Fetal Velocimetry & Amino Acid Transport in Pregnancy

描述（由申请人提供）：概述的研究是针对营养转运及其与胎儿宫内发育迟缓（IUGR）并发症的妊娠血流的关系。将使用稳定同位素研究9种必需氨基酸穿过胎盘的转运，并确定正常和IUGR妊娠中胎儿/母体富集和示踪剂浓度比。IUGR妊娠根据血流速度测定结果和胎心率数据按临床严重程度分类。将分析氨基酸转运的这些数据，以了解能量多普勒技术直接测量的脐血流变化的影响。这将确定IUGR妊娠中向胎儿输送氨基酸是否受到脐带血流量减少的影响，以及这种关系是否是非线性的。将在正常和IUGR妊娠中测量非葡萄糖碳水化合物，包括多元醇。特别注意的是D-甘露糖和肌醇的研究与稳定同位素的每种糖和D-葡萄糖注入母体循环，直到建立稳态富集。此时，测定肌醇和D-甘露糖的胎儿/母体富集比。葡萄糖碳掺入甘露糖和肌醇将在正常和IUGR妊娠进行比较。这些研究将确定这些碳水化合物中的哪些（如果有的话）依赖于经胎盘转运与胎儿或胎盘组织内的合成。它将确定在IUGR妊娠中某些碳水化合物和多元醇的经胎盘梯度是否增加，因为梯度是葡萄糖。最后，对宫内发育迟缓新生儿在子宫内肝血流量的巨大减少的影响进行评估。肝血流量明显减少的新生儿可以在子宫内从脐血流量减少加上静脉导管分流增加中检测到。在分娩时通过分析脐带血中的特异性凝血因子和肝酶来寻找肝细胞损伤的证据。此外，将通过母乳喂养后新生儿的D-半乳糖血浆清除率评估新生儿肝功能的功能障碍。这些研究将建立胎儿血流变化与胎儿营养输送之间的重要联系。

DESCRIPTION (provided by applicant): The studies outlined are directed at nutrient transport and its relationship to blood flow in pregnancies complicated by intrauterine growth retardation (IUGR). The transport of the 9 essential amino acids across the placenta will be studied using stable isotopes and determining the fetal/maternal enrichments and tracer concentration ratios in normal and IUGR pregnancies. IUGR pregnancies are classified by clinical severity based upon velocimetry findings and FHR data. These data on amino acid transport will be analyzed for the impact of variations in umbilical blood flow directly measured with power Doppler techniques. This will establish whether delivery of amino acids to the fetus in IUGR pregnancies is impacted by a reduction in umbilical blood flow and whether this relationship is nonlinear. The non-glucose carbohydrates including the polyols will be measured in normal and IUGR pregnancies. Specific attention is given to D-mannose and myoinositol which are studied with stable isotopes of each sugar and of D-glucose infused into the maternal circulation till steady state enrichments are established. At that time, the fetal/maternal enrichment ratios for both myoinositol and D-mannose are determined. The glucose carbon incorporation into both mannose and myoinositol will be compared in normal and IUGR pregnancies. The studies will establish which, if any, of these carbohydrates relies upon transplacental transport vs. synthesis within the fetal or placental tissues. It will determine if the transplacental gradient for some carbohydrates and polyols are increased in IUGR pregnancies as the gradient is for glucose. Finally, the impact upon the IUGR newborn of an enormous reduction in hepatic blood flow in utero will be assessed. The newborns with a marked reduction in hepatic blood flow can be detected in utero from the reduction in umbilical blood flow coupled with an increase in the ductus venosus shunt. Evidence of hepatocellular damage will be sought at delivery by analysis of cord blood for specific clotting factors and hepatic enzymes. In addition, functional disturbance in neonatal liver function will be assessed by D-galactose plasmal clearance in the newborn after a milk feeding. These studies will establish important links between blood flow changes in the fetus and nutrient delivery to the fetus.