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运输及其与妊娠合并宫内生长迟缓（IUGR）的血流的关系。将使用稳定同位素研究9种必需氨基酸在胎盘中的运输，并测定正常妊娠和IUGR妊娠中胎儿/母体的富集程度和示踪剂浓度比。IUGR妊娠根据临床严重程度根据流速测量结果和FHR数据进行分类。这些关于氨基酸运输的数据将被用于分析用功率多普勒技术直接测量的脐血流量变化的影响。这将确定IUGR妊娠中氨基酸向胎儿的输送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妊娠和IUGR妊娠中测量。对d -甘露糖和肌醇进行了特别关注，用每种糖的稳定同位素和注入母体循环的d -葡萄糖的稳定同位素对它们进行了研究，直到建立稳定的富集状态。同时，测定肌醇和d -甘露糖的胎儿/母体富集比。葡萄糖碳合并到甘露糖和肌醇将比较在正常和IUGR妊娠。这些研究将确定，如果有的话，这些碳水化合物依赖于胎盘转运还是胎儿或胎盘组织内的合成。它将决定在IUGR妊娠中，某些碳水化合物和多元醇的胎盘梯度是否会增加，就像葡萄糖的梯度一样。最后，将评估宫内肝血流大量减少对IUGR新生儿的影响。新生儿肝血流明显减少，可在子宫内通过脐带血流减少和静脉导管分流增加来检测。肝细胞损伤的证据将在分娩时通过分析脐带血的特定凝血因子和肝酶来寻找。此外，通过母乳喂养后新生儿d -半乳糖血浆清除率来评估新生儿肝功能的功能障碍。这些研究将确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.