PLACENTAL VASCULAR DETERMINANTS OF FETAL GROWTH

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Fetal growth is an important trait that influences an individual's lifelong health. Fetal growth has been studied intensively for many years, and the epidemiologic risk factors for clinically important outcomes, like intrauterine growth restriction, are well documented. However, the physiologic systems that link these risk factors to perinatal outcomes are not well characterized. In this regard, the birth of a healthy infant requires the establishment and ongoing development of the placental vascular system. Disordered placental vascular development is responsible for a number of pregnancy complications, including impaired fetal growth. Despite this knowledge, the relationships among physiologic factors associated with placental vascular development and their relationship to fetal growth have not been adequately studied. Among these factors, the vascular endothelial growth factor (VEGF) family plays a particularly important role in vascular development. Thus, we hypothesize that fetal growth impairment may arise from dysregulation of coordinated expression of these factors through their influence on placental vascular development. We propose a prospective cohort study to analyse the interrelationships among classic epidemiologic risk factors for fetal growth impairment and time-dependent changes in serologic measures of factors in the VEGF family, physiologic measures of placental vascular function, and morphometric measures to fetal growth for women sampled early in pregnancy on the basis of the C936T polymorphism in the gene for VEGF. This polymorphism has been associated with variations in VEGF plasma levels and may be related to several adverse pregnancy outcomes. Women will be monitored during pregnancy to measure time-dependent changes in maternal and fetal health, physiology, and outcomes. We will use analytic models that describe the time-dependent interactions among the genetic, physiologic, and environmental factors to carry out the following three specific aims: Specific Aim 1. Estimate the relationship between morphometric measures of fetal growth and time dependent changes in: (i) serologic measures of VEGF related factors and (ii) physiologic measures of placental vascular blood flow. Specific Aim 2. Estimate the relationship of time dependent measures of (i) serologic levels of VEGF related factors and (ii) placental vascular blood flow with VEGF C936T status and classic epidemiologic risk factors (i.e. maternal size and weight gain; maternal parity; maternal smoking; maternal hypertension; and fetal sex). Specific Aim 3. Estimate the relationship of morphometric measures of fetal growth to VEGF C936T status and classic epidemiologic risk factors beyond that predicted by time-dependent changes in measures of serologic levels of VEGF related factors or placental vascular blood flow.'