BACKGROUND:Hypertensive disorders of pregnancy (HDP) are a leading cause of postpartum morbidity and readmission, yet patterns of monitoring fidelity and persistent hypertension are incompletely characterized. We evaluated postpartum blood pressure (BP) trajectories, monitoring fidelity, and predictors of persistent hypertension and readmission in a large remote BP cohort. STUDY DESIGN:We conducted a retrospective analysis of 5940 postpartum individuals with HDP enrolled in a standardized 14-day text-based remote BP monitoring program from 2020 to 2025. BP patterns and monitoring fidelity was descriptively analyzed. Multivariable logistic regression identified predictors of persistent hypertension and 6-week readmission; linear probability models evaluated associations between early postpartum BP and persistent hypertension. MAIN OUTCOME MEASURES:Persistent hypertension was defined as systolic BP ≥130 mmHg and/or diastolic BP ≥80 mmHg at the end of monitoring. RESULTS:Among 4531 participants with end-of-monitoring BP data, 67.3% met criteria for persistent hypertension (≥130/80 mmHg). Median consecutive monitoring days were 8; only 31.3% completed all 14 days. Black race (adjusted odds ratio [aOR] 1.91, 95% CI 1.62-2.26) and preeclampsia with severe features (aOR 1.72, 95% CI 1.56-1.92) were associated with persistent hypertension and readmission. Early diastolic BP strongly predicted persistent hypertension. CONCLUSIONS:Hypertension is common following HDP. Although 87% of participants submitted at least one BP after the first week, participation declined substantially thereafter, potentially limiting detection of ongoing risk. Early diastolic BP, Black race, and preeclampsia with severe features were associated with persistent hypertension after rBPM. Extended BP surveillance, coupled with strategies to sustain monitoring engagement may be warranted.
OBJECTIVE:This study aims to investigate the diagnostic performance of Podocalyxin for the early detection of Preeclampsia METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was prospectively registered in PROSPERO CRD420261369096. A comprehensive search of PubMed, Scopus, Web of Science, CINAHL, and the Cochrane Library was conducted from inception to May 2026. Methodological quality was assessed using QUADAS-2 and the Joanna Briggs Institute (JBI) tools. Diagnostic accuracy outcomes were synthesized using a bivariate random-effects model. Summary receiver operating characteristic (SROC) curves were constructed to evaluate overall test performance. In addition, pooled standardized mean differences (SMD) were calculated using a random-effects model with 95% confidence intervals (CI). Heterogeneity was assessed using the I2 statistic and Cochran's Q test. Statistical significance was set at P < 0.05. RESULTS:Sixteen studies published between 2007 and 2026 across diverse populations were included. Seven studies were eligible for diagnostic accuracy meta-analysis. Most studies measure Podocalyxin using ELISA with reported sensitivities ranging from 36.1% to 100% and specificities from 75% to 98%. Overall, the pooled sensitivity was 83% (95% CI: 0.78-0.88) and specificity of 83% (95% CI: 0.80-0.87). The SROC curve demonstrated excellent diagnostic performance (AUC = 0.94). No significant threshold effect was observed (Spearman correlation = -0.234, p = 0.613). The pooled positive likelihood ratio was 5.91 (95% CI: 2.89-12.06), and the negative likelihood ratio was 0.11 (95% CI: 0.03-0.52). Fourteen studies were eligible to estimate effect size. Maternal Podocalyxin levels were significantly higher in women with PE compared to controls (SMD = 1.05; 95% CI: 0.71-1.39, p < 0.0001). Sensitivity analysis identified one influential study and its exclusion reduced heterogeneity to I2 = 78.3%. CONCLUSION AND RECOMMENDATION:Podocalyxin shows strong potential as a non-invasive biomarker for the early detection of PE, though our findings predominantly reflect proteinuric presentations. Well-designed, large-scale prospective studies are needed to confirm generalizability across the full PE spectrum and support clinical implementation.
OBJECTIVE:To compare prenatal exercise modalities for gestational systolic/diastolic blood pressure (BP) and gestational hypertension (GH). METHODS:We performed a PRISMA 2020/PRISMA-NMA systematic review with random effects pairwise and network meta-analyses. Five databases were initially searched from inception to 31 July 2025, and an updated supplementary search was conducted on 30 November 2025. English-language randomized controlled trials in pregnant women (≥18 years) prescribing structured exercise for ≥4 weeks versus usual care or another eligible modality were included. Pairwise analyses pooled mean differences (MD) for BP and odds ratios (OR) for GH. The network compared aerobic, aquatic, resistance, combined aerobic-resistance, and mind-body exercise and ranked modalities using SUCRA. RESULTS:Thirty-four trials involving 4565 pregnant participants were included. SBP and DBP outcomes were each reported in 28 trials involving 2480 participants, whereas gestational hypertension was reported in 17 trials involving 3184 participants. Compared with usual care, exercise reduced systolic BP (MD -3.67 mmHg, 95% CI -6.08 to -1.25) and diastolic BP (MD -3.51 mmHg, 95% CI -5.85 to -1.17), and lowered GH risk (OR 0.56, 95% CI 0.40 to 0.78). Benefits were more evident when programs began in the second-third trimester and among older participants. Interventions ≤16 weeks favored reductions in continuous BP, whereas >16 weeks more consistently reduced hypertensive events. In network analyses, aquatic, mind body, and aerobic exercise ranked highest for diastolic control. For GH risk, mind body and aerobic exercise showed statistically significant reductions versus usual care, whereas aquatic exercise ranked favorably but had imprecise, non-significant estimates. Systolic differences between modalities were not statistically significant. CONCLUSION:Structured prenatal exercise lowers BP and reduces GH. Mind body and aerobic exercise showed clearer evidence for reducing GH risk, whereas aquatic exercise showed a favorable but preliminary signal for blood pressure control because it was supported by only two trials. Initiating exercise in the second-third trimester and sustaining participation may maximize benefit.
OBJECTIVES:To identify clinical and biochemical factors associated with the development of acute kidney injury (AKI) in critically ill patients with severe hypertensive disorders of pregnancy (HDP) and to evaluate associated maternal and fetal outcomes. STUDY DESIGN:A prospective single-center cohort study was conducted in an Argentinian intensive care unit (ICU) between November 2017 and July 2022, including 179 women with severe HDP. MAIN OUTCOME MEASURES:The primary outcome was the development of AKI, defined by either a pregnancy-adjusted admission serum creatinine threshold (>0.87 mg/dL) or fulfillment of Kidney Disease Improving Global Outcomes (KDIGO) criteria. Secondary outcomes included maternal and fetal mortality. RESULTS:Out of 179 patients, AKI was diagnosed in 119 patients (66.3%) and was associated with higher illness severity scores and increased fetal mortality (18% vs. 5%; p = 0.022), In the final multivariable analysis, independent predictors of AKI included the corrected Sequential Organ Failure Assessment (SOFA) score (OR 1.37; 95% CI 1.04-1.81), serum uric acid (OR 1.03; 95% CI 1.01-1.05), lactate dehydrogenase (OR 1.01; 95% CI 1.00-1.01), and base excess (OR 0.87; 95% CI 0.78-0.96). HELLP syndrome represented the most severe phenotype, carrying the highest risk for advanced AKI and the need for renal replacement therapy. CONCLUSIONS:AKI is highly prevalent in critically ill patients with severe HDP and serves as a key determinant of adverse maternal and fetal prognosis, Simple biochemical markers and organ dysfunction scores enable early risk stratification, the limited specificity of standard criteria highlights the necessity for pregnancy-adapted diagnostic approaches.
Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by endothelial dysfunction and immune dysregulation, with delivery remaining the only curative treatment. Although aberrant macrophage (MΦ) polarization has been implicated in PE, the mechanisms by which placental MΦs contribute to endothelial dysfunction remain incompletely understood. We hypothesized that MΦs isolated from preeclamptic placentas secrete factors that promote endothelial activation, oxidative stress, and impaired angiogenesis compared with MΦ from normal pregnancies (NP). Primary placental MΦs from NP and PE women were co-cultured with human umbilical vein endothelial cells (HUVECs) in a transwell culture system, and endothelial oxidative stress, angiogenic capacity, viability, and activation marker expression were assessed alongside circulating cytokines and growth factors. Women with PE exhibited significantly elevated blood pressure, increased body mass index, reduced gestational age at delivery, and lower fetal weight compared with NP controls (p < 0.01). NP serum demonstrated significantly higher MCP-1 (300 ± 233 vs. 124 ± 89.9 pg/mL; p = 0.0348) and IL-4 concentrations (45.4 ± 41.9 vs. 7.84 ± 10.7 pg/mL; p = 0.0106), with a trend toward higher epidermal growth factor levels. PE serum demonstrated significantly higher PDGF-BB (2.46 × 104 ± 1.55 × 104 vs 1.19 × 104 ± 7.43 × 103 pg/mL; p = 0.0080). HUVECs co-cultured with PE-derived MΦ exhibited increased mitochondrial superoxide production (18.22 ± 6.81 vs. 9.40 ± 5.73%; p < 0.001), reduced tube formation and mesh area (p < 0.05), and increased preproendothelin-1 and ICAM-1 (p < 0.05). Collectively, these findings demonstrate that soluble factors released by placental MΦs from preeclamptic pregnancies promote endothelial oxidative stress, activation, and impaired angiogenesis in vitro, supporting a role for MΦ-endothelial crosstalk in PE-associated vascular dysfunction.
OBJECTIVE:Hypertensive Disorders of Pregnancy (HDP) are major contributors to maternal and perinatal morbidity and mortality. This study aimed to evaluate the awareness (knowledge and attitude) and behaviors regarding HDP among pregnant Lebanese women, and to identify associated factors. STUDY DESIGN:This cross-sectional study surveyed 400 pregnant women across Lebanon using a validated online questionnaire. Descriptive statistics, bivariate, and multivariate analyses were performed to identify independent predictors of higher awareness and behavior scores. MAIN OUTCOMES:Participants had a mean age of 29.14 ± 5.06 years, and 78.8% had a university education. Overall knowledge of HDP was moderate (Mean score 8.10 ± 4.08 out of 15), while attitude was generally positive (median 8, interquartile range [IQR] 2, out of 10), and moderate scores were noted for behaviors during pregnancy (score 9.56 ± 1.53 out of 13). Higher education, particularly a medical university degree, was a significant and independent predictor of knowledge, attitude, and behavior (p < 0.001). A family history of hypertension was significantly correlated with better knowledge (p < 0.001) and attitudes (p= 0.002). Conversely, lower educational attainment was associated with reduced knowledge and attitude scores, whereas residence in Beirut, Mount Lebanon, or North Lebanon (compared with South Lebanon) was independently associated with lower knowledge scores. CONCLUSIONS:Lebanese pregnant women demonstrated moderate knowledge, generally positive attitudes toward HDP, and exhibited moderate health-related behaviors during pregnancy. Nonetheless, gaps persist, especially among women with lower education and without a family history of hypertension. These findings underscore the importance of culturally tailored educational interventions in enhancing awareness, promoting the adoption of healthy behaviors, and ultimately improving maternal and fetal outcomes.
This study evaluated whether, in pregnancies with extreme angiogenic imbalance, defined by a soluble fms-like tyrosine kinase-1 to placental growth factor ratio greater than 600, the absolute ratio provides additional prognostic value for perinatal death or severe morbidity beyond gestational age and estimated fetal weight. A secondary objective was to assess the contribution of ratio kinetics and placental growth factor levels in fetal growth restriction.We conducted a retrospective observational cohort study including 132 singleton pregnancies managed at a tertiary referral hospital between June 2015 and September 2024. Outcomes were intrauterine fetal death, death within the first week, death within the first year, severe morbidity with major sequelae, and a composite adverse outcome. Baseline models including gestational age and estimated fetal weight at the time of ratio greater than 600 were compared with models additionally including the logarithm of the ratio.Event rates were 8.3%, 15.9% week, 20.6%, 29.5%, and 43.9%, respectively. Adding the ratio did not improve discrimination for any endpoint. A ratio greater than 600 was, however, associated with shorter time to delivery. In the serial subset, the rate of increase of the ratio improved prediction of death within the first week. In fetuses with growth restriction, lower placental growth factor levels were associated with severe morbidity.In this extreme range, the ratio mainly reflects disease imminence rather than outcome severity. Ratio kinetics may identify acute deterioration, whereas placental growth factor may better reflect residual placental reserve and fetal viability, especially in growth-restricted fetuses.
Hypertensive disorders of pregnancy affect 13-16% of U.S. pregnancies and remain a leading cause of maternal and neonatal morbidity. Management is complicated by diagnostic uncertainty, as most markers rise only after end-organ injury. The sFlt-1/PlGF ratio has shown strong prognostic value, but its effect, on U.S. clinical management decisions, is unknown. We conducted a case-based webinar with obstetric and maternal-fetal medicine providers (n = 68) to assess changes in management intent after a low ratio result. Expectant management intent rose from 20.9% to 87.8%, while delivery intent decreased. These findings suggest sFlt-1/PlGF biomarker data may influence intended patient management.
Hypertensive disorders of pregnancy (HDP) affect the incidence of preterm birth. The sFlt-1/PlGF ratio test predicts preeclampsia progression, but its effect on neonatal outcomes is understudied. This study estimated reductions in neonatal mortality and morbidity through sFlt-1/PlGF-guided management for hospitalized patients with HDP. Using a decision-analytic model with PRAECIS and BEACON data and neonatal outcomes from a U.S. cohort of 760,000 infants, outcomes were estimated for patients with HDP at 24-35 weeks' gestation. Results indicated biomarker-guided management was associated with averting 1 death and 75 morbidity cases per 1000 preterm deliveries. sFlt-1/PlGF-guided management could reduce preterm neonatal mortality and morbidity.
OBJECTIVE:To estimate the prevalence of undiagnosed hypertension among pregnant women in Peru, assess socioeconomic inequities, and characterize departmental geographic variability during 2014-2024. METHODS:We conducted an analytical cross-sectional study using the Demographic and Family Health Survey (ENDES) 2014-2024. The sample included 5243 pregnant women aged 15-49 years with valid blood pressure measurements and no prior hypertension diagnosis. Undiagnosed hypertension was defined as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg among women without self-reported diagnosis. Weighted prevalences and 95% confidence intervals (95% CI) were estimated. Socioeconomic inequities were assessed using the Slope Index of Inequality (SII), Relative Index of Inequality (RII), and Erreygers concentration index. Spatial autocorrelation was assessed using Moran's I. RESULTS:The prevalence of undiagnosed hypertension was 5.6% (95% CI: 4.4-6.7). Prevalence was higher in urban than rural areas (6.1% vs 4.2%) and in the richest versus poorest quintile (6.4% vs 3.8%), although these contrasts were imprecise. The SII was 3.36 percentage points (95% CI: -0.72 to 7.44), the RII was 1.83 (95% CI: 0.92-3.64), and the Erreygers index was 0.021 (95% CI: 0.007-0.035; p = 0.003), indicating a small pro-rich concentration. Moran's I was positive and statistically significant after correction to 25 ENDES spatial units (I = 0.294; p = 0.013). CONCLUSIONS:Undiagnosed hypertension affected approximately one in eighteen pregnant women in Peru. Findings suggest modest pro-rich concentration and significant departmental spatial autocorrelation.
Objectives This study investigated whether necroptosis-associated proteins are elevated in urinary extracellular vesicles (uEVs) from women with preeclampsia (PE) compared with normotensive pregnancies (NP), and explored uEV origin. Study design Urine was collected from 22 women with PE and 22 gestation-matched NP controls (Cohort A). A separate cohort of four PE samples with heavy proteinuria, gestation-matched to NP controls, was examined (Cohort B). uEVs were isolated using differential ultracentrifugation. Main outcome measures Western blot determined presence of necroptotic markers, total mixed lineage kinase domain-like protein (MLKL) and phosphorylated MLKL (pMLKL), together with small EV markers CD9 and TSG101. Placental alkaline phosphatase (PALP) and the renal cotransporter NKCC2 were used to assess EV organ origin. Nanoparticle tracking analysis (NTA) characterised uEVs. Results uEV pMLKL was detected more frequently in the PE group than NP controls (6/22 versus 0/22, P = 0.021). There was a non-significant increase in total MLKL in PE (10/22 versus 5/22, P = 0.203). PALP was detected in 2/12 PE and 1/12 NP samples, suggesting a placental contribution to uEVs in some participants. NTA confirmed uEVs in a subset of samples, with no significant differences in size or concentration between groups. In heavily proteinuric PE subjects (Cohort B), pMLKL was detected in 3/4 samples. Conclusions pMLKL was detected more frequently in uEVs from women with PE. Detection of PALP in a subset of uEVs suggests possible placental contribution to the uEV pool. These findings are consistent with increased necroptosis-related signalling in the urinary tract/kidney in women with PE.
Gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and intrauterine growth restriction represent major contributors to maternal and neonatal morbidity worldwide. Traditional screening methods relying on single biomarkers or linear models often demonstrate limited predictive accuracy. This review examines the transformative role of machine learning (ML) in shifting obstetric care toward predictive, preventive, and personalized approaches. Advanced computational models integrating multimodal data sources clinical records, biochemical markers, multi-omics profiles, medical imaging, and lifestyle factors show promising performance. Ensemble methods such as Random Forest and XGBoost, alongside deep learning architectures, frequently outperform conventional logistic regression, achieving AUC values above 0.90 in selected cohorts. Emphasis is placed on preprocessing techniques for class imbalance (e.g., SMOTE), model interpretability via Explainable AI (SHAP), and privacy-preserving strategies like federated learning. While technical and ethical challenges including bias, external validation, and data heterogeneity remain, robust ML frameworks offer substantial potential for early risk stratification and timely intervention in precision obstetrics. Prospective, multicenter validation is essential for clinical translation.
Pre-Eclampsia (PE) is characterized by an imbalance of angiogenic and inflammatory modulators, with clinical symptoms emerging after 20 weeks of gestation. Fibroblast Growth Factor-2 (FGF2) promotes angiogenesis, whereas the acute-phase protein Pentraxin-3 (PTX3) binds FGF2 and blocks its interaction with receptors. In this cross-sectional case-control study, we compared plasma levels of PTX3 and FGF2 in normotensive (NT) and PE pregnancies and evaluated their ability to discriminate early-onset (<34 weeks) from late-onset PE (≥ 34 weeks). PTX3 and FGF2 concentrations were quantified by sandwich ELISA in non-pregnant women (NP, n = 19) and in third-trimester samples from NT women (n = 29) and women with PE (n = 30; early-onset PE = 11, late-onset PE = 19). Both PTX3 and FGF2 levels were significantly higher (p < 0.05) in PE compared to NT pregnancies. Moreover, their concentrations in early-onset PE were, on average, twice as high as those observed in NT and late-onset PE groups. Pearson's correlation analysis revealed a negative association between PTX3 and FGF2 levels in PE (r = -0.5160; p = 0.0167). In conclusion, PTX3 and FGF2 are both elevated in PE, particularly in early-onset cases. Their inverse correlation suggests a disrupted PTX3-FGF2 axis that may contribute to the angiogenic deficit found in PE. These findings suggest that PTX3 and FGF2 are candidate biomarkers associated with disease severity and may contribute to a molecular signature related to early-onset PE. Further prospective studies are required to establish their predictive value and clinical applicability.
Comparing Severity of Different Subtypes of Preeclampsia Using Different Diagnostic Criteria - A Retrospective Cohort Study. BACKGROUND:New diagnostic criteria introduced by ISSHP in 2018 and ACOG in 2020 lowered diagnostic thresholds to create distinct subtypes. OBJECTIVES:We assess changes in prevalence and compare biochemical profiles and outcomes of patients diagnosed by different criteria. We evaluated associations of each diagnostic component with adverse outcomes. STUDY DESIGN:Singleton pregnancies with any hypertensive disorder in pregnancy diagnosed between 1/1/2011 and 31/12/2019 had demographics and outcomes retrieved from an electronic records system. Patients were reclassified by ISSHP 2001, ACOG 2020, and ISSHP 2018 criteria. Additional patients identified were analysed separately. MAIN OUTCOME MEASURES:Prevalence and associations between categorical variables and adverse outcomes were calculated. Multivariate logistic regression between components of each criteria and adverse outcomes was performed. RESULTS:Prevalence increased by 4.0-21.6% from 1.99% to 2.07-2.42% (ACOG 2020, ISSHP 2018 respectively). Additional patients diagnosed by ISSHP 2018 and ACOG 2020 had less severe hypertension (0.7% and 0.0% vs 15.6%, p < 0.001), MgSO4 use (0.0% vs 8.6%, p < 0.05), preterm birth <37 weeks (8.5% and 4.0% vs 35.7%, p < 0.001), Caesarean section (36.2% and 12.0% vs 56%, p < 0.001) and NICU admission >24 h (2.8 and 8.0% vs 10.1%, p < 0.001 and not significant) than patients diagnosed by ISSHP 2001. Proteinuria, thrombocytopenia, elevated creatinine and transaminases were significantly associated with adverse outcomes across most groups. CONCLUSION:Using newer diagnostic criteria increases incidence. Additional patients had milder disease and better outcomes despite management as gestational hypertension.
Objectives Previous studies demonstrated that preeclampsia (PE) with proteinuria is associated with concurrent renal injury. However, it is unclear how renal damage that occurs during pregnancy changes after delivery. This study was conducted to assess postpartum renal impairment in women with PE and to examine its possible link to the subsequent development of chronic kidney disease (CKD). Study design We conducted a retrospective cohort study analyzing a group of women with PE and proteinuria (PE-UP (+)) (N = 30). Control data were obtained from normotensive participants at 35 weeks of gestation (N = 20) and 12 weeks postpartum (N = 15).Main Outcome Measures.Serum hyaluronan (glycocalyx injury), urinary podocalyxin (podocyte injury), urinary liver-type fatty acid-binding protein (L-FABP) and N-acetyl-β-D-glucosaminidase (NAG) (tubular injury) were measured at PE diagnosis and at 12 weeks postpartum. Results Based on the urinary protein/creatinine ratio (UPCR) at 12 weeks postpartum, the PE-UP (+) group was stratified into the PE-UP improved group (UPCR <0.15 g/g Cr; N = 20) and PE-UP persistent group (UPCR ≥0.15 g/g Cr; N = 10). The urinary L-FABP and NAG levels in the PE-UP improved group were significantly lower than those in the PE-UP persistent group. In contrast, the levels of hyaluronan and podocalyxin remained significantly elevated in both PE subgroups compared to those in the postpartum controls. Conclusions Postpartum women with PE and prolonged proteinuria exhibit residual tubular dysfunction. Women with PE in whom proteinuria has resolved may still have residual glomerular damage at 12 weeks postpartum.The clinical trial described in this paper was registered at the UMIN Clinical Trials Registry under registration number UMIN000058351.URL of registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000066708
We thank Liu et al. for their constructive comments on our article reporting the internal and external validation of a reduced-feature machine learning model for the prediction of preeclampsia-related adverse outcomes. The letter raises four points, which we address in turn. Regarding calibration and clinical utility, we generated calibration curves for the gradient-boosted tree model in both cohorts. Neither cohort shows a systematic, clinically concerning miscalibration pattern; deviations are concentrated at the extremes of the risk distribution, where observations are fewest. Brier scores were 0.010 (German cohort) and 0.068 (North American cohort), indicating good overall probabilistic accuracy. We agree that a formal clinical utility analysis, such as net benefit across threshold probabilities, represents an important next step. Regarding incremental value over the sFlt-1/PlGF ratio, we note that while the ratio offers strong short-term rule-out performance, its positive predictive value for ruling in preeclampsia related adverse outcomes remains limited. Our model, which incorporates the sFlt 1/PlGF ratio alongside ten additional routine clinical features, achieved AUCs of 92% and 87% in the German and North American cohorts, respectively. A formal head-to head comparison remains an important direction for future work. Regarding dataset heterogeneity, we acknowledge the structural differences between cohorts as a relevant limitation, while noting that discriminative performance remained statistically indistinguishable across cohorts despite significant differences in baseline characteristics. Regarding longer-term outcomes, we agree this is a valuable direction and intend to pursue it as follow-up data become available.
Objectives SIGLEC6, a human-specific transmembrane receptor, is highly expressed in placenta. SIGLEC6 is elevated in maternal circulation preceding preeclampsia and in women with preeclampsia, correlating with disease severity. This study aimed to investigate the regulatory mechanisms of placental SIGLEC6 and its involvement in processes associated with preeclampsia pathogenesis. Study design To determine cell source, SIGLEC6 was measured in (cyto)trophoblasts, syncytiotrophoblasts, and extravillous trophoblasts. We then assessed the impact of hypoxia (1% vs 8% Oxygen), inflammatory cytokines (Interleukin 6 (IL-6) or Tumour Necrosis Factor alpha (TNFα)), or Brefeldin A (impairs protein trafficking) on SIGLEC6 production/secretion. We also assessed whether treatment with recombinant SIGLEC6 induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs). Main outcomes measures SIGLEC6 expression across trophoblast subpopulations; its regulation under hypoxia, inflammation and Brefeldin A treatment; and its effect on endothelial dysfunction markers. Results SIGLEC6 was expressed in all cell types and upregulated during differentiation of human trophoblast stem cells into syncytiotrophoblasts and extravillous trophoblasts. Exposure of syncytiotrophoblasts to hypoxia elevated SIGLEC6 expression (p = 0.0079), and protein secretion (p = 0.0079). Similarly, pro-inflammatory cytokines increased SIGLEC6 expression (IL-6: p = 0.0016, and TNFα: p = 0.0015) and protein secretion (IL-6: p = 0.002, and TNFα: p = 0.01) from syncytiotrophoblasts. Treatment with Brefeldin A reduced SIGLEC6 secretion in cell lysates (p = 0.001) and conditioned media (p = 0.02). Recombinant SIGLEC6 had no effect on pro- and anti-angiogenic factors and endothelial dysfunction markers in HUVECs. Conclusion SIGLEC6 expression is induced by hypoxia and inflammation in syncytialised hTSCs, but recombinant SIGLEC6 did not induce endothelial dysfunction in HUVECs.
OBJECTIVES:To identify latent trajectories of blood pressure throughout pregnancy and evaluate their associations with body mass index (BMI), physical fitness (estimated via oxygen uptake), and serum relaxin levels in a cohort of healthy pregnant women. STUDY DESIGN:Prospective inception cohort study. Group-based trajectory modelling was used to characterize systolic and diastolic blood pressure patterns across gestation. Multiple logistic regression analyses were conducted to identify predictors of trajectory group membership. MAIN OUTCOME MEASURES:Longitudinal trajectories of systolic and diastolic blood pressure during pregnancy. RESULTS:A total of 492 women were included in early pregnancy. Three distinct and stable trajectories were identified for both systolic and diastolic blood pressure. Nulliparous women and those with BMI >25 kg/m2 had significantly increased odds of belonging to the highest blood pressure trajectory group (adjusted odds ratio [aOR] 2.47; 95% CI: 1.58-3.86 and aOR 1.61: 95% CI 1.04-2.49), respectively). No significant associations were observed between trajectory group membership and maternal age, physical fitness, or early-pregnancy serum relaxin concentrations. CONCLUSIONS:Early pregnancy blood pressure may serve as a clinically relevant marker for gestational hypertension risk. Women with lower baseline readings may require less frequent antenatal monitoring, whereas those with elevated initial values could benefit from closer surveillance. Nulliparity and overweight status were associated with higher blood pressure trajectories, highlighting their relevance in antenatal risk stratification. Physical fitness and relaxin levels did not demonstrate predictive value in this context.
