Because of the putative efects of sodium restriction for preeclampsia prevention, diuretic therapy became popular with the introduction of chlorothiazide in 1957 (Finnerty, 1958; Flowers, 1962). In one metaanalysis of nine randomized trials with more than 7000 pregnancies, women given diuretics had a lower incidence of edema and hypertension but not of preeclampsia (Churchill, 2007). Because women with chronic hypertension are at high risk for preeclampsia, several randomized trials have evaluated various antihypertensive drugs to reduce the incidence of superimposed preeclampsia (Chap. 50, p. 980). A critical analysis of these trials by Staf and coworkers (2015) failed to demonstrate benefits for this goal.
Data imply that an imbalance between oxidant and antioxidant activity plays a role in preeclampsia pathogenesis. Thus, naturally occurring antioxidants-vitamins C, D, and Emight reduce such oxidation. Several randomized studies have assessed antioxidant vitamin supplementation for women at high risk for preeclampsia (Poston, 2006; Rumbold, 2006; Villar, 2009). he Combined Antioxidant and Preeclampsia Prediction Studies (CAPPS) by the MFMU Network included almost 10,000 low-risk nulliparas (Roberts, 2010). None of these studies showed reduced preeclampsia rates in women provided vitamins C and E compared with those given placebo.
Statins were proposed to prevent preeclampsia because they stimulate hemoxygenase-1 expression, which inhibits sFlt-1 release. Preliminary animal data suggest that statins may prevent hypertensive disorders of pregnancy (Lewis, 2017). The MFMU Network plans a randomized trial to test pravastatin for this purpose (Costantine, 2013, 2016).
Meormin inhibits hypoxic inducible actor 1. by lowering mitochondrial electron transport chain activity. It reduces sFlt-1 and sEng activity and thus has potential to prevent preeclampsia (Brownfoot, 2016). However, clinical studies are lacking.
As noted earlier (p. 715), preeclampsia is characterized by vasospasm, endothelial cell dysfunction, and inlammation, as well as activation of platelets and the coagulation-hemostasis system. Other sequelae include placental infarction and spiral artery thrombosis (Nelson, 2014b). Thus, antithrombotic agents have been evaluated to reduce the incidence of preeclampsia.
Low-molecular-weight heparin for prophylaxis has been studied in several randomized trials. Rodger and colleagues (2016) performed a metaanalysis using individual patient data from 963 women. The risk for recurrent preeclampsia, abruption, or fetal-growth restriction was similar in women receiving heparin or placebo.