Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother This results in infant morbidity and substantial healthcare expenditure4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic

Both hypertension and proteinuria implicate the endothelium as the target of the disease The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop

Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops12 Approximately 20% of …

Preeclampsia, a Disease of the Maternal Endothelium The Role of Antiangiogenic Factors and Implications for Later Cardiovascular Disease

https://ir.library.oregonstate.edu/downloads/bv73c226n

National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2.

Objective  To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia. Design  Systematic review and meta-analysis of cohort studies. Data sources  PubMed and Embase databases, 2000-15. Eligibility criteria for selecting studies  Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation. Data extraction  Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors. Results  There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors. Conclusions  There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

https://www.bmj.com/content/bmj/353/bmj.i1753.full.pdf

Clinical risk factors for pre-eclampsia determined in early pregnancy: systematic review and meta-analysis of large cohort studies

There is increasing evidence that pre-eclampsia, a principal cause of maternal morbidity, may also be a risk factor for future cardiovascular and cerebrovascular events. This review aimed to assess the current evidence and quantify the risks of cardiovascular disease (CVD), cerebrovascular events and hypertension associated with prior diagnosis of pre-eclampsia. Medline and Embase were searched with no language restrictions, as were core journals and reference lists from reviews up until January 2012. Case–control and cohort studies which reported cardiovascular and cerebrovascular diseases or hypertension diagnosed more than 6 weeks postpartum, in women who had a history of pre-eclampsia relative to women who had unaffected pregnancies, were included. Fifty articles were included in the systematic review and 43 in the meta-analysis. Women with a history of pre-eclampsia or eclampsia were at significantly increased odds of fatal or diagnosed CVD [odds ratio (OR) = 2.28, 95 % confidence interval (CI): 1.87, 2.78], cerebrovascular disease (OR = 1.76, 95 % CI 1.43, 2.21) and hypertension [relative risk (RR) = 3.13, 95 % CI 2.51, 3.89]. Among pre-eclamptic women, pre-term delivery was not associated with an increased risk of a future cardiovascular event (RR = 1.32, 95 % CI 0.79, 2.22). Women diagnosed with pre-eclampsia are at increased risk of future cardiovascular or cerebrovascular events, with an estimated doubling of odds compared to unaffected women. This has implications for the follow-up of all women who experience pre-eclampsia, not just those who deliver pre-term. This association may reflect shared common risk factors for both pre-eclampsia and cardiovascular and cerebrovascular disease.

Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis

Preeclampsia, a systemic syndrome of pregnancy clinically characterized by new onset of proteinuria and hypertension, is associated with significant morbidity and mortality to both mothers and fetuses. The pathogenesis of preeclampsia has been enigmatic; this review will focus on understanding the origins of this disorder. Preeclampsia originates in the placenta, starting with inadequate cytotrophoblast invasion and ending with widespread maternal endothelial dysfunction. Production of placental anti-angiogenic factors, specifically soluble fms-related tyrosine kinase 1 and soluble endoglin, have been shown to be upregulated in preeclampsia. These placental anti-angiogenic factors are released into the maternal circulation; their actions disrupt the maternal endothelium and result in hypertension, proteinuria, and the other systemic manifestations of preeclampsia. The molecular basis for placental dysregulation of these pathogenic factors remains unknown, remains unknown. Hypoxia is likely an important regulator. Other factors such as alterations in the renin-angiotensin-aldosterone axis, immune maladaption, excessive shedding of trophoblast debris, oxidative stress, and genetic factors likely contribute to the pathogenesis of the abnormal placentation. As of 2009, the only successful treatment for preeclampsia is delivery. No definitive preventive strategies have been identified. However, several of the recent observations related to phenotypic causality provide stimuli for the development of novel therapies.

Preeclampsia: the role of angiogenic factors in its pathogenesis.

A history of preeclampsia identifies women who have underlying cardiovascular risk factors

Objective: To assess the utilization of health care services by pregnant women affected by preeclampsia (PE). Design: Population-based study. Setting: Perinatal partnership hospitals in Ontario. Population: Obstetric deliveries in 2005 Canadian province of Ontario (about 95% of births). Methods: For each PE case, four subjects without PE matched by age, parity, plurality, and hospital at childbirth were chosen as the controls. We compared the utilization of intra-partum care services and infant outcomes between the two groups. We also estimated the extra costs to the health care system in Ontario for caesarean delivery and caring of extremely low birth weight infants attributable to PE during the neonatal period and in the first 2 years of life. Main Outcome Measures: Cesarean delivery, hospital stay, extremely low birth weight infants, cost. Results: Of the 120,611 obstetric deliveries included in this analysis, 1240 (1.3%) were diagnosed with PE. Patients with PE and matched controls were similar in mat...

Aizhong Liu

Papers

A history of preeclampsia identifies women who have underlying cardiovascular risk factors

Utilization of Health Care Services of Pregnant Women Complicated by Preeclampsia in Ontario