Pre-eclampsia, the placenta and the maternal systemic inflammatory response--a review.
The central role of the placenta in the pathogenesis of pre-eclampsia is undisputed. The evidence that maternal syndrome of pre-eclampsia is caused by a maternal systemic inflammatory response (MSIR) is reviewed. The polymorphic nature of the inflammatory network explains the diversity of the varied signs of this condition. A key observation is that an MSIR is also a feature of normal third trimester pregnancy, but less severe than in pre-eclampsia. Hence pre-eclampsia is simply the extreme end of a continuum common to all pregnancies, with multiple contributing factors. Evidence is presented that apoptotic or necrotic debris shed from the syncytial surface of the placenta constitutes the inflammatory stimulus in all pregnancies. This model explains many features of pre-eclampsia including its occurrence with either larger placentae or small oxidatively stressed placentae. The clinical implications are that in terms of diagnosis or prediction there can never be a clear distinction between normal and abnormal. No test, predictive or diagnostic, can be expected to distinguish absolutely between different degrees of a problem that is common to all pregnancies. The possibility that the MSIR associated with third trimester pregnancy is nothing more than the maternal price for sustaining gestation is considered. Insulin resistance is a feature of normal pregnancy and also of systemic inflammatory states in non-pregnant individuals. It has been previously proposed that the insulin resistance of pregnancy is an important adaptation to divert maternal glucose to meet the needs of the foetus. Hence the MSIR, by causing maternal insulin resistance, may have substantial foetal advantages so long as it is not too severe.
Redman
C W G
CW
Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Oxford OX3 9DU, UK. christopher.redman@obsgyn.oxford.ac.uk
Sargent
I L
IL
D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D008431:Maternal-Fetal Exchange / Q000276:immunology; D018384:Oxidative Stress; D010920:Placenta / Q000098:blood supply / Q000276:immunology* / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology; D011247:Pregnancy