A clinical study which relates to a theoretical simulation of the glucose transport in the human placenta under various diabetic conditions.

AIMS: To characterize placental glucose delivery under normoglycemic conditions, gestational and pre-gestational diabetes and to relate the clinical data to theoretical predictions. METHODS: Data from 125 pregnancies: 50 normal gestations and 75 ones with various types of diabetes were collected. In parallel, we formulated a theoretical model for the transport of glucose under various diabetic conditions. Measured glucose blood levels were fed into the theoretical model that predicts glucose supply to the fetus and the results were confronted with measured fetal weights. RESULTS: Measured fetal weight and computed glucose delivery in gestational diabetic parturients resemble the situation in normal pregnancies. However, pre-gestational diabetes has a major effect as it involves heavier fetuses and enhanced computed glucose fluxes via placental membranes. CONCLUSIONS: Fetal weight (increased in pre-gestational and unaltered in gestational diabetes) correlates with the predicted rate of glucose delivery through the placenta.

A theoretical model of glucose transport suggests symmetric GLUT1 characteristics at placental membranes.

The process of glucose transport via the placenta is not fully deciphered. Here, we apply a theoretical model to compute glucose fluxes via the terminal villi of the human placenta for various sets of parameter values and conclude on characteristics of transport across the two bordering membranes. Based on available measured data, the spatial geometry of the terminal villi is being simulated. Within this region, glucose concentrations and fluxes are computed by a numerical scheme that solves the diffusion equation with boundary conditions that account for transporter mediated diffusion at the membranes. Feasible parameter values (ones that induce physiological glucose fluxes) are determined for four optional symmetry characteristics of the membranes. Confronting computed results with clinical knowledge reveals the most plausible scenario-symmetric activity of the transporter at the microvillous membrane. Thus, sensitivity analysis of the computed results enables deduction about micro-scale mechanisms at the bordering membranes based on macro-scale knowledge.

Glucose transport from mother to fetus--a theoretical study.

The factors that affect and govern the glucose transfer from maternal blood to the fetus are not completely deciphered. We present a steady state, one dimensional mathematical simulation which integrates the main mechanisms that have been shown to exist: metabolic consumption of the placenta, simple and facilitated diffusion via the two membranes of the microvillous and simple diffusion within the placenta. The model uses all available physiologic data we could collect. Numerical results indicate that the most crucial factor in determining the fetal glucose concentration is the facilitated diffusion process at the basal membrane or, more specifically: the permeability of the basal membrane and the density of the transporter GLUT1 on its faces. The gradient between the maternal and the fetal glucose concentration is important as is the metabolic consumption of the placenta. The diffusion within the placenta and the conditions that prevail at the apical microvillous plasma membrane are much less significant. Intrasyncytial concentration of glucose is close to that of maternal blood. The adjustment of the fetal glucose concentration to abrupt changes of its surrounding is estimated to be quite rapid hence for all practical purposes this steady state model can serve as a reasonable approximation. Parameters that await experimental determination are identified.

The coagulation profile of preterm delivery.

INTRODUCTION: Hypercoagulation was suggested to be involved in preterm birth etiology; however, the coagulation state of preterm parturients remains unelucidated. The study aim was to evaluate the haemostatic system of pregnant women with premature uterine contractions (PUC). MATERIALS AND METHODS: The cohort study population consisted of 76 healthy pregnant women admitted with regular PUC. The study group included 38 women who experienced preterm birth; 14 of them had preterm premature rupture of membranes (PPROM). The control group included 38 women who eventually had term delivery. Groups were matched for maternal age, number of births and gestational age at admission. Blood samples were tested for haemostatic parameters and coagulation activation markers. RESULTS: Significantly shorter PT and aPTT were documented in the study compared to control group (25.7±2 vs. 27.4±2.7seconds, P=0.003, and 9.96±0.5 vs. 10.1±0.4seconds, P=0.05, respectively), although differences in absolute values were small. There was no significant difference between the two groups in levels of: fibrinogen, D-dimer, protein C-global, free protein S antigen, factor VIII activity, Von Willebrand factor, plasminogen activator inhibitor-1, prothrombin fragments F1+2 (PT F1+2), tissue factor and tissue factor pathway inhibitor. Women with PPROM had significantly lower PT F1+2 levels compared to those who had preterm delivery with intact membranes (351±99 vs. 561±242pmol/L, P=0.003). CONCLUSIONS: Shortened PT and aPTT, reflecting increased thrombotic activity in maternal plasma, could serve as a marker of real preterm labor in women with premature uterine contractions. Further prospective studies in a larger cohort are warranted to validate these findings.

Activation of coagulation in amniotic fluid during normal human pregnancy.

INTRODUCTION: Amniotic fluid (AF) is an important medium for fetal development which exhibits high procoagulant activities; however, the role of these procoagulants during pregnancy has not been elucidated and might be associated with pregnancy complications. The current study aimed to evaluate factor X (FX) activation and its association with tissue factor (TF), tissue factor pathway inhibitor (TFPI) and coagulation activation markers in AF during normal human pregnancy. METHODS: Activation of FX and concentration of TF, free TFPI, D-dimer and prothrombin fragments (F1+2) were evaluated in AF samples obtained for chromosome analysis from 91 women with normal pregnancy: 65 samples were taken from patients at 16-20 weeks of gestation, 9 samples were drawn at 21-30 weeks and 17 samples--after 30 weeks of gestation. RESULTS: Activation of FX in AF significantly increased during normal pregnancy (from 65±41 to 205±80 equivalent RVV ng/mg total protein, P<0.0001). TF and TFPI levels in AF also rose with gestational age. In contrast, the AF concentration of D-dimer and F1+2, markers of coagulation activation significantly decreased when expressed per mg total protein. Levels of free TFPI correlated with TF (r=0.5, P<0.001), and were 8-fold higher than those of TF during pregnancy. CONCLUSION: High levels of TFPI might be associated with the inhibition of procoagulant activity in amniotic fluid during normal pregnancy, which may account for the rarity of clinical amniotic fluid embolism.