Preeclampsia: An excessive maternal inflammatory response to pregnancy

The maternal syndrome of preeclampsia has previously been ascribed to gener alized maternal endothelial cell dysfunction. In this review we suggest tha t the endothelial dysfunction is a part of a more generalized intravascular inflammatory reaction involving intravascular leukocytes as well as the cl otting and complement systems. We provide evidence from our recent work and that of others that not only supports this proposal but indicates that suc h an inflammatory response is already well developed in normal pregnancy an d that the differences between normal pregnancy and preeclampsia are less s triking than those between the normal pregnant and nonpregnant states. From this we argue that preeclampsia arises when a universal maternal intravasc ular inflammatory response to pregnancy decompensates in particular cases, which may occur because either the stimulus or the maternal response is too strong. We conclude that there is no specific cause for the disorder, whic h can be better considered as the extreme end of the range of maternal adap tation to pregnancy. We propose that poor placentation is not the cause of preeclampsia but is a powerful predisposing factor. We predict that a singl e preeclampsia gene will not be found, nor will either a single specific pr edictive test or single preventive effective measure be devised. Aspects of the hypothesis are testable, and future work should allow its confirmation or refutation.