Well, I was away again this weekend. Drove to Indianapolis for my niece’s wedding. That area, like so much of the rest of the country, has been suffering from a drought, but it decided to come to an end this weekend. Of course, the wedding rehearsal dinner, wedding itself, and the reception were all planned for the outdoors, and went forward despite the downpour. The weather, as usual, showed no respect for protocol. But, everyone had a great time. Our congratulations, love, and best wishes (for everything but twins) to the beautiful couple, Karen Wilson and Daniel Wielunski.
Anyway, let’s chat a little more about preeclampsia. The next question to address is how do we treat preeclampsia? Believe it or not, the answer to that is rather simple. In most cases, we don’t. Since the most common forms of preeclampsia are the ‘end-stage’ manifestation of events occurring earlier in pregnancy, we cannot correct the conditions (and probably never will be able to) once we have gotten to the point of preeclampsia. About all we can do is stabilize the mother and the baby temporarily (in the U.S., this involves primarily the use of bed rest, magnesium sulfate, antihypertensives, and fetal assessment) and then deliver, regardless of the gestational age, whenever the maternal and/or the fetal condition deteriorate to the point that it is dangerous for either/both to continue the pregnancy. In some cases, we buy a fair amount of time, and in others delivery is required almost immediately. The old adage that the sun should not set on a severely preeclamptic woman until the placenta is in the bucket to be sent to pathology holds a lot of truth. Even then, the most severely affected women (and sometimes those not so severely affected before delivery) may continue to deteriorate for days after the source of the problem (the placenta) is removed because of the hypertension, endothelial cell damage, consumptive coagulopathy, kidney and liver damage, brain swelling, and fluid shifts that occur before and may continue after delivery! Since at least two-thirds of preeclampsia occurs in women having their first babies, and we currently have no reliable and cost-effective means of identifying those at greatest risk, this is about the only recourse we have to ‘manage’ the bulk of cases of preeclampsia.
Some efforts have been made at what would have to be considered ‘empiric preventive therapy’ in an effort to reduce the number of patients who develop preeclampsia and its complications. In the general obstetrical population, the only ‘therapy’ to date that has shown any real promise is low-dose aspirin (81 mg), preferably begun very early (if not before in my opinion) in pregnancy. Recent metanalyses by Askie, et al., (Lancet 2007;369:1791-98) and Duley, at al., ((Cochrane Database Rev 2007;April 18(2)) suggested small, but significant, benefits of aspirin therapy in randomized trials involving 32,217 and 37,560 women, respectively. Askie reported a 10% reduction in risk of developing preeclampsia, delivering before 34 weeks, and serious adverse pregnancy outcome. Importantly, they also demonstrated “no identifiable risks of therapy.” Duley reported comparable results: 17% reduction in preeclampsia; 8% reduction in risk of preterm birth; 10% reduction in ‘small-for-gestational-age (SGA)’ babies; 14% reduction in fetal/neonatal deaths. The numbers might not seem great, but this is one of those situations where any little bit helps and represents a significant improvement in outcomes, a minimal investment in cost of medical therapy, and a significant cost savings to the health care system. Indeed, if this data holds, and I believe it will, we should soon be making a strong case for including aspirin in the category of ‘prenatal vitamins and folic acid.’
Other attempts at prevention of preeclampsia have had sensible reasons for being tried but have been very disappointing. High-dose vitamins C and E (‘antioxidants’) showed no benefit and may actually be accompanied by increased risk for complications (Rumbold, et al., NEJM 2006;354:1796-1806). Cochrane Database System Reviews have also shown no benefit of diuretics (Churchill, et al., 2007;Jan 24(1):CD004451); progesterone (Meher, et al., 2006;Oct 18(4):CD006175); garlic (Meher, et al., 2006;Jul 19:CD006065); or fish oil and other prostaglandin precursors (Makrides, et al., 2006;Jul 19:CD003042). The benefits of calcium supplementation have shown mixed results. Although an FDA review showed no benefit (Trumbo, et al., Nutr Rev 2007;65:78-87), another Cochrane Database Review suggested that there might be some (Hofmeyr, et al., 2006;Jul 19(3):CD001059).
In the next post, we will look at a group of patients who are at significant risk for developing preeclampsia, those whohad it previously and others who have medical conditions that put them at risk, and review the current thinking on what we can do to help them….