Preeclampsia in 2018: Revisiting Concepts, Physiopathology, and Prediction

Preeclampsia currently remains one of the leading causes of death and severe maternal morbidity. Although its prevalence is still underestimated in some places due to underreporting, preeclampsia is a disease that health professionals need to know how to deal with and take action. For this reason, the studies about the theme remain along with the advances in their understanding that often implies improvement and change of concepts and conducts. The complexity of its etiology is a challenge and requires further studies for its full understanding. Apparently, poor adaptation of the maternal organism to the conceptus, marked by the nonoccurrence of changes in the uterine spiral arteries, determines a series of systemic repercussions that compound the various forms of preeclampsia presentation. In recent years, the use of acetylsalicylic acid to prevent cases of early onset of the disease has been consolidated and, alongside, studies have advanced the development of accessible and effective methods of identifying women at risk of preeclampsia. The aim of this review is to discuss updates on the occurrence, concept, pathophysiology, repercussion, prevention, and prediction of preeclampsia.

[1]  D. Wright,et al.  Multicenter screening for pre‐eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations , 2017, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[2]  K. Nicolaides,et al.  First‐trimester maternal factors and biomarker screening for preeclampsia , 2014, Prenatal diagnosis.

[3]  A. Hingorani,et al.  Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis , 2007, BMJ : British Medical Journal.

[4]  B. Gh Application of metabolomics to preeclampsia diagnosis. , 2018 .

[5]  Kypros H Nicolaides,et al.  An integrated model for the prediction of preeclampsia using maternal factors and uterine artery Doppler velocimetry in unselected low-risk women. , 2005, American journal of obstetrics and gynecology.

[6]  R. Pijnenborg,et al.  The uterine spiral arteries in human pregnancy: facts and controversies. , 2006, Placenta.

[7]  L. Hinton,et al.  Support for mothers and their families after life-threatening illness in pregnancy and childbirth: a qualitative study in primary care , 2015, The British journal of general practice : the journal of the Royal College of General Practitioners.

[8]  B. Sibai,et al.  Management of Hypertensive Disorders in Pregnancy , 2014, Women's health.

[9]  Özge Tunçalp,et al.  Global causes of maternal death: a WHO systematic analysis. , 2014, The Lancet. Global health.

[10]  K. Barnhart Assisted reproductive technologies and perinatal morbidity: interrogating the association. , 2013, Fertility and sterility.

[11]  James M. Roberts,et al.  Hypertension in Pregnancy: Executive Summary , 2013 .

[12]  N. Gleicher Principles of Medical Therapy in Pregnancy , 1985, Springer US.

[13]  D. Chou,et al.  Global and regional estimates of preeclampsia and eclampsia: a systematic review. , 2013, European journal of obstetrics, gynecology, and reproductive biology.

[14]  C. Begley,et al.  Risks associated with obesity in pregnancy, for the mother and baby: a systematic review of reviews , 2015, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[15]  M. Lindheimer,et al.  Chesley's Hypertensive Disorders in Pregnancy , 2009 .

[16]  Yves Giguère,et al.  Early Administration of Low-Dose Aspirin for the Prevention of Severe and Mild Preeclampsia: A Systematic Review and Meta-Analysis , 2012, American Journal of Perinatology.

[17]  S. Benton,et al.  Andrée Gruslin award lecture: Metabolomics as an important modality to better understand preeclampsia. , 2017, Placenta.

[18]  J. Karemaker,et al.  Serial assessment of cardiovascular control shows early signs of developing pre-eclampsia , 2004, Journal of hypertension.

[19]  B. Mol,et al.  Preeclampsia; short and long-term consequences for mother and neonate. , 2016, Early human development.

[20]  T. Bathen,et al.  Metabolomic Biomarkers in Serum and Urine in Women with Preeclampsia , 2014, PloS one.

[21]  A. Khalil,et al.  Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta‐analysis of randomized trials , 2018, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[22]  B. F. Nobakht M. Gh,et al.  Application of metabolomics to preeclampsia diagnosis , 2018, Systems biology in reproductive medicine.

[23]  A. Heazell,et al.  Statistical risk prediction models for adverse maternal and neonatal outcomes in severe preeclampsia in a low-resource setting: proposal for a single-centre cross-sectional study at Mpilo Central Hospital, Bulawayo, Zimbabwe , 2019, BMC Research Notes.

[24]  J. Cecatti,et al.  The Burden of Eclampsia: Results from a Multicenter Study on Surveillance of Severe Maternal Morbidity in Brazil , 2013, PloS one.

[25]  L. Magee,et al.  The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. , 2014, Pregnancy hypertension.

[26]  I. Sargent,et al.  Inflammation and pre-eclampsia. , 2006, Seminars in fetal & neonatal medicine.

[27]  K. D. Black,et al.  Inflammatory Markers and Preeclampsia: A Systematic Review , 2018, Nursing research.

[28]  A. Shennan,et al.  Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. , 2015, Obstetrics and gynecology.

[29]  S. Walsh,et al.  Preeclampsia: an imbalance in placental prostacyclin and thromboxane production. , 1985, American journal of obstetrics and gynecology.

[30]  D. Wright,et al.  Management of pregnancies after combined screening for pre‐eclampsia at 19–24 weeks' gestation , 2018, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[31]  Argyro Syngelaki,et al.  Integrated Proteomic and Metabolomic prediction of Term Preeclampsia , 2017, Scientific Reports.

[32]  R. Romero,et al.  The "Great Obstetrical Syndromes" are associated with disorders of deep placentation. , 2011, American journal of obstetrics and gynecology.

[33]  David S. Wishart,et al.  Metabolomics and first-trimester prediction of early-onset preeclampsia , 2012, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[34]  João Paulo Souza,et al.  Risk Factors of Pre-Eclampsia/Eclampsia and Its Adverse Outcomes in Low- and Middle-Income Countries: A WHO Secondary Analysis , 2014, PloS one.

[35]  J. Pennings,et al.  First-Trimester Serum Acylcarnitine Levels to Predict Preeclampsia: A Metabolomics Approach , 2015, Disease markers.

[36]  Tamara Stampalija,et al.  Utero-placental Doppler ultrasound for improving pregnancy outcome. , 2010, The Cochrane database of systematic reviews.

[37]  S. Cicero,et al.  Accuracy of competing‐risks model in screening for pre‐eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation , 2017, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[38]  T. Benedetti,et al.  Maternal Hemodynamics in Normal and Preeclamptic Pregnancies: A Longitudinal Study , 1990, Obstetrics and gynecology.

[39]  J. Cecatti,et al.  Maternal near miss and death among women with severe hypertensive disorders: a Brazilian multicenter surveillance study , 2014, Reproductive Health.

[40]  K. Lim,et al.  Clinical Risk Factors for Preeclampsia in the 21st Century , 2014, Obstetrics and gynecology.

[41]  D. Rolnik,et al.  Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction , 2018, Revista Brasileira de Ginecologia e Obstetricia / RBGO - Gynecology and Obstetrics.

[42]  E. Main Decisions required for operating a maternal mortality review committee: the California experience. , 2012, Seminars in perinatology.

[43]  G. Saade,et al.  First-Trimester Prediction of Preeclampsia in Nulliparous Women at Low Risk , 2012, Obstetrics and gynecology.

[44]  J. Pennings,et al.  Metabolomics Profiling for Identification of Novel Potential Markers in Early Prediction of Preeclampsia , 2014, PloS one.

[45]  S. Snydal Major changes in diagnosis and management of preeclampsia. , 2014, Journal of midwifery & women's health.

[46]  A. Coomarasamy,et al.  Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review , 2009, BMC medicine.

[47]  T. Okai,et al.  Cellular mRNA expressions of anti‐oxidant factors in the blood of preeclamptic women , 2009, Prenatal diagnosis.

[48]  L. Poston,et al.  Early Pregnancy Prediction of Preeclampsia in Nulliparous Women, Combining Clinical Risk and Biomarkers: The Screening for Pregnancy Endpoints (SCOPE) International Cohort Study , 2014, Hypertension.

[49]  D. Wishart,et al.  First-trimester metabolomic detection of late-onset preeclampsia. , 2013, American journal of obstetrics and gynecology.

[50]  J. Kingdom,et al.  Preeclampsia , 2016, Canadian Medical Association Journal.

[51]  R. Romero,et al.  Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity , 2017, American journal of obstetrics and gynecology.

[52]  L. Myatt,et al.  Preeclampsia: Syndrome or Disease? , 2015, Current Hypertension Reports.

[53]  W. Lowe,et al.  Genetics, genomics and metabolomics: new insights into maternal metabolism during pregnancy , 2014, Diabetic medicine : a journal of the British Diabetic Association.

[54]  A. Shennan,et al.  Faculty Opinions recommendation of Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. , 2015 .

[55]  U. Reddy,et al.  First trimester screening cannot predict adverse outcomes yet , 2014, Prenatal diagnosis.

[56]  Desmond Mwembe,et al.  Determinants of adverse maternal and perinatal outcomes in severe preeclampsia and eclampsia in a low-resource setting, Mpilo Central Hospital, Bulawayo, Zimbabwe , 2019, BMC Research Notes.

[57]  K. Nicolaides,et al.  Maternal risk factors for hypertensive disorders in pregnancy: a multivariate approach , 2010, Journal of Human Hypertension.

[58]  M. Mugglestone,et al.  Management of hypertensive disorders during pregnancy: summary of NICE guidance , 2010, BMJ : British Medical Journal.

[59]  Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. , 1991 .

[60]  D. Nelson,et al.  Placental pathology suggesting that preeclampsia is more than one disease. , 2014, American journal of obstetrics and gynecology.

[61]  L. Brown,et al.  Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial. , 2015, American journal of obstetrics and gynecology.

[62]  R. Romero,et al.  Pre-eclampsia part 1: current understanding of its pathophysiology , 2014, Nature Reviews Nephrology.

[63]  J. Cecatti,et al.  Situational analysis of facilitators and barriers to availability and utilization of magnesium sulfate for eclampsia and severe preeclampsia in the public health system in Brazil , 2016, BMC Pregnancy and Childbirth.

[64]  L. Say,et al.  Maternal near miss--towards a standard tool for monitoring quality of maternal health care. , 2009, Best practice & research. Clinical obstetrics & gynaecology.

[65]  A. W. Woods,et al.  Rheological and Physiological Consequences of Conversion of the Maternal Spiral Arteries for Uteroplacental Blood Flow during Human Pregnancy , 2009, Placenta.

[66]  Marie Brown,et al.  Robust Early Pregnancy Prediction of Later Preeclampsia Using Metabolomic Biomarkers , 2010, Hypertension.

[67]  A. Di Mauro,et al.  Dysbiosis and Prematurity: Is There a Role for Probiotics? , 2019, Nutrients.

[68]  W. Holzgreve,et al.  Reproductive Biology and Endocrinology Open Access Potential Markers of Preeclampsia – a Review , 2022 .

[69]  D. Wishart,et al.  Validation of metabolomic models for prediction of early-onset preeclampsia. , 2015, American journal of obstetrics and gynecology.

[70]  C. Tsioufis,et al.  Assisted reproductive technology and pregnancy-related hypertensive complications: a systematic review , 2013, Journal of Human Hypertension.

[71]  D. Charnock-Jones,et al.  Placental Endoplasmic Reticulum Stress and Oxidative Stress in the Pathophysiology of Unexplained Intrauterine Growth Restriction and Early Onset Preeclampsia , 2009, Placenta.

[72]  C. Redman,et al.  Preeclampsia, biomarkers, syncytiotrophoblast stress, and placental capacity. , 2015, American journal of obstetrics and gynecology.

[73]  J. Bernardi,et al.  Hypertensive disorders during pregnancy and health outcomes in the offspring: a systematic review. , 2016, Journal of developmental origins of health and disease.

[74]  P. Tsao,et al.  Delivery before 32 weeks of gestation for maternal pre-eclampsia: neonatal outcome and 2-year developmental outcome. , 2003, Early human development.

[75]  D. Nelson,et al.  First‐trimester prediction of preeclampsia using metabolomic biomarkers: a discovery phase study , 2011, Prenatal diagnosis.

[76]  L. Magee,et al.  The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. , 2018, Pregnancy hypertension.

[77]  J. Moutquin,et al.  The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). , 2001 .

[78]  R. Pattinson,et al.  Delays in receiving obstetric care and poor maternal outcomes: results from a national multicentre cross-sectional study , 2014, BMC Pregnancy and Childbirth.

[79]  J. Cecatti,et al.  Network for Surveillance of Severe Maternal Morbidity: a powerful national collaboration generating data on maternal health outcomes and care , 2016, BJOG : an international journal of obstetrics and gynaecology.

[80]  Nicola Persico,et al.  Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia , 2017, The New England journal of medicine.

[81]  K. Bailey,et al.  Podocyturia Predates Proteinuria and Clinical Features of Preeclampsia: Longitudinal Prospective Study , 2013, Hypertension.

[82]  P. Froment,et al.  Involvement of Novel Adipokines, Chemerin, Visfatin, Resistin and Apelin in Reproductive Functions in Normal and Pathological Conditions in Humans and Animal Models , 2019, International journal of molecular sciences.

[83]  H. Alfthan,et al.  Low maternal pregnancy‐associated plasma protein A during the first trimester of pregnancy and pregnancy outcomes , 2017, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[84]  S. Fisher Why is placentation abnormal in preeclampsia? , 2015, American journal of obstetrics and gynecology.

[85]  R. Romero,et al.  Evidence of in vivo generation of thrombin in patients with small-for-gestational-age fetuses and pre-eclampsia , 2002, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[86]  K. Nicolaides Turning the Pyramid of Prenatal Care , 2011, Fetal Diagnosis and Therapy.

[87]  B. Sibai,et al.  Obesity epidemic: impact from preconception to postpartum , 2016, Future science OA.

[88]  B. Sibai,et al.  Maternal mortality from preeclampsia/eclampsia. , 2012, Seminars in perinatology.

[89]  G. Girardi Pravastatin to treat and prevent preeclampsia. Preclinical and clinical studies. , 2017, Journal of reproductive immunology.

[90]  K. Salvesen,et al.  First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study , 2015, International journal of molecular sciences.

[91]  D. Wright,et al.  Competing‐risks model in screening for pre‐eclampsia by maternal factors and biomarkers at 35–37 weeks' gestation , 2016, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[92]  K. Khan,et al.  Accuracy of mean arterial pressure and blood pressure measurements in predicting pre-eclampsia: systematic review and meta-analysis , 2008, BMJ : British Medical Journal.

[93]  B. Thilaganathan,et al.  First‐trimester uterine artery Doppler indices in term and preterm pre‐eclampsia , 2008, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[94]  D. Wright,et al.  Mean arterial pressure at 12, 22, 32 and 36 weeks' gestation in screening for pre‐eclampsia , 2016, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[95]  D. Wright,et al.  Screening for pre‐eclampsia by maternal factors and biomarkers at 11–13 weeks' gestation , 2018, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[96]  V. Tsatsaris,et al.  Angiogenic balance (sFlt-1/PlGF) and preeclampsia. , 2016, Annales d'endocrinologie.

[97]  P. He,et al.  Biomarker identification and pathway analysis of preeclampsia based on serum metabolomics. , 2017, Biochemical and biophysical research communications.