Blood Pressure Control in Pregnant Patients with Chronic Hypertension and Diabetes: Should <130/80 be the Target?

BACKGROUND: The Chronic Hypertension and Pregnancy Study (CHAP) demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure (BP) <130/80 mm Hg. OBJECTIVE: We compared perinatal outcomes in patients with hypertension and diabetes who achieved BP <130/80 versus 130-139/80-89 mm Hg. STUDY DESIGN: This was a secondary analysis of a multi-center randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks' gestation and at least two recorded BP measurements prior to delivery. Average systolic and diastolic BP were calculated using ambulatory antenatal BPs. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). Comparisons were made between those with an average systolic BP <130 mm Hg and average diastolic BP <80 mm Hg and those with an average systolic blood pressure 130-139 mm Hg or diastolic blood pressure 80-89 mm Hg using Student's t-test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates. RESULTS: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed DM prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk (aRR) 0.43, 95% CI 0.30-0.61, p<0.01), with decreased risks specifically of preeclampsia with severe features (aRR 0.35, 95% CI 0.23-0.54) and indicated preterm birth prior to 35 weeks (aRR 0.44, 95% CI 0.24-0.79). The risk of NICU admission was lower in the lower blood pressure group (aRR 0.74, 95% CI 0.59-0.94). No differences were noted in cesarean delivery (aRR 1.04, 95% CI 0.90-1.20), fetal or neonatal death (aRR 0.59, 95% CI 0.12-2.92). SGA less than the 10th percentile was lower in the lower blood pressure group (aRR 0.37, 95% CI 0.14-0.96). CONCLUSION: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes.

Effects of Antihypertensive Therapy During Pregnancy on Postpartum Blood Pressure Control.

OBJECTIVE: To compare differences in postpartum blood pressure (BP) control (BP below 140/90 mm Hg) for participants with hypertension randomized to receive antihypertensive treatment compared with no treatment during pregnancy. METHODS: This study was a planned secondary analysis of a multicenter, open-label, randomized controlled trial (The CHAP [Chronic Hypertension and Pregnancy] trial). Pregnant participants with mild chronic hypertension (BP below 160/105 mm Hg) were randomized into two groups: active (antihypertensive treatment) or control (no treatment unless severe hypertension, BP 160/105 mm Hg or higher). Study outcomes were BP control below 140/90 mm Hg (primary) and medication nonadherence based on a composite score threshold (secondary) at the 6-week postpartum follow-up visit. Participants without follow-up BP measurements were excluded from analysis of the BP control outcome. Participants without health care professional-prescribed antihypertensives at delivery were excluded from the analysis of the adherence outcome. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: Of 2,408 participants, 1,684 (864 active, 820 control) were included in the analysis. A greater percentage of participants in the active group achieved BP control (56.7% vs 51.5%; adjusted odds ratio [aOR] 1.22, 95% CI, 1.00-1.48) than in the control group. Postpartum antihypertensive prescription was higher in the active group (81.7% vs 58.4%, P<.001), and nonadherence did not differ significantly between groups (aOR 0.81, 95% CI, 0.64-1.03). CONCLUSION: Antihypertensive treatment of mild chronic hypertension during pregnancy was associated with better BP control below 140/90 mm Hg in the immediate postpartum period.

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.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.

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.

Natural history of blood pressure in sickle cell disease pregnancy.

In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD-related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non-SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSß0 group than in the non-SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSß0 group and non-SCD controls, whereas the mean SBP and DBP in the HbSC/HbSß+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSß0 .

Perinatal Outcomes Associated With Management of Stage 1 Hypertension.

OBJECTIVE: To evaluate the association between maternal blood pressure (BP) below 130/80 mm Hg compared with 130-139/80-89 mm Hg and pregnancy outcomes. METHODS: We conducted a planned secondary analysis of CHAP (Chronic Hypertension and Pregnancy), an open label, multicenter, randomized controlled trial. Participants with mean BP below 140/90 mm Hg were grouped as below 130/80 mm Hg compared with 130-139/80-89 mm Hg by averaging postrandomization clinic BP throughout pregnancy. The primary composite outcome was preeclampsia with severe features, indicated preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The secondary outcome was small for gestational age (SGA). RESULTS: Of 2,408 patients in CHAP, 2,096 met study criteria; 1,328 had mean BP 130-139/80-89 mm Hg and 768 had mean BP below 130/80 mm Hg. Participants with mean BP below 130/80 mm Hg were more likely to be older, on antihypertensive medication, in the active treatment arm, and to have lower BP at enrollment. Mean clinic BP below 130/80 mm Hg was associated with lower frequency of the primary outcome (16.0% vs 35.8%, adjusted relative risk 0.45; 95% CI 0.38-0.54) as well as lower risk of severe preeclampsia and indicated birth before 35 weeks of gestation. There was no association with SGA. CONCLUSION: In pregnant patients with mild chronic hypertension, mean BP below 130/80 mm Hg was associated with improved pregnancy outcomes without increased risk of SGA. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

Appraising the Preclinical Evidence of the Role of the Renin-Angiotensin-Aldosterone System in Antenatal Programming of Maternal and Offspring Cardiovascular Health Across the Life Course: Moving the Field Forward: A Scientific Statement From the American Heart Association.

There is increasing interest in the long-term cardiovascular health of women with complicated pregnancies and their affected offspring. Emerging antenatal risk factors such as preeclampsia appear to increase the risk of hypertension and cardiovascular disease across the life course in both the offspring and women after pregnancy. However, the antenatal programming mechanisms responsible are complex and incompletely understood, with roots in alterations in the development, structure, and function of the kidney, heart, vasculature, and brain. The renin-angiotensin-aldosterone system is a major regulator of maternal-fetal health through the placental interface, as well as kidney and cardiovascular tissue development and function. Renin-angiotensin-aldosterone system dysregulation plays a critical role in the development of pregnancy complications such as preeclampsia and programming of long-term adverse cardiovascular health in both the mother and the offspring. An improved understanding of antenatal renin-angiotensin-aldosterone system programming is crucial to identify at-risk individuals and to facilitate development of novel therapies to prevent and treat disease across the life course. Given the inherent complexities of the renin-angiotensin-aldosterone system, it is imperative that preclinical and translational research studies adhere to best practices to accurately and rigorously measure components of the renin-angiotensin-aldosterone system. This comprehensive synthesis of preclinical and translational scientific evidence of the mechanistic role of the renin-angiotensin-aldosterone system in antenatal programming of hypertension and cardiovascular disease will help (1) to ensure that future research uses best research practices, (2) to identify pressing needs, and (3) to guide future investigations to maximize potential outcomes. This will facilitate more rapid and efficient translation to clinical care and improve health outcomes.

An Intensive Longitudinal Assessment Approach to Surveilling Trajectories of Burnout over the First Year of the COVID Pandemic.

Frontline clinicians responding to the COVID-19 pandemic are at increased risk of burnout, but less is known about the trajectory of clinician burnout as caseloads increase and decrease. Personal and professional resources, including self-efficacy and hospital support, can attenuate the risk of burnout. Yet, empirical data documenting how burnout and resources changed as the pandemic waxed and waned are limited. This intensive longitudinal prospective study employed ecological momentary assessment methods to examine trajectories of burnout and resources over the pandemic's first year in a New York City hospital. A 10-item survey was emailed every 5 days to frontline clinicians (physicians, nurses, and physician assistants). The primary outcome was a single-item validated measure of burnout; predictors included daily hospital COVID-19-related caseloads and personal and professional resources. Clinicians (n = 398) completed the initial survey and an average of 12 surveys over the year. Initially, 45.3% of staff reported burnout; over the year, 58.7% reported burnout. Following the initial COVID peak, caseloads declined, and burnout levels declined. During the second wave of COVID, as caseloads increased and remained elevated and personal and professional resource levels decreased, burnout increased. This novel application of intensive longitudinal assessment enabled ongoing surveillance of burnout and permitted us to evaluate how fluctuations in caseload intensity and personal and professional resources related to burnout over time. The surveillance data support the need for intensified resource allocation during prolonged pandemics.

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial.

BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

Finerenone and effects on mortality in chronic kidney disease and type 2 diabetes: a FIDELITY analysis.

AIMS: Finerenone reduces the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We investigated the causes of mortality in the FIDELITY population. METHODS AND RESULTS: The FIDELITY prespecified pooled data analysis from FIDELIO-DKD and FIGARO-DKD excluded patients with heart failure and reduced ejection fraction. Outcomes included intention-to-treat and prespecified on-treatment analyses of the risk of all-cause and cardiovascular mortality. Of 13 026 patients [mean age, 64.8 years; mean estimated glomerular filtration rate (eGFR), 57.6 mL/min/1.73 m2], 99.8% were on renin-angiotensin system inhibitors. Finerenone reduced the incidence of all-cause and cardiovascular mortality vs. placebo (8.5% vs. 9.4% and 4.9% vs. 5.6%, respectively) and demonstrated significant on-treatment reductions [hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70-0.96; P = 0.014 and HR, 0.82; 95% CI, 0.67-0.99; P = 0.040, respectively]. Cardiovascular-related mortality was most common, and finerenone lowered the incidence of sudden cardiac death vs. placebo [1.3% (incidence rate 0.44/100 patient-years) vs. 1.8% (0.58/100 patient-years), respectively; HR, 0.75; 95% CI, 0.57-0.996; P = 0.046]. The effects of finerenone on mortality were similar across all Kidney Disease: Improving Global Outcomes risk groups. Event probability with finerenone at 4 years was consistent irrespective of baseline urine albumin-to-creatinine ratio, but seemingly more pronounced in patients with higher baseline eGFR. CONCLUSION: In FIDELITY, finerenone significantly reduced the risk of all-cause and cardiovascular mortality vs. placebo in patients with T2D across a broad spectrum of CKD stages while on treatment, as well as sudden cardiac death in the intention-to-treat population. CLINICAL TRIALS REGISTRATION: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association.

Hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Affected women are also at increased risk for cardiovascular disease later in life, independently of traditional cardiovascular disease risks. Despite the immediate and long-term cardiovascular disease risks, recommendations for diagnosis and treatment of HDP in the United States have changed little, if at all, over past decades, unlike hypertension guidelines for the general population. The reasons for this approach include the question of benefit from normalization of blood pressure treatment for pregnant women, coupled with theoretical concerns for fetal well-being from a reduction in utero-placental perfusion and in utero exposure to antihypertensive medication. This report is based on a review of current literature and includes normal physiological changes in pregnancy that may affect clinical presentation of HDP; HDP epidemiology and the immediate and long-term sequelae of HDP; the pathophysiology of preeclampsia, an HDP commonly associated with proteinuria and increasingly recognized as a heterogeneous disease with different clinical phenotypes and likely distinct pathological mechanisms; a critical overview of current national and international HDP guidelines; emerging evidence that reducing blood pressure treatment goals in pregnancy may reduce maternal severe hypertension without increasing the risk of pregnancy loss, high-level neonatal care, or overall maternal complications; and the increasingly recognized morbidity associated with postpartum hypertension/preeclampsia. Finally, we discuss the future of research in the field and the pressing need to study socioeconomic and biological factors that may contribute to racial and ethnic maternal health care disparities.

FOXP3 mRNA Profile Prognostic of Acute T Cell-mediated Rejection and Human Kidney Allograft Survival.

BACKGROUND: T cell-mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes are nonresponsive to therapy, and molecular mechanisms for the nonresponsiveness are unknown. Our single-center study identified that urinary cell FOXP3 mRNA abundance predicts TCMR reversibility and allograft survival. METHODS: We developed PCR assays and measured absolute copy numbers of transcripts for FOXP3, CD25, CD3E, perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in the multicenter Clinical Trials in Organ Transplantation-04. In this replication study, we investigated the association between mRNA profile and TCMR diagnosis, TCMR reversibility, and allograft survival. RESULTS: 18S rRNA normalized levels of mRNA for FOXP3 (P = 0.01, Kruskal-Wallis test), CD25 (P = 0.01), CD3E (P < 0.0001), and perforin (P < 0.0001) were diagnostic of TCMR, but only FOXP3 mRNA level predicted TCMR reversibility (ROC AUC = 0.764; 95% confidence interval, 0.611-0.917; P = 0.008). Multivariable logistic regression analyses showed that urinary cell FOXP3 mRNA level predicted reversal, independent of clinical variables. A composite model of clinical variables and FOXP3 mRNA (AUC = 0.889; 95% CI, 0.781-0.997; P < 0.001) outperformed FOXP3 mRNA or clinical variables in predicting TCMR reversibility (P = 0.01, likelihood ratio test). Multivariable Cox proportional hazards regression analyses showed that FOXP3 mRNA level predicts kidney allograft survival (P = 0.047) but not after controlling for TCMR reversal (P = 0.477). CONCLUSIONS: Urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts TCMR reversibility, and is prognostic of kidney allograft survival via a mechanism involving TCMR reversal.

Safety of Antihypertensive Medications in Pregnancy: Living With Uncertainty.

See Article by Mito et al.

Renin-Angiotensin-Aldosterone Profiles in Pregnant Women With Chronic Hypertension.

Pregnant women with chronic hypertension are at risk for increased blood pressure and superimposed preeclampsia (SPE) in late pregnancy. Alterations in the renin-aldosterone system are a feature of normal pregnancy; however, their role in chronic hypertension with and without SPE is less clear. We performed a prospective, longitudinal trial of 108 women with chronic hypertension and measured plasma renin activity (PRA), 24-hour urine sodium, urine potassium, and urine aldosterone (Ualdo) at 12, 20, 28, and 36 weeks and postpartum. SPE developed in 34% of pregnancies. PRA was lower in women who developed SPE at weeks 28 (5.99 versus 6.22 ng/mL per hour; P<0.001) and 36 (5.71 versus 7.74 ng/mL per hour; P=0.002). Ualdo was lower in women with SPE compared with those without SPE at 28 weeks (59.6 versus 81.3 µg/d; P=0.039). Mean arterial pressure was inversely related to both PRA (r=-0.23; P<0.0001) and Ualdo (r=-0.11; P=0.029). PRA and Ualdo were positively associated with each other (r=0.5327; P<0.0001) after adjusting for urine potassium, urine sodium, serum potassium, and mean arterial pressure. PRA and Ualdo were lower in women of black race compared with other racial groups (P<0.001). Our results demonstrate that in women with chronic hypertension PRA and Ualdo increase in early pregnancy and subsequently decrease in women who develop SPE. These findings are consistent with the hypothesis that sodium retention may contribute to the elevation in blood pressure in SPE.