Preeclampsia: Syndrome or Disease?

The focus on disease mechanisms underlying the hypertension and proteinuria defining preeclampsia has increased knowledge of the pathophysiology yet we lack both therapy and predictors. We propose this is in part due to the fact that diagnostic findings identify a "preeclampsia syndrome" but do not necessarily indicate the most important pathophysiology nor if organs are involved as cause or consequence. The increased risk for later life cardiovascular disease in women who develop preeclampsia suggests the stress test of pregnancy exposes pre-existing subclinical vascular disease. The dogma that inadequate trophoblast invasion and ischemia/reperfusion injury to the placenta is "the" cause of preeclampsia is more relevant to early onset preeclampsia (<34 weeks). There is much less evidence for defective placentation in late onset preeclampsia where maternal constitutive factors or susceptibility to vascular damage is more relevant. The contribution of differing disease phenotypes to the syndrome may explain the inability of biomarker studies to identify all preeclampsia. Identification of phenotypes will require large amounts of prospective clinical data and biospecimens, collected in a harmonized manner with analysis in an unbiased discovery approach.