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.

Analysis of risk factors of preeclampsia in pregnant women with chronic hypertension and its impact on pregnancy outcomes.

OBJECTIVE: To investigate the risk factors and maternal and fetal outcomes of preeclampsia after pregnancy in patients with primary chronic hypertension. METHODS: A total of 500 singleton pregnant women with a history of hypertension who were admitted for delivery at our Hospital from March 2015 to May 2022 were retrospectively collected by random sampling and divided into the non-occurrence group (n = 200) and the occurrence group (n = 300) according to whether they were complicated by preeclampsia. Afterward, the general data and the pregnancy-related data of patients were collected for comparison. RESULTS: The univariate analysis showed significant differences between the non-occurrence group and the occurrence group in terms of the proportion of preeclampsia history (4.00% VS 24.67%, χ2 = 37.383, P < 0.001), duration of hypertension > 3 years (18.00% VS 31.67%, χ2 = 11.592, P < 0.001), systemic therapy (20.50% VS 10.00%, χ2 = 10.859, P < 0.001), gestational age at admission [37.72 (34.10, 38.71) VS 35.01 (31.91, 37.42) weeks, Z = -9.825, P < 0.001]. Meanwhile, the multivariate analysis showed that a history of preeclampsia (OR = 6.796, 95% CI: 3.575 ∼ 10.134, χ2 = 8.234, P < 0.001), duration of hypertension > 3 years (OR = 3.456, 95% CI: 2.157 ∼ 5.161, χ2 = 9.348, P < 0.001), and a lack of systemic antihypertensive treatment (OR = 8.983, 95% CI: 7.735 ∼ 9.933, χ2 = 9.123, P < 0.001) were risk factors for chronic hypertension complicated by preeclampsia during pregnancy. CONCLUSION: A history of preeclampsia, a longer duration of hypertension, and a lack of systematic antihypertensive treatment are risk factors for chronic hypertension complicated by preeclampsia during pregnancy. The occurrence of preeclampsia in pregnant women with chronic hypertension increases the incidence of maternal HELLP syndrome and fetal distress.

Angiotensin II-mediated hippocampal hypoperfusion and vascular dysfunction contribute to vascular cognitive impairment in aged hypertensive rats.

INTRODUCTION: Chronic hypertension increases the risk of vascular cognitive impairment (VCI) by ∼60%; however, how hypertension affects the vasculature of the hippocampus remains unclear but could contribute to VCI. METHODS: Memory, hippocampal perfusion, and hippocampal arteriole (HA) function were investigated in male Wistar rats or spontaneously hypertensive rats (SHR) in early (4 to 5 months old), mid (8 to 9 months old), or late adulthood (14 to 15 months old). SHR in late adulthood were chronically treated with captopril (angiotensin converting enzyme inhibitor) or apocynin (antioxidant) to investigate the mechanisms by which hypertension contributes to VCI. RESULTS: Impaired memory in SHR in late adulthood was associated with HA endothelial dysfunction, hyperconstriction, and ∼50% reduction in hippocampal blood flow. Captopril, but not apocynin, improved HA function, restored perfusion, and rescued memory function in aged SHR. DISCUSSION: Hippocampal vascular dysfunction contributes to hypertension-induced memory decline through angiotensin II signaling, highlighting the therapeutic potential of HAs in protecting neurocognitive health later in life. HIGHLIGHTS: Vascular dysfunction in the hippocampus contributes to vascular cognitive impairment. Memory declines with age during chronic hypertension. Angiotensin II causes endothelial dysfunction in the hippocampus in hypertension. Angiotensin II-mediated hippocampal arteriole dysfunction reduces blood flow. Vascular dysfunction in the hippocampus impairs perfusion and memory function.

Prevalence and outcome of chronic hypertension and its complications with gestational diabetes. / æ ¢æ€§é«˜è¡€åŽ‹åŠå ¶åˆå¹¶å¦Šå¨ æœŸç³–å°¿ç— çš„æ‚£ç— çŽ‡å’Œå¦Šå¨ ç»“å±€.

OBJECTIVES: With the full liberalization of China's fertility policy, the gradual increase in maternal age during pregnancy, and the rising proportion of overweight and obesity among women of childbearing age, the number of pregnant women with chronic hypertension (CHTN) combined with gestational diabetes mellitus (GDM) is increasing, leading to a significantly increased risk of adverse pregnancy outcomes. This study aims to analyze the prevalence of CHTN and CHTN complications with GDM, and compare the adverse pregnancy outcomes between the 2 conditions, providing a basis for intervention measures. METHODS: This study was a prospective cohort study. A total of 378 366 cases from a large cohort of pregnant women between January 1, 2016 to December 31, 2020 were screened to identify 1 418 cases of pregnant women with CHTN, among which 1 027 were cases of CHTN alone and 391 were cases of CHTN combined with GDM. SAS9.4 was used to statistically analyze the basic characteristics, clinical data, and pregnant outcomes of pregnant women and to analyze the risk factors affecting the pregnancy outcomes of patients with CHTN and its complications with GDM. RESULTS: The prevalence rate of CHTN with pregnancy was 3.8‰, and the prevalence rate of CHTN combined with GDM was 1.0‰. Patients with CHTN combined with GDM accounted for 27.57% (391/1 418) of all pregnant women with CHTN. Maternal age, number of pregnancies, parity, previous cesarean section, systolic blood pressure, diastolic blood pressure, and mean arterial pressure at the time of enrollment were statistically significant differences between the 2 groups (all P<0.05). After adjusting for potential confounding factors such as maternal age, parity, and number of pregnancies, binary Logistic regression analysis showed that pregnant women with CHTN combined with GDM had a 1.348 times higher risk of cesarean section (OR=1.348, 95% CI 1.043 to 1.741), a 2.029 times higher risk of placental adhesion (OR=2.029, 95% CI 1.190 to 3.462), a 1.540 times higher risk of preeclampsia (OR=1.540, 95% CI 1.101 to 2.152), and a 2.670 times higher risk of macrosomia (OR=2.670, 95% CI 1.398 to 5.100) compared to pregnant women with CHTN alone. CONCLUSIONS: Pregnant women with CHTN combined with GDM have a high risk, and their pregnancy outcomes differ from those of pregnant women with CHTN alone in terms of cesarean section, placental adhesion, preeclampsia, and macrosomia. Prenatal care for this population, especially the management of blood pressure and blood sugar, needs to be given special attention.

Emerging concepts since the Chronic Hypertension and Pregnancy trial.

The recent publication of the Chronic Hypertension and Pregnancy (CHAP) trial has already changed the management of pregnant people with mild chronic hypertension. However, similar to any new intervention or change in management, we have encountered confusion regarding the management and implementation of the "Treatment for mild chronic hypertension during pregnancy" trial findings. In this clinical opinion, we addressed the aspects relating to the implementation that cannot be gleaned from the manuscript but were part of the trial conduct. Furthermore, we discussed several clinical questions that may affect the management of a patient with chronic hypertension following the "Treatment for mild chronic hypertension during pregnancy" trial and provided suggestions based on our experience and opinion.

American College of Cardiology and American Heart Association blood pressure categories-a systematic review of the relationship with adverse pregnancy outcomes in the first half of pregnancy.

OBJECTIVE: A relationship between the 2017 American College of Cardiology and American Heart Association blood pressure thresholds and adverse pregnancy outcomes has been reported, but few studies have explored the diagnostic test properties of these cutoffs. DATA SOURCES: We systematically searched electronic databases (from 2017 to 2021) for reports of blood pressure measurements in pregnancy, classified according to 2017 American College of Cardiology and American Heart Association criteria, and their relationship with pregnancy outcomes. STUDY ELIGIBILITY CRITERIA: Studies recording blood pressure at <20 weeks gestation were included. METHODS: Meta-analyses were used to investigate the strength of the association between blood pressure cutoffs and adverse outcomes, and the diagnostic test properties were calculated. RESULTS: Of 23 studies included, there was a stepwise relationship between the American College of Cardiology and American Heart Association blood pressure category (when compared with normal blood pressure of <120/80 mmHg) and the strength of the association with preeclampsia. The category of elevated blood pressure had a risk ratio of 2.0 (95% prediction interval, 0.8-4.8), the stage 1 hypertension category had a risk ratio of 3.0 (95% prediction interval, 1.1-8.5), and the stage 2 hypertension category had a risk ratio of 7.9 (95% prediction interval, 1.8-35.1). Between-study variability was related to the magnitude of the association with stronger relationships in larger studies at low risk of bias and with unselected populations with multiple routine blood pressure measurements. None of the systolic blood pressure measurements of <120 mmHg, <130/80 mmHg, or <140/90 mmHg were useful to rule out the development of preeclampsia (all negative likelihood ratios >0.2). Only a blood pressure measurement of ≥140/90 mmHg was a good predictor for the development of preeclampsia (positive likelihood ratio, 5.95). The findings were similar for other outcomes. CONCLUSION: Although a blood pressure of 120 to 140 over 80 to 90 mmHg at <20 weeks gestation is associated with a heightened risk for preeclampsia and adverse pregnancy outcomes and may assist in risk prediction in multivariable modelling, lowering the diagnostic threshold for chronic hypertension would not assist clinicians in identifying women at heightened risk.

Low-dose aspirin for the prevention of superimposed preeclampsia in women with chronic hypertension: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of low-dose aspirin during pregnancy by women with chronic hypertension reduces the odds of superimposed preeclampsia and poor perinatal outcomes. DATA SOURCES: In September 2021, the following sources were searched: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and EU Clinical Trials Register. Only human studies were included, with no time or language restrictions. STUDY ELIGIBILITY CRITERIA: Cohort, case-control, and randomized controlled studies reporting women with chronic hypertension pregnant with a singleton were included. Eligible studies compared low-dose aspirin use during pregnancy with a control arm. METHODS: Risk of bias was assessed using the RoB 2 and ROBINS-I tools. A meta-analysis was performed using a random-effects model, estimating odds ratios and 95% confidence and prediction intervals, and the quality of data was assessed with the GRADE approach. Heterogeneity was investigated in regard to study methodology, timing of commencement of aspirin, and the outcome of preterm preeclampsia. RESULTS: Nine studies (3 retrospective cohort studies and 6 randomized trials) including 2150 women with chronic hypertension were included. Low-dose aspirin prophylaxis did not significantly reduce the odds of superimposed preeclampsia in the randomized controlled trials (odds ratio, 0.83; 95% confidence interval, 0.55-1.25; prediction interval, 0.27-2.56; low-quality evidence) or observational studies (odds ratio, 1.21; 95% confidence interval, 0.78-1.87; prediction interval, 0.07-20.80; very low-quality evidence). Low-dose aspirin also did not reduce the odds of preterm preeclampsia (odds ratio, 1.17; 95% confidence interval, 0.74-1.86), and early aspirin initiation had no significant impact. There was no significant effect on small-for-gestational-age neonates or perinatal mortality; however, there was a significant reduction in preterm birth (odds ratio, 0.63; 95% confidence interval, 0.45-0.89; moderate-quality evidence). The quality of the evidence is limited by heterogeneity and risk of bias. CONCLUSION: This meta-analysis was unable to demonstrate a significant change in the odds of superimposed preeclampsia, small-for-gestational-age infants, or perinatal mortality with the use of low-dose aspirin in women with chronic hypertension. However, significant reduction in preterm birth justifies the continued use of aspirin prophylaxis. This work was prospectively registered on the International Prospective Register of Systematic Reviews (registration number CRD42021285921).

Hypertensive disorders of pregnancy and long-term risk of maternal stroke-a systematic review and meta-analysis.

OBJECTIVE: Hypertensive disorders of pregnancy are associated with a long-term risk for cardiovascular disease among parous patients later in life. However, relatively little is known about whether hypertensive disorders of pregnancy are associated with an increased risk for ischemic stroke or hemorrhagic stroke in later life. This systematic review aimed to synthesize the available literature on the association between hypertensive disorders of pregnancy and the long-term risk for maternal stroke. DATA SOURCES: PubMed, Web of Science, and CINAHL were searched from inception to December 19, 2022. STUDY ELIGIBILITY CRITERIA: Studies were only included if the following criteria were met: case-control or cohort studies that were conducted with human participants, were available in English, and that measured the exposure of a history of hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, chronic hypertension, or superimposed preeclampsia) and the outcome of maternal ischemic stroke or hemorrhagic stroke. METHODS: Three reviewers extracted the data and appraised the study quality following the Meta-analyses of Observational Studies in Epidemiology guidelines and using the Newcastle-Ottawa scale for risk of bias assessment. RESULTS: The primary outcome was any stroke (undifferentiated) and secondary outcomes included ischemic stroke and hemorrhagic stroke. The protocol for this systematic review was registered in the International Prospective Register of Systematic Reviews under identifier CRD42021254660. Of 24 studies included (10,632,808 study participants), 8 studies examined more than 1 outcome of interest. Hypertensive disorders of pregnancy were significantly associated with any stroke (adjusted risk ratio, 1.74; 95% confidence interval, 1.45-2.10). Preeclampsia was significantly associated with any stroke (adjusted risk ratio, 1.75; 95% confidence interval, 1.56-1.97), ischemic stroke (adjusted risk ratio, 1.74; 95% confidence interval, 1.46-2.06), and hemorrhagic stroke (adjusted risk ratio, 2.77; 95% confidence interval, 2.04-3.75). Gestational hypertension was significantly associated with any stroke (adjusted risk ratio, 1.23; 95% confidence interval, 1.20-1.26), ischemic stroke (adjusted risk ratio, 1.35; 95% confidence interval, 1.19-1.53), and hemorrhagic stroke (adjusted risk ratio, 2.66; 95% confidence interval, 1.02-6.98). Chronic hypertension was associated with ischemic stroke (adjusted risk ratio, 1.49; 95% confidence interval, 1.01-2.19). CONCLUSION: In this meta-analysis, exposure to hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension, seems to be associated with an increased risk for any stroke and ischemic stroke among parous patients in later life. Preventive interventions may be warranted for patients who experience hypertensive disorders of pregnancy to reduce their long-term risk for stroke.

Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study.

BACKGROUND: The increased maternal cardiocerebrovascular risk after a pregnancy complicated by hypertensive disorders of pregnancy, is well documented in the literature. Recent evidence has suggested a shorter timeframe for the development of these postnatal outcomes, which could have major clinical implications. OBJECTIVE: This study aimed to determine the risk of and time to onset of maternal cardiovascular and cerebrovascular outcomes after a pregnancy complicated by hypertensive disorders of pregnancy. STUDY DESIGN: This study included 2,227,711 women, without preexisting chronic hypertension, who delivered during the period 2008 to 2010: 37,043 (1.66%) were diagnosed with preeclampsia, 34,220 (1.54%) were diagnosed with gestational hypertension, and 2,156,448 had normotensive pregnancies. Hospitalizations for chronic hypertension, heart failure, coronary heart disease, cerebrovascular disease, and peripheral arterial disease were studied. A classical Cox regression was performed to estimate the average effect of hypertensive disorders of pregnancy over 10 years compared with normotensive pregnancy; moreover, an extended Cox regression was performed with a step function model to estimate the effect of the exposure variable in different time intervals: <1, 1 to 3, 3 to 5, and 5 to 10 years of follow-up. RESULTS: The risk of chronic hypertension after a pregnancy complicated by preeclampsia was 18 times higher in the first year (adjusted hazard ratio, 18.531; 95% confidence interval, 16.520-20.787) to only 5 times higher at 5 to 10 years after birth (adjusted hazard ratio, 4.921; 95% confidence interval, 4.640-5.218). The corresponding risks of women with gestational hypertension were 12 times higher (adjusted hazard ratio, 11.727; 95% confidence interval, 10.257-13.409]) and 6 times higher (adjusted hazard ratio, 5.854; 95% confidence interval, 5.550-6.176), respectively. For other cardiovascular and cerebrovascular outcomes, there was also a significant effect with preeclampsia (heart failure: adjusted hazard ratio, 6.662 [95% confidence interval, 4.547-9.762]; coronary heart disease: adjusted hazard ratio, 3.083 [95% confidence interval, 1.626-5.844]; cerebrovascular disease: adjusted hazard ratio, 3.567 [95% confidence interval, 2.600-4.893]; peripheral arterial disease: adjusted hazard ratio, 4.802 [95% confidence interval, 2.072-11.132]) compared with gestational hypertension in the first year of follow-up. A dose-response effect was evident for the severity of preeclampsia with the averaged 10-year adjusted hazard ratios for developing chronic hypertension after early, preterm, and late preeclampsia being 10, 7, and 6 times higher, respectively. CONCLUSION: The risks of cardiovascular and cerebrovascular outcomes were the highest in the first year after a birth complicated by hypertensive disorders of pregnancy. We found a significant relationship with both the severity of hypertensive disorders of pregnancy and the gestational age of onset suggesting a possible dose-response relationship for the development of cardiovascular and cerebrovascular outcomes. These findings call for an urgent focus on research into effective postnatal screening and cardiocerebrovascular risk prevention for women with hypertensive disorders of pregnancy.

Association between hypertensive disorders of pregnancy and cardiovascular diseases within 24 months after delivery.

BACKGROUND: Despite the well-known association between hypertensive disorders of pregnancy and cardiovascular diseases, there are limited data on which specific cardiovascular diagnoses have the greatest risk profiles during the first 24 months after delivery. Most existing data on hypertensive disorders of pregnancy and short-term cardiovascular disease risks are limited to the immediate postpartum period; however, it is crucial to determine cardiovascular disease risk up to 24 months after delivery to inform cardiovascular disease screening protocols during the extended postpartum period. OBJECTIVE: This study aimed to delineate the risk of cardiovascular diagnoses in the first 24 months after delivery among patients with hypertensive disorders of pregnancy compared with patients without hypertensive disorders of pregnancy. STUDY DESIGN: This longitudinal population-based study included pregnant individuals with deliveries during 2007 to 2019 in the Maine Health Data Organization's All Payer Claims Data. This study excluded patients with preexisting cardiovascular disease, with multifetal pregnancies, or without continuous insurance during pregnancy. Hypertensive disorders of pregnancy and cardiovascular diseases (categorized by specific conditions: heart failure, ischemic heart disease, arrhythmia or cardiac arrest, cardiomyopathy, cerebrovascular disease or stroke, and new chronic hypertension) were identified using International Classification of Diseases, Ninth Revision, and International Classification of Diseases, Tenth Revision, diagnosis codes. Cox proportional hazards models were used to estimate hazard ratios, adjusting for potential confounding factors. RESULTS: Of the 119,422 pregnancies examined, the cumulative risk of cardiovascular disease within 24 months after delivery for those with hypertensive disorders of pregnancy vs those without hypertensive disorders of pregnancy was 0.6% vs 0.2% for heart failure, 0.3% vs 0.1% for ischemic heart disease, 0.2% vs 0.2% for arrhythmia or cardiac arrest, 0.6% vs 0.2% for cardiomyopathy, 0.8% vs 0.4% for cerebrovascular disease or stroke, 1.6% vs 0.7% for severe cardiac disease (composite outcome of heart failure, cerebrovascular disease or stroke, or cardiomyopathy), and 9.7% vs 1.5% for new chronic hypertension. After adjustment for potential confounders, those with hypertensive disorders of pregnancy had an increased risk of heart failure, cerebrovascular disease, cardiomyopathy, and severe cardiac disease within the first 24 months after delivery (adjusted hazard ratio, 2.81 [95% confidence interval, 1.90-4.15], 1.43 [95% confidence interval, 1.07-1.91], 2.90 [95% confidence interval, 1.96-4.27], and 1.90 [95% confidence interval, 1.54-2.30], respectively) compared with those without hypertensive disorders of pregnancy. In addition, those with hypertensive disorders of pregnancy had an increased risk for new chronic hypertension diagnosed after 42 days after delivery (adjusted hazard ratio, 7.29; 95% confidence interval, 6.57-8.09). There was no association between hypertensive disorders of pregnancy and ischemic heart disease (adjusted hazard ratio, 0.92; 95% confidence interval, 0.55-1.54) or cardiac arrest or arrhythmia (adjusted hazard ratio, 0.90; 95% confidence interval, 0.52-1.57). In addition, among women with hypertensive disorders of pregnancy, the highest proportion of first cardiovascular disease diagnoses occurred during the first month after delivery for cardiomyopathy (44%), heart failure (39%), cerebrovascular disease or stroke (39%), and severe cardiac disease (41%). CONCLUSION: Patients with hypertensive disorders of pregnancy had an increased risk of developing new chronic hypertension, heart failure, cerebrovascular disease, and cardiomyopathy within 24 months after delivery. There was no association between hypertensive disorders of pregnancy and ischemic heart disease or cardiac arrest or arrhythmia. Patients with hypertensive disorders of pregnancy need targeted early postpartum interventions and increased monitoring in the first 24 months after delivery. This may preserve long-term health and improve maternal and neonatal outcomes in a subsequent pregnancy.

Accuracy of placental growth factor alone or in combination with soluble fms-like tyrosine kinase-1 or maternal factors in detecting preeclampsia in asymptomatic women in the second and third trimesters: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to: (1) identify all relevant studies reporting on the diagnostic accuracy of maternal circulating placental growth factor) alone or as a ratio with soluble fms-like tyrosine kinase-1), and of placental growth factor-based models (placental growth factor combined with maternal factors±other biomarkers) in the second or third trimester to predict subsequent development of preeclampsia in asymptomatic women; (2) estimate a hierarchical summary receiver-operating characteristic curve for studies reporting on the same test but different thresholds, gestational ages, and populations; and (3) select the best method to screen for preeclampsia in asymptomatic women during the second and third trimester of pregnancy by comparing the diagnostic accuracy of each method. DATA SOURCES: A systematic search was performed through MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform databases from January 1, 1985 to April 15, 2021. STUDY ELIGIBILITY CRITERIA: Studies including asymptomatic singleton pregnant women at >18 weeks' gestation with risk of developing preeclampsia were evaluated. We included only cohort or cross-sectional test accuracy studies reporting on preeclampsia outcome, allowing tabulation of 2×2 tables, with follow-up available for >85%, and evaluating performance of placental growth factor alone, soluble fms-like tyrosine kinase-1- placental growth factor ratio, or placental growth factor-based models. The study protocol was registered on the International Prospective Register Of Systematic Reviews (CRD 42020162460). METHODS: Because of considerable intra- and interstudy heterogeneity, we computed the hierarchical summary receiver-operating characteristic plots and derived diagnostic odds ratios, ß, θi, and Λ for each method to compare performances. The quality of the included studies was evaluated by the QUADAS-2 tool. RESULTS: The search identified 2028 citations, from which we selected 474 studies for detailed assessment of the full texts. Finally, 100 published studies met the eligibility criteria for qualitative and 32 for quantitative syntheses. Twenty-three studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the second trimester, including 16 (with 27 entries) that reported on placental growth factor test alone, 9 (with 19 entries) that reported on the soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 6 (16 entries) that reported on placental growth factor-based models. Fourteen studies reported on performance of placental growth factor testing for the prediction of preeclampsia in the third trimester, including 10 (with 18 entries) that reported on placental growth factor test alone, 8 (with 12 entries) that reported on soluble fms-like tyrosine kinase-1-placental growth factor ratio, and 7 (with 12 entries) that reported on placental growth factor-based models. For the second trimester, Placental growth factor-based models achieved the highest diagnostic odds ratio for the prediction of early preeclampsia in the total population compared with placental growth factor alone and soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 63.20; 95% confidence interval, 37.62-106.16 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 6.96; 95% confidence interval, 1.76-27.61 vs placental growth factor alone, 5.62; 95% confidence interval, 3.04-10.38); placental growth factor-based models had higher diagnostic odds ratio than placental growth factor alone for the identification of any-onset preeclampsia in the unselected population (28.45; 95% confidence interval, 13.52-59.85 vs 7.09; 95% confidence interval, 3.74-13.41). For the third trimester, Placental growth factor-based models achieved prediction for any-onset preeclampsia that was significantly better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio (placental growth factor-based models, 27.12; 95% confidence interval, 21.67-33.94 vs placental growth factor alone, 10.31; 95% confidence interval, 7.41-14.35 vs soluble fms-like tyrosine kinase-1-placental growth factor ratio, 14.94; 95% confidence interval, 9.42-23.70). CONCLUSION: Placental growth factor with maternal factors ± other biomarkers determined in the second trimester achieved the best predictive performance for early preeclampsia in the total population. However, in the third trimester, placental growth factor-based models had predictive performance for any-onset preeclampsia that was better than that of placental growth factor alone but similar to that of soluble fms-like tyrosine kinase-1-placental growth factor ratio. Through this meta-analysis, we have identified a large number of very heterogeneous studies. Therefore, there is an urgent need to develop standardized research using the same models that combine serum placental growth factor with maternal factors ± other biomarkers to accurately predict preeclampsia. Identification of patients at risk might be beneficial for intensive monitoring and timing delivery.

Postpartum home blood pressure monitoring and lifestyle intervention in overweight and obese individuals the first year after gestational hypertension or pre-eclampsia: A pilot feasibility trial.

OBJECTIVE: To test the feasibility of a randomised trial of home blood pressure monitoring paired with a remote lifestyle intervention (Heart Health 4 New Moms) versus home blood pressure monitoring alone versus control in individuals with a hypertensive disorder of pregnancy in the first year postpartum. DESIGN: Single-blinded three-arm randomised clinical trial. SETTING: Two tertiary care hospitals and a community organisation. POPULATION: Postpartum overweight and obese individuals with a hypertensive disorder of pregnancy and without pre-pregnancy hypertension or diabetes. METHODS: We assessed the feasibility of recruitment and retention of 150 participants to study completion at 1-year postpartum with randomisation 1:1:1 into each arm. Secondary aims were to test effects of the interventions on weight, blood pressure and self-efficacy. RESULTS: Over 23 months, we enrolled 148 of 400 eligible, screened individuals (37%); 28% black or other race and mean pre-pregnancy body mass index (BMI) of 33.4 ± 6.7 kg/m2 . In total, 129 (87%) participants completed the 1-year postpartum study visit. Overall, 22% of participants developed stage 2 hypertension (≥140/90 mmHg or on anti-hypertensive medications) by 1 year postpartum. There were no differences in weight or self-efficacy across the study arms. CONCLUSION: In this pilot, randomised trial, we demonstrate feasibility of HBPM paired with a lifestyle intervention in the first year postpartum. We detected high rates of ongoing hypertension, emphasising the need for the development of effective interventions in this population.

Low pregnancy-specific beta-1-glycoprotein is associated with nondipper hypertension and increased risk of preeclampsia in pregnant women with newly diagnosed chronic hypertension.

Chronic hypertension is one of the major risk factors for preeclampsia. Pregnancy-specific beta-1-glycoprotein (PSG-1) is a protein that plays a critical role in fetomaternal immune modulation and has been shown to be closely associated with pregnancy adverse events such as preeclampsia. It is also known that PSG-1 and its source placenta are associated with many molecular pathways associated with blood pressure regulation. In addition, the nondipping pattern (NDP) of chronic hypertension has been shown to be an independent risk factor for preeclampsia. Dipper individuals experience a notable nighttime drop in blood pressure, typically around 10% or more compared to daytime levels, while nondipper individuals show a smaller nighttime blood pressure decrease, indicating potential circadian blood pressure regulation disruption. In this context, we aimed to reveal the relationship between PSG-1, NDP and preeclampsia in this study. A total of 304 pregnant women who were newly diagnosed in the first trimester and started on antihypertensive medication were included in this study. All subjects performed 24-h ambulatory blood pressure monitoring twice throughout pregnancy, the first in the 1. trimester to confirm the diagnosis of hypertension and the second between 20+0 and 21+1 gestational weeks to determine the dipper-nondipper status of hypertension. Subjects were grouped as dipper and nondipper according to blood pressure, and groups were compared in terms of PSG-1 levels. In this study, low PSG-1 levels and NDP were independently associated with preeclampsia. Findings from this study suggest that PSG-1 may play an important role in the causal relationship between NDP and preeclampsia.

Literature Review: The sFlt1/PlGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia.

One of the main causes of maternal and neonatal morbidity and mortality is pre-eclampsia. It is characterized by a high sFlt1/PlGF ratio, according to prior research. Pregestational diseases in mothers may increase the risk of developing pre-eclampsia. Only a few studies have looked at the connection between maternal comorbidities before conception and the sFlt1/PlGF ratio. The most recent information regarding the association between maternal pregestational diseases and the ratio of sFlt1/PlGF is described in this review. The paper also examines current research suggesting that changes in pregnancy hormones and metabolites are related to a high sFlt1/PlGF ratio. Certain maternal disorders have been found to dramatically raise sFlt-1 and sFlt1/PlGF levels, according to an analysis of the literature. There is still debate about the data on the association between the sFlt1/PlGF ratio and maternal disorders such as HIV, acute coronary syndromes, cardiovascular function in the mother between 19 and 23 weeks of pregnancy, thyroid hormones, diabetes, and cancer. Additional research is needed to confirm these findings.

Society for Maternal-Fetal Medicine Statement: Antihypertensive therapy for mild chronic hypertension in pregnancy-The Chronic Hypertension and Pregnancy trial.

The recently published Chronic Hypertension and Pregnancy study provides important data to inform the management of mild chronic hypertension in pregnancy. The purpose of this statement is to review the results of this trial and provide guidance for the implementation of the study findings. Based on the available evidence, SMFM recommends treatment with antihypertensive therapy for mild chronic hypertension in pregnancy to a goal blood pressure of <140/90 mm Hg. Patients with treated chronic hypertension should continue established antihypertensive therapy during pregnancy or change to a regimen compatible with pregnancy to achieve this treatment goal.

Toward personalized management of chronic hypertension in pregnancy.

Chronic hypertension complicates 1% to 2% of pregnancies, and it is increasingly common. Women with chronic hypertension are an easily recognized group who are in touch with a wide variety of healthcare providers before, during, and after pregnancy, mandating that chronic hypertension in pregnancy be within the scope of many practitioners. We reviewed recent data on management to inform current care and future research. This study is a narrative review of published literature. Compared with normotensive women, women with chronic hypertension are at an increased risk of maternal and perinatal complications. Women with chronic hypertension who wish to be involved in their care can do by measuring blood pressure at home. Accurate devices for home blood pressure monitoring are now readily available. The diagnostic criteria for superimposed preeclampsia remain problematic because most guidelines continue to include deteriorating blood pressure control in the definition. It has not been established how angiogenic markers may aid in confirmation of the diagnosis of superimposed preeclampsia when suspected, over and above information provided by routinely available clinical data and laboratory results. Although chronic hypertension is a strong risk factor for preeclampsia, and aspirin decreases preeclampsia risk, the effectiveness specifically among women with chronic hypertension has been questioned. It is unclear whether calcium has an independent effect in preeclampsia prevention in such women. Treating hypertension with antihypertensive therapy halves the risk of progression to severe hypertension, thrombocytopenia, and elevated liver enzymes, but a reduction in preeclampsia or serious maternal complications has not been observed; however, the lack of evidence for the latter is possibly owing to few events. In addition, treating chronic hypertension neither reduces nor increases fetal or newborn death or morbidity, regardless of the gestational age at which the antihypertensive treatment is started. Antihypertensive agents are not teratogenic, but there may be an increase in malformations associated with chronic hypertension itself. At present, blood pressure treatment targets used in clinics are the same as those used at home, although blood pressure values tend to be inconsistently lower at home among women with hypertension. Although starting all women on the same antihypertensive medication is usually effective in reducing blood pressure, it remains unclear whether there is an optimal agent for such an approach or how best to use combinations of antihypertensive medications. An alternative approach is to individualize care, using maternal characteristics and blood pressure features beyond blood pressure level (eg, variability) that are of prognostic value. Outcomes may be improved by timed birth between 38 0/7 and 39 6/7 weeks' gestation based on observational literature; of note, confirmatory trial evidence is pending. Postnatal care is facilitated by the acceptability of most antihypertensives (including angiotensin-converting enzymes inhibitors) for use in breastfeeding. The evidence base to guide the care of pregnant women with chronic hypertension is growing and aligning with international guidelines. Addressing outstanding research questions would inform personalized care of chronic hypertension in pregnancy.

Society for Maternal-Fetal Medicine Special Statement: Quality metric for timely postpartum follow-up after severe hypertension.

Hypertensive disorders of pregnancy are a leading cause of maternal morbidity and mortality. Because postpartum exacerbation of severe hypertension is common, the American College of Obstetricians and Gynecologists recommends that patients with severe hypertension during the childbirth hospitalization be seen within 72 hours after discharge. In this statement, the Society for Maternal-Fetal Medicine proposes a uniform metric reflecting the rate of timely postpartum follow-up of patients with severe hypertension. The metric is designed to be measured using automated calculations based on billing codes derived from claims data. The metric can be used in quality improvement projects to increase the rate of timely follow-up in patients with severe hypertension during the childbirth hospitalization. Suggested steps for implementing such a project are outlined.

Society for Maternal-Fetal Medicine Special Statement: A quality metric for evaluating timely treatment of severe hypertension.

Severe hypertension in pregnancy is a medical emergency. Although expeditious treatment within 30 to 60 minutes is recommended to reduce the risk of maternal death or severe morbidity, treatment is often delayed by >1 hour. In this statement, we propose a quality metric that facilities can use to track their rates of timely treatment of severe hypertension. We encourage facilities to adopt this metric so that future reports from different facilities will be based on a uniform definition of timely treatment.

The diagnostic value of angiogenic and antiangiogenic factors in differential diagnosis of preeclampsia.

The definition of preeclampsia is changing. However, with the addition of organ symptoms to the presence of hypertension in pregnancy instead of relying only on proteinuria, a more precise detection of women at risk of preeclampsia-associated adverse events has not been achieved. Instead, under the new definitions of the American College of Obstetricians and Gynecologists and of the International Society for the Study of Hypertension in Pregnancy, more women are classified as preeclamptic, with a tendency to milder disease. Furthermore, angiogenic and antiangiogenic factors have emerged as essential tools for predicting and diagnosing preeclampsia at high accuracies. Next to being rooted in the pathophysiology of the disease, they have been proven to be reliable tools for predicting and diagnosing the disease. In addition, 2 cutoffs have been evaluated for the clinical setting. As shown in the Prediction of Short-Term Outcome in Pregnant Women With Suspected Preeclampsia Study, at the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio cutoff of 38, a preeclampsia can be ruled out for 1 week with a negative predictive value of 99.3% (95% confidence interval, 97.9-99.9) and ruled in with a positive predictive value of 36.7% (95% confidence interval, 28.4-45.7). The diagnostic cutoff of 85 has been shown to accurately identify women with preeclampsia, with a sensitivity of up to 88% and a specificity of 99.5%. In this review, we highlight the central role of angiogenic and antiangiogenic factors in the differential diagnosis of women presenting at high risk of the disease, such as patients with chronic hypertension or chronic kidney disease. We will focus on their ability to predict preeclampsia-associated adverse fetal and maternal outcomes. This is only possible when critically reviewing the evolution of the definition of "preeclampsia." We show how changes in this definition shape our clinical picture of the condition and how angiogenic and antiangiogenic biomarkers might be included to better identify women destined to develop preeclampsia-related adverse outcomes.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.