Relationship of maternal placental blood flow to the placental clearance of maternal plasma dehydroisoandrosterone sulfate through placental estradiol formation

We have suggested that the placental clearance of maternal plasma dehydroisoandrosterone sulfate (DS) through estradiol (E2) formation (PC-DSE2) is reflective of uteroplacental blood flow (F). Clewell and Meschia13 suggested that PC-DSE2 is related to F as follows: Cobs = F(1-e-C/F), where Cobs = PC-DSE2 and C = total placental clearance of maternal plasma DS. This equation contains two unknown quantities, F and C. To solve the equation, Clewell and Meschia assumed that C was constant. Using 19.7 ml/min for C, they allowed PC-DSE2 to vary widely and computed F. Upon finding that F was unrealistically low for some values of PC-DSE2, they concluded that reductions in PC-DSE2 do not reflect alterations in uteroplacental blood flow. In the analysis of the relationship of F to PC-DSE2, it is important to know the value of C. Since the direct measurement of C is not possible at this time, we have evaluated C by measuring the difference between the metabolic clearance rate of DS (MCR-DS) prior to and immediately following delivery. Any change in MCR-DS before and after delivery should be a reflection of the amount of maternal plasma DS cleared by the placenta through all metabolic routes including PC-DSE2, providing nonplacental clearances of maternal plasma DS before and immediately after delivery are the same. We measured MCR-DS and PC-DSE2 in 15 pregnant women within 5 days before delivery and repeated the MCR-DS measurement in these women beginning 90 minutes after delivery. Among these 15 women, C ranged from a low of 4.7 ml/min in a woman with severe pre-eclampsia to a high of 28.5 ml/min in a woman with twins. In addition to the finding that C varied widely, it was also ascertained that PC-DSE2 was positively correlated with C (r = 0.908; p less than 0.001). The finding that low or high values for PC-DSE2, observed in complicated pregnancies, were associated with similar changes in C is suggestive that a change in PC-DSE2 is reflective of a change in uteroplacental blood flow.