Patterns of Antihypertensive Medication Use in the First 2 Years Post Partum.

Importance: Women who had a hypertensive disorder of pregnancy (HDP) have a well-documented risk of chronic hypertension within a few years of delivery, but management of postpartum hypertension among these women remains inconsistent. Objective: To assess the incidence of initiation of antihypertensive medication use in the first 2 years after delivery by HDP status and antenatal antihypertensive medication use. Design, Setting, and Participants: This Danish register-based cohort study used data from women with at least 1 pregnancy lasting 20 or more gestational weeks (only the first pregnancy in the period was considered) who delivered from January 1, 1995, to December 31, 2018. Statistical analysis was conducted from October 2022 to September 2023. Exposure: Hypertensive disorders of pregnancy. Main Outcomes and Measures: Cumulative incidences and hazard ratios of initiating antihypertensive medication use within 2 years post partum (5 postpartum time intervals) by HDP status and antenatal medication use. Results: The cohort included 784 782 women, of whom 36 900 (4.7% [95% CI, 4.7%-4.8%]) had an HDP (HDP: median age at delivery, 29.1 years [IQR, 26.1-32.7 years]; no HDP: median age at delivery, 29.0 years [IQR, 25.9-32.3 years]). The 2-year cumulative incidence of initiating postpartum antihypertensive treatment ranged from 1.8% (95% CI, 1.8%-1.8%) among women who had not had HDPs to 44.1% (95% CI, 40.0%-48.2%) among women with severe preeclampsia who required antihypertensive medication during pregnancy. Most women who required postpartum antihypertensive medication after an HDP initiated use within 3 months of delivery (severe preeclampsia, 86.6% [95% CI, 84.6%-89.4%]; preeclampsia, 75.3% [95% CI, 73.8%-76.2%]; and gestational hypertension, 75.1% [95% CI, 72.9%-77.1%]). However, 13.4% (95% CI, 11.9%-14.1%) of women with severe preeclampsia, 24.7.% (95% CI, 24.0%-26.0%) of women with preeclampsia, 24.9% (95% CI, 22.5%-27.5%) of women with gestational hypertension, and 76.7% (95% CI, 76.3%-77.1%) of those without an HDP first filled a prescription for antihypertensive medication more than 3 months after delivery. Women with gestational hypertension had the highest rate of initiating medication after more than 1 year post partum, with 11.6% (95% CI, 10.0%-13.2%) starting treatment after this period. Among women who filled a prescription in the first 3 months post partum, up to 55.9% (95% CI, 46.2%-66.1%) required further prescriptions more than 3 months post partum, depending on HDP status and antenatal medication use. Conclusions and Relevance: In this cohort study of postpartum women, the incidence of initiation of postnatal antihypertensive medication use varied by HDP status, HDP severity, and antenatal antihypertensive medication use. Up to 24.9% of women initiated antihypertensive medication use more than 3 months after an HDP, with up to 11.6% initiating treatment after 1 year. Routine postpartum blood pressure monitoring might prevent diagnostic delays in initiation of antihypertensive medication use and improve cardiovascular disease prevention among women.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Update on Preeclampsia and Hypertensive Disorders of Pregnancy.

There have been recent advances in the prevention, diagnosis, and management of hypertensive disorders of pregnancy which complicate approximately 16% of pregnancies in the United States. Initiation of low-dose aspirin by 16 weeks' gestation reduces preeclampsia in high-risk women. The Food and Drug Administration approved the use of the soluble fms-like tyrosine kinase 1/placental growth factor ratio for the short-term prediction of preeclampsia. Pregnancy outcomes are improved in women with chronic hypertension when antihypertensives are initiated at a threshold blood pressure of 140/90 mm Hg. Women with prior preeclampsia have increased cardiovascular disease risk and should receive risk reduction counseling.

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

BACKGROUND: Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. METHODS: We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. RESULTS: In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. CONCLUSIONS: Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Chronic Hypertension During Pregnancy: Prevalence and Treatment in the United States, 2008-2021.

BACKGROUND: Treatment of chronic hypertension during pregnancy has been shown to reduce the risk of adverse perinatal outcomes. In this study, we examined the prevalence and treatment of chronic hypertension during pregnancy and assessed changes in these outcomes following the release of the updated 2017 hypertension guidelines of the American College of Cardiology and American Heart Association. METHODS: We analyzed the MerativeTM Marketscan® Research Database of United States commercial insurance claims from 2007 to 2021. We assessed the prevalence of chronic hypertension during pregnancy and oral antihypertensive medication use over time. We then performed interrupted time series analyses to evaluate changes in these outcomes. RESULTS: The prevalence of chronic hypertension steadily increased from 1.8% to 3.7% among 1 900 196 pregnancies between 2008 and 2021. Antihypertensive medication use among pregnant individuals with chronic hypertension was relatively stable (57%-60%) over the study period. The proportion of pregnant individuals with chronic hypertension treated with methyldopa or hydrochlorothiazide decreased (from 29% to 2% and from 11% to 5%, respectively), while the proportion treated with labetalol or nifedipine increased (from 19% to 42% and from 9% to 17%, respectively). The prevalence or treatment of chronic hypertension during pregnancy did not change following the 2017 American College of Cardiology and American Heart Association hypertension guidelines. CONCLUSIONS: The prevalence of chronic hypertension during pregnancy doubled between 2008 and 2021 in a nationwide cohort of individuals with commercial insurance. Labetalol replaced methyldopa as the most commonly used antihypertensive during pregnancy. However, only about 60% of individuals with chronic hypertension in pregnancy were treated with antihypertensive medications.

The Nitrate-Nitrite-Nitric Oxide Pathway: Potential Role in Mitigating Oxidative Stress in Hypertensive Disorders of Pregnancy.

Hypertensive diseases of pregnancy (HDPs) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDPs are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDPs. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDPs.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Hypertensive Disorders of Pregnancy.

Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.

Discharge medication delivery location and postpartum blood pressure control in patients with hypertensive disorders of pregnancy.

OBJECTIVE: This study examined whether use of bedside medication delivery (Meds to Beds, M2B) or on-campus pharmacy at discharge was associated with improved postpartum blood pressure (BP) control compared to outside pharmacy use in patients with hypertensive disorders of pregnancy (HDP). STUDY DESIGN: This was a secondary analysis of 357 patients with HDP enrolled in STAMPP-HTN (Systematic Treatment and Management of Postpartum Hypertension Program) who were discharged from delivery admission with antihypertensives between October 2018 and June 2020. Patients were grouped by discharge medication location: M2B/on-campus pharmacy (on-site) versus outside pharmacy (off-site). MAIN OUTCOME MEASURES: The primary outcome was BP values at the immediate postpartum visit. Secondary outcomes included six-week visit BP values, attendance at both visits, and readmission within six weeks. RESULTS: Median BP values were no different based on pharmacy location at immediate postpartum visit for both systolic ((135 [IQR 127, 139] on-site vs 137 [127, 145] off-site, p = 0.22) and diastolic (81 [74, 91] vs 83 [76, 92], p = 0.45) values. Similar findings were noted at six weeks. Patients who used an off-site pharmacy had higher attendance rates at the immediate postpartum visit but this difference was attenuated after adjusting for group differences (OR 0.67 [95 % CI 0.37-1.20], p = 0.18). Readmission rates were also not different between groups (12.2 % on-site vs 15.8 % off-site pharmacy, p = 0.43). CONCLUSION: In the context of a preexisting multicomponent HDP quality improvement program, on-campus pharmacy and bedside medication delivery use was not associated with additional improvement in postpartum BP control, follow-up rates, or readmission rates.

Evaluation of antihypertensives for post partum management of hypertensive disorders of pregnancy: A systematic review and meta-analysis.

BACKGROUND: There is a lack of evidence that directly shows the best antihypertensive treatment options for post partum management of the hypertensive disorders of pregnancy. Our objective was to analyze the safest and most effective antihypertensive drugs post partum for patients with hypertensive disorders of pregnancy. METHODS: PubMed, Cochrane, and MEDLINE were searched to find relevant articles published from inception to Feb 2024. We included randomized control trials, in English, featuring a population of postnatal women with hypertensive disorders of pregnancy or postpartum women with de novo hypertension with a follow-up of up to 6 months in which any antihypertensive medication was compared with Placebo or a comparison between different doses of antihypertensives was done. The statistical analyses were conducted using Review Manager with a random-effects model. RESULTS: Our analysis revealed that almost all antihypertensives are effective in treating postpartum hypertension. However, some medications had alternating roles in controlling specific outcomes. Using calcium channel blockers resulted in a faster time to sustain BP control than the control (SMD: -0.37; 95% CI: -0.73 to -0.01; P = 0.04). In contrast, using ACE inhibitors or ARBs demanded the use of other antihypertensives in contrast to all other drugs assessed (RR: 2.09; 95% CI: 1.07 to 4.07; P = 0.03). CONCLUSION: Timely management of the hypertensive disorders of pregnancy postpartum is life-saving. All the traditional antihypertensives we assessed effectively manage hypertension postpartum, thus allowing the physician to tailor the particular drug regimen according to the patient's needs and comorbidities without any hindrance.

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Hypertensive states of pregnancy.

Hypertensive disorders in pregnancy (HDP) remain a leading cause of pregnancy-related maternal and foetal morbidity and mortality worldwide, including chronic hypertension, gestational hypertension, and pre-eclampsia. Affected women and newborns also have an increased risk of cardiovascular disease later in life, independent of traditional cardiovascular disease risks. Despite these risks, recommendations for optimal diagnosis and treatment have changed little in recent decades, probably due to fear of the foetal repercussions of decreased blood pressure and possible drug toxicity. In this document we review the diagnostic criteria and classification of (HDP), as well as important aspects regarding pathophysiology and early detection that allows early identification of women at risk, with the aim of preventing both immediate and long-term consequences. Prophylactic treatment with aspirin is also reviewed early and a therapeutic approach is carried out that involves close maternal and foetal monitoring, and if necessary, the use of safe drugs in each situation. This review aims to provide an updated vision for the prevention, diagnosis, and treatment of HDP that is useful in our usual clinical practice.

Clinical Trials That Have Changed Obstetric Practice: The Chronic Hypertension and Pregnancy (CHAP) Trial.

We describe the evolution of treatment recommendations for chronic hypertension (CHTN) in pregnancy, the CHTN and pregnancy (CHAP) trial, and its impact on obstetric practice. The US multicenter CHAP trial showed that antihypertensive treatment for mild CHTN in pregnancy [blood pressures (BP)<160/105 mm Hg] to goal<140/90 mm Hg, primarily with labetalol or nifedipine compared with no treatment unless BP were severe reduced the composite risk of superimposed severe preeclampsia, indicated preterm birth <35 weeks, placental abruption, and fetal/neonatal death. As a result of this trial, professional societies in the United States recommended treatment of patients with CHTN in pregnancy to BP goal<140/90 mm Hg.

Efficacy and safety of oral and vaginal administration of misoprostol for induction of labor in high-risk obese pregnant women with hypertension or diabetes mellitus.

OBJECTIVE: This study aims to compare the safety and efficacy of misoprostol administered orally and vaginally in obese pregnant women at term with either gestational hypertension or diabetes. METHODS: A total of 264 pregnant women were enrolled and categorized into two groups based on their primary condition: hypertension (134 cases) or diabetes mellitus (130 cases) and were further divided into subgroups for misoprostol administration: orally (Oral group) or vaginally (Vaginal group). The primary outcomes measured were changes in the Bishop score following treatment, induction of labor (IOL) success rates, requirement for oxytocin augmentation, duration of labor, mode of delivery, and cesarean section rates. RESULTS: Significant enhancements in Bishop scores, decreased cesarean section rates and increased success rates of IOL were noted in both administration groups. The incidence of vaginal delivery within 24 h was significantly higher in the Vaginal group compared to the Oral group. Adverse effects, including nausea, uterine overcontraction, hyperfrequency of uterine contraction and uterine hyperstimulation without fetal heart rate deceleration, were significantly more prevalent in the Vaginal group than in the Oral group. CONCLUSION: Misoprostol administration, both orally and vaginally, proves effective for labor induction in obese pregnant women with hypertension or diabetes. However, the oral route presents a lower risk of adverse maternal and neonatal outcomes, suggesting its preference for safer labor induction in this demographic.

Furosemide to lower antenatal severe hypertension: a randomized placebo-controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy are a leading cause of perinatal morbidity, and timely treatment of severely elevated blood pressure is recommended to prevent serious sequelae. In acute hypertension marked by increased blood volume, it is unknown whether diuretics used as an adjunct to antihypertensive medications lead to more effective blood pressure control. OBJECTIVE: This study aimed to evaluate whether the addition of intravenous furosemide to first-line antihypertensive agents reduces systolic blood pressure in acute-onset, severe antenatal hypertension with wide (≥60 mm Hg) pulse pressure. STUDY DESIGN: In this double-blinded randomized trial, participants received 40 mg of intravenous furosemide or placebo in addition to a first-line antihypertensive agent. The primary outcome was mean systolic blood pressure during the first hour after intervention. Secondary outcomes included corresponding diastolic blood pressure; systolic blood pressure, diastolic blood pressure, and pulse pressure at 2 hours after intervention; total reduction from qualifying blood pressure; duration of blood pressure control; need for additional antihypertensive doses within 1 hour; and electrolytes and urine output. A sample size of 35 participants per group was planned to detect a 15-mm Hg difference in blood pressure. RESULTS: Between January 2021 and March 2022, 65 individuals were randomized: 33 to furosemide and 32 to placebo. Baseline characteristics were similar between the groups. There was no difference in the primary outcome of mean 1-hour systolic blood pressure (147 [14.8] vs 152 [13.8] mm Hg; P=.200). We found a reduction in 2-hour systolic blood pressure (139 [18.5] vs 154 [18.4] mm Hg; P=.007) and a decrease in 2-hour pulse pressure (55 [12.5] vs 67 [15.1]; P=.003) in the furosemide group. Subgroup analysis according to hypertension type showed a significant reduction in 2-hour systolic blood pressure and 2-hour pulse pressure among patients with new-onset hypertension, but not among those with preexisting hypertension. Urine output was greater in the furosemide group, with no difference in electrolytes and creatinine before and after intervention. CONCLUSION: Intravenous furosemide in conjunction with a first-line antihypertensive agent did not significantly reduce systolic blood pressure in the first hour after administration. However, both systolic blood pressure and pulse pressure at 2 hours were decreased in the furosemide group. These findings suggest that a 1-time dose of intravenous furosemide is a reasonable adjunct to achieve blood pressure control, particularly in patients in whom increased volume is suspected.

Effects of intravenous nicardipine followed by oral labetalol in combination with nifedipine controlled-release tablet on severe peripartum hypertension.

OBJECTIVES: To investigate the effects of intravenous nicardipine as initial therapy and oral labetalol combined with nifedipine controlled-release tablet as subsequent treatment of severe peripartum hypertension. MATERIAL AND METHODS: Intravenous nicardipine was delivered as the initial treatment, after the target blood pressure (BP) had been achieved, oral labetalol was used to maintain the target BP. If oral labetalol failed to maintain the target BP, oral labetalol combined with nifedipine controlled-release tablet was used. RESULTS: A total number of 131 patients were enrolled. The target BP (BP < 140/90 mmHg) was achieved in all patients within 60 minutes by intravenous nicardipine. After receiving labetalol orally, the target BP was maintained in nine patients. However, in 104 patients, we had to combine oral labetalol and nifedipine controlled-release tablet due to re-elevation of their systolic BP to 140-159 mmHg. In 18 patients, we restarted intravenous nicardipine because their systolic BP re-elevated above 160 mm Hg. Among the 104 patients who received oral labetalol and nifedipine controlled-release tablet, the target BP was achieved and maintained in 96 patients, and eight patients had to restart nicardipine. Of the total number of 26 patients in whom intravenous nicardipine was resumed, the target BP was successfully maintained in 22 patients with oral labetalol combined with nifedipine controlled-release tablet. CONCLUSIONS: Intravenous nicardipine rapidly and safely lowered severe peripartum hypertension. As subsequent therapy, oral labetalol combined with nifedipine controlled-release tablet protocol may be applied to effectively maintain a target BP.

Integrating evidence and causal mapping of factors that influence medication decision-making by pregnant women at risk of hypertensive disorder: protocol for a scoping review.

INTRODUCTION: In 2018, the American College of Obstetricians and Gynecologists recommended low-dose aspirin to prevent the onset of pre-eclampsia among women who were at high risk. Factors influencing women's acceptance of this recommendation span multiple sectors and levels. Understanding how these factors interact will help stakeholders design effective population-level intervention strategies. Our study aims to identify and map relationships among factors influencing the medication decisions of pregnant women at risk of hypertensive disorders. METHODS AND ANALYSIS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines will be followed for this review. A research librarian developed a comprehensive search strategy to retrieve published and unpublished English studies after 1 January 1980, involving factors that influence pregnant women's uptake and adherence to medication for gestational hypertensive disorders. This literature includes perceptions, patterns, acceptance, refusal, tendencies, probability and service utilisation. We will search PubMed, Embase, Web of Science and CINAHL. Reference lists of the selected papers will be searched manually to identify more relevant studies. A two-stage independent screening, consisting of title and abstract screening, followed by full-text screening, will be conducted by two independent reviewers to identify eligible articles. Extracted data will be recorded in a customised variable extraction form and input into a Microsoft Access database. The PRISMA-ScR will be used to guide the presentation of the results, which will be presented in a table and causal map to demonstrate the relationships between extracted variables and medication uptake and adherence. A conceptual simulation model will be formulated to validate the logic of the relationships between variables and identify knowledge gaps. Lastly, experts and stakeholders will be invited to critique and comment on the results. ETHICS AND DISSEMINATION: This study does not require ethical approval. The full review results will be presented at a relevant conference and submitted to a peer-reviewed scientific journal for publication.

Risks associated with antidepressants in patients with hypertension during pregnancy: a retrospective cohort study.

PURPOSE: In a cohort of pregnant women using antihypertensive drugs, we compared exposure to antidepressants versus no exposure and the possible association with birth weight, APGAR scores, NICU admission, and maternal admission to an obstetrical intensive care unit (OHC). It was hypothesized that pregnant women with hypertensive disorders using antidepressants are at greater risk of complications. METHODS: A retrospective cohort study in a general teaching hospital in Zwolle, in the Middle-Northern part of The Netherlands. Finally, 58 pregnancies in the exposed group and 273 pregnancies in the reference group met all inclusion and exclusion criteria. We compared the neonate's birthweight between the exposed to antidepressants group and the reference group as the primary outcome. Secondary outcomes were the APGAR score at 1 and 5 min and obstetric high care (OHC) admission of the mother and neonatal intensive care unit (NICU) admission of the child. RESULTS: We found no differences in birth weight in neonates of mothers with hypertensive disorders and whether or not to use antidepressants. Besides a possible higher risk of admission to an OHC in women with hypertension-complicated pregnancies using antidepressants, we found no other maternal or neonatal risks in this population. CONCLUSION: We found no additional maternal or neonatal risks of using antidepressants prescribed to women with hypertension disorders during pregnancy.

Predictive modeling of postpartum blood pressure spikes.

BACKGROUND: Hypertensive disorders of pregnancy are one of the leading causes of maternal morbidity and mortality worldwide. Management of these conditions can pose many clinical dilemmas and can be particularly challenging during the immediate postpartum period. Models for predicting and managing postpartum hypertension are necessary to help address this clinical challenge. OBJECTIVE: This study aimed to evaluate predictive models of blood pressure spikes in the postpartum period and to investigate clinical management strategies to optimize care. STUDY DESIGN: This was a retrospective cohort study of postpartum women who participated in remote blood pressure monitoring. A postpartum blood pressure spike was defined as a blood pressure measurement of ≥140/90 mm Hg while on an antihypertensive medication and a blood pressure measurement of ≥150/100 mm Hg if not on an antihypertensive medication. We identified 3 risk level patient clusters (low, medium, and high) when predicting patient risk for a blood pressure spike on postpartum days 3 to 7. The variables used in defining these clusters were peak systolic blood pressure before discharge, body mass index, patient systolic blood pressure per trimester, heart rate, gestational age, maternal age, chronic hypertension, and gestational hypertension. For each risk cluster, we focused on 2 treatments, namely (1) postpartum length of stay (<3 days or ≥3 days) and (2) discharge with or without blood pressure medications. We evaluated the effectiveness of the treatments in different subgroups of patients by estimating the conditional average treatment effect values in each cluster using a causal forest. Moreover, for all patients, we considered discharge with medication policies depending on different discharge blood pressure thresholds. We used a doubly robust policy evaluation method to compare the effectiveness of the policies. RESULTS: A total of 413 patients were included, and among those, 267 (64.6%) had a postpartum blood pressure spike. The treatments for patients at medium and high risk were considered beneficial. The 95% confidence intervals for constant marginal average treatment effect for antihypertensive use at discharge were -3.482 to 4.840 and - 5.539 to 4.315, respectively; and for a longer stay they were -5.544 to 3.866 and -7.200 to 4.302, respectively. For patients at low risk, the treatments were not critical in preventing a blood pressure spike with 95% confidence intervals for constant marginal average treatment effect of 1.074 to 15.784 and -2.913 to 9.021 for the different treatments. We considered the option to discharge patients with antihypertensive use at different blood pressure thresholds, namely (1) ≥130 mm Hg and/or ≥80 mm Hg, (2) ≥140 mm Hg and/or ≥90 mm Hg, (3) ≥150 mm Hg and/or ≥ 100 mm Hg, or (4) ≥160 mm Hg and/or ≥ 110 mm Hg. We found that policy (2) was the best option with P<.05. CONCLUSION: We identified 3 possible strategies to prevent outpatient blood pressure spikes during the postpartum period, namely (1) medium- and high-risk patients should be considered for a longer postpartum hospital stay or should participate in daily home monitoring, (2) medium- and high-risk patients should be prescribed antihypertensives at discharge, and (3) antihypertensive treatment should be prescribed if patients are discharged with a blood pressure of ≥140/90 mm Hg.