Preeclampsia is a severe hypertensive disorder of pregnancy associated with low SIRT1 (sirtuin 1) levels in trophoblasts. Single-cell sequencing showed abnormal activation of trophoblast Rarres2 (retinoic acid receptor responder 2) and macrophage Cmklr1 (chemokine-like receptor 1) at the maternal-fetal interface in systemic Sirt1 heterozygous knockout mice. This study investigated how low SIRT1 in trophoblasts increases RARRES2 expression, affecting macrophage polarization and preeclampsia pathogenesis. We conducted coculture experiments to analyze trophoblast RARRES2 and macrophage CMKLR1 interactions, performed luciferase and chromatin immunoprecipitation assays to validate transcription factors for RARRES2 in trophoblasts, and utilized mass spectrometry and immunoprecipitation to identify transcriptional coregulators. cKO (trophoblast-specific Sirt1 knockout) mice were generated and treated with Rarres2 knockout or progesterone supplementation to validate the role of the SIRT1/RARRES2 axis in preeclampsia pathogenesis and prevention by progesterone. Finally, we measured RARRES2 and SIRT1 levels in the plasma of patients with preeclampsia. Low-SIRT1 expression in trophoblasts promoted M1-type macrophage polarization and inhibited trophoblast invasion, mediated by the RARRES2-CMKLR1 interaction. SIRT1 regulated RARRES2 expression in trophoblasts by recruiting NCOR2 (nuclear receptor corepressor 2). cKO mice showed preeclampsia-like symptoms and RARRES2-CMKLR1 activation at the maternal-fetal interface, which were reversed by Rarres2 knockout or progesterone supplementation. Notably, RARRES2 levels were higher and were a risk factor, whereas SIRT1 levels were lower and were a protective factor for preeclampsia in early pregnancy. This study highlights SIRT1's potential role in regulating abnormal trophoblast-macrophage interactions at the maternal-fetal interface in preeclampsia and offers a new strategy for its early prediction and prevention.

Background Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are associated with an increased risk of cardiovascular disease (CVD) later in life. Mechanisms that link HDP to CVD, however, remain unclear. Methods We used a high-dimensional single-cell mass cytometry approach to profile the distribution and functional responses of maternal immune cells in three separate groups of HDP cases and normotensive controls, sampled antepartum, postpartum, and several years postpartum (midlife). We used multivariable sparse modeling to distinguish HDP cases from controls. Results We accurately distinguished HDP cases from controls at all three study timepoints, with area under the receiver operator characteristic (AUROC) curve values of 0.814 for the antepartum group, 0.757 for the postpartum group, and 0.692 for the midlife group. Distinct immune signatures for each model underscore the dynamic dysregulation of the immune system throughout life. In addition, we identified a persistent immune dysregulation signal among HDP cases at all three timepoints, characterized by increased B cell frequency and decreased pSTAT3 response upon cytokine stimulation in classical monocytes. Conclusions Persistent immune dysregulation among women with a history of an HDP may contribute to elevated long-term risk of CVD development.

Hypertensive disorders of pregnancy (HDP) remain a major contributor to maternal and perinatal morbidity and mortality in low- and middle-income countries (LMICs). While clinical risk factors are well-described, non-biological determinants including environmental, psychosocial, and health-system factors play a critical but underexplored role. This systematic review synthesizes evidence on these determinants, with particular focus on Kano State Northern Nigeria and sub-Saharan Africa. A systematic review was conducted following PRISMA 2020 guidelines. Key electronic databases were searched, including PubMed, Scopus, and Web of Science, along with grey literature sources such as WHO, ACOG, and the Nigerian Federal Ministry of Health, for studies published between 2000 and 2025. Observational and mixed-methods studies reporting on hypertensive disorders of pregnancy (HDP) and non-biological determinants in low- and middle-income countries (LMICs) were included. Data on study characteristics, HDP prevalence, maternal and neonatal outcomes, and environmental, psychosocial, and health-system exposures were extracted. Study quality was assessed using standardized checklists appropriate for observational studies, and findings were synthesized narratively and, where feasible, quantitatively. Forty-eight studies involving over 138 women met the inclusion criteria. In Nigeria, HDP prevalence ranged from 6% to 17%, with preeclampsia at 4–8% and eclampsia at 1–2%. Key non-biological determinants included psychosocial stressors (chronic stress, domestic violence, low social support), socioeconomic disadvantage (low education, poverty), environmental exposures (ambient heat, household air pollution), and health-system constraints (limited antenatal care, delayed booking, inadequate monitoring, insufficient referral systems). These factors were linked to delayed diagnosis, severe maternal complications (eclampsia, HELLP syndrome, renal impairment). This study highlights a critical and underexplored dimension of hypertensive disorders of pregnancy (HDP) by examining non-biological determinants in low- and middle-income countries (LMICs). By synthesizing evidence on psychosocial, environmental, and health-system factors, it broadens the understanding of HDP beyond traditional clinical risk factors. The focus on Kano State Northern Nigeria and sub-Saharan Africa provides context-specific insights for regions with high maternal morbidity and mortality. These findings are valuable for researchers, clinicians, and policymakers, informing the design of targeted interventions, the strengthening of antenatal care services, and the implementation of community-based strategies. Ultimately, this work contributes to improving maternal and neonatal health outcomes and advancing Sustainable Development Goal 3 by 2030.

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.

The systems regulating blood pressure and calcium-magnesium (Ca2+-Mg2+) homeostasis are increasingly recognized to have clinically relevant interactions, where alterations in one can lead to significant changes in the other. In this study, we developed a computational model integrating blood pressure regulation and Ca2+-Mg2+ homeostasis in a male rat. We simulated various conditions, including hypertension, Ca2+, Mg2+, and vitamin D3 deficiencies, and primary hyperparathyroidism. Simulations of hypertension, induced by various stimuli like increased renin or aldosterone secretion, demonstrated significant effects on parathyroid hormone (PTH), calcitriol, renal Ca2+/Mg2+ handling, and bone resorption. Dietary Ca2+, Mg2+, and vitamin D3 deficiencies was predicted to elevate mean arterial pressure, with Mg2+ deficiency having a stronger effect. Furthermore, the model predicted that primary hyperparathyroidism elevates PTH, Ca2+, and calcitriol, leading to increased mean arterial pressure and bone loss. Overall, this model provides valuable insights into the mechanistic links between blood pressure regulation and Ca2+-Mg2+ homeostasis, offering insights into clinical conditions like hypertension and hyperparathyroidism.

This study investigates the impact of maternal high-fat diet (HFD) on the development of hypertension and associated metabolic changes in offspring across multiple generations of Wistar rats. Pregnant female rats were assigned to either a normal standard diet or a HFD during gestation. We assessed body weight, heart weight, systolic blood pressure (SBP), catechol-O-methyl transferase (COMT), and vanillyl mandelic acid (VMA) in first, second, and third-generation offspring. Our findings revealed that HFD offspring exhibited significantly elevated SBP compared to controls in all generations, with the most pronounced increase in F1. In addition, plasma EP, NE, and urinary VMA were markedly increased in F1, attenuated in F2, and remained elevated though less pronounced in F3. Also, the cardiac COMT expression was downregulated in all HFD offspring, most strongly in F1. Furthermore, the body weights were significantly higher in F1 compared to controls, whereas differences were minimal in F2 and F3. Moreover, dyslipidemia (elevated TC, TG, LDL; reduced HDL) was observed in F1 and partially persisted in F2 and F3. Finally, histopathological analysis revealed cardiac hypertrophy, cytoplasmic vacuolation, and pyknotic nuclei in F1, with milder alterations in F2 and F3. These results suggest that maternal HFD during pregnancy might affect the offspring cardiovascular health, potentially mediated by alterations in catecholamine dynamics. The study underscores the importance of maternal nutrition in the context of fetal programming and its implications for the prevention of hypertension and related metabolic disorders in future generations.

The study aims to determine whether the time of day influences these parameters compared to normotensive pregnancies.This prospective, single-center study included 60 pregnant women diagnosed with hypertensive disorders (gestational hypertension, chronic hypertension, or preeclampsia) and 60 normotensive controls, all between 30 and 37 weeks of gestation. Umbilical artery Doppler measurements were performed twice daily, between 08:00-10:00 and 20:00-22:00, by the same experienced operator. Measurements were taken at both the fetal and placental ends of the umbilical artery, recording systolic/diastolic ratios, pulsatility index, and resistance index values.In Doppler measurements, the morning and evening evaluations revealed that S/D, PI, and RI values near the fetus and placenta were significantly higher in the study group compared to the control group. Notably, in the preeclampsia subgroup, the morning S/D values (3.3±1.1 vs. 2.3±0.5, p<0.001) were found to reach the highest levels. Regarding neonatal outcomes, the study group demonstrated significantly higher rates of cesarean delivery (71.7% vs. 33.3%, p<0.001) and neonatal intensive care unit admission (36.7% vs. 6.7%, p<0.001), while birth weight was significantly lower (2724.9±759.1 g vs. 3241.1±422.7 g, p<0.001).This study demonstrates that hypertensive disorders during pregnancy have a significant adverse effect on umbilical artery Doppler measurements and neonatal outcomes. These findings underscore the importance of early diagnosis and meticulous monitoring.

To assess temporal trends in outcomes of pregnancies with maternal or paternal type 1 diabetes compared to the general population. Register-based study. Denmark. 1 551 893 pregnancies from 1997 to 2021, hereof 5478 with maternal and 8072 with paternal type 1 diabetes. Crude and adjusted logistic regression analyses allowing for interaction between diabetes and time compared outcomes of pregnancies with maternal or paternal type 1 diabetes to the general population and evaluated temporal trends over a 25-year period. Hypertensive disorders of pregnancy, caesarean delivery, preterm delivery (< 37-week gestation), very preterm delivery (< 34-week gestation), large for gestational age (LGA) (birth weight > 90th percentile) and extreme LGA (birth weight > 97.5th percentile). We observed an increasing prevalence of maternal (0.3%-0.4%) and paternal (0.5%-0.6%) diabetes during the study period. From 1997-2001 to 2017-2021, pregnancies with maternal diabetes had decreasing odds of preterm delivery (aOR 0.62, 95% CI 0.51;0.74), very preterm delivery (aOR 0.62, 95% CI 0.44;0.87) and extreme LGA (aOR 0.73, 95% CI 0.61;0.88) but remained associated with higher odds of each considered pregnancy outcome in both first and last period (aOR 3.59-18.86) compared to the general population. Pregnancies exposed to paternal diabetes were comparable to the general population. Despite a decline in adverse outcomes in pregnancies with maternal type 1 diabetes over the last 25 years, the odds remain greatly increased. These findings support a predominant role of maternal diabetes management rather than parental diabetes genes for pregnancy outcomes.

COVID-19 vaccination during or just prior to pregnancy and hypertensive disorders of pregnancy.

Minimum Wage Policies and Obstetric Disorders in the U.S.

Diurnal variation in urine protein-to-creatinine ratio among pregnant women with and without hypertensive disorders: A retrospective clinical study.

Designing a lifestyle intervention to optimise cardiometabolic health in high-risk prenatal and postnatal women: A pre-implementation study.

Preeclampsia, a serious hypertensive disorder of pregnancy, is associated with increased long-term risk of cardiovascular disease in adult offspring, particularly stroke. Although low-dose aspirin (LDA) is used prophylactically to prevent preeclampsia, its impact on offspring is unclear. This study investigated the effect of maternal LDA treatment during experimental preeclampsia (ePE) on adult first-generation (F1) offspring, including stroke outcome. ePE was induced in pregnant Sprague-Dawley rats via a high-cholesterol diet starting on gestational day 7 and treated with LDA (1.5 mg/kg) or vehicle. Offspring were weaned and fed standard chow until transient middle cerebral artery occlusion at 12 to 18 weeks (3-hour ischemia and 1-hour reperfusion). Fetal and juvenile weights were taken at gestational day 20 and from weeks 10 to 13. Infarct and edema were quantified using 2,3,5-triphenyltetrazolium chloride staining. Multisite laser Doppler was used to measure cerebral hemodynamics, including cerebral blood flow autoregulation and collateral flow. Circulating proinflammatory and anti-inflammatory factors were measured via multiplex immunoassay. Male offspring from ePE dams (ePE-F1) had larger infarction and edema versus male offspring from normal pregnant dams (NormP-F1, 48%±6 versus 11%±4; P<0.01) and all female offspring. Maternal treatment with LDA was protective of male offspring (ePE+Asp-F1) that had reduced infarct and edema. Increased infarction in ePE-F1 males was associated with greater collateral perfusion deficit and elevated levels of TNF-α (tumor necrosis factor-alpha) and IL (interleukin)-1β that were prevented by maternal LDA treatment. There were no differences in infarct, edema, or perfusion deficit in female offspring. Prenatal exposure to ePE worsened stroke severity and inflammation in male but not female offspring, which was largely mitigated by maternal LDA treatment, potentially due to an improved intrauterine environment. These findings highlight a sex-specific impact of prenatal preeclampsia exposure on long-term cerebrovascular health and suggest that maternal LDA may confer long-lasting protection to the offspring in addition to the mother.

Angiogenic and anti-angiogenic factors are the shared mechanistic pathways between preeclampsia and Alzheimer's disease: Perspective and take-away.

Aspirin is one of the most commonly used medications in pregnancy, particularly for the prevention of hypertensive disorders. Despite aspirin's widespread use in pregnancy for preeclampsia prevention, its pharmacokinetics (PK) across all trimesters remain poorly characterized, complicating optimal dosing recommendations. To develop a pregnancy-specific physiologically based pharmacokinetic (PBPK) model for aspirin that could be individualized to patient-specific parameters, illustrating differences in aspirin PK across the different trimesters of pregnancy. A PBPK model was developed using GastroPlus (a mechanistically driven simulation software) for nonpregnant and pregnant people at each trimester of pregnancy. The nonpregnant PBPK model was first established and validated against existing data from healthy adult volunteers. Once validated, the model was adapted for pregnant people and verified using observed pharmacokinetic profiles. The simulated PK parameters of aspirin in pregnant and nonpregnant women closely matched the clinical observations reported in the literature, with fold errors ≤ 1.04 (less than 1.5 is considered an acceptable simulation model). The predicted systemic exposure (AUC0-24h) of salicylic acid (SA), the active metabolite of aspirin decreased throughout gestation, showing a reduction of approximately 20% at 10 weeks and 30% at 40 weeks. An increase in clearance was observed as gestation progressed. The model predicted a modest decrease of 10% in systemic exposure in pregnant women and a 20% increase in fetal exposure to SA as pregnancy progresses. A PBPK model using GastroPlus was developed to describe the PK and pharmacodynamics of aspirin in both pregnant and nonpregnant healthyadults.

Risk factors and pregnancy outcomes of hypertensive disorders of pregnancy: a case-control study.

Due to limitations in observational studies, the link between COVID-19 and adverse pregnancy outcomes (APOs) remains inconclusive. This study uses two-sample Mendelian randomization (MR) analyses to assess COVID-19's causal effects on APO traits. We applied inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode to thoroughly evaluate the effects of COVID-19 infection, hospitalization, and critical status on eight APO traits. Our findings indicate that COVID-19 infection is associated with a decreased risk of eclampsia (OR: 0.35, 95%CI [0.13, 0.94]; p = 0.033) and the number of spontaneous miscarriages (OR: 0.95, 95%CI [0.91, 0.99]; p = 0.014), and an increased risk of preterm labor and delivery (OR: 1.30, 95%CI [1.04, 1.63]; p = 0.019). Hospitalized COVID-19 is associated with pre-eclampsia (OR: 1.13, 95%CI [1.00, 1.28]; p = 0.040), pre-eclampsia or eclampsia (OR: 1.14, 95%CI [1.01, 1.28]; p = 0.029), pregnancy hypertension (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), hypertension complicating pregnancy, childbirth, and the puerperium (OR: 1.09, 95%CI [1.01, 1.18]; p = 0.021), and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR: 1.10, 95%CI [1.03, 1.19]; p = 0.005). Critical COVID-19 is a risk factor for pre-eclampsia or eclampsia (OR: 1.08, 95%CI [1.00, 1.17]; p = 0.044) and oedema, proteinuria, and hypertensive disorders in pregnancy, childbirth, and the puerperium (OR:1.05, 95%CI [1.00, 1.11]; p = 0.031). Our study uncovered genetic evidence supporting COVID-19 as a causal risk factor for APOs, suggesting the importance of prioritizing therapeutic interventions for pregnant women infected with COVID-19 within society.

Imperfect first-trimester screening for hypertensive disorders of pregnancy (HDP) means many high-risk women miss the window for preventive aspirin, and the biological heterogeneity of HDPs is overlooked. This study aimed to leverage first-trimester serum proteomics to create a more precise tool for predicting preeclampsia (PE) and differentiating it from other HDPs. A prospective nested case–control study (n = 172) was conducted using targeted liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) proteomic profiling of 115 proteins. Machine learning (ML) methods were used to develop classifiers from the proteomic data. The signature predictive of PE was characterized by dysregulation of the complement and coagulation cascades (F10, C8A, C1QA, SERPING1, VTN). The profile differentiating gestational hypertension (GAH) from chronic hypertension (CAH) was linked to lipid metabolism (HRG, APOA4, APOC2). An 18-protein support vector machine (SVM) model for predicting PE demonstrated exceptional performance, with 94% sensitivity and 100% specificity, significantly outperforming the standard Fetal Medicine Foundation (FMF) screening algorithm. Pathway analysis confirmed that PE is associated with early activation of innate immunity and coagulation pathways, while GAH is linked to a pregnancy-induced metabolic response. A targeted serum proteomic combined with ML approach represents a new perspective diagnostic tool with strong potential to personalize monitoring for women at the highest risk for specific hypertensive pregnancy complications.

Perinatal and maternal morbidity in the setting of preterm birth may differ by delivery indication. We compared perinatal and maternal outcomes of second trimester (24 0/7 - 27 6/7 weeks' gestation) deliveries indicated for preeclampsia with severe features (PE-SF) with those following preterm premature rupture of membranes (PPROM). Secondary analysis of an observational cohort study of singleton and twin preterm deliveries before 35 weeks' gestation at 33 hospitals across the United States. Singletons without congenital anomalies who were delivered due to PE-SF or PPROM from 24 0/7 - 27 6/7 weeks gestation were included. The primary outcome was a composite of perinatal morbidity or death, defined as fetal or neonatal death, severe bronchopulmonary dysplasia grade III, intraventricular hemorrhage grade III-IV, necrotizing enterocolitis stage IIA or greater, periventricular leukomalacia, retinopathy of prematurity stage III-IV, or culture-proven sepsis. Secondary outcomes included components of the primary outcome, small-for-gestational-age (SGA) birth, and a composite of maternal morbidity. Among 7515 in the original cohort, 164 deliveries for PE-SF and 119 deliveries following PPROM were included. Individuals with PE-SF were more likely to have BMI ≥ 30 kg/m2, hypertensive disorder of pregnancy in a prior pregnancy, chronic hypertension, and cesarean birth (p <0.05) compared with those who delivered following PPROM. Composite perinatal morbidity or death did not differ between groups (aOR 1.60, 95% CI 0.89, 2.85, p=0.11), but fetal death was significantly higher in the PE-SF group (aOR 6.04, 95% CI 1.42, 25.71). Neonates delivered for PE-SF were more likely to be SGA (aOR 13.45, 95% CI 2.92, 61.94). Composite maternal morbidity did not differ between groups (aOR 1.18, 95% CI 0.62, 2.26). Second-trimester preterm birth indicated for PE-SF was associated with a higher rate of fetal death than birth for PPROM. Composite neonatal and maternal morbidity did not differ by indication.

Abstract Introduciton We present initial echocardiographic results of a study aimed at evaluating cardiovascular system adaptation depending on development of gestational hypertension and preclampsia. Purpose The purpose of the study was to analyze the morphological and functional changes in the heart during pregnancy and postpartum period in women with and without hypertension. Our hypothesis was that in women with hypertension diastolic function abnormalities and lower global longitudinal strain will be observed during pregnancy. Methods Into the study we recruited 150 pregnant women with hypertensive disorders of pregnancy. Each women underwent 2 echocardiographic examinations -one during pregnancy around 30th week of pregnancy and one over six months postpartum. Additionally results of gestational ultrasound and blood tests were analyzed. Heretofore follow up data including the postpartum echo is available for 27 participants. For statistical analysis Statistica 13 was used. Results The mean age was 35.9 years (±4.6). The echo was performed at the 28.7 (±5.3) week of pregnancy, the control echo at 7.3 (±3.2) months postpartum. 17 women did not have any form of hypertension, 6 had hypertension diagnosed prior to pregnancy and 4 had gestational hypertension. During pregnancy the unadjusted to body surface area size of left atrium (LA diameter 35vs 37mm, p=0.001) left ventricle (46vs 47mm, p=0.04) and right ventricle (27vs 28mm, p=0.02) were larger compared to postpartum. Indexed left atrial volume was similar (30.9 vs 28.5ml/m2, p=0.38). There was a significant difference in the thickness of intraventricle septum (8.2 vs 7.5mm, p=0.015) but not posterior wall (7.7 vs 7.3mm, p=0.2). Diastolic parameters (E/A, E/E’avg) were similar during pregnancy and postpartum. Left ventricular ejection fraction was higher during pregnancy (65% vs 64%, p=0.003) but global longitudinal strain was lower (-23.4 vs -24.3%, p=0.04) comparing to postpartum period. Comparison of differences in echocardiographic parameters during and post pregnancy between women with and without hypertension reveled significant differences in left ventricle diameter (3.1 vs 0.4mm, p=0.04) and motion velocities of medial and lateral parts of mitral annulus (E’med -1.7 vs 0.68cm/s, p=0.02; E’lat -3.29 vs -0.15, p=0.01). Conclusions To conclude, presented preliminary results show that in women with hypertensive disorders of pregnancy the increase in left ventricular size is larger during pregnancy. There are also some differences in diastolic function - motion velocities changes of medial and lateral parts of mitral annulus are greater in women with hypertensive disorders of pregnancy.