In our last post on this subject, we described an abnormality of placental development, incomplete or abnormal invasion of the maternal spiral arterioles by fetal placental cells (trophoblasts) early in pregnancy, as perhaps the most common sentinel event associated with preeclampsia later in pregnancy. This abnormality of placentation can, albeit variably, restrict blood flow into the placental bed from the spiral arterioles on the maternal side and can also limit the size, arborization (branching), and the total surface area of the fetal-placental villi that are bathed by the maternal blood that enters the placental bed. This is significant because all the oxygen and nutrients the baby gets to survive have to cross the surface of the villi to get into the fetal circulation. If the abnormality of placentation is extensive enough, this will eventually limit the growth of the baby and stress the capacity of the placenta to maintain a ‘healthy’ environment for both baby and placenta. At the risk of taking an overly simplistic approach, it seems almost intuitive that preeclampsia results then from an attempt on the part of the placenta to improve its condition by whatever ‘homeostatic’ mechanisms it has at its disposal. The ultimate goal of these homeostatic mechanisms seems to be an attempt to increase the amount of maternal blood (oxygen?) actually flowing into the placental bed.
Over the years, many clinical observations have been made that are consistent with this model of abnormal placentation and also with the attempt of the placenta to improve its lot in life. Let me give you a few examples to illustrate these points. In circumstances of normal placentation, that is a pregnancy not destined to end in preeclampsia, the mother’s blood pressure usually starts to drop at the transition of first to second trimester. This timing of the blood pressure drop coincides with the time when the adequately ‘invaded and plugged’ spiral arterioles become unplugged and the now sac-like ‘remodeled’ vessels allow the maternal blood to flow freely into the placental bed with very little resistance. The placental bed thus becomes an ‘arteriovenous shunt’ and as a consequence the maternal blood pressure falls.
With abnormal invasion of the spiral arterioles, the vessels remain narrow, coiled and responsive to factors that can cause them to constrict. As a result, the ‘midtrimester drop’ in maternal blood pressure either does not occur or is much less dramatic than in normal circumstances. This abnormality of placentation in women at increased risk to become preeclamptic was suggested by observations made half a century ago. When pressors (drugs that cause blood vessels to constrict and raise blood pressure) such as norepinephrine are infused into ‘normal’ pregnant women, they have a very blunted response to the blood pressure elevating effects of these drugs. However, when these drugs are given to women who eventually became preeclamptic, their blood pressure rises the same as it would if they were not pregnant at all. Can’t you see those tight little spiral arterioles clamping down right now?!? Decreasing blood flow to the placenta just cannot be a good thing.
In the last 25 years, we have figured out a less invasive way of ascertaining abnormalities of both spiral arteriole remodeling and fetal placental vascular development. Using Doppler flow velocimetry, we can assess resistance to blood flow in vessels by simply using ultrasound. Since the blood vessel abnormalities occur early in pregnancy, Doppler flow studies can show abnormal resistance patterns often long before the onset of preeclampsia and be used to identify ‘women at risk.’ Indeed, increased resistance in the uterine arteries (reflecting increased resistance ion the spiral aretrioles) beginning early in the second trimester, and in the fetal umbilical arteries (reflecting increased resistance in the placental villi), sometimes as early as 16-20 weeks, are well-correlated with later development of fetal growth restriction, preeclampsia, fetal deaths, need for early delivery, and risk for cesarean delivery because of babies developing nonreassuring fetal heart rate patterns secondary to oxygen deprivation.
So, if the placentation is abnormal, how is it that the placenta eventually recognizes and responds to its hostile environment to try to improve its (and the baby’s) situation. We don’t know for sure, but I believe the clinical features of preeclampsia reflect the placenta’s efforts. As we mentioned in our first posts on this subject, preeclampsia is characterized by intense vasospasm (constriction) of the mother’s blood vessels. Vasospasm causes the mother’s blood pressure to rise and suggests that the placenta is using the only means it has at its disposal (whatever the mechanism) to force more blood into the placental bed from the maternal side, somehow forcing the mother’s blood pressure higher. Unfortunately, the narrow abnormal maternal spiral arterioles only have so much capacity to allow blood to pass through them; and, it is possible that the placenta’s production of factors that lead to vasoconstriction of peripheral blood vessels might also cause some constriction of the spiral arterioles as well, thereby worsening an already deteriorating situation. Such a ‘vicious cycle’, once started, could rapidly lead to the full-blown picture of preeclampsia: vasospasm, hypertension, plasma volume constriction, endothelial cell damage, and activation of the coagulation pathways.
In our next post, we will present an overview of the limited information we have available to us regarding interventions we might take to reduce the risk of preeclampsia…