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DOI: 10.1055/s-0039-1701023
Preeclampsia: The Need for a Biological Definition and Diagnosis
Abstract
The centuries-old approach to the prevention of eclampsia and its associated maternal morbidity and mortality is based on the recognition of the presence of premonitory signs and symptoms such as hypertension and proteinuria. The spectrum of preceding signs and symptoms came to be known as preeclampsia, which is debatably considered to be an early stage on a clinical continuum possibly leading to eclampsia. The premonitory signs and symptoms were then construed as diagnostic criteria for the poorly understood syndrome of preeclampsia, and this led to a perpetual debate that remains subject to wide disagreement and periodic updates. In this commentary, we will draw attention to the fact that the criteria for preeclampsia should be viewed from the prism of a screening test rather than as diagnostic of a condition in itself. Focusing research on developing better diagnostic and screening methods for what is clinically important, namely maternal and perinatal morbidity and mortality from hypertensive disorders of pregnancy, a long overdue upgrade from what was possible centuries ago, will ultimately lead to better management approaches to what really matters.
Publication History
Received: 29 August 2019
Accepted: 13 December 2019
Article published online:
27 January 2020
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References
- 1 Bell MJ. A historical overview of preeclampsia-eclampsia. J Obstet Gynecol Neonatal Nurs 2010; 39 (05) 510-518
- 2 Chesley LC. History and epidemiology of preeclampsia-eclampsia. Clin Obstet Gynecol 1984; 27 (04) 801-820
- 3 Lever JC. Cases of puerperal convulsions with remarks. Guys Hosp Rep 1843; 1: 495-517
- 4 Ballantyne JW. Sphygmographic tracings in puerperal eclampsia. Trans Edinb Obstet Soc 1885; 10: 56-70
- 5 Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001; 20 (01) IX-XIV
- 6 Sibai BM. Diagnosis, prevention, and management of eclampsia. Obstet Gynecol 2005; 105 (02) 402-410
- 7 Homer CS, Brown MA, Mangos G, Davis GK. Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension. J Hypertens 2008; 26 (02) 295-302
- 8 Lowe SA, Brown MA, Dekker GA. et al; Society of Obstetric Medicine of Australia and New Zealand. Guidelines for the management of hypertensive disorders of pregnancy 2008. Aust N Z J Obstet Gynaecol 2009; 49 (03) 242-246
- 9 Brown MA. Pre-eclampsia: proteinuria in pre-eclampsia-does it matter any more?. Nat Rev Nephrol 2012; 8 (10) 563-565
- 10 Payne B, Magee LA, Côté AM. et al; PIERS Study Group (Appendix). PIERS proteinuria: relationship with adverse maternal and perinatal outcome. J Obstet Gynaecol Can 2011; 33 (06) 588-597
- 11 Matthys LA, Coppage KH, Lambers DS, Barton JR, Sibai BM. Delayed postpartum preeclampsia: an experience of 151 cases. Am J Obstet Gynecol 2004; 190 (05) 1464-1466
- 12 Barton JR, Sibai BM. Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets syndrome. Clin Perinatol 2004; 31 (04) 807-833 , vii
- 13 Redman C, Jacobson SL, Russell R. Hypertension in pregnancy. In: Powrie RO, Greene ME, Camann W. eds. De Swiet's Medical Disorders in Obstetric Practice. 5th ed. Hoboken, NJ: Wiley-Blackwell; 2010: 153-181
- 14 Higby K, Suiter CR, Phelps JY, Siler-Khodr T, Langer O. Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 1994; 171 (04) 984-989
- 15 Waugh J, Bell SC, Kilby MD, Lambert P, Shennan A, Halligan A. Urine protein estimation in hypertensive pregnancy: which thresholds and laboratory assay best predict clinical outcome?. Hypertens Pregnancy 2005; 24 (03) 291-302
- 16 Boehlen F, Hohlfeld P, Extermann P, Perneger TV, de Moerloose P. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol 2000; 95 (01) 29-33
- 17 Sainio S, Kekomäki R, Riikonen S, Teramo K. Maternal thrombocytopenia at term: a population-based study. Acta Obstet Gynecol Scand 2000; 79 (09) 744-749
- 18 Reese JA, Peck JD, Deschamps DR. et al. Platelet counts during pregnancy. N Engl J Med 2018; 379 (01) 32-43
- 19 Reese JA, Peck JD, McIntosh JJ, Vesely SK, George JN. Platelet counts in women with normal pregnancies: a systematic review. Am J Hematol 2017; 92 (11) 1224-1232
- 20 Giles C, Inglis TC. Thrombocytopenia and macrothrombocytosis in gestational hypertension. Br J Obstet Gynaecol 1981; 88 (11) 1115-1119
- 21 Fisher KA, Luger A, Spargo BH, Lindheimer MD. Hypertension in pregnancy: clinical-pathological correlations and remote prognosis. Medicine (Baltimore) 1981; 60 (04) 267-276
- 22 Douglas KA, Redman CW. Eclampsia in the United Kingdom. BMJ 1994; 309 (6966): 1395-1400
- 23 Cooray SD, Edmonds SM, Tong S, Samarasekera SP, Whitehead CL. Characterization of symptoms immediately preceding eclampsia. Obstet Gynecol 2011; 118 (05) 995-999
- 24 Katz VL, Farmer R, Kuller JA. Preeclampsia into eclampsia: toward a new paradigm. Am J Obstet Gynecol 2000; 182 (06) 1389-1396
- 25 Noraihan MN, Sharda P, Jammal AB. Report of 50 cases of eclampsia. J Obstet Gynaecol Res 2005; 31 (04) 302-309
- 26 Terwisscha van Scheltinga JA, Krabbendam I, Spaanderman MEA. Differentiating between gestational and chronic hypertension; an explorative study. Acta Obstet Gynecol Scand 2013; 92 (03) 312-317
- 27 Redman C. Pre-eclampsia: a complex and variable disease. Pregnancy Hypertens 2014; 4 (03) 241-242
- 28 Haram K, Trovik J, Sandset PM, Hordnes K. Severe syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP) in the 18th week of pregnancy associated with the antiphospholipid-antibody syndrome. Acta Obstet Gynecol Scand 2003; 82 (07) 679-680
- 29 Hazra S, Waugh J, Bosio P. 'Pure' pre-eclampsia before 20 weeks of gestation: a unique entity. BJOG 2003; 110 (11) 1034-1035
- 30 Imasawa T, Nishiwaki T, Nishimura M. et al. A case of “pure” preeclampsia with nephrotic syndrome before 15 weeks of gestation in a patient whose renal biopsy showed glomerular capillary endotheliosis. Am J Kidney Dis 2006; 48 (03) 495-501
- 31 Bornstein E, Barnhard Y, Atkin R, Divon MY. HELLP syndrome: a rare, early presentation at 17 weeks of gestation. Obstet Gynecol 2007; 110 (2 Pt 2): 525-527
- 32 Maya ID. Hypertension and proteinuria in a 17-year-old at 19 weeks' gestation. Am J Kidney Dis 2008; 51 (01) 155-159
- 33 Schena FP, Thomas W, Griffiths M, Nelson-Piercy C, Sinnamon K. Pre-eclampsia before 20-week gestation: diagnosis, investigation and management. Clin Kidney J 2012; 5 (06) 597-599
- 34 Pawelec M, Karmowski A, Karmowski M. et al. Inability to have children caused by recurrent HELLP syndrome in early pregnancies - implications for a review of literature. Adv Clin Exp Med 2013; 22 (05) 753-758
- 35 Berry EL, Iqbal SN. HELLP syndrome at 17 weeks gestation: a rare and catastrophic phenomenon. J Clin Gynecol Obstet 2014; 3 (04) 147-150
- 36 Tanaka M, Tsujimoto Y, Goto K. et al. Preeclampsia before 20 weeks of gestation: a case report and review of the literature. CEN Case Rep 2015; 4 (01) 55-60
- 37 Myer E, Hill J. First trimester hemolysis, elevated liver enzymes, low platelets syndrome in a surrogate pregnancy. AJP Rep 2015; 5 (02) e212-e214
- 38 Parrott J, Fields TA, Parrish M. Previable preeclampsia diagnosed by renal biopsy in setting of novel diagnosis of C4 glomerulopathy. Case Rep Obstet Gynecol 2017; 2017: 8698670
- 39 Fitzpatrick KE, Hinshaw K, Kurinczuk JJ, Knight M. Risk factors, management, and outcomes of hemolysis, elevated liver enzymes, and low platelets syndrome and elevated liver enzymes, low platelets syndrome. Obstet Gynecol 2014; 123 (03) 618-627
- 40 Alsulyman OM, Castro MA, Zuckerman E, McGehee W, Goodwin TM. Preeclampsia and liver infarction in early pregnancy associated with the antiphospholipid syndrome. Obstet Gynecol 1996; 88 (4 Pt 2): 644-646
- 41 Piccoli GB, Daidola G, Attini R. et al. Kidney biopsy in pregnancy: evidence for counselling? A systematic narrative review. BJOG 2013; 120 (04) 412-427
- 42 Whelton PK, Carey RM, Aronow WS. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018; 71 (06) 1269-1324
- 43 Saudan P, Brown MA, Buddle ML, Jones M. Does gestational hypertension become pre-eclampsia?. Br J Obstet Gynaecol 1998; 105 (11) 1177-1184
- 44 Wolf M, Shah A, Jimenez-Kimble R, Sauk J, Ecker JL, Thadhani R. Differential risk of hypertensive disorders of pregnancy among Hispanic women. J Am Soc Nephrol 2004; 15 (05) 1330-1338
- 45 Morgan MA, Thurnau GR. Pregnancy-induced hypertension without proteinuria: is it true preeclampsia?. South Med J 1988; 81 (02) 210-213
- 46 Yamada T, Yamada T, Morikawa M. et al. Isolated proteinuria as an initial sign of severe preeclampsia. Open J Obstet Gynecol 2011; 1: 13-16
- 47 Macdonald-Wallis C, Lawlor DA, Heron J, Fraser A, Nelson SM, Tilling K. Relationships of risk factors for pre-eclampsia with patterns of occurrence of isolated gestational proteinuria during normal term pregnancy. PLoS One 2011; 6 (07) e22115
- 48 Akaishi R, Yamada T, Morikawa M, Nishida R, Minakami H. Clinical features of isolated gestational proteinuria progressing to pre-eclampsia: retrospective observational study. BMJ Open 2014; 4 (04) e004870
- 49 Romero R, Mazor M, Lockwood CJ. et al. Clinical significance, prevalence, and natural history of thrombocytopenia in pregnancy-induced hypertension. Am J Perinatol 1989; 6 (01) 32-38
- 50 Sarno L, Maruotti GM, Saccone G, Sirico A, Mazzarelli LL, Martinelli P. Pregnancy outcome in proteinuria-onset and hypertension-onset preeclampsia. Hypertens Pregnancy 2015; 34 (03) 284-290
- 51 Airoldi J, Weinstein L. Clinical significance of proteinuria in pregnancy. Obstet Gynecol Surv 2007; 62 (02) 117-124
- 52 Morikawa M, Yamada T, Minakami H. Outcome of pregnancy in patients with isolated proteinuria. Curr Opin Obstet Gynecol 2009; 21 (06) 491-495
- 53 Shinar S, Asher-Landsberg J, Schwartz A, Ram-Weiner M, Kupferminc MJ, Many A. Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria. J Perinatol 2016; 36 (01) 25-29
- 54 Martin Jr JN, Rinehart BK, May WL, Magann EF, Terrone DA, Blake PG. The spectrum of severe preeclampsia: comparative analysis by HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome classification. Am J Obstet Gynecol 1999; 180 (6 Pt 1): 1373-1384
- 55 Brown MA, Buddle ML. Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features. Med J Aust 1996; 165 (07) 360-365
- 56 Hauth JC, Ewell MG, Levine RJ. et al; Calcium for Preeclampsia Prevention Study Group. Pregnancy outcomes in healthy nulliparas who developed hypertension. Obstet Gynecol 2000; 95 (01) 24-28
- 57 Buchbinder A, Sibai BM, Caritis S. et al; National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia. Am J Obstet Gynecol 2002; 186 (01) 66-71
- 58 Zhang J, Klebanoff MA, Roberts JM. Prediction of adverse outcomes by common definitions of hypertension in pregnancy. Obstet Gynecol 2001; 97 (02) 261-267
- 59 Benton SJ, Leavey K, Grynspan D, Cox BJ, Bainbridge SA. The clinical heterogeneity of preeclampsia is related to both placental gene expression and placental histopathology. Am J Obstet Gynecol 2018; 219 (06) 604.e1-604.e25
- 60 Roberts JM, Bell MJ. If we know so much about preeclampsia, why haven't we cured the disease?. J Reprod Immunol 2013; 99 (1-2): 1-9
- 61 Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69 (03) 89-95
- 62 Conde-Agudelo A, Villar J, Lindheimer M. World Health Organization systematic review of screening tests for preeclampsia. Obstet Gynecol 2004; 104 (06) 1367-1391
-
63
Huppertz B.
Biology of preeclampsia: combined actions of angiogenic factors, their receptors and placental proteins. Biochim Biophys Acta Mol Basis Dis 2018. Doi: 10.1016/j.bbadis.2018.11.024
- 64 Jeyabalan A. Epidemiology of preeclampsia: impact of obesity. Nutr Rev 2013; 71 (Suppl. 01) S18-S25
- 65 Tanz LJ, Stuart JJ, Missmer SA. et al. Cardiovascular biomarkers in the years following pregnancies complicated by hypertensive disorders or delivered preterm. Pregnancy Hypertens 2018; 13: 14-21
- 66 Kane SC. First trimester screening for pre-eclampsia. Obstet Med 2016; 9 (03) 106-112
- 67 Shear RM, Rinfret D, Leduc L. Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction?. Am J Obstet Gynecol 2005; 192 (04) 1119-1125
- 68 Tranquilli AL, Dekker G, Magee L. et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: a revised statement from the ISSHP. Pregnancy Hypertens 2014; 4 (02) 97-104
- 69 American College of Obstetricians and Gynecologists. ACOG practice bulletin no. 202, January 2019. Gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133 (01) e1-e25
- 70 Haddad B, Kayem G, Deis S, Sibai BM. Are perinatal and maternal outcomes different during expectant management of severe preeclampsia in the presence of intrauterine growth restriction?. Am J Obstet Gynecol 2007; 196 (03) 237.e1-237.e5
- 71 Weiler J, Tong S, Palmer KR. Is fetal growth restriction associated with a more severe maternal phenotype in the setting of early onset pre-eclampsia? A retrospective study. PLoS One 2011; 6 (10) e26937
- 72 Balogun OA, Khanagura RK, Kregel HR, Amro FH, Sibai BM, Chauhan SP. Preterm preeclampsia with severe features: composite maternal and neonatal morbidities associated with fetal growth restriction. Am J Perinatol 2018; 35 (08) 785-790
- 73 Witlin AG, Saade GR, Mattar F, Sibai BM. Predictors of neonatal outcome in women with severe preeclampsia or eclampsia between 24 and 33 weeks' gestation. Am J Obstet Gynecol 2000; 182 (03) 607-611
- 74 Aoki S, Toma R, Kurasawa K, Okuda M, Takahashi T, Hirahara F. Expectant management of severe preeclampsia with severe fetal growth restriction in the second trimester. Pregnancy Hypertens 2014; 4 (01) 81-86
- 75 Poljak B, Agarwal U, Jackson R, Alfirevic Z, Sharp A. Diagnostic accuracy of individual antenatal tools for prediction of small-for-gestational age at birth. Ultrasound Obstet Gynecol 2017; 49 (04) 493-499