Maternal hyperglycemia in diabetes mellitus is associated with fetal morbidity and mortality and hypertrophic cardiomyopathy in the newborn with varying degrees of cardiorespiratory distress. In the fetal sheep there is evidence that hyperglycemia by itself may alter cardiac performance and umbilical circulation. We propose to investigate in the human if there are specific, end- organ effects of maternal hyperglycemia on umbilical circulation in the fetus and on cardiovascular anatomy and performance in the fetus and infant. We will use state-of-the-art technology including high-resolution, two-dimensional realtime ultrasound imaging, M-mode echocardiography and Doppler ultrasound to gain non-invasive access to the fetal cardiovascular system. We will use an interdisciplinary approach to document umbilical vein mean flow, umbilical artery impedance to blood flow and a series of intracardiac variables that describe right and left ventricular anatomy and performance in the fetus and infant. We will first examine the normal late gestation pregnancy flow effects of maternal hyperglycemia alone upon umbilical blood flow. We will investigate if an acute sustained maternal hyperglycemia produced by the glucose-clamp technique results in decreased umbilical vein flow. We will examine if there is s corresponding increase in impedance to blood flow in the umbilical artery suggesting control of flow in the microvasculature of the placenta. We will next examine serially in the late second trimester and third trimester of pregnancy the effects of chronic, intermittent maternal hyperglycemia (gestational diabetes) on umbilical vein flow and umbilical artery impedance to flow and correlate any alterations with the quality of maternal glycemic control. We will also correlate prenatal and postnatal findings of hypertrophic cardiomyopathy to extend this diagnosis into the prenatal period and correlate the quality of glycemic control with the degree of hypertrophy and other measures of cardiac performance. We believe that such acute studies in the prenatal period and serial studies in the prenatal and postnatal period may lead to an understanding of the pre-morbid events in the human fetal cardiovascular system that may progress or regress with varying quality of glycemic control and thus explain some of the metabolic alterations of physiologic events that lead to fetal and infant morbidity and mortality in diabetic pregnancies.
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