Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands : a national cohort study

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Optimal treatment for women with acute hypertension in pregnancy; a randomized trial comparing intravenous labetalol versus nicardipine

Objectives: Blood pressure control in severe hypertension of pregnancy is crucial for mother and neonate. In absence of evidence, guidelines recommend either intravenous labetalol or nicardipine. We compared the effectiveness and safety of these two drugs in women with severe hypertension in pregnancy. Study design: We performed an open label randomized controlled trial. Women with a singleton pregnancy complicated by severe hypertension (systolic ≥ 160 mmHg and/or diastolic ≥ 110 mmHg) requiring intravenous antihypertensive treatment were randomized to intravenous labetalol or intravenous nicardipine. The primary outcome was a composite adverse neonatal outcome defined as severe Respiratory Distress Syndrome (RDS), Broncho Pulmonary Dysplasia (BPD), Intraventricular Hemorrhage (IVH) IIB or worse, Necrotizing Enterocolitis (NEC), or perinatal death defined as fetal death or neonatal death before discharge from the neonatal intensive care unit (NICU). Based on a power analysis, we estimated that 472 women (236 per group) needed to be included to detect a difference of 15% in the primary outcome with 90% power. The study was halted prematurely at 30 inclusions because of slow recruitment and trial fatigue. Results: Between August 2018 and April 2022, we randomized 30 women of which 16 were allocated to intravenous nicardipine and 14 to intravenous labetalol. The composite adverse neonatal outcome was not significantly different between the two groups (25 % versus 43 % OR 0.28 (95 % CI 0.05–1.43), p = 0.12)). Respiratory distress syndrome occurred more often in the labetalol group than in the nicardipine group (42.9 % versus 12.5 %). Neonatal hypoglycemia occurred more often in the nicardipine group than in the labetalol group (31 % versus 7 %). Time until blood pressure control was faster in women treated with nicardipine than in women treated with labetalol (45 (15–150 min vs. 120 (60–127,5) min). Conclusion: In our prematurely halted small RCT, we were unable to provide evidence for the optimal choice of treatment for severe hypertension to improve neonatal outcome and/or to obtain faster blood pressure control. Differences in Respiratory distress syndrome and neonatal hypoglycemia between the groups might be the result of coincidental finding due to the small groups included in the study. A larger randomized trial would be needed to determine the safest and most efficacious (intravenous) therapy for severe hypertension in pregnancy. This study emphasizes the challenges of conducting a RCT for the optimal treatment for these women

10-Year cardiovascular event risks for women who experienced hypertensive disorders in late pregnancy: the HyRAS study

ABSTRACT: BACKGROUND: Cardiovascular disease is the cause of death in 32% of women in the Netherlands. Prediction of an individual's risk for cardiovascular disease is difficult, in particular in younger women due to low sensitive and specific tests for these women. 10% to 15% of all pregnancies are complicated by hypertensive disorders, the vast majority of which develop only after 36 weeks of gestation. Preeclampsia and cardiovascular disease in later life show both features of "the metabolic syndrome" and atherosclerosis. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar vascular risk factors. Vascular damage occurring during preeclampsia or gestational hypertension may contribute to the development of future cardiovascular disease, or is already present before pregnancy. At present clinicians do not systematically aim at the possible cardiovascular consequences in later life after a hypertensive pregnancy disorder at term. However, screening for risk factors after preeclampsia or gestational hypertension at term may give insight into an individual's cardiovascular risk profile. METHODS: Women with a history of preeclampsia or gestational hypertension will be invited to participate in a cohort study 2,5 years after delivery. Participants will be screened for established modifiable cardiovascular risk indicators. The primary outcome is the 10-year cardiovascular event risk. Secondary outcomes include differences in cardiovascular parameters, SNP's in glucose metabolism, and neonatal outcome. DISCUSSION: This study will provide evidence on the potential health gains of a modifiable cardiovascular risk factor screening program for women whose pregnancy was complicated by hypertension or preeclampsia. The calculation of individual 10-year cardiovascular event risks will allow identification of those women who will benefit from primary prevention by tailored interventions, at a relatively young age. Trail registration The HYPITAT trial is registered in the clinical trial register as ISRCTN08132825

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study) : A multicentre, randomised, double-blinded, placebo-controlled trial

Funding: MdB, LV, TN, BM, MO and CdG received funding from ZonMw, The Dutch Organisation for Health Research and Development (grant number 836041006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

SUGAR-DIP trial: Oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial

Introduction In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. Methods The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. Ethics and dissemination The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior

Objective: To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. Methods: Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as chance of health or risk of disease. Results: 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. Conclusion: Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence

Reduction of cardiovascular risk after preeclampsia: the role of framing and perceived probability in modifying behavior

Objective: To reduce cardiovascular risk after preeclampsia, we investigated the effect of framing, the perceived probability and its interaction, on the willingness to modify behavior. Methods: Participants scored their willingness to modify behavior on two cases with different probabilities of developing cardiovascular disease. Both cases were either presented as chance of health or risk of disease. Results: 165 questionnaires were analyzed. ANOVA revealed a significant effect of probability, non-significant effect of framing and a non-significant interaction between probability and framing. Conclusion: Perceived probability influences willingness to modify behavior to reduce cardiovascular risk after preeclampsia; framing and the interaction was not of influence

Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study

Background: Hypertensive disorders of pregnancy are associated with cardiovascular disease later in life. Given that hypertensive disorders of pregnancy often occur at a relatively young age, there might be an opportunity to use preventive measures to reduce the risk of early cardiovascular disease and mortality. The aim of this study was to assess the risk of cardiovascular mortality in women after a hypertensive disorder of pregnancy. Methods: In this population-based cohort study, the Netherlands Perinatal Registry (PRN) and the national death registry at the Dutch Central Bureau for Statistics were linked. We analysed women in the Netherlands with a first birth during 1995–2015 to determine the association between cardiovascular mortality and hypertensive disorders of pregnancy (based on recorded diastolic blood pressure or proteinuria, or both). We analysed the association between the highest diastolic blood pressure measured in pregnancy and cardiovascular mortality and constructed survival curves to assess cardiovascular mortality after hypertensive disorders of pregnancy, specifically pre-eclampsia and gestational hypertension. To differentiate between the severity of hypertensive disorders of pregnancy, cardiovascular mortality was assessed in women with a combination of hypertensive disorders of pregnancy with preterm birth (gestational age <37 weeks) and growth restriction (birthweight in the 10th percentile or less). All hazard ratios (HRs)were adjusted for maternal age. Findings: Between Jan 1, 1995, and Dec 31, 2015, the PRN contained 2 462 931 deliveries and 1 625 246 women. In 1 243 890 women data on their first pregnancy were available and were included in this analysis after linkage, with a median follow-up time of 11·2 years (IQR 6·1–16·3). 259 177 (20·8%) women had hypertensive disorders of pregnancy, and of these 45 482 (3·7%) women had pre-eclampsia and 213 695 (17·2%) women had gestational hypertension; 984 713 (79·2%) women did not develop hypertension in their first pregnancy. Compared with women without hypertensive disorders of pregnancy, the risk of death from any cause was higher in women who had hypertensive disorders (HR 1·30 [95% CI 1·23–1·37], p<0·001), pre-eclampsia (1·65 [1·48–1·83]; p<0·0001), and gestational hypertension (1·23 [1·16–1·30]; p<0·0001). Those women with pre-eclampsia had a higher risk of cardiovascular mortality compared with those without any hypertensive disorders of pregnancy (adjusted HR 3·39 [95% CI 2·67–4·29]), as did those with gestational hypertension (2·22 [1·91–2·57]). For women with a history of hypertensive disorders of pregnancy combined with preterm birth (gestational age <37 weeks) and birthweight in the 10th percentile or less, the adjusted HR for cardiovascular mortality was 6·43 (95% CI 4·36–9·47), compared with women without a hypertensive disorder of pregnancy. The highest diastolic blood pressure measured during pregnancy was the strongest risk factor for cardiovascular mortality (for 80–89 mm Hg: adjusted HR 1·47 [95% CI 1·00–2·17]; for 130 mm Hg and higher: 14·70 [7·31–29·52]). Interpretation: Women with a history of hypertensive disorders of pregnancy have a risk of cardiovascular mortality that is 2–3 times higher than that of women with normal blood pressure during pregnancy. The highest measured diastolic blood pressure during pregnancy is an important predictor for cardiovascular mortality later in life; therefore, women who have hypertensive disorders of pregnancy should be given personalised cardiovascular follow-up plans to reduce their risk of cardiovascular mortality. Funding: None

Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands: a national cohort study

BACKGROUND: Hypertensive disorders of pregnancy are associated with cardiovascular disease later in life. Given that hypertensive disorders of pregnancy often occur at a relatively young age, there might be an opportunity to use preventive measures to reduce the risk of early cardiovascular disease and mortality. The aim of this study was to assess the risk of cardiovascular mortality in women after a hypertensive disorder of pregnancy. METHODS: In this population-based cohort study, the Netherlands Perinatal Registry (PRN) and the national death registry at the Dutch Central Bureau for Statistics were linked. We analysed women in the Netherlands with a first birth during 1995-2015 to determine the association between cardiovascular mortality and hypertensive disorders of pregnancy (based on recorded diastolic blood pressure or proteinuria, or both). We analysed the association between the highest diastolic blood pressure measured in pregnancy and cardiovascular mortality and constructed survival curves to assess cardiovascular mortality after hypertensive disorders of pregnancy, specifically pre-eclampsia and gestational hypertension. To differentiate between the severity of hypertensive disorders of pregnancy, cardiovascular mortality was assessed in women with a combination of hypertensive disorders of pregnancy with preterm birth (gestational age <37 weeks) and growth restriction (birthweight in the 10th percentile or less). All hazard ratios (HRs)were adjusted for maternal age. FINDINGS: Between Jan 1, 1995, and Dec 31, 2015, the PRN contained 2 462 931 deliveries and 1 625 246 women. In 1 243 890 women data on their first pregnancy were available and were included in this analysis after linkage, with a median follow-up time of 11·2 years (IQR 6·1-16·3). 259 177 (20·8%) women had hypertensive disorders of pregnancy, and of these 45 482 (3·7%) women had pre-eclampsia and 213 695 (17·2%) women had gestational hypertension; 984 713 (79·2%) women did not develop hypertension in their first pregnancy. Compared with women without hypertensive disorders of pregnancy, the risk of death from any cause was higher in women who had hypertensive disorders (HR 1·30 [95% CI 1·23-1·37], p<0·001), pre-eclampsia (1·65 [1·48-1·83]; p<0·0001), and gestational hypertension (1·23 [1·16-1·30]; p<0·0001). Those women with pre-eclampsia had a higher risk of cardiovascular mortality compared with those without any hypertensive disorders of pregnancy (adjusted HR 3·39 [95% CI 2·67-4·29]), as did those with gestational hypertension (2·22 [1·91-2·57]). For women with a history of hypertensive disorders of pregnancy combined with preterm birth (gestational age <37 weeks) and birthweight in the 10th percentile or less, the adjusted HR for cardiovascular mortality was 6·43 (95% CI 4·36-9·47), compared with women without a hypertensive disorder of pregnancy. The highest diastolic blood pressure measured during pregnancy was the strongest risk factor for cardiovascular mortality (for 80-89 mm Hg: adjusted HR 1·47 [95% CI 1·00-2·17]; for 130 mm Hg and higher: 14·70 [7·31-29·52]). INTERPRETATION: Women with a history of hypertensive disorders of pregnancy have a risk of cardiovascular mortality that is 2-3 times higher than that of women with normal blood pressure during pregnancy. The highest measured diastolic blood pressure during pregnancy is an important predictor for cardiovascular mortality later in life; therefore, women who have hypertensive disorders of pregnancy should be given personalised cardiovascular follow-up plans to reduce their risk of cardiovascular mortality. FUNDING: None