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Nature Reviews. Nephrology Sep 2014An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The... (Review)
Review
An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences.
Topics: Biomarkers; Female; Humans; Pre-Eclampsia; Pregnancy; Prognosis; Risk Assessment; Risk Factors
PubMed: 25003612
DOI: 10.1038/nrneph.2014.103 -
Lancet (London, England) May 2019Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes.
METHODS
We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000-9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031.
FINDINGS
Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (<1%) woman in the concealed testing group withdrew consent to follow-up data collection, so 446 (>99%) women in this group were included in the analyses. The median time to pre-eclampsia diagnosis was 4·1 days with concealed testing versus 1·9 days with revealed testing (time ratio 0·36, 95% CI 0·15-0·87; p=0·027). Maternal severe adverse outcomes were reported in 24 (5%) of 447 women in the concealed testing group versus 22 (4%) of 573 women in the revealed testing group (adjusted odds ratio 0·32, 95% CI 0·11-0·96; p=0·043), but there was no evidence of a difference in perinatal adverse outcomes (15% vs 14%, 1·45, 0·73-2·90) or gestation at delivery (36·6 weeks vs 36·8 weeks; mean difference -0·52, 95% CI -0·63 to 0·73).
INTERPRETATION
We found that the availability of PlGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PlGF was implemented, we found a lower incidence of maternal adverse outcomes, consistent with adoption of targeted, enhanced surveillance, as recommended in the clinical management algorithm for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study.
FUNDING
National Institute for Health Research.
Topics: Adult; Algorithms; Female; Fetal Growth Retardation; Gestational Age; Humans; Hypertension; Infant, Newborn; Outcome Assessment, Health Care; Perinatal Death; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Proteinuria
PubMed: 30948284
DOI: 10.1016/S0140-6736(18)33212-4 -
Reproductive Health Jul 2016Women with a history of pre-eclampsia have a higher risk of developing pre-eclampsia in subsequent pregnancies. However, the role of the inter-pregnancy interval on this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Women with a history of pre-eclampsia have a higher risk of developing pre-eclampsia in subsequent pregnancies. However, the role of the inter-pregnancy interval on this association is unclear.
OBJECTIVE
To explore the effect of inter-pregnancy interval on the risk of recurrent pre-eclampsia or eclampia.
SEARCH STRATEGY
MEDLINE, EMBASE and LILACS were searched (inception to July 2015).
SELECTION CRITERIA
Cohort studies assessing the risk of recurrent pre-eclampsia in the immediate subsequent pregnancy according to different birth intervals.
DATA COLLECTION AND ANALYSIS
Two reviewers independently performed screening, data extraction, methodological and quality assessment. Meta-analysis of adjusted odds ratios (aOR) with 95 % confidence intervals (CI) was used to measure the association between various interval lengths and recurrent pre-eclampsia or eclampsia.
MAIN RESULTS
We identified 1769 articles and finally included four studies with a total of 77,561 women. The meta-analysis of two studies showed that compared to inter-pregnancy intervals of 2-4 years, the aOR for recurrent pre-eclampsia was 1.01 [95 % CI 0.95 to 1.07, I(2) 0 %] with intervals of less than 2 years and 1.10 [95 % CI 1.02 to 1.19, I(2) 0 %] with intervals longer than 4 years.
CONCLUSION
Compared to inter-pregnancy intervals of 2 to 4 years, shorter intervals are not associated with an increased risk of recurrent pre-eclampsia but longer intervals appear to increase the risk. The results of this review should be interpreted with caution as included studies are observational and thus subject to possible confounding factors.
Topics: Adult; Birth Intervals; Cohort Studies; Databases, Factual; Eclampsia; Electronic Health Records; Evidence-Based Medicine; Female; Humans; Male; Observational Studies as Topic; Pre-Eclampsia; Pregnancy; Recurrence; Risk; Secondary Prevention; Sexual Partners
PubMed: 27430353
DOI: 10.1186/s12978-016-0197-x -
CMAJ : Canadian Medical Association... Nov 2016
Topics: Aspirin; Female; Humans; Pre-Eclampsia; Pregnancy; Risk Factors
PubMed: 27573744
DOI: 10.1503/cmaj.151551 -
Journal of the American College of... May 2014Cardiovascular disease continues to be the leading cause of death in the western world. Due to advancements in diagnosis, prevention, and treatment, cardiovascular... (Review)
Review
Cardiovascular disease continues to be the leading cause of death in the western world. Due to advancements in diagnosis, prevention, and treatment, cardiovascular mortality has fallen in recent years. Previous studies have evaluated the impact of traditional risk factors such as hypercholesterolemia and smoking. However, limited studies have been conducted to evaluate sex discrepancies among patients with cardiovascular disease. Pre-eclampsia is a multisystem placentally mediated disease, which usually arises after 32 weeks of gestation and classically presents with hypertension and proteinuria. Pre-eclampsia affects 2% to 8% of all pregnancies worldwide and is often complicated by fetal growth restriction. Women with a history of pre-eclampsia are at increased risk of future cardiovascular complications. Therefore, this topic is of significance to the cardiovascular health of over 300 million women worldwide. The goal of this review is to determine the association of pre-eclampsia and future cardiovascular risk and to explore the potential management options for these high-risk women.
Topics: Animals; Cardiovascular Diseases; Female; Forecasting; Humans; Hypertension; Pre-Eclampsia; Pregnancy; Proteinuria; Risk Factors
PubMed: 24613324
DOI: 10.1016/j.jacc.2014.02.529 -
PharmacoEconomics Oct 2015Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of... (Review)
Review
BACKGROUND
Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia.
METHODS
We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included.
RESULTS
From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia.
DISCUSSION
This study is the first to provide a comprehensive overview on the economic aspects of pre-eclampsia in its broadest sense, ranging from screening to treatment options. The main limitation of the present study lies in the variety of topics in combination with the limited number of papers that could be included; this restricted the comparisons that could be made. In conclusion, novel biomarkers in screening for and diagnosing pre-eclampsia show promise, but their accuracy is a major driver of cost effectiveness, as is prevalence. Universal screening for pre-eclampsia, using a biomarker, will be feasible only when accuracy is significantly increased.
Topics: Adult; Cost-Benefit Analysis; Female; Humans; Labor, Induced; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prenatal Care; Prenatal Diagnosis
PubMed: 26048352
DOI: 10.1007/s40273-015-0291-x -
Diabetologia Dec 2016Pre-eclampsia is a pregnancy-specific multisystem disorder and a state of physiological insulin resistance. Our aim was to systematically evaluate and quantify the... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
Pre-eclampsia is a pregnancy-specific multisystem disorder and a state of physiological insulin resistance. Our aim was to systematically evaluate and quantify the evidence on the relationship between pre-eclampsia and the future risk of diabetes.
METHODS
We conducted a systematic review and meta-analysis of studies that evaluated diabetes in women with and without pre-eclampsia. We performed a systematic search of MEDLINE and EMBASE to identify relevant studies. Independent double data extractions were conducted by four reviewers. Random-effects meta-analysis was used to estimate the risk of future diabetes following pre-eclampsia.
RESULTS
A total of 21 studies were identified with more than 2.8 million women, including more than 72,500 women with pre-eclampsia. Meta-analysis of studies that adjusted for potential confounders demonstrated that pre-eclampsia was independently associated with an increased risk of future diabetes (RR 2.37 [95% CI 1.89, 2.97]). This risk appeared in studies that followed women from less than 1 year postpartum (RR 1.97 [95% CI 1.35, 2.87]) and persisted to more than 10 years postpartum (RR 1.95 [95% CI 1.28, 2.97]). After adjusting for BMI or gestational diabetes, pre-eclampsia remained linked with an increased risk of future diabetes (RR 2.38 [95% CI 1.74, 3.24] and RR 2.36 [95% CI 1.94, 2.88], respectively).
CONCLUSIONS/INTERPRETATION
Pre-eclampsia is independently associated with a twofold increase in future diabetes. Our study highlights the importance of clinical risk assessment for the future development of diabetes in women with pre-eclampsia. We recommend detailed evaluation of a screening programme for diabetes in this high-risk population.
Topics: Diabetes, Gestational; Female; Humans; Postpartum Period; Pre-Eclampsia; Pregnancy; Risk Factors
PubMed: 27646865
DOI: 10.1007/s00125-016-4098-x -
Annales de Biologie Clinique Jun 2017Preeclampsia which affects approximatively 2% of pregnancies is a major cause of maternal and perinatal morbidity and mortality. Pathogenesis of pre-eclampsia is... (Review)
Review
Preeclampsia which affects approximatively 2% of pregnancies is a major cause of maternal and perinatal morbidity and mortality. Pathogenesis of pre-eclampsia is nowadays increasingly understood. It implies multiple actors and biomarkers appear to be playing a major role. New uses of those biomarkers for risk stratification and diagnosis of predisposed preeclamptic patients followed by obstetricians is an hot topic. The combined approach of biomarkers, medical history and obstetrical ultrasounds enables risk estimation in the first quarter and later on. A better understanding of this risk would enable better monitoring of obstetrical patients and reduce the occurrence of adverse complications for them and for the fetal well-being.
Topics: Biomarkers; Disease Susceptibility; Female; Humans; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prognosis; Risk Factors
PubMed: 28540849
DOI: 10.1684/abc.2017.1240 -
The Australian & New Zealand Journal of... Aug 2019The current approach to screening for pre-eclampsia is based on guidelines that rely on medical and obstetric history in early pregnancy to select a high-risk group that... (Review)
Review
The current approach to screening for pre-eclampsia is based on guidelines that rely on medical and obstetric history in early pregnancy to select a high-risk group that might benefit from low-dose aspirin. However, combined screening tests with the addition of biophysical and biochemical measurements have shown significantly better detection rates for preterm pre-eclampsia. Furthermore, the administration of aspirin for the 10% screen-positive group can lead to a significant reduction in severe and preterm forms of pre-eclampsia. This review aims to answer frequently asked questions related to the clinical implementation of screening and the management of screening results.
Topics: Female; Humans; Pre-Eclampsia; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 31119729
DOI: 10.1111/ajo.12982 -
Cells Feb 2022The pathophysiology of pre-eclampsia involves two major pathways, namely systemic oxidative stress and subsequent generalised inflammatory response, which eventually... (Review)
Review
The pathophysiology of pre-eclampsia involves two major pathways, namely systemic oxidative stress and subsequent generalised inflammatory response, which eventually culminates in endothelial cell injury and the syndrome of pre-eclampsia with multi-organ dysfunction. Aspirin has been used to reduce the risk of pre-eclampsia, but it only possesses anti-inflammatory properties without any antioxidant effect. Hence, it can only partially alleviate the problem. Tocotrienols are a unique form of vitamin E with strong antioxidant and anti-inflammatory properties that can be exploited as a preventive agent for pre-eclampsia. Many preclinical models showed that tocotrienol can also prevent hypertension and ischaemic/reperfusion injury, which are the two main features in pre-eclampsia. This review explores the mechanism of action of tocotrienol in relation to the pathophysiology of pre-eclampsia. In conclusion, the study provides sufficient justification for the establishment of a large clinical trial to thoroughly assess the capability of tocotrienol in preventing pre-eclampsia.
Topics: Anti-Inflammatory Agents; Antioxidants; Female; Humans; Oxidative Stress; Pre-Eclampsia; Pregnancy; Tocotrienols
PubMed: 35203265
DOI: 10.3390/cells11040614