Computational model captures cardiac growth in hypertensive pregnancies and in the postpartum period.

Heart growth in the pregnant patient helps maintain cardiovascular function while supporting the growing fetus. However, in some cases, the cardiovascular demand of pregnancy can trigger life-threatening conditions, including hypertensive disorders of pregnancy and peripartum cardiomyopathy. The mechanisms that control heart growth throughout pregnancy are unclear, and treating these diseases remains elusive. We previously developed a computational model that accounts for hormonal and hemodynamic interactions throughout pregnancy and demonstrated its ability to capture realistic cardiac growth in normal rat pregnancy. In this study, we evaluated whether this model could capture heart growth beyond normal pregnancy. After further validation of our normal pregnancy predictions, we tested our model predictions of three rat studies of hypertensive pregnancies. We next simulated the postpartum period and examined the impact of lactation on cardiac growth in rats. We demonstrate that our multiscale model can capture cardiac growth associated with new-onset hypertension during pregnancy and lactation status in the postpartum period. We conclude by elaborating on the potential clinical utility of our model in the future.NEW & NOTEWORTHY Our multiscale model predicts appropriate heart growth beyond normal pregnancy, including elevated heart weights in rats with induced hypertension during pregnancy and in lactating mice and decreased heart weight in nonlactating mice. Our model captures distinct mechanisms that result in similar organ-level growth, highlighting its potential to distinguish healthy from diseased pregnancy-induced growth.

Adverse pregnancy outcomes and pharyngeal flow limitation during sleep: Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b).

BACKGROUND: Pharyngeal flow limitation during pregnancy may be a risk factor for adverse pregnancy outcomes but was previously challenging to quantify. Our objective was to determine whether a novel objective measure of flow limitation identifies an increased risk of pre-eclampsia (primary outcome) and other adverse outcomes in a prospective cohort: Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b). METHODS: Flow limitation severity scores (0%=fully obstructed, 100%=open airway), quantified from breath-by-breath airflow shape, were obtained from home sleep tests during early (6-15 weeks) and mid (22-31 weeks) pregnancy. Multivariable logistic regression quantified associations between flow limitation (median overnight severity, both time-points averaged) and pre-eclampsia, adjusting for maternal age, body mass index (BMI), race, ethnicity, chronic hypertension and flow limitation during wakefulness. Secondary outcomes were hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM) and infant birthweight. RESULTS: Of 1939 participants with flow limitation data at both time-points (mean±sd age 27.0±5.4 years and BMI 27.7±6.1 kg·m-2), 5.8% developed pre-eclampsia, 12.7% developed HDP and 4.5% developed GDM. Greater flow limitation was associated with increased pre-eclampsia risk: adjusted OR 2.49 (95% CI 1.69-3.69) per 2sd increase in severity. Findings persisted in women without sleep apnoea (apnoea-hypopnoea index <5 events·h-1). Flow limitation was associated with HDP (OR 1.77 (95% CI 1.33-2.38)) and reduced infant birthweight (83.7 (95% CI 31.8-135.6) g), but not GDM. CONCLUSIONS: Greater flow limitation is associated with increased risk of pre-eclampsia, HDP and lower infant birthweight. Flow limitation may provide an early target for mitigating the consequences of sleep disordered breathing during pregnancy.

Vascular health years after a hypertensive disorder of pregnancy: The EPOCH study.

BACKGROUND: Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum. METHODS: Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound. RESULTS: Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses, cases (N = 68) were more likely than controls (N = 71) to have hypertension (18% vs 4%, P = .034), higher calculated ASCVD risk (0.6 vs 0.4, P = .02), higher blood pressures (systolic: 118.5 vs 111.6 mm Hg, P = .0004; diastolic: 75.2 vs 69.8 mm Hg, P = .0004), and higher augmentation index values (7.7 vs 2.3, P = .03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs 0.5, P = .29) or reactive hyperemia index (2.1 vs 2.1, P = .93), nor in pulse wave amplitude (416 vs 326, P = .11), carotid elastic modulus (445 vs 426, P = .36), or carotid beta stiffness (2.8 vs 2.8, P = .86). CONCLUSION: Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

First-trimester screening identifies maternal cardiac maladaptation in midgestation.

OBJECTIVE: We have previously established that a logistic regression model, based on maternal demographic characteristics and blood pressure measured at 11-13 weeks' gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the 3 years following pregnancy, at a screen-positive rate of 10%. Furthermore, in midgestation, women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery. In this study, we set out to examine whether use of the first-trimester risk model for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation in midgestation. METHODS: This was a prospective observational study of 3812 women with singleton pregnancy attending for a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation and again at 19 + 1 to 23 + 3 weeks at King's College Hospital, London, UK, between December 2019 and August 2020. The first-trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. In midgestation, detailed maternal cardiovascular assessment was carried out. The association between risk for development of CH, determined from first-trimester assessment, and cardiovascular indices in midgestation was examined. RESULTS: Women who were at high risk for development of future CH, compared to those at low risk, had a higher incidence of HDP. In addition, high-risk women had reduced systolic and diastolic function in midgestation. Among women with HDP, those who were at high risk for future CH, compared to those at low risk, had worse cardiac function in midgestation. CONCLUSIONS: Use of a model for first-trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation in midgestation. Further studies are needed to clarify whether women who screen as high risk for future CH, compared to those at low risk, have reduced cardiac function beyond pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Impact of hypertensive disorders of pregnancy on offspring cardiovascular function: from fetal life to early childhood.

OBJECTIVE: Epidemiological studies suggest that, following in-utero exposure to hypertensive disorder of pregnancy (HDP), children may be at increased long-term cardiovascular risk, but data in early childhood are lacking. We aimed to investigate the independent influence of HDP on infant cardiac structure and function, after accounting for differences in childhood risk-factor profile. METHODS: This was a longitudinal study of 71 children born of a pregnancy complicated by HDP (gestational hypertension or pre-eclampsia) and 304 children born of a normotensive pregnancy. Detailed cardiovascular assessment was performed at mid gestation and at a median of 2.3 (interquartile range, 2.1-2.4) years postnatally. Linear mixed-effects modeling was used to determine the independent influence of HDP on infant cardiac function and structure after accounting for differences in childhood risk-factor profile. RESULTS: There were no differences in demographic characteristics between children whose mother developed HDP and those born of a normotensive pregnancy, but delivery was earlier and birth weight was lower in the HDP group. In fetal life, there were no significant differences in cardiac function or structure between the HDP and non-HDP groups. In early childhood, in the HDP group compared with the non-HDP group, there was greater relative wall thickness (mean ± SD, 0.7 ± 0.3 vs 0.6 ± 0.3; P = 0.047) and increased left ventricular mass (indexed to body surface area) (mean ± SD, 80.9 ± 20.4 g/m2 vs 75.7 ± 16.5 g/m2; P = 0.024); however, these differences did not persist on multivariable analysis. Longitudinal analysis revealed that there was no difference in the change in cardiac functional indices from fetal life to early childhood between the HDP and non-HDP groups. CONCLUSION: There is no evidence that HDP has an adverse effect on offspring cardiovascular health in fetal life or in early childhood. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler in women with hypertensive disorders of pregnancy: relationship to blood pressure control and renal dysfunction at 6-9 weeks postnatally.

OBJECTIVES: To examine the postnatal course of ophthalmic artery (OA) Doppler in women with hypertensive disorders of pregnancy (HDP) and to evaluate the correlation between OA Doppler parameters and poor postnatal blood pressure control and renal dysfunction at 2-3 weeks and 6-9 weeks postnatally. METHODS: This was a prospective cohort study of women with a singleton pregnancy and HDP seen at a tertiary pregnancy hypertension clinic between 2019 and 2021. Three visits were included: Visit 1, the last visit to the antenatal hypertension clinic within 2 weeks prior to delivery; Visit 2, at 2-3 weeks postnatally; and Visit 3, at 6-9 weeks postnatally. At each visit, maternal demographic characteristics, medical history, blood pressure and OA Doppler were obtained. In addition, fetal growth and fetal Dopplers were examined antenatally and, at 6-9 weeks postnatally, estimated glomerular filtration rate and proteinuria were quantified. Study participants were divided into four hypertension groups, according to longitudinal changes in blood pressure at the three visits. For the postnatal visits, hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg in the absence of antihypertensive medication, and SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg whilst taking antihypertensives. Group 1 was hypertensive at all three visits; Group 2 was hypertensive at Visits 1 and 2 but normotensive at Visit 3; Group 3 was hypertensive at Visits 1 and 3 but normotensive at Visit 2; and Group 4 was hypertensive at Visit 1 but normotensive at Visits 2 and 3. The longitudinal changes in mean arterial pressure (MAP), peak systolic velocity (PSV) 1, PSV2 and the ratio of PSV2/PSV1 over the three timepoints were examined by a repeated-measures, multilevel, linear mixed-effects analysis, controlling for maternal age, weight at presentation and use of antihypertensive medication. In addition, we examined the longitudinal change in OA Doppler parameters in women with different degrees of postnatal blood pressure control and in those with and those without renal dysfunction at 6-9 weeks postnatally. RESULTS: A total of 108 women were recruited to the study, of whom 86 had new-onset hypertension and 22 had chronic hypertension. When controlling for maternal age, weight at presentation and use of antihypertensive medication, a significant decline in log10 MAP (P < 0.001), log10 PSV1 (P < 0.001) and log10 PSV2 (P = 0.01) was seen between Visits 1 and 3. Log10 PSVR did not change with time. When assessing OA Doppler against hypertension group, log10 PSV1 and log10 PSV2 did not differ between the hypertension groups, whilst Group 4 had a lower log10 PSVR compared with Group 1 (P < 0.01), Group 2 (P = 0.03) and Group 3 (P < 0.01). At 6-9 weeks postnatally, log10 PSVR was lower in those without compared to those with renal dysfunction (-0.021, P = 0.01), whilst log10 MAP, log10 PSV1 and log10 PSV2 values did not differ. Log10 PSVR did not change with time and remained at -0.12 (95% CI, -0.13 to -0.11) across the three visits. CONCLUSIONS: In women with HDP, the OA-PSVR was significantly higher in those with labile or persistently raised blood pressure postnatally compared to women whose blood pressure normalized. Similarly, the OA-PSVR at 6-9 weeks postnatally was significantly higher in women with renal dysfunction vs those without dysfunction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

BACKGROUND: Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. METHODS: A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. RESULTS: A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. CONCLUSION: A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

The Relationship between the Level of Coagulative Function Hypertensive Disorder Complicating Pregnancy.

BACKGROUND AND AIM: Preeclampsia, a pregnancy complication associated with significant maternal and perinatal mortality and morbidity, has been found to be closely linked to dysfunction in the blood coagulation-fibrinolysis system. However, the relationship between hematologic data and severity and onset time of preeclampsia remains unclear. This study aimed to identify specific hematologic parameters in both preeclamptic and normotensive pregnant women and determine their potential significance in the pathogenesis of preeclampsia. MATERIALS AND METHODS: A total of 112 patients with gestational hypertension disease were divided into two groups: early-onset preeclampsia (32 cases) and late-onset preeclampsia (80 cases). A control group of 82 normotensive pregnant women matched for age and parity was also selected. Blood samples were collected from all participants to test for specific hematologic parameters. RESULTS: Mild and severe preeclampsia were associated with lower hemoglobin level (P = 0.01 and P = 0.03, respectively), higher mean platelet volume (P = 0.01 and P = 0.01, respectively) and fibrinogen (P = 0.01 and P = 0.01, respectively), and shorter prothrombin time (P = 0.02 and P = 0.01, respectively) and activated partial thromboplastin time (P = 0.01 and P = 0.02, respectively). CONCLUSION: These findings have provided evidence on the hematologic coagulative actors in the pathogenesis and severity of preeclampsia.

A comparison among oscillometric waveforms in healthy nonpregnant women, pregnancy and hypertensive disorders of pregnancy.

OBJECTIVE: Understanding of how oscillometric waveforms (OMW) vary between pregnant and nonpregnant individuals remains low. An exploratory analysis was completed to assess for quantitative and qualitative changes in OMW and oscillometric envelope features in pregnancy. DESIGN AND METHODS: Eighteen pregnant individuals (over 20 weeks gestational age) and healthy, nonpregnant (HNP) women were recruited. Six HNP were matched to six healthy pregnant (HP) women, and six pregnant women with a hypertensive disorder of pregnancy (HDP) by age, arm circumference, and cuff size. Blood pressure measurements were completed per the International Organization for Standardization (ISO) protocol using a custom-built oscillometric device as the test device and two-observer mercury auscultation as the reference measurement. Auscultatory blood pressure and blood pressure derived from slope-based and fixed ratio algorithms were determined. OMW and envelope features were compared among groups. RESULTS: In HNP, HP, and HDP groups respectively: mean auscultatory blood pressure (systolic mean ± SD/diastolic mean ± SD) was 103.4 ±â€…12.2/67.1 ±â€…7.9; 109.5 ±â€…3.1/58.1 ±â€…6.4; 135.6 ±â€…18.9/85.1 ±â€…14.2 mmHg. HDP had significantly higher auscultatory systolic and diastolic blood pressure than the HP group ( P  = 0.001). The pregnant groups had a lower average pulse width (mean ± SD: HNP = 0.8 ±â€…0 s, HP = 0.6 ±â€…0.1 s, HDP = 0.6 ±â€…0.1 s; HP vs. HNP mean difference [adjusted P value]: 0.2 [ P  = 0.004], HDP vs. HNP 0.1 [ P  = 0.018]) compared with the HNP group. The HDP group had a larger area under the OMW envelope than the HNP group (mean ± SD: HNP = 22.6 ±â€…3.4; HDP = 28.5 ±â€…4.2; HDP vs. HNP mean difference [adjusted P value]: 5.9 P  = 0.05). CONCLUSION: In this exploratory work, differences in the OMW morphology and parameters were found in pregnancy and in hypertensive disorders of pregnancy compared with healthy controls. Even small differences may have important implications in algorithm development; further work comparing OMW envelopes in pregnancy is needed to optimize the algorithms used to determine blood pressure in pregnancy.

An in vitro study of coagulation evaluation in obstetric hemorrhage for pregnancy-induced hypertension with coagulation and platelet function analyzer.

This study aimed to establish in vitro hemodilution and resupplementation assays for obstetric hemorrhage in pregnancy-induced hypertension (PIH) and to monitor the coagulation function dynamically using a coagulation and platelet function analyzer. Forty-seven singleton pregnant women were divided into normal (n = 24) and PIH (n = 23) groups. Peripheral blood samples were used to construct the assays, and the activated clotting time (ACT), clotting rate (CR), and platelet function index (PF) were measured. The results showed that the baseline ACT was higher in the PIH group (p < 0.01). Hemodilution assays showed decreased ACT and increased CR and PF, with ACT changes significantly lower in the PIH group (p < 0.05). CR changed most in both groups at lower dilution ratios (35% to 50%), while ACT changed most at a higher dilution ratio (75%). In the resupplementation assay, ACT exhibited the most significant response. The analyzer effectively detected differences between pregnant women with and without PIH. Thus, we need to pay more attention to the changes of ACT in the actual clinical application to assess the coagulation status of parturients.

Relationship between hypertensive disorders of pregnancy (HDP) and cardiac remodeling during pregnancy: Systematic review and meta-analysis.

OBJECTIVES: Hypertensive disorders of pregnancy (HDP) are among the leading causes of maternal morbidity and mortality. The primary objective of this study was to ascertain whether maternal cardiac remodeling is more prevalent in HDP than normotensive pregnancy and if significant change in aortic root size is involved. The secondary objective was to determine the types of cardiac remodeling often associated with HDP. METHODS: A systematic search was conducted across four electronic databases, including Medline, PubMed, Cochrane and EMBASE. The reference lists of selected articles were also searched to ensure no relevant studies were missed. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in this systematic review. RESULTS: Out of 5,278 articles identified by the search terms, 9 were eligible for inclusion in the meta-analysis. The investigation unveiled a greater prevalence of maternal cardiac remodeling in HDP than normotensive pregnancies. The commonest type of maternal cardiac remodeling in both HDP and normotensive pregnancies was eccentric left ventricular hypertrophy, followed by concentric left ventricular remodeling which was more specific to HDP. Notably, left atrial diameter was significantly increased in HDP than normotensive pregnancies, suggesting higher prevalence of diastolic dysfunction. Additionally, the aortic root dimension was significantly increased in HDP than normotensive pregnancies. CONCLUSION: This study underscores the importance of monitoring cardiac health in pregnancy, particularly in those with hypertensive disorders, in order to mitigate potential complications and improve maternal outcomes. Finally, the risk of aortic dissection that may occur as a long-term effect of aortic root enlargement in women with history of HDP ought to be investigated in future studies.

Postpartum Weight Change Association With Readmission and Blood Pressure Trend Among Individuals With Hypertensive Disorders of Pregnancy.

BACKGROUND: The aim of this study was to evaluate the association between early postpartum weight change and (1) hospital readmission and (2) 2-week blood pressure trajectory. METHODS AND RESULTS: This retrospective study cohort included 1365 individuals with a hypertensive disorder of pregnancy enrolled in a postpartum hypertension remote monitoring program. Exposure was percentage weight change from delivery to first weight recorded within 10 days postpartum. We first modeled likelihood of hospital readmission within 8 weeks postpartum using logistic regression adjusting for age, race, insurance, type of hypertensive disorder of pregnancy, early body mass index, gestational weight gain, mode of delivery, and any discharge antihypertensive medications. We then performed case-control analysis additionally matching in a 1:3 ratio on breastfeeding, early body mass index, discharge on antihypertensive medications, and days between weight measurements. Both analytic approaches were repeated, limiting to readmissions attributable to hypertension or heart failure. Finally, we compared blood pressure trajectories over first 2 weeks postpartum. Individuals who did not lose weight in the early postpartum period had more admissions compared with weight loss groups (group 3: 14.1% versus group 2: 5.8% versus group 1: 4.5%). These individuals had 4 times the odds of postpartum readmissions (adjusted odds ratio [aOR], 3.9 [95% CI, 1.8-8.6]) to 7 (aOR, 7.8 [95% CI, 2.3-26.5]) compared with those with the most weight loss. This association strengthened when limited to hypertension or heart failure readmissions. These individuals also had more adverse postpartum blood pressure trajectories, with significant differences by weight change group. CONCLUSIONS: Weight change is readily accessible and may identify individuals at high risk for postpartum readmission following a hypertensive disorder of pregnancy who could benefit from targeted interventions.

Implementation of a Cell-Enabled Remote Blood Pressure Monitoring Program During the Postpartum Period at a Safety-Net Hospital.

BACKGROUND: Postpartum hypertension is a risk factor for severe maternal morbidity; however, barriers exist for diagnosis and treatment. Remote blood pressure (BP) monitoring programs are an effective tool for monitoring BP and may mitigate maternal health disparities. We aimed to describe and evaluate engagement in a remote BP monitoring program on BP ascertainment during the first 6-weeks postpartum among a diverse patient population. METHODS AND RESULTS: A postpartum remote BP monitoring program, using cell-enabled technology and delivered in multiple languages, was implemented at a large safety-net hospital. Eligible patients are those with hypertensive disorders before or during pregnancy. We describe characteristics of patients enrolled from January 2021 to May 2022 and examine program engagement by patient characteristics. Linear regression models were used to calculate mean differences and 95% CIs between characteristics and engagement metrics. We describe the prevalence of patients with BP ≥140/or >90 mm Hg. Among 1033 patients, BP measures were taken an average of 15.2 days during the 6-weeks, with the last measurement around 1 month (mean: 30.9 days), and little variability across race or ethnicity. Younger maternal age (≤25 years) was associated with less frequent measures (mean difference, -4.3 days [95% CI: -6.1 to -2.4]), and grandmultiparity (≥4 births) was associated with shorter engagement (mean difference, -3.5 days [95% CI, -6.1 to -1.0]). Prevalence of patients with BP ≥140/or >90 mm Hg was 62.3%, with differences by race or ethnicity (Black: 72.9%; Hispanic: 52.4%; White: 56.0%). CONCLUSIONS: A cell-enabled postpartum remote BP monitoring program was successful in uniformly monitoring BP and capturing hypertension among a diverse, safety-net hospital population.

Echocardiographic assessment of left atrial mechanics in women with hypertensive disorders of pregnancy: A systematic review and meta-analysis.

OBJECTIVE: The influence of hypertensive disorders of pregnancy (HDP) on left atrial (LA) mechanics assessed by speckle tracking echocardiography (STE) has been poorly investigated. Accordingly, we performed a meta-analysis to summarize the main findings of STE studies who measured LA reservoir (LASr), conduit (LAScd) and contractile (LASct) strain in HDP women. STUDY DESIGN: All echocardiographic studies assessing LA strain parameters in HDP women vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. Continuous data (LASr, LAScd and LASct) were pooled as standardized mean difference (SMD) comparing HDP group with healthy controls. The overall SMDs of LASr, LAScd and LASct were calculated using the random-effect model. RESULTS: The full-texts of 8 studies with 566 HDP women and 420 healthy pregnant women were analyzed. Average LASr (34.3 ± 6.4 vs 42.7 ± 5.3 %, P = 0.01) and LAScd (23.4 ± 6.3 vs 32.5 ± 6.0 %, P < 0.001) were significantly lower in HDP women than controls, whereas LASct (-13.0 ± 5.4 vs -13.7 ± 4.5 %, P = 0.18) was similar in the two groups of women. Substantial heterogeneity was detected among the studies evaluating LASr (I2 = 94.3 %), LAScd (I2 = 64.9 %) and LASct (I2 = 86.4 %). SMDs were large and statistically significant for LASr (-1.70, 95 %CI -2.34,-1.06, P < 0.001) and LAScd (-1.35, 95 %CI -1.69,-1.00, P < 0.001), small and not statistically significant for LASct (-0.11, 95 %CI -0.60,0.39, P = 0.678) assessment. Egger's test gave P-values of 0.10, 0.34 and 0.75 for LASr, LAScd and LASct measurement respectively, indicating no publication bias. On meta-regression analysis, none of the moderators was significantly associated with effect modification for LASr and its components (all P < 0.05). CONCLUSIONS: HDPs are independently associated with LASr impairment in pregnancy. STE allows to identify, among HDP women, those who might benefit from a more aggressive antihypertensive treatment and/or a closer clinical follow-up, aimed at reducing the risk of adverse maternal outcome and cardiovascular complications later in life.

Prospective validation of a mobile health application for blood pressure management in patients with hypertensive disorders of pregnancy: study protocol for a randomized controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) pose significant risks to both maternal and fetal health, contributing to global morbidity and mortality. Management of HDP is complex, particularly because of concerns regarding potential negative effects on utero-placental circulation and limited therapeutic options due to fetal safety. Our study investigates whether blood pressure monitoring through a mobile health (mHealth) application can aid in addressing the challenges of blood pressure management in pregnant individuals with HDP. Additionally, we aim to assess whether this intervention can improve short-term maternal and fetal outcomes and potentially mitigate long-term cardiovascular consequences. METHODS: This prospective, randomized, single-center trial will include 580 pregnant participants who meet the HDP criteria or who have a heightened risk of pregnancy-related hypertension due to factors such as multiple pregnancies, obesity, diabetes, or a history of HDP in prior pregnancies leading to preterm birth. Participants will be randomized to either the mHealth intervention group or the standard care group. The primary endpoint is the difference in systolic blood pressure from enrollment to 1 month after childbirth. The secondary endpoints include various blood pressure parameters, obstetric outcomes, body mass index trajectory, step counts, mood assessment, and drug adherence. CONCLUSIONS: This study emphasizes the potential of mHealth interventions, such as the Heart4U application, to improve blood pressure management in pregnant individuals with HDP. By leveraging technology to enhance engagement, communication, and monitoring, this study aims to positively impact maternal, fetal, and postpartum outcomes associated with HDP. This innovative approach demonstrates the potential of personalized technology-driven solutions for managing complex health conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05995106. Registered on 16 August 2023.

Association of Hypertensive Disorders of Pregnancy With Coronary Microvascular Dysfunction 8 to 10 Years After Delivery.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling. METHODS: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive ß, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of ß at peak stress to ß at rest, averaged across LV myocardial regions of interest. RESULTS: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498). CONCLUSIONS: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.

Maternal pregnancy hypertension impairs nitric oxide formation and results in increased arterial blood pressure in first-generation offspring female rats.

OBJECTIVES: Maternal endothelial dysfunction in pregnancy hypertension is related to impairment of nitric oxide (NO) formation. However, NO levels and hemodynamic repercussions on the female offspring remain unclear. Therefore, this study hypothesized that maternal pregnancy hypertension reduces circulating NO metabolites and increases arterial blood pressure in first-generation offspring female rats. STUDY DESIGN: Descendant female rats were distributed in four groups as follows: virgin offspring of normotensive (VN) and hypertensive (VH) mothers and pregnant offspring of normotensive (PN) and hypertensive (PH) mothers. Hemodynamic and biochemical analyses were performed. MAIN OUTCOME MEASURES: The systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), and body weight were measured. NO metabolites in plasma, NO formation in human umbilical vein endothelial cells (HUVECs) incubated with plasma, and endothelial NO synthase (eNOS) expression in aortas were determined. RESULTS: Increased SBP, DBP, and reduced HR were found on the 60 days of life in the VH group, whereas the PH group showed increased SBP and HR on pregnancy day 7. All groups showed no differences in body weight gain and eNOS expression. Plasma levels of NO metabolites were increased in the PN compared to the other groups. Increases in the NO formation were greater in HUVECs incubated with plasma from VN and PN groups compared to the VH and PH groups. CONCLUSIONS: Female virgin and pregnant first-generation offspring rats from hypertensive pregnant mothers may have negative cardiovascular repercussions featured by increases in SBP, and possibly impaired NO formation is involved.

Leptin in reproduction and hypertension in pregnancy.

Leptin has important roles in numerous physiological functions, including those in the regulation of energy balance, and in immune and reproductive systems. However, in the recent years, evidence has implicated it in a number of obesity-related diseases, where its concentrations in serum are significantly elevated. Elevated serum leptin concentrations and increased placental leptin secretion have been reported in women with hypertensive disorders of pregnancy. Whether leptin is responsible for this disorder remains to be established. Leptin injections in healthy rats and mice during pregnancy result in endothelial activation, increased blood pressure and proteinuria. A potential role for leptin in the pathogenesis of pre-eclampsia is hypothesised, particularly in women who are overweight or obese where serum leptin concentrations are often elevated. This review summarises pertinent information in the literature on the role of leptin in puberty, pregnancy, and hypertensive disorders of pregnancy. In particular, the possible mechanism that may be involved in leptin-induced increase in blood pressure and proteinuria during pregnancy and the potential role of marinobufagenin in this disease entity. We hypothesise a significant role for oxidative stress in this, and propose a conceptual framework on the events that lead to endothelial activation, raised blood pressure and proteinuria following leptin administration.

Postpartum Ambulatory Blood Pressure Patterns Following New-Onset Hypertensive Disorders of Pregnancy.

Importance: After a hypertensive disorder of pregnancy, hypertension can worsen in the postpartum period following hospital discharge. Risk factors for ongoing hypertension and associated outcomes have not been well characterized. Objective: To identify risk factors and characterize outcomes for individuals with ongoing hypertension and severe hypertension following hospital discharge post partum through a hospital system's remote blood pressure (BP) management program. Design, Setting, and Participants: This cohort study involved a population-based sample of individuals with a new-onset hypertensive disorder of pregnancy (preeclampsia or gestational hypertension) and no prepregnancy hypertension who delivered between September 2019 and June 2021. Participants were enrolled in a remote BP monitoring and management program at a postpartum unit at a referral hospital. Data analysis was performed from August 2021 to January 2023. Exposure: Inpatient postpartum BP categories. Main Outcomes and Measures: The primary outcomes were readmission and emergency department visits within the first 6 weeks post partum. Logistic regression was used to model adjusted odds ratios (aORs) and 95% CIs. Results: Of 2705 individuals in the cohort (mean [SD] age, 29.8 [5.7] years), 2214 (81.8%) had persistent hypertension post partum after hospital discharge, 382 (14.1%) developed severe hypertension after discharge, and 610 (22.6%) had antihypertensive medication initiated after discharge. Individuals with severe hypertension had increased odds of postpartum emergency department visits (aOR, 1.85; 95% CI, 1.17-2.92) and hospital readmissions (aOR, 6.75; 95% CI, 3.43-13.29) compared with individuals with BP normalization. When inpatient postpartum BP categories were compared with outpatient home BP trajectories to inform optimal thresholds for inpatient antihypertensive medication initiation, there was significant overlap between postdischarge BP trajectories among those with inpatient systolic BP greater than or equal to 140 to 149 mm Hg and/or diastolic BP greater than or equal to 90 to 99 mm Hg and those with systolic BP greater than or equal to 150 mm Hg and/or diastolic BP greater than or equal to 100 mm Hg. Conclusions and Relevance: This cohort study found that more than 80% of individuals with hypertensive disorders of pregnancy had ongoing hypertension after hospital discharge, with approximately 14% developing severe hypertension. These data support the critical role of remote BP monitoring programs and highlight the need for improved tools for risk stratification and consideration of liberalization of thresholds for medication initiation post partum.

Finger pulse plethysmography predicts gestational hypertension, preeclampsia and gestational diabetes.

BACKGROUND: Pregnancy complications related to hypertension can affect both mother and newborn. Pulse wave attenuation (PWA) captured through fingertip photoplethysmography (PPG) provide valuable insights into maternal acute hemodynamic and autonomic vascular function. Here, we quantify the nocturnal dynamics of PWA during early pregnancy and assess their association with the development of gestational hypertension, preeclampsia and gestational diabetes. METHODS: PWA dynamics were assessed on overnight polysomnography-derived PPG signals from a cohort of 2714 pregnant women (mean age: 26.8 ±â€Š5.5 years) enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). We determined the average duration (PWA duration ) and depth (PWA depth ) of PWA events in all women. RESULTS: Odds ratio (OR) analysis-adjusted common confounders indicates that an average PWA duration greater than 8.74 s was associated with the increased risk of gestational hypertension [OR = 1.75 (1.27-2.39), P  < 0.001]. Similarly, average PWA depth greater than 1.19 was associated with an increased risk of preeclampsia [OR = 1.53 (1.01-2.33), P  = 0.045] and gestational diabetes [OR = 1.66 (1.01-2.73), P  = 0.044]. CONCLUSION: PWA attenuation dynamics during early pregnancy predict the risk of developing gestational hypertension and diabetes condition for women in their later trimesters. Potentially obtainable from smart wearable consumer devices, PWA analysis offers a low-cost, accessible and scalable marker that can enhance the management of pregnancy-induced cardiometabolic issues.