In our last post on the subject of hypertensive disorders in pregnancy, we pointed out that once preeclampsia has developed, we are limited in our ability to “treat” the condition. Indeed, the only situations I have seen in which the clinical syndrome of preeclampsia has resolved have been those in which an adverse fetal condition was first reversed. An example of this is severe fetal anemia (usually associated with fetal hydrops) secondary to isoimmunization or Parvovirus infection that responded to intrauterine transfusion. Nevertheless, there are other circumstances in which we may be able to prevent or reduce the risk for preeclampsia.
As mentioned in our third post on this subject, there are several well-known prepregnancy and intrapregnancy risk factors for preeclampsia. While we cannot change a woman’s race or age, or the presence of a first pregnancy, new partner, or multiple gestation, there are two groups of women we can identify from this list who would probably benefit from more aggressive medical management to reduce their risks for preeclampsia. There are those who previously had a pregnancy complicated by preeclampsia and those who have not (or who have never been pregnant) and/or have significant risk factors or medical conditions that might lend themselves to medical intervention as a preventive measure prior to conception or very early in pregnancy.
In the first case (previous history), we know that recurrence risks for preeclampsia are correlated with the severity of disease and the earlier in gestation the preeclampsia occurred. Indeed, rates of recurrence for a history of severe, early onset preeclampsia approach 40-50% in some studies. So we do have a ready-made subgroup of women to which we should direct efforts at prevention. Similarly, women who have hypertension, renal disease, diabetes, polycystic ovary syndrome and other conditions associated with insulin resistance, an autoimmune disease, or known autoimmune or genetic thrombophilia also shake out as a group to which extra attention should be directed.
So, what can we do to help these women? The first thing we would recommend is to optimize their medical conditions and general health. If a woman is overweight, then a weight reduction and exercise program should be encouraged prior to conception with some realistic ‘goals’ in mind before attempting pregnancy. If she is hypertensive, diabetic, or has another treatable medical condition, control of this (these) should be optimized, again, prior to conception. In women who have polycystic ovary syndrome or other conditions associated with insulin resistance, the use of an ‘insulin-sensitizing’ drug such as metformin may play a role, can be started before conception, and can be continued during the pregnancy.
Beyond this, almost all efforts at intervention would have to be considered ‘empiric’. In my own practice, I offer all of these women with significant risk factors the regimen of low-dose aspirin (81 mg daily) and supplemental folic acid (usually 2-4 mg daily). If a woman has a known autoimmune or genetic thrombophilia, I have a low threshold for adding prophylactic use of heparin or low molecular weight heparin; and, if there is a history (or strong family history) of venous or arterial thrombosis, therapeutic doses of these same drugs. The latter are relatively safe to use in pregnancy (they do not cross the placenta), their doses can be monitored and adjusted as the pregnancy progresses, and at least one study would support their use in the ‘prevention’ of preeclampsia (Sergio, et al., Hypertens Pregnancy 2006;25:115).
I have on occasion also used both prophylactic and therapeutic doses of heparin and low molecular weight heparin in women who have had severe early onset preeclampsia in a previous pregnancy (or more than one) and no identifiable thrombophilia or other risk factor for which these drugs would ordinarily be indicated. Under these circumstances, once the pregnancy is well-established, and if normal fetal growth and Doppler flow studies can be documented (usually by 28 weeks gestation), I will discontinue these drugs.
I will close this series on hypertensive disorders in pregnancy with (perhaps) one last post wherein I will address other possible diagnostic, therapeutic, and possibly preventive approaches that might be taken in the future to reduce the frequency and severity of preeclampsia…