The perplexing pregnancy disorder preeclampsia: what next?

Abstract

Preeclampsia occurs in 3–5% of pregnancies and is a leading cause of deaths of mothers and their infants worldwide. It was initially described over 100 yr ago as a pregnancy abnormality defined by new-onset hypertension and proteinuria. Progress in understanding the pathophysiology was impeded by attention to these diagnostic findings. Hypertension and proteinuria were actually serendipitously recognized components of a complex multisystemic syndrome and not especially pertinent to outcome. With the recognition of inflammatory activation with consequent endothelial dysfunction 30 yr ago redirection of research resulted in an explosive increase in understanding of the disorder. The immunological origins, the role of the placenta and its functional alterations due to endoplasmic reticulum and oxidative stress, identification of placental products linking placental dysfunction to maternal systemic pathophysiology, and the role of the maternal constitution have been elegantly demonstrated by clinical, fundamental, and epidemiological findings and clever animal experimentation. Nonetheless, this increase in knowledge has not translated into improved prediction and prevention of preeclampsia. In this presentation the likelihood is discussed that this is secondary to a much greater complexity than has been previously considered and the existence of subtypes of preeclampsia that may not share an identical pathophysiology. The necessity for collaboration with data, sample, and intellectual sharing is addressed. An approach to addressing the challenges posed to such collaboration exemplified by the Global Pregnancy Collaboration is presented.