In our last two posts, we have discussed the general significance of hypertensive disorders in pregnancy and the spectrum of pregnancy-induced hypertensive disorders classified as preeclampsia. The problem with preeclampsia is that most of the time it is the end-stage manifestation of irreversible pathologic changes that took place early in pregnancy and by the time we recognize that a pregnant woman is developing the condition, there is little if anything we can do to ‘treat’ it. I will elaborate on these points in a subsequent post, but the bottom line is that we will have to learn to identify women ‘at risk’ by the end of first trimester and early second trimester if there is to be any hope of decreasing the incidence and severity of preeclampsia. Theoretically and, perhaps, practically in the not-to-distant future, we should be able to do just that.
For the time being, however, we must rely on known risk factors to identify a subset of women in whom it is appropriate to offer some form of medical intervention. With this in mind, the questions arise: What are risk factors for preeclampsia?; Which are those that may be most amenable to intervention?; What sort of interventions are possible and practical?; and, When should such interventions be started? The common risk factors, occurring before and during pregnancy are well-known and there is little argument about their association with preeclampsia:
· First pregnancies and, to a lesser degree, first pregnancies with a new partner · Multiple gestations · Chronic hypertension · Chronic kidney disease · African-American ethnicity · Women over age 35 · History of pregnancy-induced hypertension · Obesity · Pregestational diabetes – especially long-standing with kidney or vascular disease · Gestational diabetes · Autoimmune diseases such as systemic lupus erythematosus · Family history of preeclampsia · Abnormal maternal serum pregnancy markers (AFP, hCG, estriol, inhibin A) · Isoimmunization with fetal hydrops (and other conditions with hydrops) · Molar and partial molar pregnancies
Other, less well-known, risk factors also seem to place a woman at greater risk for hypertensive disorders in pregnancy as well and among the more likely to do so are:
· Polycystic ovary syndrome · Insulin resistance and ‘metabolic syndrome’ · Hyperthyroidism · Antiphospholipid antibody syndrome · Thrombophilias (genetic abnormalities of the coagulation system) · Hyperhomocysteinemia · Pregnancies achieved by egg donation
Sticking to the mantra that “the best prenatal care begins prior to conception,” the best opportunity for risk assessment and potential intervention starts with a preconceptional or interconceptional (between pregnancy) visit. Some of the interventions are obvious. If a patient has an underlying medical condition such as diabetes, chronic hypertension, thyroid disease, systemic lupus, etc., those medical conditions should be ‘optimized’ with treatment that is ‘safe’ for pregnancy before ever conceiving. Women who are overweight, and have any accompanying condition (e.g. PCOS, hypertension, diabetes, insulin resistance) should attempt a supervised exercise and diet weight reduction program prior to conception (personally, I believe ‘Atkins’ and exercise’ is ideal for these women!).
Preeclampsia is often considered to be a ‘disease of women carrying their first babies’ and indeed it occurs at least twice as often under these circumstances as in women who have previously had a baby. Since we have no early diagnostic or reliable screening test to tell us which of these first-time pregnant women are at risk, the most we can hope to do at present is address beforehand any medical issues, optimize control of such conditions, give them prenatal vitamins with folic acid, and follow them carefully during their pregnancies. If a major risk factor taken from the list above is identified, other options for intervention should be considered, but that discussion is beyond the scope of today’s post.
I have learned through the years that two of the most significant predictors of preeclampsia are previous history of preeclampsia and family history of the same. A rule of thumb is that the more severe the preeclampsia, the earlier it occurred in a previous pregnancy, the more complications with which it was associated (e.g. eclampsia, HELLP syndrome, severe fetal growth restriction, placental abruption, decreased amniotic fluid, fetal or neonatal death, placental vascular abnormalities) the greater the likelihood for recurrence with a subsequent pregnancy, even if no other ‘risk factor’ is ever identified. The fact that we haven’t ‘identified’ such risk factors probably speaks more to our current level of ignorance regarding these matters than to their nonexistence!
By the way, if you hadn’t noticed, there is one ‘risk factor’ that is conspicuously absent from the lists above – SMOKING! I am almost afraid to mention this because there is nothing that justifies the habit in pregnancy, but fact of the matter is that smoking appears to REDUCE the risk of preeclampsia. As has been recently summarized by England, et al., (Front Biosci 2007;12:2471-83), the “beneficial effects” of smoking are present in a “dose-related” fashion and are consistently found regardless of parity, number of babies, and severity of preeclampsia that is found. The overall risk reduction approaches 50%! Believe me, this is not an endorsement of smoking during pregnancy (or ever for that matter), but perhaps someday we will be able to identify a relatively ‘safe’ by-product of tobacco that can help prevent or reduce the severity of preeclampsia!
In our next post, we will look at the role of abnormal early placental development in setting the stage for developing preeclampsia and some of the ongoing evaluation that can be done during pregnancy to anticpate risk…