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Novel drug development for pregnancy-specific conditions remains a challenge. The reasons for this sentiment are many, but lack of a sound understanding of the pathogenesis for various conditions in pregnancy ranks high among them. Preeclampsia, one of the most common medical complications of pregnancy, has thus far eluded comprehensive biological understanding.1 In the absence of a sound understanding of its biological underpinnings, our first attempts to alleviate the consequences of this disorder targeted the classic signs and symptoms of preeclampsia (hypertension and proteinuria) with agents such as antihypertensive compounds.1 Trials of these agents, numbering over a dozen, failed to demonstrate that control of blood pressure itself could reduce the systemic consequences of preeclampsia. Nevertheless, lack of success in these early efforts did not deter further attempts, and primary prevention trials premised on biochemical differences in women with and without preeclampsia represented the next generation of such clinical trials.Low urine calcium and low calcium intake noted in preeclampsia, in combination with the vasodilatory activity of calcium itself, prompted primary prevention trials with calcium supplementation.1 Similarly, imbalances between prostacyclin and thromboxane led to large trials examining the use of aspirin to prevent preeclampsia.1 Primary prevention trials have been informative, and given that the incidence of preeclampsia is ≈4% to 7% in nulliparous women, these have necessitated inclusion of thousands of women enrolled over an extended period of time. Although noteworthy in their magnitude and outstanding execution, these trials have, for the most part, been neutral or negative. Primary prevention studies, by their nature, require large numbers of subjects, especially in the setting of outcomes that are relatively infrequent. Furthermore, given the history of these trials in preeclampsia, mustering the appetite to initiate yet another trial of similar nature (unless upcoming primary prevention trials reveal surprises [eg, www.clinicaltrials.gov …

Inching Towards A Targeted Therapy for Preeclampsia