title: If we know so much about preeclampsia, why haven't we cured the disease?
abstract: Preeclampsia has been recognized for at least 100 years. In the last 20 years, the consideration of the disorder as more than simply hypertension in pregnancy has led to an explosion in knowledge about preeclampsia pathophysiology. It is now evident that for most cases of preeclampsia, the root cause is the placenta. Relatively reduced placental perfusion leads to inflammation, oxidative stress, and endoplasmic reticulum stress, which converge to modify maternal physiology, with endothelium an important target. Although preeclampsia is characteristically diagnosed in the last third of pregnancy, it is evident that many of these pathophysiological changes can be detected long before clinically evident disease. Furthermore, it is evident that the "maternal constitution," including genetic, behavioral, and metabolic factors, influences the maternal response to the abnormal placentation of preeclampsia. These insights would seem to provide a guide for the prediction of the disorder in early pregnancy, along with targets for intervention. However, this has not been the case. Predictive tests guided by this knowledge do not predict well and several interventions guided by the expanded understanding of pathophysiology do not prevent the disease. We propose that these failures are secondary to the fact that preeclampsia is more than one disorder. Further, we suggest that future progress toward prediction and prevention will require research guided by this concept.
authors.affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Obstetrics Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA; Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Clinical and Translational Research, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: jroberts@mwri.magee.edu.
authors.forename: James M
authors.initials: JM
authors.lastname: Roberts
authors.forename: Mandy J
authors.initials: MJ
authors.lastname: Bell
mesh_terms: D000818:Animals; D035843:Biomedical Research; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D010920:Placenta / Q000473:pathology*; D011225:Pre-Eclampsia / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D011237:Predictive Value of Tests; D011247:Pregnancy; D011379:Prognosis
keywords: Pathophysiology; Prediction; Preeclampsia; Prevention; Translation
references.citation: Int J Gynaecol Obstet. 1983 Aug;21(4):271-8
references.pmid: 6141080
references.citation: N Engl J Med. 2006 Apr 27;354(17):1796-806
references.pmid: 16641396
references.citation: Obstet Gynecol. 2012 Jun;119(6):1234-42
references.pmid: 22617589
references.citation: Am J Obstet Gynecol. 2006 Mar;194(3):639-49
references.pmid: 16522392
references.citation: Placenta. 2011 Jun;32(6):413-9
references.pmid: 21497901
references.citation: Early Pregnancy. 2001 Jan;5(1):67-9
references.pmid: 11753519
references.citation: Placenta. 2001 May;22(5):405-11
references.pmid: 11373150
references.citation: Am J Reprod Immunol. 2011 Dec;66(6):468-75
references.pmid: 21623995
references.citation: Hypertension. 2009 May;53(5):812-8
references.pmid: 19273739
references.citation: Semin Nephrol. 2011 Jan;31(1):33-46
references.pmid: 21266263
references.citation: Am J Obstet Gynecol. 1966 Sep 1;96(1):141-3
references.pmid: 4288066
references.citation: Am J Obstet Gynecol. 2005 Jul;193(1):185-91
references.pmid: 16021077
references.citation: Placenta. 2002 May;23(5):359-72
references.pmid: 12061851
references.citation: Am J Obstet Gynecol. 1993 Nov;169(5):1112-8
references.pmid: 8238169
references.citation: N Engl J Med. 1993 Oct 21;329(17):1213-8
references.pmid: 8413387
references.citation: Placenta. 2006 Jan;27(1):56-61
references.pmid: 16310038
references.citation: Eur J Obstet Gynecol Reprod Biol. 1999 May;84(1):37-41
references.pmid: 10413224
references.citation: Placenta. 2009 Mar;30 Suppl A:S32-7
references.pmid: 19070896
references.citation: Hypertension. 2007 Jan;49(1):15-6
references.pmid: 17116760
references.citation: Reprod Biol Endocrinol. 2009 Jul 14;7:70
references.pmid: 19602262
references.citation: N Engl J Med. 1997 Jul 10;337(2):69-76
references.pmid: 9211675
references.citation: JAMA. 1996 Apr 10;275(14):1113-7
references.pmid: 8601931
references.citation: Am J Obstet Gynecol. 1989 Nov;161(5):1200-4
references.pmid: 2589440
references.citation: Hypertension. 2012 Jul;60(1):239-46
references.pmid: 22647886
references.citation: Placenta. 2009 Jun;30(6):473-82
references.pmid: 19375795
references.citation: Biol Reprod. 2003 Jul;69(1):1-7
references.pmid: 12620937
references.citation: Semin Fetal Neonatal Med. 2006 Oct;11(5):309-16
references.pmid: 16828580
references.citation: J Exp Med. 2004 Oct 18;200(8):957-65
references.pmid: 15477349
references.citation: JAMA. 1991 Jul 10;266(2):260-4
references.pmid: 1829118
references.citation: Paediatr Perinat Epidemiol. 2004 May;18(3):186-91
references.pmid: 15130157
references.citation: Eur J Obstet Gynecol Reprod Biol. 2010 Aug;151(2):122-9
references.pmid: 20457483
references.citation: Arch Pathol. 1959 Dec;68:593-9
references.pmid: 13833162
references.citation: Clin Exp Hypertens B. 1983;2(1):163-9
references.pmid: 6872277
references.citation: Am J Obstet Gynecol. 1999 Feb;180(2 Pt 1):499-506
references.pmid: 9988826
references.citation: Science. 2005 Jun 10;308(5728):1592-4
references.pmid: 15947178
references.citation: J Clin Invest. 1973 Nov;52(11):2682-9
references.pmid: 4355997
references.citation: Lancet. 1999 Sep 4;354(9181):810-6
references.pmid: 10485722
references.citation: Lancet. 1994 Mar 12;343(8898):619-29
references.pmid: 7906809
references.citation: Lancet. 2006 Apr 8;367(9517):1145-54
references.pmid: 16616557
references.citation: Am J Obstet Gynecol. 2011 Mar;204(3):193-201
references.pmid: 21094932
references.citation: Hypertension. 2004 Oct;44(4):374-80
references.pmid: 15326082
references.citation: Lancet. 2007 May 26;369(9575):1791-1798
references.pmid: 17512048
references.citation: Hypertension. 2010 Jul;56(1):166-71
references.pmid: 20516394
references.citation: J Exp Med. 2004 Oct 18;200(8):951-5
references.pmid: 15492121
references.citation: Reprod Biomed Online. 2006 Nov;13(5):680-6
references.pmid: 17169180
references.citation: Am J Obstet Gynecol. 1996 Mar;174(3):975-82
references.pmid: 8633679
references.citation: N Engl J Med. 2010 Apr 8;362(14):1282-91
references.pmid: 20375405
references.citation: J Clin Invest. 1997 May 1;99(9):2139-51
references.pmid: 9151786
references.citation: Lancet. 1993 Jun 5;341(8858):1447-51
references.pmid: 8099148
references.citation: Front Biosci. 2007 Jan 01;12:2403-11
references.pmid: 17127250
references.citation: Semin Thromb Hemost. 1999;25(5):451-4
references.pmid: 10625201
references.citation: Am J Obstet Gynecol. 1990 Jan;162(1):121-5
references.pmid: 2301480
references.citation: BMJ. 2007 Nov 10;335(7627):974
references.pmid: 17975258