UNASSIGNED: Hypertension is one of the most common medical complications during pregnancy and a leading cause of maternal mortality and morbidity. Severe preeclampsia is defined as blood pressure (BP) >160/110 mmHg with warning signs such as headache, blurring of vision, and epigastric pain. Nifedipine (C17H18N2O6), labetalol (C19H24N2O3), and hydralazine (C8H8N4) are commonly used drugs, and all are recommended as first-line agents. Hydralazine is associated with a higher incidence of adverse outcomes, so oral nifedipine has been proposed as a first-line alternative to intravenous labetalol. Consequently, this study aims to compare the efficacy and safety of oral nifedipine with that of intravenous labetalol. The objective is to compare the ability/effectiveness of oral nifedipine and intravenous labetalol to normalize acute hypertension in severe preeclampsia and to assess the birth outcome. Relations between different factors were established by appropriate statistical tests. The p-value <0.05 was considered statistically significant.
UNASSIGNED: The study was conducted on 120 antenatal women with blood pressure ≥160/110 mmHg admitted to our hospital, a tertiary care center, from January 1st, 2020 to June 30th, 2021. Patients were randomized by a single blinding method to receive intravenous labetalol and oral nifedipine. The primary outcome measures were the time taken to control the blood pressure and the number of doses of drugs required. The secondary outcome measures were the birth outcome like a method of delivery, side effect profile, and the number of admissions in the neonatal intensive care unit.
UNASSIGNED: A total of 120 patients were included with 60 patients in each group. The labetalol group took 48.67 ± 17.80 minutes and the nifedipine group took 64.33 ± 9.81 minutes to achieve a target BP of <=140/90 mmHg (p < 0.05). No side effects were seen in 70% of patients in the labetalol group and 71.67% in the nifedipine group (p > 0.05).
UNASSIGNED: Intravenous labetalol is faster in restoring blood pressure in pregnant women with preeclampsia than oral nifedipine and may be used as a first-line drug in the acute control of blood pressure in a hypertensive emergency during pregnancy. More studies are needed in order to evaluate the findings from this pilot study in a large sample of patients.

OBJECTIVE: 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.
METHODS: 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).
CONCLUSIONS: 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.

Introduction Pregnancies complicated by hypertensive disorders contribute to enormous burden on economy and health-care facilities. Eclampsia is one of the clinical markers of near-miss mortality. To achieve optimal outcomes, efforts should be directed at both periphery and tertiary care levels. This study aimed to compare the feto-maternal outcome in patients presenting with eclampsia and a matched control population. Methodology A comparative observational study was conducted among 70 cases and 70 controls. Detailed history and general and obstetrical examinations were carried out. Data was extracted from case files, labor room, and ICU records. Maternal and fetal outcomes were noted from January 2023 to January 2024. Statistical software STATA 14.2 (StataCorp LLC, College Station, Texas, USA) was used for data analysis. Observational descriptive statistics and chi-square and Fisher extract tests were applied. Results In our study, the incidence of eclampsia was 0.7% (70 per 1000 live births). The maternal mortality rate was 102.8/100000 live births and the perinatal mortality rate was 10.2/ 1000 live births in our study. The study observed a relatively young aged population and a significant bulk of cases belonged to late gestation or post-partum. Events like HELLP syndrome, abruption, liver, and renal failure were found to be frequently linked to eclampsia. Neonatal asphyxia (P-0.005), NICU requirement 41.43% vs 29% (P<0.01) preterm delivery 45.7% vs 14% (P=<0.001), and low birth weight were more commonly observed among the cases than the controls. Conclusions Eclampsia was found to be a significant contributor to elevated rates of morbidity and mortality in mothers and newborns. Poor antenatal care, severe anemia, and late referrals were some of the modifiable risk factors. Health care and economic burden on society is immense due to the significant utilization of intensive care and high dependency units.

BACKGROUND: Nifedipine has previously exhibited superior efficacy to labetalol in managing hypertension in the non-pregnant Black population, establishing itself as a first-line treatment option. However, the unique challenges of hypertension during pregnancy, especially prevalent in Black individuals, remain underexplored in terms of effective medication choices. This gap highlights the need for targeted research on antihypertensive efficacy specifically within this population.
OBJECTIVE: This study aims to evaluate the effectiveness of nifedipine versus labetalol in managing blood pressure in Black pregnancies. The primary measure is the mean systolic and diastolic blood pressure trajectories throughout pregnancy, determining the superiority of nifedipine in this context.
METHODS: A retrospective cohort study was conducted at a multi-center institution in the metropolitan Detroit area, encompassing data from 1,235 Black pregnancies affected by chronic hypertension between 2015 and 2022. Mean blood pressure trajectories during pregnancy were fit by linear mixed effects model with a random intercept and time effect.
RESULTS: Patients on nifedipine had an estimated 2.08 mmHg lower mean systolic and 1.60 mmHg lower mean diastolic blood pressure compared to those on labetalol, with significant p-values of 0.040 and 0.028. Additionally, nifedipine users were less likely to need increased doses, with an odds ratio of 0.28 (95 % CI: 0.19-0.40, p < 0.001) compared to labetalol users.
CONCLUSIONS: This study provides compelling evidence that nifedipine outperforms labetalol in managing blood pressure during Black pregnancies. These findings suggest that the initiation of nifedipine should be considered in the management of chronic hypertension among Black pregnant individuals, offering a potentially more effective treatment option.

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.

As detailed information on the pharmacokinetics (PK) of labetalol in pregnant people are lacking, the aims of this study were: (1) to build a physiologically based PK (PBPK) model of labetalol in non-pregnant individuals that incorporates different CYP2C19 genotypes (specifically, *1/*1, *1/*2 or *3, *2/*2, and *17/*17); (2) to translate this model to the second and third trimester of pregnancy; and (3) to combine the model with a previously published direct pharmacodynamic (PD) model to predict the blood pressure lowering effect of labetalol in the third trimester. Clinical data for model evaluation was obtained from the scientific literature. In non-pregnant populations, the mean ratios of simulated versus observed peak concentration (Cmax), time to reach Cmax (Tmax), and exposure (area under the plasma concentration-time curve, AUC) were 0.94, 0.82, and 1.16, respectively. The pregnancy PBPK model captured the observed PK adequately, but clearance was slightly underestimated with mean ratios of simulated versus observed Cmax, Tmax, and AUC of 1.28, 1.30, and 1.39, respectively. The results suggested that pregnant people with CYP2C19 *2/*2 alleles have similar labetalol exposure and trough levels compared to non-pregnant controls, whereas those with other alleles were found to have increased exposure and trough concentrations. Importantly, the pregnancy PBPK/PD model predicted that, despite increased exposure in some genotypes, the blood pressure lowering effect was broadly comparable across all genotypes. In view of the large inter-individual variability and the potentially increasing blood pressure during pregnancy, patients may need to be closely monitored for achieving optimal therapeutic effects and avoiding adverse events.

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.
CONCLUSIONS: 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.
BACKGROUND: ClinicalTrials.gov, NCT02299414.

Background Recommendations on optimal agents to manage blood pressure (BP) in patients with an intracranial hemorrhage (ICH) are lacking. A case series suggests that hydralazine can cause intracranial pressure (ICP) elevation in an ICH. The purpose of this study was to compare the effects of intravenous (IV) hydralazine to IV labetalol on ICP in patients with ICH. Materials and methods A retrospective chart review from September 2015 to September 2021 on adults admitted to a level I trauma center with ICH, requiring an external ventricular drain or ICP monitor, and pharmacologic intervention with IV hydralazine or IV labetalol. ICP measurements and clinical interventions 0-80 minutes prior to and after medication administration were compared. Data points were excluded if multiple antihypertensive agents were administered. Results A total of 27 patients were included (three received only hydralazine, 13 only labetalol, and 11 both). Twenty-seven doses of hydralazine and 115 doses of labetalol were compared. There was no significant difference in mean ICP 0-80 minutes following hydralazine and labetalol administration (p = 0.283). Of the hydralazine doses, 29.6% received intervention for elevated ICP, while 25.2% of labetalol doses received intervention (p = 0.633). Hydralazine patients received m = 0.56 interventions for ICP, and labetalol patients received m = 0.36 interventions (p = 0.223). Of the patients that required intervention for ICP management, hydralazine patients required m = 1.88 interventions, while labetalol patients required m = 1.41 interventions (p = 0.115).  Conclusion There was no significant difference in mean ICP at 0-80 minutes following administration of hydralazine or labetalol. There was also no significant difference in interventions required for elevated ICP management between groups. Larger studies are needed to confirm these findings.

OBJECTIVE: This paper was aimed at unveiling the effect of low-molecular-weight heparin calcium (LMWH) combined with magnesium sulfate and labetalol on coagulation, vascular endothelial function, and pregnancy outcome in early-onset severe preeclampsia (EOSP).
METHODS: Pregnant women with EOSP were divided into the control group and the study group, each with 62 cases. Patients in the control group were treated with labetalol and magnesium sulfate, and those in the study group were treated with LMWH in combination with the control grou Blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]), 24-h urine protein, coagulation indices [D-dimer (D-D), plasma fibrinogen (Fg), prothrombin time (PT), activated partial thromboplastin time (APTT), and prothrombin time (TT)], endothelial function [endothelin (ET-1) and nitric oxide (NO)], oxidative stress indices [oxidized low-density lipoproteins (ox-LDL), lipid peroxidation (LPO), superoxide dismutase (SOD), and malondialdehyde (MDA)], pregnancy outcome, and adverse effects occurred in the two groups were compared.
RESULTS: After treatment, lower SBP, DBP, and 24-h urine protein levels; lower Fg and D-D levels; higher PT, APPT, and TT levels; higher NO levels; lower ET-1 levels; lower ox-LDL, MDA, and LPO levels; higher SOD levels; and lower incidence of adverse pregnancy and adverse reactions were noted in the study group in contrast to the control group.
CONCLUSIONS: EOSP patients given with LMWH combined with magnesium sulfate and labetalol can effectively reduce the patient\'s blood pressure and urinary protein level; improve coagulation function, oxidative stress, and vascular endothelial function indices; reduce the adverse pregnancy outcomes; and improve the safety of treatment.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.