HEART RATE AND BLOOD FLOW VELOCITY VARIABILITY IN HUMAN EMBRYO AND FETUS

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Perinatal morbidity and mortality remain a large public health problem, accounting for 8 to 10 deaths per 1000 pregnancies in the United States and Europe. Pregnancy induced hypertension occurs i 10% of all pregnancies. Uteroplacental insufficiency likely results in intrauterine growth retardation and fetal hypoxemia-identified by abnormal feta heart rate and cardiovascular flow velocity patterns. While these complications are apparent only late in pregnancy, the pathogenesis of pregnancy induced hypertension and intrauterine growth retardation begins with abnormal trophoblast invasion of the spiral arteries of the placenta that occurs between 10 and 18 weeks gestation. Early identification of an affected fetus would permit intensive observation and potential treatment, thereby reducing the consequences of fetal pathology. At present, there are no accurate techniques to identify early fetal cardiovascular pathologic hemodynamic states. Long term aim: Develop a non-invasive measure of fetal cardiovascular well being that allows early identification of the fetus with cardiovascular dysfunction and thereby permit potential therapeutic intervention. We hypothesize: There are specific heart rate frequency and blood velocity amplitude variabilities that indicate cardiovascular health in the 10 to 18 week human embryo-fetus. Fetal heart rate and arterial and venous flow velocity amplitude variability correlate directly with fetal cardiovascular function during the critical transition of trophoblast invasion. Variation from these profiles is a measure of cardiovascular dysfunction that correlate directly wit poor outcome. We study the human fetus at 10 to 18 weeks gestation using Doppler ultrasound techniques of blood velocity profile measurements from a trans-vaginal and/or trans abdominal probe of: maternal uterine artery, fetal umbilical artery, descending aorta and ductus venosus. Fetal age is determined by fetal crown-rump length or biparietal diameter. Digital signal processing is used to define frequency and amplitude variability and wave form analysis. Statistical correlation is determined by sensitivity, specificity, positive and negative predictive value and multiple logistic regression. The specific aims include: Develop an automated algorithm to analyze arterial and venous Doppler velocity waveforms for frequency and amplitude variability. Define normal frequency and amplitude variability in a cross sectional study of 300 human fetuses from 10 to 18 weeks gestation. Correlate fetal arterial and venous frequency and amplitude variability wit fetal outcome in a longitudinal study in a cohort of 200 human fetuses. Significance: This study is essential to our understanding of the early human cardiovascular system because there are no measures of the developing embryo or fetus define normal or abnormal cardiovascular function at less than 20 weeks. There is a clear and present need for an early accurate measure that identifies the fetus at risk and allow for careful monitoring and early intervention. Early identification of the affected fetus leads to timely intervention reducing the burden of disease, improving fetal outcome and reducing health care cost.