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Objective: Hypertensive disorders affect 3-10% of pregnancies. Delayed delivery carries maternal risks, while early delivery increases fetal risk, so appropriate timing is important. The aim of this study was to compare immediate delivery with expectant management for prevention of adverse maternal and neonatal outcomes in women with hypertensive disease in pregnancy., Methods: CENTRAL, PubMed, MEDLINE and ClinicalTrials.gov were searched for randomized controlled trials comparing immediate delivery to expectant management in women presenting with gestational hypertension or pre-eclampsia without severe features from 34 weeks of gestation. The primary neonatal outcome was respiratory distress syndrome (RDS) and the primary maternal outcome was a composite of HELLP syndrome and eclampsia. The PRISMA-IPD guideline was followed and a two-stage meta-analysis approach was used. Relative risks (RR) and numbers needed to treat or harm (NNT/NNH) with 95% CI were calculated to evaluate the effect of the intervention., Results: Main outcomes were available for 1724 eligible women. Compared with expectant management, immediate delivery reduced the composite risk of HELLP syndrome and eclampsia in all women (0.8% vs 2.8%; RR, 0.33 (95% CI, 0.15-0.73); I 2  = 0%; NNT, 51 (95% CI, 31.1-139.3)) as well as in the pre-eclampsia subgroup (1.1% vs 3.5%; RR, 0.39 (95% CI, 0.15-0.98); I 2  = 0%). Immediate delivery increased RDS risk (3.4% vs 1.6%; RR, 1.94 (95% CI 1.05-3.6); I 2  = 24%; NNH, 58 (95% CI, 31.1-363.1)), but depended upon gestational age. Immediate delivery in the 35 th week of gestation increased RDS risk (5.1% vs 0.6%; RR, 5.5 (95% CI, 1.0-29.6); I 2  = 0%), but immediate delivery in the 36 th week did not (1.5% vs 0.4%; RR, 3.4 (95% CI, 0.4-30.3); I 2 not applicable)., Conclusion: In women with hypertension in pregnancy, immediate delivery reduces the risk of maternal complications, whilst the effect on the neonate depends on gestational age. Specifically, women with a-priori higher risk of progression to HELLP, such as those already presenting with pre-eclampsia instead of gestational hypertension, were shown to benefit from earlier delivery. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: This study assessed the external validity of all published first trimester prediction models for the risk of preeclampsia (PE) based on routinely collected maternal predictors. Moreover, the potential utility of the best-performing models in clinical practice was evaluated., Material and Methods: Ten prediction models were systematically selected from the literature. We performed a multicenter prospective cohort study in the Netherlands between July 1, 2013, and December 31, 2015. Eligible pregnant women completed a web-based questionnaire before 16 weeks' gestation. The outcome PE was established using postpartum questionnaires and medical records. Predictive performance of each model was assessed by means of discrimination (c-statistic) and a calibration plot. Clinical usefulness was evaluated by means of decision curve analysis and by calculating the potential impact at different risk thresholds., Results: The validation cohort contained 2,614 women of whom 76 developed PE (2.9%). Five models showed moderate discriminative performance with c-statistics ranging from 0.73 to 0.77. Adequate calibration was obtained after refitting. The best models were clinically useful over a small range of predicted probabilities., Discussion: Five of the ten included first trimester prediction models for PE showed moderate predictive performance. The best models may provide more benefit compared to risk selection as used in current guidelines., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women., Methods: We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792)., Findings: Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred., Interpretation: For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered., Funding: ZonMw., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes., Study Design: We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI., Results: Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1)., Conclusion: Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The objective of the study was to determine the neonatal morbidity in late preterm infants born from mothers with a hypertensive disorder., Study Design: Data were obtained from the national Perinatal Registry in The Netherlands on women who delivered between 34(+0) and 36(+6) weeks with gestational hypertension (n = 4316), preeclampsia (n = 1864), and normotensive controls (n = 20,749)., Results: Children from mothers with preeclampsia had an increased risk for admission to the neonatal intensive care unit compared with children from normotensive mothers (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2). A cesarean delivery and decreasing gestational age were independent risk factors for neonatal respiratory morbidity. Gestational hypertension or preeclampsia reduced the risk of respiratory distress syndrome compared with the control group (OR, 0.81; 95% CI, 0.64-1.0 and OR, 0.69; 95% CI, 0.49-0.96, respectively)., Conclusion: Neonatal morbidity in the late preterm period is considerable. Hypertensive disorders appear to protect for neonatal respiratory morbidity, but higher rates of cesarean section diminish this protective effect., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Objective: To develop a model to identify women at very low risk of recurrent early-onset preeclampsia., Methods: We enrolled 407 women who had experienced early-onset preeclampsia in their first pregnancy, resulting in a delivery before 34 weeks' gestation. Preeclampsia was defined as hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) after 20 weeks' gestation with de novo proteinuria (≥300 mg urinary protein excretion/day). Based on the previous published evidence and expert opinion, 5 predictors (gestational age at previous birth, prior small-for-gestational-age newborn, fasting blood glucose, body mass index, and hypertension) were entered in a logistic regression model. Discrimination and calibration were evaluated after adjusting for overfitting by bootstrapping techniques., Results: Early-onset disease recurred in 28 (6.9%) of 407 women. The area under the receiver operating characteristic (ROC) curve of the model was 0.65 (95% CI: 0.56-0.74). Calibration was good, indicated by a nonsignificant Hosmer-Lemeshow test (P = .11). Using a predicted absolute risk threshold of, for example, 4.6% (ie, women identified with an estimated risk either above or below 4.6%), the sensitivity was 100%, with a specificity of 26%. In such a strategy, no women who developed preeclampsia were missed, while 98 of the 407 women would be regarded as low risk of recurrent early-onset preeclampsia, not necessarily requiring intensified antenatal care., Conclusion: Our model may be helpful in the identification of women at very low risk of recurrent early-onset preeclampsia. Before widespread application, our model should be validated in other populations.

Pre-eclampsia is associated with increased maternal and perinatal mortality and morbidity. Early recognition of women at risk of pre-eclampsia will enable the identification of high-risk women who may benefit from enhanced surveillance and prophylaxis. In this chapter, we summarise the accuracy of various tests used to predict the onset of pre-eclampsia and the effectiveness of preventative treatment. The tests used to predict pre-eclampsia include clinical history, examination findings, laboratory and haemodynamic tests. In general, tests in early pregnancy for predicting later development of pre-eclampsia have better specificity than sensitivity, as Body Mass Index greater than 34, alpha-fetoprotein, fibronectin and uterine artery Doppler (bilateral notching) all have specificities above 90%. Only uterine artery Doppler resistance index and combinations of indices have a sensitivity of over 60%. Test such as kallikreinuria not used in clinical practice, has shown high sensitivity above 80%, without compromising specificity, and require further investigation. None of the tests are sufficiently accurate to recommend them for routine use in clinical practice. The various treatment options for preventing pre-eclampsia include pharmacological agents, dietary supplementation and lifestyle modification. Antiplatelet agents, primarily low-dose aspirin, reduce the risk of pre-eclampsia by 10% (RR 0.90, 95% CI 0.84 to 0.97). Calcium effectively prevents pre-eclampsia (RR 0.45, 95% CI 0.31 to 0.65); the beneficial effect being observed in the high-risk group (RR 0.22; 95% CI 0.12 to 0.42) and in the group with low nutritional calcium intake (RR 0.36, 95% CI 0.20 to 0.65). Pharmacological agents, such as low molecular weight heparin, progesterone, nitric oxide donors, anti-hypertensive medication and diuretics are not effective in preventing pre-eclampsia. Dietary supplements, such as magnesium, anti-oxidants, marine oils and folic acid, do not reduce the incidence of pre-eclampsia. Evidence is lacking to support lifestyle preventative interventions for pre-eclampsia, such as rest, exercise and reduced dietary salt intake., (Copyright © 2011. Published by Elsevier Ltd.)

Background: Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term., Methods/design: Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised., Discussion: This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity., Trial Registration: NTR1792 CLINICAL TRIAL REGISTRATION: http://www.trialregister.nl.

Objective: The aim of this study was to report outcomes of the subsequent pregnancy after early-onset pre-eclampsia in a first pregnancy (index), and to evaluate the potential risk factors for recurrence of pre-eclampsia and preterm delivery., Design: We performed a retrospective cohort study of all women who developed early-onset pre-eclampsia (delivery before 34 weeks of gestation) in their first pregnancy between January 1996 and December 2004 in two perinatal centres with regional function. All patients were included consecutively. Information was retrieved on the course of subsequent pregnancies., Setting: Two tertiary centres with regional function., Population: Women with a delivery under 34 weeks due to a hypertensive disorder (N=380)., Main Outcome Measures: We determined the absolute risk of recurrence of an adverse outcome, defined as a hypertensive complication resulting in delivery before 34 weeks of gestation. The available clinical parameters were evaluated as predictors for recurrence using logistic regression analysis., Results: We identified 380 patients, of whom 46 were lost to follow-up. In total, 123 patients refrained from subsequent pregnancy (79 [64%] from fear of recurrence). Of the 211 patients with a subsequent pregnancy, 36 (17%, 95% CI 12-22%) had a recurrent delivery before 34 weeks of gestation, 30 (14%, 95% CI 9.5-19%) delivered between 34 and 37 weeks of gestation, and 145 (69%, 95% CI 62-75%) delivered later than 37 weeks of gestation. Of this last group, only 67 (32%, 95% CI 25-38%) pregnancies were completely uneventful. Chronic hypertension, maximum diastolic blood pressure, caesarean delivery and level of 24-h proteinuria were independent predictors for an adverse pregnancy outcome., Conclusions: Women that had early severe pre-eclampsia in their first pregnancy have a 17% risk of recurrence, with a delivery before 34 weeks of gestation. Only 32% had a completely uneventful pregnancy., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Please cite this paper as: van Oostwaard M, Langenveld J, Bijloo R, Wong K, Scholten I, Loix S, Hukkelhoven C, Vergouwe Y, Papatsonis D, Mol B, Ganzevoort W. Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37 weeks of gestation: a retrospective cohort study. BJOG 2012;119:840-847. Objective To assess the recurrence risk of late-preterm hypertensive disease of pregnancy, and to determine whether potential risk factors are predictive. Design Retrospective cohort study. Setting Three secondary and three tertiary care hospitals in the Netherlands. Population We identified women with a hypertensive disorder in the index pregnancy and delivery at 34-37 weeks of gestation, between January 2000 and December 2002. Methods Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. An adverse outcome was defined as the recurrence of a hypertensive disorder in the next subsequent pregnancy. Main outcome measures Absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive for adverse outcome. Results We identified 425 women who matched the criteria, of whom 351 could be contacted. Of these women, 189 (54%) had had a subsequent pregnancy. Hypertensive disorders recurred in 96 (51%, 95% CI 43-58%) women, of whom 17 (9%, 95% CI 5-14%) delivered again before 37 weeks of gestation. Chronic hypertension and maternal age were the strongest predictors for recurrence. Women undergoing recurrence had a nine-fold chance of developing chronic hypertension (37% versus 6%, OR 8.7, 95% CI 3.3-23). Conclusions Women with hypertensive disorders and late-preterm delivery have a 50% chance of recurrence, but only a 9% chance of recurrence resulting in delivery before 37 weeks of gestation. Women with chronic hypertension are prone to develop recurrence, and women with a recurrence more often developed chronic hypertension. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Langenveld J, Buttinger A, van der Post J, Wolf H, Mol B, Ganzevoort W. Recurrence risk and prediction of a delivery under 34 weeks of gestation after a history of a severe hypertensive disorder. BJOG 2011;118:589-595. The aim of this study was to report outcomes of the subsequent pregnancy after early-onset pre-eclampsia in a first pregnancy (index), and to evaluate the potential risk factors for recurrence of pre-eclampsia and preterm delivery. We performed a retrospective cohort study of all women who developed early-onset pre-eclampsia (delivery before 34 weeks of gestation) in their first pregnancy between January 1996 and December 2004 in two perinatal centres with regional function. All patients were included consecutively. Information was retrieved on the course of subsequent pregnancies. Two tertiair centres with regional function. Women with a delivery under 34 weeks due to a hypertensive disorder (N = 380). We determined the absolute risk of recurrence of an adverse outcome, defined as a hypertensive complication resulting in delivery before 34 weeks of gestation. The available clinical parameters were evaluated as predictors for recurrence using logistic regression analysis. We identified 380 patients, of whom 46 were lost to follow-up. In total, 123 patients refrained from subsequent pregnancy (79 [64%] from fear of recurrence). Of the 211 patients with a subsequent pregnancy, 36 (17%, 95% CI 12-22%) had a recurrent delivery before 34 weeks of gestation, 30 (14%, 95% CI 9.5-19%) delivered between 34 and 37 weeks of gestation, and 145 (69%, 95% CI 62-75%) delivered later than 37 weeks of gestation. Of this last group, only 67 (32%, 95% CI 25-38%) pregnancies were completely uneventful. Chronic hypertension, maximum diastolic blood pressure, caesarean delivery and level of 24-h proteinuria were independent predictors for an adverse pregnancy outcome. Women that had early severe pre-eclampsia in their first pregnancy have a 17% risk of recurrence, with a delivery before 34 weeks of gestation. Only 32% had a completely uneventful pregnancy. [ABSTRACT FROM AUTHOR]