Fetal Velocimetry & Amino Acid Transport in Pregnancy

描述(由申请人提供)：概述的研究针对的是营养物质的转运及其与胎儿宫内发育迟缓(IUGR)合并妊娠的血流的关系。在正常和IUGR妊娠中，将使用稳定的同位素和测定胎儿/母体的富集物和示踪剂浓度比率来研究9种必需氨基酸在胎盘中的转运。IUGR妊娠根据血流速度测量结果和胎心率数据按临床严重程度进行分类。这些关于氨基酸转运的数据将被分析，以了解利用能量多普勒技术直接测量的脐血流量变化的影响。这将确定胎儿宫内发育迟缓时氨基酸的分泌是否受到脐血流量减少的影响，以及这种关系是否是非线性的。包括多元醇在内的非葡萄糖碳水化合物将在正常和IUGR怀孕时进行测量。特别关注D-甘露糖和肌醇，研究每种糖和D-葡萄糖的稳定同位素注入母体循环，直到建立稳定的浓缩状态。届时，测定胎儿/母体对肌醇和D-甘露糖的富集率。在正常和IUGR妊娠中，甘露糖和肌醇中的葡萄糖碳结合情况将被比较。这些研究将确定这些碳水化合物中的哪一种依赖于胎盘转运，而不是胎儿或胎盘组织内的合成。它将确定一些碳水化合物和多元醇的胎盘梯度是否像葡萄糖的梯度一样在IUGR妊娠中增加。最后，将评估宫内肝脏血流的巨大减少对IUGR新生儿的影响。肝脏血流明显减少的新生儿在宫内可从脐带血流量减少和静脉导管分流增加中检测到。分娩时将通过分析脐带血中特定的凝血因子和肝酶来寻找肝细胞损伤的证据。此外，新生儿喂奶后D-半乳糖的血浆清除量将评估新生儿肝功能的功能障碍。这些研究将在胎儿血流变化和向胎儿输送营养之间建立重要联系。

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.