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Background Most pregnancy hypertension estimates in less-developed countries are from cross-sectional hospital surveys and are considered overestimates. We estimated population-based rates by standardised methods in 27 intervention clusters of the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised trials. Methods and findings CLIP-eligible pregnant women identified in their homes or local primary health centres (2013-2017). Included here are women who had delivered by trial end and received a visit from a community health worker trained to provide supplementary hypertension-oriented care, including standardised blood pressure (BP) measurement. Hypertension (BP [greater than or equal to] 140/90 mm Hg) was defined as chronic (first detected at Conclusions Pregnancy hypertension is common in less-developed settings. Most women in this study presented with gestational hypertension amenable to surveillance and timed delivery to improve outcomes. Trial registration This study is a secondary analysis of a clinical trial - ClinicalTrials.gov registration number NCT01911494., Author(s): Laura A. Magee 1,*, Sumedha Sharma 2, Hannah L. Nathan 1, Olalekan O. Adetoro 3, Mrutynjaya B. Bellad 4, Shivaprasad Goudar 4, Salécio E. Macuacua 5, Ashalata Mallapur 6, [...]

Antenatal corticosteroids (ACS) are an established intervention to improve outcomes in preterm birth. ACS are optimally timed if the administration-to-birth interval is greater than 24 h and <7 days. Evidence has emerged suggesting harm associated with administration-to-birth intervals greater than seven days, or with repeated courses of ACS. Pre-eclampsia is a leading cause of iatrogenic preterm birth, as delivery of the fetus and placenta remains the only cure. This study investigated optimal ACS use in women delivering before 35 weeks' gestation in the United Kingdom with a diagnosis of preterm pre-eclampsia. Of 1,632 women with suspected pre-eclampsia, 250 delivered before 35 weeks' gestation with pre-eclampsia. 31 % (78/250) received optimally timed ACS, 49 % (122/250) received ACS more than seven days pre-delivery and 20 % (50/250) did not receive ACS. There were no significant differences in gestational age, mean birthweight, respiratory distress syndrome, neonatal unit admission or neonatal death between groups. There was a higher rate of intrauterine fetal death in the group of women who did not receive ACS (p < 0.05), and a corresponding increase in vaginal delivery and reduction in caesarean section (p < 0.05). Optimal ACS administration is poor in women delivering preterm with pre-eclampsia and the largest group of mistimed ACS administration were those given more than 7 days prior to birth. Clinicians should defer ACS until a decision for delivery has been made, at which point ACS should be prioritised. Judicious use of ACS may improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a complex pregnancy disorder, characterised by new or worsening hypertension associated with multi-organ dysfunction. Adverse outcomes include eclampsia, liver rupture, stroke, pulmonary oedema, and acute kidney injury in the mother, and stillbirth, foetal growth restriction, and iatrogenic preterm delivery for the foetus. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing for suspected preterm pre-eclampsia has been incorporated into national guidance. The role of repeat PlGF-based testing and its effect on maternal and perinatal adverse outcomes have yet to be evaluated.Methods: The PARROT-2 trial is a multi-centre randomised controlled trial of repeat revealed PlGF-based testing compared to repeat concealed testing, in women presenting with suspected pre-eclampsia between 22+0 and 35+6 weeks' gestation. The primary objective is to establish whether repeat PlGF-based testing decreases a composite of perinatal severe adverse outcomes (stillbirth, early neonatal death, or neonatal unit admission). All women prior to enrolment in the trial will have an initial revealed PlGF-based test. Repeat PlGF-based tests will be performed weekly or two-weekly, depending on the initial PlGF-based test result, with results randomised to revealed or concealed.Discussion: National guidance recommends that all women presenting with suspected preterm pre-eclampsia should have a single PlGF-based test when disease is first suspected, to help rule out pre-eclampsia. Clinical and cost-effectiveness of repeat PlGF-based testing has yet to be investigated. This trial aims to address whether repeat PlGF-based testing reduces severe maternal and perinatal adverse outcomes and whether repeat testing is cost-effective.Trial Registration: ISRCTN 85912420 . Registered on 25 November 2019. [ABSTRACT FROM AUTHOR]

Accurate assessment of blood pressure is fundamental to the provision of safe obstetrical care. It is simple, cost effective, and life-saving. Treatments for preeclampsia, including antihypertensive drugs, magnesium sulfate, and delivery, are available in many settings. However, the instigation of appropriate treatment relies on prompt and accurate recognition of hypertension. There are a number of different techniques for blood pressure assessment, including the auscultatory method, automated oscillometric devices, home blood pressure monitoring, ambulatory monitoring, and invasive monitoring. The auscultatory method with a mercury sphygmomanometer and the use of Korotkoff sounds was previously recommended as the gold standard technique. Mercury sphygmomanometers have been withdrawn owing to safety concerns and replaced with aneroid devices, but these are particularly prone to calibration errors and regular calibration is imperative to ensure accuracy. Automated oscillometric devices are straightforward to use, but the physiological changes in healthy pregnancy and pathologic changes in preeclampsia may affect the accuracy of a device and monitors must be validated. Validation protocols classify pregnant women as a "special population," and protocols must include 15 women in each category of normotensive pregnancy, hypertensive pregnancy, and preeclampsia. In addition to a scarcity of devices validated for pregnancy and preeclampsia, other pitfalls that cause inaccuracy include the lack of training and poor technique. Blood pressure assessment can be affected by maternal position, inappropriate cuff size, conversation, caffeine, smoking, and irregular heart rate. For home blood pressure monitoring, appropriate instruction should be given on how to use the device. The classification of hypertension and hypertensive disorders of pregnancy has recently been revised. These are classified as preeclampsia, transient gestational hypertension, gestational hypertension, white-coat hypertension, masked hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. Blood pressure varies across gestation and by ethnicity, but gestation-specific thresholds have not been adopted. Hypertension is defined as a sustained systolic blood pressure of ≥140 mm Hg or a sustained diastolic blood pressure of ≥90 mm Hg. In some guidelines, the threshold of diagnosis depends on the setting in which blood pressure measurement is taken, with a threshold of 140/90 mm Hg in a healthcare setting, 135/85 mm Hg at home, or a 24-hour average blood pressure on ambulatory monitoring of >126/76 mm Hg. Some differences exist among organizations with respect to the criteria for the diagnosis of preeclampsia and the correct threshold for intervention and target blood pressure once treatment has been instigated. Home blood pressure monitoring is currently a focus for research. Novel technologies, including early warning devices (such as the CRADLE Vital Signs Alert device) and telemedicine, may provide strategies that prompt earlier recognition of abnormal blood pressure and therefore improve management. The purpose of this review is to provide an update on methods to assess blood pressure in pregnancy and appropriate technique to optimize accuracy. The importance of accurate blood pressure assessment is emphasized with a discussion of preeclampsia prediction and treatment of severe hypertension. Classification of hypertensive disorders and thresholds for treatment will be discussed, including novel developments in the field. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care.Methods: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model.Results: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy.Conclusions: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care. [ABSTRACT FROM AUTHOR]

Objective: To assess the diagnostic performance of angiogenic biomarkers in determining need for delivery in seven days in women with late preterm preeclampsia.Study Design: In a prospective observational cohort study in 36 maternity units across England and Wales, we studied the diagnostic accuracy of placental growth factor (PlGF) and sFlt-1 in determining the risk of complications requiring delivery in late preterm (34+0 to 36+6 weeks' gestation) preeclampsia. Angiogenic biomarkers were measured using the Quidel (PlGF) and Roche (sFlt-1:PlGF ratio) assays. Additional clinical data was obtained for use within the established 'Prediction of complications in early-onset pre-eclampsia' (PREP)-S prognostic model. Biomarkers were assessed using standard methods (sensitivity, specificity, Receiver Operator Curve areas). Estimated probability of early delivery from PREP-S was compared to actual event rates.Main Outcome Measures: Clinically indicated need for delivery for pre-eclampsia within seven days.Results: PlGF (Quidel) testing had high sensitivity (97.9%) for delivery within seven days, but negative predictive value was only 71.4%, with low specificity (8.4%), with similar results from sFlt-1/PlGF assay. The area under the curve for PlGF was 0.60 (SE 0.03), and 0.65 (0.03), and 0.64 (0.03) for PREP-S in combination with PlGF, and sFlt-1:PlGF, respectively.Conclusions: Angiogenic biomarkers do not add to clinical assessment to help determine need for delivery for women with late preterm pre-eclampsia. Existing models developed in women with early-onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity globally. Planned delivery between 34+0 and 36+6 weeks may reduce adverse pregnancy outcomes but is yet to be evaluated in a low and middle-income setting. Prior to designing a randomised controlled trial to evaluate this in India and Zambia, we carried out a 6-month feasibility study in order to better understand the proposed trial environment and guide development of our intervention. Methods: We used mixed methods to understand the disease burden and current management of pre-eclampsia at our proposed trial sites and explore the acceptability of the intervention. We undertook a case notes review of women with pre-eclampsia who delivered at the proposed trial sites over a 3-month period, alongside facilitating focus group discussions with women and partners and conducting semi-structured interviews with healthcare providers. Descriptive statistics were used to analyse audit data. A thematic framework analysis was used for qualitative data. Results: Case notes data (n = 326) showed that in our settings, 19.5% (n = 44) of women with pre-eclampsia delivering beyond 34 weeks experienced an adverse outcome. In women delivering between 34+0 and 36+6 weeks, there were similar numbers of antenatal stillbirths [n = 3 (3.3%)] and neonatal deaths [n = 3 (3.4%)]; median infant birthweight was 2.2 kg and 1.9 kg in Zambia and India respectively. Lived experience of women and healthcare providers was an important facilitator to the proposed intervention, highlighting the serious consequences of pre-eclampsia. A preference for spontaneous labour and limited neonatal resources were identified as potential barriers. Conclusions: This study demonstrated a clear need to evaluate the intervention and highlighted several challenges relating to trial context that enabled us to adapt our protocol and design an acceptable intervention. Our study demonstrates the importance of assessing feasibility when developing complex interventions, particularly in a low-resource setting. Additionally, it provides a unique insight into the management of pre-eclampsia at our trial settings and an understanding of the knowledge, attitudes and beliefs underpinning the acceptability of planned early delivery. Plain language summary: Pre-eclampsia is a complication of pregnancy and is one of the major causes of pregnancy-related death and serious illness for women and babies around the world. Most of these deaths occur in lower income countries in Africa and Asia. Signs of pre-eclampsia include high blood pressure and protein in the urine. It is unpredictable and may affect different organs within the woman, leading to seizures, stroke and even death if not well managed. It can also affect the baby's growth and in severe cases lead to stillbirth. We know that birth of the baby (and placenta) is the only cure for pre-eclampsia. Currently, it is recommended by the World Health Organisation that all women with pre-eclampsia are offered planned early birth once they reach 37 weeks of pregnancy, unless they develop severe complications needing intervention sooner than this. However, research from higher income countries has shown that planned early birth from 34 weeks of pregnancy may reduce serious complications in the woman, without causing harm to the baby. We are designing a clinical trial to find out whether, in women with pre-eclampsia between 34 and 37 weeks of pregnancy, it is better to offer planned early birth or to offer close monitoring until either they reach 37 weeks, or a complication develops requiring emergency intervention. Before designing this trial, we carried out a study in order to establish whether the main trial would be possible, and acceptable to the local community, at our potential trial sites in India and Zambia. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Objective: Placental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms.Study Design: This was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia.Main Outcome Measures: Maternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration.Results: 1006 women were included. PlGF < 100 pg/ml identified women with more marked hypertension, increased adverse maternal outcomes and preterm delivery rates, and higher rates of small for gestational age infants. There was a reduction in adverse maternal outcomes in women whose results were revealed when PlGF levels were 12-100 pg/ml compared to usual care (3.8% vs 6.9%; aOR 0.15(95% CI 0.03-0.92). There was no significant difference in gestation at delivery between concealed or revealed groups in any PlGF categories.Conclusion: Low PlGF concentrations are associated with severe preeclampsia. The reduction in severe adverse maternal outcomes may be mediated through quicker diagnosis and intensive surveillance, as recommended by the management algorithm for those at increased risk. PlGF is particularly beneficial in those who test 12-100 pg/ml, as these may be women with silent multi-organ disease who otherwise may go undetected. [ABSTRACT FROM AUTHOR]

Objectives: To reduce all-cause maternal and perinatal mortality and major morbidity through Lady Health Worker (LHW)-facilitated community engagement and early diagnosis, stabilization and referral of women with preeclampsia, an important contributor to adverse maternal and perinatal outcomes given delays in early detection and initial management.Study Design: In the Pakistan Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494), LHWs engaged the community, recruited pregnant women from 20 union councils (clusters), undertook mobile health-guided clinical assessment for preeclampsia, and referral to facilities after stabilization.Main Outcome Measures: The primary outcome was a composite of maternal, fetal and newborn mortality and major morbidity.Findings: We recruited 39,446 women in intervention (N = 20,264) and control clusters (N = 19,182) with minimal loss to follow-up (3∙7% vs. 4∙5%, respectively). The primary outcome did not differ between intervention (26·6%) and control (21·9%) clusters (adjusted odds ratio, aOR, 1∙20 [95% confidence interval 0∙84-1∙72]; p = 0∙31). There was reduction in stillbirths (0·89 [0·81-0·99]; p = 0·03), but no impact on maternal death (1·08 [0·69, 1·71]; p = 0·74) or morbidity (1·12 [0·57, 2·16]; p = 0·77); early (0·95 [0·82-1·09]; p = 0·46) or late neonatal deaths (1·23 [0·97-1·55]; p = 0·09); or neonatal morbidity (1·22 [0·77, 1·96]; p = 0·40). Improvements in outcome rates were observed with 4-7 (p = 0·015) and ≥8 (p < 0·001) (vs. 0) CLIP contacts.Interpretation: The CLIP intervention was well accepted by the community and implemented by LHWs. Lack of effects on adverse outcomes could relate to quality care for mothers with pre-eclampsia in health facilities. Future strategies for community outreach must also be accompanied by health facility strengthening.Funding: The University of British Columbia (PRE-EMPT), a grantee of the Bill & Melinda Gates Foundation (OPP1017337). [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia affects about 3% of singleton pregnancies and is characterized by placental dysfunction. It is associated with significant maternal and perinatal morbidity and mortality. The diagnosis of preeclampsia remains a challenge, and the clinical course can develop for weeks before a diagnosis is confirmed. National guidelines have approved placental growth factor (PlGF) testing to rule out suspected preeclampsia, but the utility of repeated PlGF measurement is unknown. The aim of this case series analysis was to evaluate the test performance of repeated PlGF sampling in women presenting with suspected preeclampsia, and to describe relevant clinical outcomes.Material and Methods: Women who presented to maternity services with suspected preeclampsia between 20+0 and 36+6  weeks' gestation who underwent repeat PlGF sampling with a minimum test interval of 7 days were assessed. The outcomes were delivery for preeclampsia within 14 days of sampling, the proportion changing PlGF categories, and time to delivery.Results: In total, 289 women with suspected preeclampsia undergoing repeat PlGF sampling were included. PlGF <100 pg/mL had a high sensitivity (87.5%, 95% confidence interval [CI] 67.6%-97.3%) and a negative predictive value (97.7%, 95% CI 93.5%-99.5%) at the initial test (receiver operating characteristic [ROC] area 0.79, 95% CI 0.68-0.89). Similar test performance was seen for PlGF <100 pg/mL when undertaken as a repeat test (sensitivity 90.7%, 95% CI 85.2%-95.9%, negative predictive value 92.2%, 95% CI 85.3-96.6%). Overall, 25.6% of women changed PlGF category between the first and second PlGF tests. For each PlGF category, determination of time to delivery was similar for first and second tests.Conclusions: Repeat PlGF measurement demonstrates high negative predictive value for determining preeclampsia requiring delivery in 14 days. Repeat testing may be clinically useful to risk stratify women with ongoing symptoms of disease. Confirmation of the impact of these findings is required in further studies. [ABSTRACT FROM AUTHOR]

Preeclampsia is a common cause of acute kidney injury (AKI) in low- and middle-income countries, but AKI incidence in preeclampsia, its risk factors, and renal outcomes are unknown. A prospective observational multicenter study of women admitted with preeclampsia in South Africa was conducted. Creatinine concentrations were extracted from national laboratory databases for women with maximum creatinine of ≥90 μmol/L (≥1.02 mg/dL). Renal injury and recovery were defined by Kidney Disease Improving Global Outcomes creatinine criteria. Predefined risk factors, maternal outcomes, and neonatal outcomes were compared between AKI stages. Of 1547 women admitted with preeclampsia 237 (15.3%) met AKI criteria: 6.9% (n=107) stage 1, 4.3% (n=67) stage 2, and 4.1% (n=63) stage 3. There was a higher risk of maternal death (n=7; relative risk, 4.3; 95% CI, 1.6-11.4) and stillbirth (n=80; relative risk, 2.2; 95% CI, 1.8-2.8) in women with AKI compared with those without. Perinatal mortality was also increased (89 of 240; 37.1%). Hypertension in a previous pregnancy was the strongest predictor of AKI stage 2 or 3 (odds ratio, 2.24; 95% CI, 1.21-4.17). Renal recovery rate reduced with increasing AKI stage. A third of surviving women (76 of 230 [33.0%]) had not recovered baseline renal function by discharge. Approximately half (39 of 76; 51.3%) of these women had no further creatinine testing post-discharge. In summary, AKI was common in women with preeclampsia and had high rates of associated maternal and perinatal mortality. Only two-thirds of women had confirmed renal recovery. History of a previous hypertensive pregnancy was an important risk factor. [ABSTRACT FROM AUTHOR]

Objective: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care.Design: Cost-effectiveness analysis.Setting: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial.Population: Women presenting with suspected pre-eclampsia between 20+0 and 36+6  weeks' gestation.Methods: Monte Carlo simulation utilising resource use data and maternal adverse outcomes.Main Outcome Measures: Cost per maternal adverse outcome prevented.Results: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England.Conclusions: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia.Tweetable Abstract: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Placental Growth Factor (PlGF) has been shown to be beneficial in diagnosing pre-eclampsia. We performed a prospective cohort study of revealed PlGF in standard clinical use in four teaching hospitals in UK, Germany, Austria and Australia.Study Design: Clinical data from women with suspected pre-eclampsia or fetal growth restriction <35 weeks' gestation with revealed PlGF measurement were collected (MAPPLE study).Main Outcome Measures: Data were compared to the PELICAN study (PlGF concealed). Pre-specified outcomes were compared using standard statistical tests (median difference or Risk Ratio). The results were further categorised by PlGF concentration: i) very low (<12 pg/ml), ii) low (12-100 pg/ml), iii) normal (>100 pg/ml).Results: 396 women managed with revealed PlGF (MAPPLE) were compared with 287 women with concealed PlGF (PELICAN). Revealed PlGF led to delivery 1.4 weeks earlier (-2.0 to -0.9, 34.9 weeks vs 36.7 weeks). There were no significant differences in maternal adverse outcomes (11.9% vs 10.1%, Risk Ratio (RR) 1.17, 95% CI 0.76-1.82) or caesarean sections (73.8% vs 64.5%; RR 1.14, 95% CI 1.03-1.26). Revealed PlGF led to fewer perinatal deaths (2 vs 9; RR 0.16, 95% CI 0.03-0.74) and fewer babies with birthweight <3rd centile (28.9% vs 36.1%; RR 0.80, 0.65-0.99), but with more neonatal adverse outcomes (30.4% vs 17.1%; RR 1.78, 95% CI 1.32-2.41).Conclusions: Revealed PlGF may be associated with lower perinatal mortality and birthweight <3rd centile but appears to lead to earlier delivery with more neonatal respiratory morbidity. Randomised trials with adequate power for clinical outcomes are needed.Funding: Financial assistance was received from Alere to support the running of the MAPPLE database. Alere had no access to the information or control over the database itself. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between blood pressure (BP) measurements and adverse outcomes in women with pre-eclampsia.Study Design: A prospective cohort study of women with pre-eclampsia admitted to three South African tertiary facilities. BP was measured using the CRADLE Vital Signs Alert (VSA), incorporated with a traffic light early warning system; green: systolic BP <140 mmHg and diastolic BP <90 mmHg, yellow: systolic BP 140-159 and/or diastolic BP 90-109 mmHg (but neither is above the upper threshold), red: systolic BP ≥160 mmHg and/or diastolic BP ≥110 mmHg.Main Outcome Measures: Maternal: death, eclampsia, stroke, kidney injury; process measures: magnesium sulfate use, Critical Care Unit (CCU) admission; perinatal: stillbirth, neonatal death, preterm delivery.Results: Of 1547 women with pre-eclampsia (including 42 twin pregnancies), 33.0% of women triggered a red light on admission and 78.6% at their highest BP. Severe hypertension and adverse outcomes were common across yellow and red categories. Comparing admission red to yellow lights, there was a significant increase in kidney injury (OR 1.74, CI 1.31-2.33, trend test p = .003), magnesium sulfate use (OR 3.40, CI 2.24-5.18, p < .001) and CCU admission (OR 1.50, CI 1.18-1.91, p < .001), but not for maternal death, eclampsia, extended perinatal death or preterm delivery.Conclusion: The CRADLE VSA, with integrated traffic light early warning system, can identify women who are hypertensive, at increased risk of severe pre-eclampsia complications and in need of escalation of care. Women who triggered a red light were at increased risk of kidney injury, magnesium sulfate use and CCU admission. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia.Methods: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome.Results: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation.Conclusion: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks’ gestation as part of a management algorithm, compared with current practice. Methods: Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks’ gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes. Results: The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice. Conclusions: This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks’ gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy cause significant maternal morbidity and mortality worldwide, particularly in developing countries. This study evaluated the accuracy of the Nissei DS-400, a low cost blood pressure (BP) device, in pregnancy according to the British Hypertension Society protocol. Forty-five pregnant women (15 with preeclampsia), were recruited from a large teaching hospital. Nine sequential same-arm BP measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the device. The Nissei DS-400 achieved the highest accuracy grade (A/A) in all subjects (n = 45) and in pregnancy alone (n = 30). The mean difference ± standard deviation between the standard and the device in pregnancy were -1.0 ± 5.1 mmHg and -1.1 ± 5.0 mmHg for systolic and diastolic BP, respectively, and -2.6 ± 5.9 mmHg and -3.4 ± 5.8 mmHg in all subjects. The Nissei-DS 400 can be recommended for clinical use in pregnancy and has potential as a good screening tool for pre-eclampsia in low resource settings. [ABSTRACT FROM AUTHOR]

Key content Accurate blood pressure (BP) measurement is fundamental to early diagnosis of hypertensive disorders in pregnancy., Poor auscultatory technique and lack of training leads to inaccuracies in BP measurement using sphygmomanometry with mercury and aneroid devices., Automated devices limit user error but require validation of accuracy because they tend to underestimate BP in pre-eclampsia., Systolic hypertension may better predict risk of adverse outcome (such as haemorrhagic stroke) than diastolic hypertension., Ambulatory/self-monitoring increases the number of representative readings available on which to base management, limiting unnecessary intervention., Detection of hypotension in pregnancy is crucial to the diagnosis of shock secondary to haemorrhage and sepsis., Learning objectives To learn how to obtain accurate BP measurements in pregnancy., To understand the significance of hypertension in pregnancy., Ethical issues A large proportion of maternal deaths are associated with substandard care, often related to poor recognition of severity of hypertension or shock and need for treatment., Lack of cheap, accurate, easy-to-use BP devices in low- and middle-income countries, where risk of maternal and perinatal mortality and morbidity secondary to pre-eclampsia and shock is highest, continues to be a challenge. [ABSTRACT FROM AUTHOR]

Objective: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia.Data Sources: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials.Study Eligibility Criteria: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward.Methods: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model.Results: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99).Conclusion: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational age, with a possible increase in short-term neonatal respiratory morbidity. The potential benefits and risks of prolonging a pregnancy complicated by preeclampsia should be discussed with women as part of a shared decision-making process. [ABSTRACT FROM AUTHOR]

The author discusses deaths of pregnant women in Great Britain and report given by the Confidential Enquiries into Maternal Deaths and Morbidity. Topics discussed include mental health conditions responsible for maternal mortality, treatment for cardiovascular and hypertensive diseases, and majority of cases related to pre-eclampsia.

Oxidative stress is widely implicated in failed reproductive performance, including infertility, miscarriage, diabetes-related congenital malformations, and preeclampsia. Maternal obesity is a strong risk factor for preeclampsia, and in a recent study we observed oxidative stress in the oocytes of obese animals before pregnancy as well as in early-stage embryos. This adds to the growing evidence that investigators need to focus more on the preconceptual period in efforts to prevent pregnancy disorders, including those related to oxidative stress. Our research has also focused on the role of free radicals and antioxidant capacity in preeclampsia. By measuring markers of lipid peroxidation and antioxidant capacity, we obtained unequivocal evidence for oxidative stress in this disorder. Partial failure of the process of placentation has been implicated, and recent findings suggest that ischemia-reperfusion in the placenta may contribute to oxidative stress in trophoblasts. Endoplasmic reticulum stress in the placenta may also play a role. Randomized controlled trials have been conducted by our group as well as others to determine whether early supplementation with vitamins C and E in women at risk of preeclampsia is beneficial, but these trials have shown no evidence that these supplements can prevent preeclampsia. Whether this indicates that an inappropriate antioxidant strategy was used or supplementation was administered too late in gestation to be beneficial is not known. Other potential approaches for preventing preeclampsia through amelioration of oxidative stress include the use of supplements in the preconceptual period, selenium supplements, antiperoxynitrite strategies, and statins. [ABSTRACT FROM AUTHOR]

Pre-eclampsia (P-EC) remains a significant problem in modern obstetrics occur- ring in 2 to 4% of women. The disease is still responsible for 60,000 maternal deaths worldwide annually. An increased understanding of the underlying pathophysiology has resulted in a more scientific approach to prophylaxis and prevention, yet the underlying disease mechanisms are not fully understood. The role of combining good prediction with prevention has yet to be established but has the potential to target health resources far more efficiently. Good prediction may also impact on tailoring antenatal care appropriately, with prophylactic measures for high-risk women becoming the highly preferred management option. Antiplatelet agents reduce the incidence and complications of P-EC and should be considered prophylactically in those at high risk of the disease. [ABSTRACT FROM AUTHOR]

Objective. To develop clinical risk tools for preeclampsia and small for gestational age (SGA) in high-risk women. Methods. Individual risk scores based on clinical risk factors were calculated using logistic regression and validated in 1687 women with obesity in first pregnancy, chronic hypertension, or previous preeclampsia. Results. The risk of preeclampsia varied from 7% in obese primiparae without hypertension to 30% when previous preeclampsia and chronic hypertension occurred together. A prediction model incorporating these risk factors had a sensitivity of 48 and 89% for preeclampsia delivered <34 weeks' gestation. Conclusion. Multiple clinical risk factors increase the risk of preeclampsia and SGA. [ABSTRACT FROM AUTHOR]

Abstract: Pre-eclampsia remains a significant problem in modern obstetrics occurring in 2–4% of women. The disease is still responsible for 60,000 maternal deaths worldwide annually. An increased understanding of the underlying pathophysiology has resulted in a more scientific approach to prophylaxis and prevention, yet the underlying disease mechanisms are not fully understood. The role of combining good prediction with prevention has yet to be established, but has the potential to target health resources far more efficiently. Good prediction may also impact on tailoring antenatal care appropriately, with prophylactic measures for high-risk women becoming the highly preferred management option. Management of established pre-eclampsia is empirical, preventing end-organ damage through timely delivery and control of fits and blood pressure, facilitated by appropriate surveillance. Risks of pulmonary complications can be limited through careful monitoring of fluid balance, and the risk of intracranial haemorrhage can be limited with judicious control of blood pressure. Fetal respiratory compromise can be reduced with timely administration of antenatal corticosteroids. Magnesium sulphate should be considered if there is a risk of eclampsia, as it has been demonstrated that those given magnesium sulphate have a 58% lower risk of seizures (95% CI 0.4–0.71). Magnesium sulphate should be used in the context of severe pre-eclampsia. [Copyright &y& Elsevier]

Please cite this paper as: Chappell L, Seed P, Enye S, Briley A, Poston L, Shennan A. Clinical and geographical variation in prophylactic and therapeutic treatments for pre-eclampsia in the UK. BJOG 2010; DOI: 10.1111/j.1471-0528.2010.02507.x. Objective To evaluate the clinical and geographical variation in the use of aspirin in women at high risk of pre-eclampsia, and in the use of antihypertensive drugs and magnesium sulphate in women with established pre-eclampsia. Design Analysis of vitamins in pre-eclampsia (VIP) trial database. Sample A total of 2399 women at increased risk of pre-eclampsia in 25 UK hospitals. Methods An analysis of a large prospectively validated database of high-risk women in the UK was undertaken to assess aspirin use across different risk groups and to evaluate the use of antihypertensives and magnesium sulphate in 370 women who developed pre-eclampsia. Logistic regression was employed to compare drug use between region and by recognised clinical indicators. Main outcome measures Usage of aspirin, antihypertensive drugs and magnesium sulphate. Results Of the women with known risk factors at trial entry, 24% (569/2399) received low-dose aspirin. Aspirin usage varied widely between risk groups [from 5% (19/378) in women with multiple pregnancy to 94% (50/53) in women with antiphospholipid syndrome] and between geographical regions [from 8% (20/248) to 49% (95/193)]. Three hundred and seventy women developed pre-eclampsia, 52% ( n = 193) of whom received new or additional antihypertensives after 20 weeks of gestation; 34% (77/224) with a maximum recorded systolic blood pressure of ≥160 mmHg in the second half of pregnancy did not receive antihypertensive treatment; 17% (62/370) of women with pre-eclampsia received magnesium sulphate prophylactically. Conclusions Prophylactic and treatment regimes for pre-eclampsia in the UK vary by region and risk group. [ABSTRACT FROM AUTHOR]

Prospective contemporaneous data on the outcome of pregnancies in women with chronic hypertension are sparse. Indices of maternal and perinatal morbidity and mortality were determined in 822 women with chronic hypertension with data prospectively collected and rigorously validated. The incidence of superimposed preeclampsia was 22% (n=180) with early-onset preeclampsia (

To assess the accuracy of an automated blood pressure device (Microlife 3BTO-A) in pregnancy and pre-eclampsia according to the British Hypertension Society (BHS) protocol. Prospective observational study. Antenatal ward and clinics at Guy's and St Thomas' Hospital, London, UK. One hundred and five pregnant women including 35 women with non-proteinuric hypertension and 35 with pre-eclampsia. Two trained observers took nine sequential same-arm measurements from each woman. Measurements alternated between a mercury sphygmomanometer and the device. Grading criteria of the BHS protocol (A/B grade= pass; C/D grade= fail). The device passed the BHS protocol by achieving an A/B grade. It also achieved criteria of the Association for the Advancement of Medical Instrumentation for systolic and diastolic pressures respectively, in normotensive [−0.5 (5.7) mmHg;−0.07 (7.7) mmHg], non-proteinuric hypertensive [−3.3 (6.9) mmHg;−2.4 (6.6) mmHg] and pre-eclamptic pregnancy [−4.1 (6.4) mmHg;−1.3 (7.9) mmHg]. The Microlife 3BTO-A can be recommended for use in a pregnant population, including pre-eclampsia, according to the BHS protocol. [ABSTRACT FROM AUTHOR]

: ObjectiveTo evaluate the accuracy of the OMRON-MIT inflationary oscillometric device for blood pressure measurement in pregnancy and pre-eclampsia.: DesignProspective observational study, using validation methods recommended by the British Hypertension Society (BHS) and the Association for the Advancement of Medical Instrumentation (AAMI).: SettingsAntenatal clinics and ward, Guy''s Hospital, London.: PopulationNormotensive pregnant women and those diagnosed with pre-eclampsia according to the definition of the International Society for the Study of Hypertension in Pregnancy.: MethodsValidation according to BHS protocol.: Main outcome measuresProportion of readings within 5, 10 and 15 mmHg (absolute differences) between the automated device and two trained, blinded observers, according to the BHS and AAMI criteria.: ResultsThe OMRON-MIT achieved an overall BHS grade B for systolic and grade A for diastolic blood pressure measurement in both pregnancy and pre-eclampsia. The mean (SD) differences between the standard and the test device were −5 (7) mmHg for systolic and 2 (6) mmHg for diastolic blood pressure in pregnancy and −4 (6) mmHg for systolic and 2 (7) mmHg for diastolic blood pressure in pre-eclampsia. This device therefore fulfils the AAMI criteria.: ConclusionThe OMRON-MIT is the only automated oscillometric device that has proven to be accurate for blood pressure measurement in pre-eclampsia according to the BHS protocol in pregnancy. Inflationary oscillometry may correct the error associated with oscillometric devices in pre-eclampsia. [Copyright &y& Elsevier]

Abstract: Pre-eclampsia remains a significant problem in modern obstetrics, contributing to 1 in 4 very low birth weight babies. Between 2–4% of women will develop pre-eclampsia. Maternal and fetal morbidity and mortality remain a significant problem. Increasing understanding of the underlying pathophysiology has resulted in a more scientific approach to prophylaxis and prevention. Larger data sets are now being analysed, and the evidence concerning the role of aspirin and calcium in preventing pre-eclampsia is clearer. The role of anti-oxidants is also currently being elucidated. Oxidative stress is thought to be fundamental to the clinical disease. The ability to predict pre-eclampsia has significantly advanced with this improved knowledge, and it is likely that good predictive algorithms will soon be available in clinical practice. The role of combining good prediction with prevention has yet to be established, but has the potential to target health resources far more efficiently. Good prediction may also impact on tailoring antenatal care appropriately. Management of pre-eclampsia is empirical, preventing end-organ damage through timely delivery and control of fits and blood pressure, facilitated by appropriate surveillance. Risks of pulmonary complications can be limited through careful monitoring of fluid balance. Magnesium sulphate should be considered in pre-eclamptic women if there is a concern of seizures. Women given magnesium sulphate have a 58% lower risk of an eclamptic seizure (95% CI 0.4–0.71). Magnesium sulphate should be used in the context of severe pre-eclampsia and under the direction of a senior obstetrician. [Copyright &y& Elsevier]

Background: Hypertensive disorders of pregnancy contribute to 14% of all maternal deaths, the majority of which occur in low- and middle-income countries. The aim of the study was to describe the maternal and perinatal clinical outcomes of women with pre-eclampsia living in middle- and low-income countries.Methods: The study was a prospective observational study of women with pre-eclampsia (n = 1547, 42 twin pregnancies) at three South African tertiary facilities. Using stepwise logistic regression model area under the receiver operating characteristic curve (AUROC) values, the association between maternal baseline and admission characteristics and risk of adverse outcomes was evaluated. Main outcome measures were eclampsia, kidney injury and perinatal death.Results: In 1547 women with pre-eclampsia, 16 (1%) died, 147 (9.5%) had eclampsia, four (0.3%) had a stroke and 272 (17.6%) had kidney injury. Of the 1589 births, there were 332 (21.0%) perinatal deaths; of these, 281 (84.5%) were stillbirths. Of 1308 live births, 913 (70.0%) delivered <37 completed weeks and 544 (41.7%) delivered <34 weeks' gestation. Young maternal age (AUROC = 0.76, 95% confidence interval (CI) = 0.71-0.80) and low Body Mass Index BMI (AUROC 0.65, 95% CI = 0.59-0.69) were significant predictors of eclampsia. Highest systolic blood pressure had the strongest association with kidney injury, (AUROC = 0.64, 95% CI = 0.60-0.68). Early gestation at admission was most strongly associated with perinatal death (AUROC = 0.81, 95% CI = 0.77-0.84).Conclusions: The incidence of pre-eclampsia complications, perinatal death and preterm delivery in women referred to tertiary care in South Africa was much higher than reported in other low- and middle-income studies and despite access to tertiary care interventions. Teenage mothers and those with low BMI were at highest risk of eclampsia. This information could be used to inform guidelines, the research agenda and policy. [ABSTRACT FROM AUTHOR]

The author discusses the report from the Confidential Enquiries into Maternal Deaths (CMAE) which reveals that substandard care has resulted in 20 out of 22 deaths related to pre-eclampsia in Great Britain. He identifies the report as disturbing as the organization considered the death as undoubtedly avoidable. He notes that the country had experienced decrease in maternal death from pre-eclampsia only twice since 1985.

The article presents abstract related to the significance of accurate blood pressure measurement in cases of preeclampsia during child delivery. It was emphasized that the use of instruments for measuring blood pressure is important in the labor ward especially with the probable occurrence of regional blocks or the cases of preeclampsia. Likewise, the use of sub set of intra-arterial measurements confirmed inaccuracy in preeclampsia.

Pre-eclampsia is a leading cause of maternal and perinatal mortality. Evidence regarding interventions in a low-income or middle-income setting is scarce. We aimed to evaluate whether planned delivery between 34+ 0 and 36+ 6 weeks' gestation can reduce maternal mortality and morbidity without increasing perinatal complications in India and Zambia. In this parallel-group, multicentre, open-label, randomised controlled trial, we compared planned delivery versus expectant management in women with pre-eclampsia from 34+ 0 to 36+ 6 weeks' gestation. Participants were recruited from nine hospitals and referral facilities in India and Zambia and randomly assigned to planned delivery or expectant management in a 1:1 ratio by a secure web-based randomisation facility hosted by MedSciNet. Randomisation was stratified by centre and minimised by parity, single-fetus pregnancy or multi-fetal pregnancy, and gestational age. The primary maternal outcome was a composite of maternal mortality or morbidity with a superiority hypothesis. The primary perinatal outcome was a composite of one or more of: stillbirth, neonatal death, or neonatal unit admission of more than 48 h with a non-inferiority hypothesis (margin of 10% difference). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The trial was prospectively registered with ISRCTN, 10672137. The trial is closed to recruitment and all follow-up has been completed. Between Dec 19, 2019, and March 31, 2022, 565 women were enrolled. 284 women (282 women and 301 babies analysed) were allocated to planned delivery and 281 women (280 women and 300 babies analysed) were allocated to expectant management. The incidence of the primary maternal outcome was not significantly different in the planned delivery group (154 [55%]) compared with the expectant management group (168 [60%]; adjusted risk ratio [RR] 0·91, 95% CI 0·79 to 1·05). The incidence of the primary perinatal outcome by intention to treat was non-inferior in the planned delivery group (58 [19%]) compared with the expectant management group (67 [22%]; adjusted risk difference –3·39%, 90% CI –8·67 to 1·90; non-inferiority p<0·0001). The results from the per-protocol analysis were similar. There was a significant reduction in severe maternal hypertension (adjusted RR 0·83, 95% CI 0·70 to 0·99) and stillbirth (0·25, 0·07 to 0·87) associated with planned delivery. There were 12 serious adverse events in the planned delivery group and 21 in the expectant management group. Clinicians can safely offer planned delivery to women with late preterm pre-eclampsia, in a low-income or middle-income country. Planned delivery reduces stillbirth, with no increase in neonatal unit admissions or neonatal morbidity and reduces the risk of severe maternal hypertension. Planned delivery from 34 weeks' gestation should therefore be considered as an intervention to reduce pre-eclampsia associated mortality and morbidity in these settings. UK Medical Research Council and Indian Department of Biotechnology. [ABSTRACT FROM AUTHOR]

Objectives:To evaluate occurrence of adverse maternal and perinatal outcomes with different thresholds of proteinuria (300-499mg and ≥500mg/24 hours) in pre-eclamptic women, comparing outcomes against women with chronic and gestational hypertension. Design:Secondary analysis of the Vitamins in Pre-Eclampsia Trial. Setting:25 UK hospitals in ten geographical areas. Population:946 women with pre-existing risk factors for pre-eclampsia. Methods:Women with pre-eclampsia and proteinuria 300-499mg/24h (PE300, referent group, n=60) or proteinuria ≥500 mg/24h (PE500, n=161) were compared with two groups of non-proteinuric women with chronic hypertension (CHT, n=615) or gestational hypertension (GH, n=110). Main Outcome Measures:Maternal: progression to severe hypertension. Perinatal: small for gestational age (SGA) <5th centile, gestation at delivery. Results:Severe hypertension occurred more frequently in PE500 (35%) and PE300 (27%) than CHT (5.9%; P≤0.01) and GH (10%; p≤0.001). Gestation at delivery was earlier in PE500 (33.2w) than PE300 (37.3w; P≤0.001), and later in CHT (38.3w; P≤0.05) and GH (39.1w; P≤0.001). SGA infants were more frequent in PE300 (32%) than in CHT (13.3%; P≤0.001) and GH (16.5%; P≤0.05). Women in PE500 were more likely to have a caesarean section than PE300 (78% vs. 48%; P≤0.001), and to receive magnesium sulphate (17% vs. 1.7%, P≤0.05). Conclusion:Women with PE300 have complication rates above those of women managed as out-patients (GH and CHT), meriting closer surveillance and confirming 300 mg/d as an appropriate threshold for determining in-patient management. Adverse perinatal outcomes are higher still in women with PE500. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to assess recurrence rates of preeclampsia and neonatal outcomes in women with a history of preeclampsia that required preterm delivery. Study Design: Five hundred women with previous preeclampsia that required delivery at <37 weeks'' gestation were followed prospectively. Results: Preeclampsia reoccurred in 117 women (23%). Predictive factors included black (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.16–4.53) or Asian (OR, 2.98; 95% CI, 1.33–6.59) ethnicity, enrollment systolic blood pressure of >130 mm Hg (OR, 2.89; 95% CI, 1.52–5.50), current antihypertensive use (OR, 6.39; 95% CI, 2.38–17.16), and proteinuria of ≥2+ on enrollment urinalysis (OR, 12.35; 95% CI, 3.45–44.21). Women who previously delivered at <34 weeks'' gestation were more likely to deliver preterm again (29% vs 17%; relative risk, 1.69; 95% CI, 1.19–2.40) than were those women with previous delivery between 34 and 37 weeks'' gestation. Conclusion: Although this study confirms that women with previous preeclampsia that required early delivery are at high risk of the development of preeclampsia, the study identifies risk factors for recurrence and illustrates that women with previous preeclampsia are at greater risk of adverse neonatal outcome. [Copyright &y& Elsevier]

Objective: We sought to investigate pregnancy outcome and biomarkers of oxidative stress in nulliparous obese pregnant women. Study Design: Pregnancy outcome and blood biomarkers were assessed prospectively in 385 obese nulliparous women from the placebo arm of a randomized controlled trial. Results: Body mass index was associated with higher rates of preeclampsia (PE) (P = .010) and cesarean section (P = .016). In all, 18.8% of infants were small for gestational age (< 10th adjusted birthweight centile), 13.4% were large for gestational age (> 90th centile), and 11.9% were preterm. The plasma ascorbic acid concentration was inversely related to small-for-gestational-age delivery (P < .025), and increased plasma triglyceride concentrations with later PE (P < .0001). Plasma uric acid concentration (P = .043) and the γ- tocopherol:α-tocopherol ratio (P = .023) were related to body mass index. Conclusion: A previously unreported risk of fetal growth restriction associated with reduced plasma ascorbic acid concentration was identified in nulliparous obese women. The high incidence of PE and preterm birth were unrelated to oxidative stress markers. [Copyright &y& Elsevier]

The article cites a research study, which revealed that antiplatelet agents, particularly aspirin reduces the incidence of pre-eclampsia in women at risk. The study led the researchers to conclude that in pregnant women at risk, prophylactic use of antiplatelet agents is effective for reducing the risk of pre-eclampsia and delivery before 37 weeks of gestation. The study suggested that the clinical value of agents such as aspirin increase considerably in higher risk women and the numbers needed to treat reduce considerably. Routine prescription of low dose aspirin can be justified in such women.

Abstract: Control of vascular resistance and blood flow in the fetoplacental circulation is incompletely understood. Reactive oxygen species (ROS), physiological and pathophysiological regulators of vascular tone, are elevated in preeclampsia (PE), a disease of pregnancy characterized by increased fetoplacental vascular resistance. We tested the hypothesis that ROS modulate vascular reactivity in placental chorionic plate arteries. Wire myography was used to examine (1) the effects of acute exposure to ROS on arterial function in normal pregnancy and (2) the effects of maternal antioxidant supplementation on arterial reactivity in women at high risk for PE participating in the Vitamins in Pre-eclampsia (VIP) trial. ROS generated by xanthine plus xanthine oxidase enhanced basal tension, vasoconstriction in response to the thromboxane mimetic U46619, and relaxation in response to sodium nitroprusside. Hydrogen peroxide and peroxynitrite increased basal tone and relaxed preconstricted arteries (U44619), respectively. In women at risk for PE, chorionic plate artery constriction in response to U46619 was greater in the women receiving placebo compared to the women supplemented with the antioxidant vitamins C and E. ROS may regulate fetoplacental vascular resistance and blood flow in the short term, and chronic exposure to raised ROS could contribute to elevated fetoplacental vascular resistance in PE and fetal growth restriction (FGR). [Copyright &y& Elsevier]

Inactivation of glucose-6-phosphate dehydrogenase (G6PD) may contribute to vascular dysfunction in preeclampsia, and oxidative stress has been implicated in the pathogenesis of this disease. We have compared the susceptibility of erythrocytes and human umbilical vein endothelial cells (HUVEC) to oxidative stress in women with normotensive or preeclamptic pregnancies. The redox status of erythrocytes was also correlated with neutrophil-mediated superoxide (O2・- ) production in women recruited to the “Vitamins in Preeclampsia” (VIP) trial. Erythrocytes and HUVEC from women with preeclampsia demonstrated impaired redox regulation and diminished response to glucose, detectable at 14–20 weeks gestation prior to onset of the clinical disease. Hexokinase and G6PD activities were decreased in erythrocytes and G6PD activity was decreased in HUVEC from preeclamptic pregnancies. Phorbol-ester-stimulated O2・- was enhanced in preeclamptic neutrophils. Impaired redox regulation in erythrocytes and HUVEC in preeclampsia may be due to diminished hexokinase and G6PD activities resulting from increased release of reactive oxygen species from activated neutrophils. Our findings provide the first evidence that decreased G6PD activity in preeclampsia is associated with impaired redox regulation in erythrocytes and fetal endothelial cells. The deficiency in G6PD in preeclampsia potentially accounts for the lack of protection against oxidative stress afforded by antioxidant vitamin C/E supplementation in the VIP trial. [Copyright &y& Elsevier]

Objective To estimate the prevalence and prognosis of proteinuria at enrolment in the 27 intervention clusters of the Community-Level Interventions for Pre-eclampsia cluster randomized trials. Methods We identified pregnant women eligible for inclusion in the trials in their communities in four countries (2013-2017). We included women who delivered by trial end and received an intervention antenatal care visit. The intervention was a community health worker providing supplementary hypertension-oriented care, including proteinuria assessment by visual assessment of urinary dipstick at the first visit and all subsequent visits when hypertension was detected. In a multilevel regression model, we compared baseline prevalence of proteinuria (≥ 1+ or ≥ 2+) across countries. We compared the incidence of subsequent complications by baseline proteinuria. Findings Baseline proteinuria was detected in less than 5% of eligible pregnancies in each country (India: 234/6120; Mozambique: 94/4234; Nigeria: 286/7004; Pakistan: 315/10 885), almost always with normotension (India: 225/234; Mozambique: 93/94; Nigeria: 241/286; Pakistan: 264/315). There was no consistent relationship between baseline proteinuria (either ≥ 1+ or ≥ 2+) and progression to hypertension, maternal mortality or morbidity, birth at < 37 weeks, caesarean section delivery or perinatal mortality or morbidity. If proteinuria testing were restricted to women with hypertension, we projected annual cost savings of 153 223 981 United States dollars (US$) in India, US$ 9 055 286 in Mozambique, US$ 53 181 933 in Nigeria and US$ 38 828 746 in Pakistan. Conclusion Our findings question the recommendations to routinely evaluate proteinuria at first assessment in pregnancy. Restricting proteinuria testing to pregnant women with hypertension has the potential to save resources. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate 47 biomarkers (selected from the current medical literature), in isolation or in combination with placental growth factor (PlGF), to determine the need for delivery within 14 days, in women presenting with suspected preterm preeclampsia.Methods: In a prospective, multicenter observational study, 47 biomarkers were measured in 423 women presenting with suspected preterm preeclampsia (in two prespecified groups: group 1 at less than 35 weeks of gestation and group 2 presenting between 35 0/7 and 36 6/7 weeks of gestation) to evaluate their ability to determine the primary endpoint: preeclampsia requiring delivery within 14 days. Using factor analysis and stepwise logistic regression, we sought one or more additional biomarkers for optimal determination of the primary endpoint.Results: In women presenting at less than 35 weeks of gestation (n=286), the best performing combination of PlGF, podocalyxin, endoglin, procalcitonin (receiver operating curve [ROC] area 0.90, 95% confidence interval [CI] 0.86-0.93) was not statistically better than PlGF alone (ROC 0.87, 95% CI 0.83-0.92; P=.43) for preeclampsia requiring delivery within 14 days. Two other single markers had test performance that was not significantly different to PlGF (soluble fms-like tyrosine kinase-1 [sFlt-1] ROC 0.83, 95% CI 0.78-0.88; endoglin ROC 0.83, 95% CI 0.79-0.88). Similar findings were found in women presenting between 35 0/7 and 36 6/7 weeks of gestation (n=137): ROC for PlGF alone 0.75 (95% CI 0.67-0.83); ROC for PlGF, cystatin, pregnancy-associated plasma protein A in combination 0.81 (95% CI 0.74-0.88; P=.40).Conclusion: This study supports the growing body of evidence that a single angiogenesis-related biomarker (PlGF, sFlt-1, or endoglin) alone represents a useful diagnostic test for women presenting with suspected preterm preeclampsia. [ABSTRACT FROM AUTHOR]

Background--Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (P1GF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results--In a prospective multicenter study, we studied the diagnostic accuracy of low plasma P1GF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks' gestation (and up to 41 weeks' gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks' gestation, P1GF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89-0.99) and negative predictive value (0.98; 0.93-0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48-0.61). Area under the receiver operating characteristic curve for low P1GF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58-0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions--In women presenting before 35 weeks' gestation with suspected preeclampsia, low P1GF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to a study by Rumbold et al, published in the April 27, 2006 issue, on the effect of vitamins C and E supplementation on the prevention of preeclampsia.

BackgroundOxidative stress has been implicated in the pathophysiology of pre-eclampsia. This randomised controlled trial investigated the effect of supplementation with vitamins C and E in women at increased risk of the disorder on plasma markers of vascular endothelial activation and placental insufficiency and the occurrence of pre-eclampsia.Methods283 women were identified as being at increased risk of pre-eclampsia by abnormal two-stage uterine-artery doppler analysis or a previous history of the disorder and were randomly assigned vitamin C (1000 mg/day) and vitamin E (400 IU/day) or placebo at 16-22 weeks' gestation. Plasma markers of endothelial activation (plasminogen-activator inhibitor 1 [PAI-1]) and placental dysfunction (PAI-2) were measured every month until delivery. Pre-eclampsia was assessed by the development of proteinuric hypertension. Analyses were done by intention to treat, and in the cohort who completed the study.FindingsSupplementation with vitamins C and E was associated with a 21% decrease in the PAI-1/PAI-2 ratio during gestation (95% CI 4-35, p=0.015). In the intention-to-treat cohort, pre-eclampsia occurred in 24 (17%) of 142 women in the placebo group and 11 (8%) of 141 in the vitamin group (adjusted odds ratio 0.39 [0.17-0.90], p=0.02). In the cohort who completed the study (81 placebo group, 79 vitamin group), the odds ratio for pre-eclampsia was 0.24 (0.08-0.70, p=0.002).InterpretationSupplementation with vitamins C and E may be beneficial in the prevention of pre-eclampsia in women at increased risk of the disease. Multicentre trials are needed to show whether vitamin supplementation affects the occurrence of pre-eclampsia in low-risk women and to confirm our results in larger groups of high-risk women from different populations. [ABSTRACT FROM AUTHOR]

While we believe that pre-eclampsia matters-because it remains a leading cause of maternal and perinatal morbidity and mortality worldwide-we are convinced that the time has come to look beyond single clinical entities (e.g. pre-eclampsia, postpartum hemorrhage, obstetric sepsis) and to look for an integrated approach that will provide evidence-based personalized care to women wherever they encounter the health system. Accurate outcome prediction models are a powerful way to identify individuals at incrementally increased (and decreased) risks associated with a given condition. Integrating models with decision algorithms into mobile health (mHealth) applications could support community and first level facility healthcare providers to identify those women, fetuses, and newborns most at need of facility-based care, and to initiate lifesaving interventions in their communities prior to transportation. In our opinion, this offers the greatest opportunity to provide distributed individualized care at scale, and soon. [ABSTRACT FROM AUTHOR]