research findings.
