The Two Stage Model of Preeclampsia: Variations on the Theme

Preeclampsia: a two stage disorder: preeclampsia is initiated by reduced placental perfusion (Stage 1). This results in the release of factor(s) that leads to the maternal systemic pathophysiological changes (Stage 2).

Maternal fetal interactions in the pathogenesis of preeclampsia: this version of the Two Stage Model emphasizes that reduced placental perfusion (Stage 1) is not sufficient to cause preeclampsia but requires interaction with maternal constitutional factors that may be genetic, behavioral or environmental. These are modified by the maternal pathophysiological changes of preeclampsia.

Different contribution of fetal/placental factors and maternal constitution to Stage 2 of preeclampsia: the contribution of reduced placental perfusion, fetal/placental () or the maternal constitution (○) to result in the maternal pathophysiological changes of preeclampsia can vary. It can be primarily fetal/placental (A), equally maternal constitutional and fetal/placental (B) or primarily maternal (C). It is a reasonable extension that some women with exquisite sensitivity to fetal/placental function could respond to the normal physiological changes of pregnancy (D).

Revised maternal fetal interactions in the pathogenesis of preeclampsia: the original Two Stage Model presented in is revised to indicate that abnormal placentation (that occurs in the first trimester) is the important contributor to Stage 1. Further, appropriate signals from the fetal/placental unit in response to abnormal placentation () modify maternal physiology, which cannot be tolerated by women resulting in preeclampsia. The same maternal constitutional changes that interact with abnormal placentation can also stimulate abnormal placentation (). Also the linkage between Stage 1 and Stage 2 is likely secondary to many factors (several arrows compared to one in the original model).