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Ananth S Karumanchi - One of the best experts on this subject based on the ideXlab platform.
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pre Eclampsia pathogenesis novel diagnostics and therapies
Nature Reviews Nephrology, 2019Co-Authors: Elizabeth A Phipps, Ravi Thadhani, Thomas Benzing, Ananth S KarumanchiAbstract:Pre-Eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. The disease presents with new-onset hypertension and often proteinuria in the mother, which can progress to multi-organ dysfunction, including hepatic, renal and cerebral disease, if the fetus and placenta are not delivered. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-Eclampsia. Risk factors for the disease include maternal comorbidities, such as chronic kidney disease, hypertension and obesity; a family history of pre-Eclampsia, nulliparity or multiple pregnancies; and previous pre-Eclampsia or intrauterine fetal growth restriction. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. In this Review, we discuss the pathogenic role of antiangiogenic proteins released by the placenta in the development of pre-Eclampsia and review novel therapeutic strategies directed at restoring the angiogenic imbalance observed during pre-Eclampsia. We also highlight other notable advances in the field, including the identification of long-term maternal and fetal risks conferred by pre-Eclampsia.
James J Walker - One of the best experts on this subject based on the ideXlab platform.
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clinical risk prediction for pre Eclampsia in nulliparous women development of model in international prospective cohort
BMJ, 2011Co-Authors: Robyn A North, Rennae S Taylor, Lesley M E Mccowan, Gustaaf A Dekker, Lucilla Poston, Eliza H Y Chan, Alistair Stewart, Michael A Black, James J Walker, Philip N BakerAbstract:Objectives To develop a predictive model for pre-Eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk, in whom specialist referral might be indicated. Design Prospective multicentre cohort. Setting Five centres in Auckland, New Zealand; Adelaide, Australia; Manchester and London, United Kingdom; and Cork, Republic of Ireland. Participants 3572 “healthy” nulliparous women with a singleton pregnancy from a large international study; data on pregnancy outcome were available for 3529 (99%). Main outcome measure Pre-Eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or both, on at least two occasions four hours apart after 20 weeks’ gestation but before the onset of labour, or postpartum, with either proteinuria or any multisystem complication. Preterm pre-Eclampsia was defined as women with pre-Eclampsia delivered before 37 +0 weeks’ gestation. In the stepwise logistic regression the comparison group was women without pre-Eclampsia. Results Of the 3529 women, 186 (5.3%) developed pre-Eclampsia, including 47 (1.3%) with preterm pre-Eclampsia. Clinical risk factors at 14-16 weeks’ gestation were age, mean arterial blood pressure, body mass index (BMI), family history of pre-Eclampsia, family history of coronary heart disease, maternal birth weight, and vaginal bleeding for at least five days. Factors associated with reduced risk were a previous single miscarriage with the same partner, taking at least 12 months to conceive, high intake of fruit, cigarette smoking, and alcohol use in the first trimester. The area under the receiver operating characteristics curve (AUC), under internal validation, was 0.71. Addition of uterine artery Doppler indices did not improve performance (internal validation AUC 0.71). A framework for specialist referral was developed based on a probability of pre-Eclampsia generated by the model of at least 15% or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors. Nine per cent of nulliparous women would be referred for a specialist opinion, of whom 21% would develop pre-Eclampsia. The relative risk for developing pre-Eclampsia and preterm pre-Eclampsia in women referred to a specialist compared with standard care was 5.5 and 12.2, respectively. Conclusions The ability to predict pre-Eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other populations. If validated, it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added. Trial registration ACTRN12607000551493.
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Outcomes of severe pre‐Eclampsia/Eclampsia in Yorkshire 1999/2003
BJOG : an international journal of obstetrics and gynaecology, 2005Co-Authors: Derek Tuffnell, D. Jankowicz, S.w. Lindow, G. Lyons, G.c. Mason, I.f. Russell, James J WalkerAbstract:To establish the risk of serious complications from severe pre-Eclampsia and Eclampsia in a region using a common guideline for the management of these conditions. A five-year prospective study. Sixteen maternity units in Yorkshire. All women managed with severe pre-Eclampsia and Eclampsia. A common guideline was developed for the management of women with these conditions. A network of midwives prospectively collected outcome data. Incidence of the conditions and serious complication rates. A total of 210,631 women delivered in the 16 units between 1 January 1999 and 31 December 2003. One thousand eighty-seven women were diagnosed with severe pre-Eclampsia or Eclampsia (5.2/1000). One hundred and fifty-one women had serious complications including 82 women (39/10,000) having eclamptic seizures and 49 women (23/10,000) requiring ICU admission. There were no maternal deaths but 54 out of 1145 babies died before discharge, giving a mortality rate of 47.2/1000. Of the 82 cases of Eclampsia, 45 occurred antenatally (55%), 18 before admission to the maternity unit. Eleven cases occurred in labour (13%), including 1 during a caesarean section, and 26 cases occurred following delivery (32%). Twenty-five women developed pulmonary oedema (2.3% of cases) and six women required renal dialysis (0.55% of cases). One hundred and sixty-five (15%) required no antihypertensive therapy and 489 (53%) of the remainder required only oral therapy. Two hundred and one (18.5%) required more than one drug. A regional guideline for severe pre-Eclampsia and Eclampsia can be developed and implemented. Its use may contribute to a low rate of serious complications.
Caroline K. Kramer - One of the best experts on this subject based on the ideXlab platform.
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Fetal sex and maternal risk of pre-Eclampsia/Eclampsia: a systematic review and meta-analysis
BJOG : an international journal of obstetrics and gynaecology, 2016Co-Authors: Diana Jaskolka, Ravi Retnakaran, B. Zinman, Caroline K. KramerAbstract:A preponderance of male fetuses in pregnancies complicated by pre-Eclampsia was described over 40 years ago. Since then, however, there has been conflicting evidence in the literature, with some studies supporting a male preponderance, some demonstrating no relationship with fetal sex, and others reporting increased risk in pregnancies bearing females. In this context, we sought to conduct a systematic review and meta-analysis to objectively evaluate the relationship between fetal sex and maternal risk of pre-Eclampsia/Eclampsia. Studies from January 1950 to April 2015 were identified from PUBMED and EMBASE. This systematic review and meta-analysis evaluated 22 articles reporting data on fetal sex and prevalence of pre-Eclampsia/Eclampsia. Data were extracted by two independent reviewers. Pooled estimates of the relative risk (RR) were calculated by random-effects model. Male fetus was considered the exposure and prevalence of maternal pre-Eclampsia/Eclampsia was the outcome of interest. We identified 534 studies through electronic searches and three studies through manual searches. Twenty-two studies fulfilled the inclusion criteria, yielding data on 3 163 735 women. Pooled analyses of these studies showed no association between male fetal sex and maternal risk of pre-Eclampsia/Eclampsia (RR 1.01; 95% confidence interval, 95% CI 0.97-1.05); however, a subgroup analysis including only studies that evaluated the non-Asian population (n = 2 931 771 women) demonstrated that male fetal sex was associated with increased maternal risk of pre-Eclampsia/Eclampsia (RR 1.05; 95% CI 1.03-1.06; I2 = 10%; P = 0.33). Male fetal sex is associated with maternal risk of pre-Eclampsia/Eclampsia in the non-Asian population. Fetal sex is associated with maternal risk of pre-Eclampsia/Eclampsia in the non-Asian population. © 2016 Royal College of Obstetricians and Gynaecologists.
Peter Von Dadelszen - One of the best experts on this subject based on the ideXlab platform.
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Health care provider knowledge and routine management of pre-Eclampsia in Pakistan
Reproductive Health, 2016Co-Authors: Sana Sheikh, Peter Von Dadelszen, Rahat Najam Qureshi, Asif Raza Khowaja, Rehana Salam, Marianne Vidler, Diane Sawchuck, Shujat Zaidi, Zulfiqar BhuttaAbstract:Background Maternal mortality ratio is 276 per 100,000 live births in Pakistan. Eclampsia is responsible for one in every ten maternal deaths despite the fact that management of this disease is inexpensive and has been available for decades. Many studies have shown that health care providers in low and middle-income countries have limited training to manage patients with Eclampsia. Hence, we aimed to explore the knowledge of different cadres of health care providers regarding aetiology, diagnosis and treatment of pre-Eclampsia and Eclampsia and current management practices. Methods We conducted a mixed method study in the districts of Hyderabad and Matiari in Sindh province, Pakistan. Focus group discussions and interviews were conducted with community health care providers, which included Lady Health Workers and their supervisors; traditional birth attendants and facility care providers. In total seven focus groups and 26 interviews were conducted. NVivo 10 was used for analysis and emerging themes and sub-themes were drawn. Results All participants were providing care for pregnant women for more than a decade except one traditional birth attendant and two doctors. The most common cause of pre-Eclampsia mentioned by community health care providers was stress of daily life: the burden of care giving, physical workload, short birth spacing and financial constraints. All health care provider groups except traditional birth attendants correctly identified the signs, symptoms, and complications of pre-Eclampsia and Eclampsia and were referring such women to tertiary health facilities. Only doctors were aware that magnesium sulphate is recommended for Eclampsia management and prevention; however, they expressed fears regarding its use at first and secondary level health facilities. Conclusion This study found several gaps in knowledge regarding aetiology, diagnosis and treatment of pre-Eclampsia among health care providers in Sindh. Findings suggest that lesser knowledge regarding management of pre-Eclampsia is due to lack of refresher trainings and written guidelines for management of pre-Eclampsia and presentation of fewer pre-eclamptic patients at first and secondary level health care facilities. We suggest to include management of pre-Eclampsia in regular trainings of health care providers and to provide management protocols at all health facilities. Trial registration NCT01911494
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Pre-Eclampsia: An Update
Current Hypertension Reports, 2014Co-Authors: Peter Von Dadelszen, Laura A. MageeAbstract:Pre-Eclampsia remains the second leading direct cause of maternal death, >99 % of which occurs in less developed countries. Over 90 percent of the observed reduction in pre-Eclampsia-related maternal deaths in the UK (1952–2008) occurred with antenatal surveillance and timed delivery. In this review, we discuss the pathogenesis, diagnostic criteria, disease prediction models, prevention and management of pre-Eclampsia. The Pre-Eclampsia Integrated Estimate of RiSk (PIERS) models and markers of angiogenic imbalance identify women at incremental risk for severe pre-Eclampsia complications. For women at high risk of developing pre-Eclampsia, low doses of aspirin (especially if started
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The complications of hypertension in pregnancy.
Minerva Medica, 2005Co-Authors: Peter Von Dadelszen, J Menzies, L.a. MageeAbstract:The hypertensive disorders of pregnancy remain a leading cause of maternal and perinatal morbidity and mortality in Europe and North America. Pre-Eclampsia, which is proteinuric gestational hypertension, accounts for the majority of the excess risks and is defined by the maternal syndrome. The maternal syndrome of pre-Eclampsia is characterised by a systemic inflammatory response and its sequelae. Sytematic multisystem evaluation of pre-Eclampsia, evidence-based antihypertensive therapy, and the use of MgSO 4 to prevent and treat the seizures of Eclampsia can reduce maternal risks. For mild-to-moderate pregnancy hypertension, maternal risks are small, and there may be adverse perinatal consequences of blood pressure normalisation. Early-onset and severe pre-Eclampsia predict an excess risk of later cardiovascular morbidity and mortality. Both Chlamydophila pneumoniae and cytomegalovirus have bee associated with pre-Eclampsia and atherosclerosis, and may provide a mechanistic link between pre-Eclampsia and the recognised cardiovascular risk. Women with a history of either early-onset and/or severe pre-Eclampsia should be considered to be at increased risk for later cardiovascular disease, and it may be prudent for them to have regular lipid profiles and tests for urinary microalbumin excretion.
Laura A. Magee - One of the best experts on this subject based on the ideXlab platform.
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Pre-Eclampsia: An Update
Current Hypertension Reports, 2014Co-Authors: Peter Von Dadelszen, Laura A. MageeAbstract:Pre-Eclampsia remains the second leading direct cause of maternal death, >99 % of which occurs in less developed countries. Over 90 percent of the observed reduction in pre-Eclampsia-related maternal deaths in the UK (1952–2008) occurred with antenatal surveillance and timed delivery. In this review, we discuss the pathogenesis, diagnostic criteria, disease prediction models, prevention and management of pre-Eclampsia. The Pre-Eclampsia Integrated Estimate of RiSk (PIERS) models and markers of angiogenic imbalance identify women at incremental risk for severe pre-Eclampsia complications. For women at high risk of developing pre-Eclampsia, low doses of aspirin (especially if started
