Glioblastoma (GB) is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after partial surgical resection or resistance to drug treatments. The study aimed to evaluate the predictive values of apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI), plasma levels of placental growth factor (PGF) and glial fibrillary acidic protein (GFAP), and their combination in GB recurrence. The study included 200 patients diagnosed with GB consisting of 136 with tumor recurrence and 64 without. DWI examinations and PGF and GFAP measurements in the plasma were performed preoperatively. The patients with recurrent disease exhibited a lower value of ADC with higher plasma PGF and GFAP levels than those with non-recurrence. The results of Pearson correlation analysis suggested the ADC shared negative correlations with plasma levels of PGF and GFAP in patients with recurrent GB. The plasma level of PGF was also found to be positively correlated with the plasma level of GFAP in patients with recurrent GB. The ADC, plasma levels of PGF and GFAP in predicting recurrent GB presented AUC: 0.75, 0.85, and 0.82, respectively. Combined analysis of two of three to evaluate the prediction showed AUCs of 0.98 (ADC and PGF), 0.96 (ADC and GFAP), and 0.84 (PGF and GFAP). Combined analysis of ADC and plasma PGF, ADC and plasma GFAP, PGF and GFAP to evaluate the prediction showed AUCs of 0.98, 0.96, and 0.84, respectively. Combined analysis of three of them to evaluate the prediction showed AUC as 0.98. The study demonstrates that combined ADC and plasma PGF showed a similar predictive value in recurrent GB after standard treatment as combined ADC, plasma PGF and GFAP together. Considering limited sample size and lack of more sample types in this study, additional value of plasma GFAP in predicting recurrent GB should be further investigated in larger-scale population or different sample sources.

Pulmonary arterial hypertension (PAH) is a progressive cardiopulmonary disorder marked by pulmonary vascular remodelling and vessel loss, paradoxically occurring despite high VEGF signaling. While VEGF/VEGFR pathways are implicated in disease pathogenesis, their role in endothelial and immune cell crosstalk remains poorly understood. Placental growth factor (PlGF), a VEGF family member that selectively binds VEGFR-1, exerts pro-inflammatory effects in other pathological contexts, but its contribution to PAH pathophysiology is unclear. This study explored the contribution of PlGF to endothelial activation and immune-mediated vascular remodelling in PAH. Serum levels of PlGF, VEGF-A, soluble VEGFR-1 (sVEGFR-1), and soluble VEGFR-2 (sVEGFR-2) were measured in 80 treatment-naïve PAH patients from the EFORT cohort and in healthy controls. Their association with survival was then assessed. VEGFR-1 expression was evaluated in human PAH lung tissue. The functional role of PlGF was investigated in Plgf-/- rats exposed to chronic hypoxia or monocrotaline, and in mechanistic studies using primary human pulmonary endothelial cells and monocyte-derived macrophages.Circulating PlGF and sVEGFR-1 were elevated in PAH and associated with worse survival. VEGFR-1 expression was increased in PAH lung endothelium. Genetic deletion of Plgf protected rats from experimental pulmonary hypertension, leading to reduced pulmonary pressures, right ventricular hypertrophy, and vascular remodelling. PlGF deficiency reduced endothelial ICAM-1/VCAM-1 expression, macrophage infiltration, and pro-inflammatory cytokine production (CCL5/RANTES, osteoprotegerin, and LIX/CXCL5). In vitro, PlGF induced endothelial adhesion molecule expression and promoted macrophage polarization toward a pro-remodelling M2-like phenotype. PlGF is upregulated in PAH, its concentration predicts adverse outcomes, and it actively drives vascular remodelling by coupling endothelial activation to immune dysregulation. These findings establish PlGF as both a prognostic biomarker and a promising therapeutic target for PAH.

To evaluate the cost-effectiveness of the Fetal Medicine Foundation (FMF) strategy, compared with the National Institute for Health and Care Excellence (NICE) strategy, for first-trimester screening for preterm preeclampsia (PE) in the United Kingdom (UK). Cost-effectiveness analysis. UK National Health Service and personal social services perspective. A total of 10 000 simulated patients with singleton pregnancies at 11-13 weeks' gestation, across a lifetime time horizon. A decision-tree model was developed to perform a cost-effectiveness analysis. In the base-case analysis, NICE-recommended screening was compared with FMF screening, using maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF). The model assumed that patients identified as high-risk for PE were prescribed 150 mg aspirin daily until 36 weeks' gestation. Scenario analyses varied PE incidence, aspirin adherence and biomarker combinations of FMF strategy components. Incremental cost-effectiveness ratios (ICERs) were calculated using incremental costs and quality-adjusted life years (QALYs). Dominant ICERs demonstrated lower costs and higher QALYs. Compared with NICE-recommended screening, the FMF strategy demonstrated a cost-saving of £3191 and QALY gain of 0.92 per 10 000 patients (dominant ICER), with a cost-saving of £199 per preterm PE case avoided. In scenario analyses, the FMF strategy was cost-effective across 3%, 5% and 7% PE incidence, and 75% and 100% aspirin adherence. The base-case FMF strategy (maternal factors + MAP + UtA-PI + PlGF) was the most clinically effective option. The FMF strategy was more cost-effective versus the NICE strategy for first-trimester preterm PE screening in the UK.

First, to evaluate whether the ratio of soluble fms-like tyrosine kinase-1 to placental growth factor (sFlt-1/PlGF) is associated with hemodynamic changes in ophthalmic artery (OA) Doppler in near-term pregnancy. Second, to assess the performance of OA Doppler to rule in and rule out angiogenic factor imbalance. This was a cross-sectional cohort study nested within the PE37 randomized controlled trial, involving nulliparous women recruited between January 2023 and January 2025 who underwent sFlt-1/PlGF ratio measurement between 35 + 0 and 36 + 6 weeks' gestation. We included a subsample of women who underwent OA Doppler evaluation, including measurement of OA peak systolic velocity (PSV) ratio and OA pulsatility index (PI), as well as assessment of mean arterial pressure (MAP) and mean uterine artery (UtA) PI. The operator was blinded to sFlt-1/PlGF ratio values. Trends in median values of OA and maternal-fetal Doppler parameters across sFlt-1/PlGF tertiles were analyzed using the Jonckheere-Terpstra test and quantile regression, adjusting for maternal body mass index, age and smoking status. The predictive performance of the OA-PSV ratio for sFlt-1/PlGF ratio ≥ 38 was evaluated using receiver-operating-characteristics-curve analysis. We included 203 women, of whom 62, 71 and 70 were in the lowest, middle and highest tertiles of the sFlt-1/PlGF ratio, respectively. With increasing sFlt-1/PlGF ratio tertile, there was a significant increase in the OA-PSV ratio (median, 0.45 (interquartile range (IQR), 0.39-0.53) vs 0.48 (IQR, 0.41-0.58) vs 0.59 (IQR, 0.50-0.66); adjusted P < 0.001), a significant decrease in OA-PI (median, 2.20 (IQR, 1.92-2.61) vs 2.13 (IQR, 1.86-2.37) vs 1.86 (IQR, 1.60-2.26); adjusted P = 0.031) and a significant increase in MAP (median, 87.0 (IQR, 82.7-92.0) mmHg vs 88.7 (IQR, 83.7-93.7) mmHgvs 94.7 (IQR, 89.3-100.0) mmHg; adjusted P < 0.001). In contrast, no significant trend was observed in mean UtA-PI across sFlt-1/PlGF ratio tertiles. Among those individuals with an OA-PSV ratio < 0.61, 90.5% truly had a sFlt-1/PlGF ratio < 38, at a 15% false-positive rate. This study provides new evidence of a significant association between the sFlt-1/PlGF ratio and OA Doppler parameters in near-term pregnancies, suggesting that OA Doppler indices, particularly the PSV ratio, reflect angiogenic imbalance. Given its non-invasive nature, accessibility and low cost, OA Doppler emerges as a promising surrogate tool for ruling out angiogenic imbalance. © 2026 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Protocol for enhancing production of human PSC-derived cardiomyocytes and endothelial cells with placental growth factor.

Testing of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) is known to reduce time-to-diagnosis of preeclampsia and identify patients at increased risk of adverse perinatal outcomes. We implemented testing of sFlt-1/PlGF and sought to compare time-to-diagnosis of preeclampsia prior to and after implementation, as well as selected outcomes and estimated costs. Singleton pregnancies between 200 and 346 weeks' gestational age with suspected preeclampsia or placental dysfunction were identified by the hospital databases retrospectively from 2019 to 2021, and prospectively after implementation of sFlt-1/PlGF from 2022-2023. Outcomes were compared using negative binomial and Poisson regression models with entropy balancing to adjust for confounding. Before and after the implementation of sFlt-1/PlGF testing, a total of 494 and 145 patients were identified, respectively. Among the 206 patients with confirmed preeclampsia, those identified after implementation had an earlier mean gestational age at the time of diagnosis (31.8 weeks vs. 33.1 weeks, P = 0.001). The post-implementation cohort had a higher risk of neonatal intensive care unit (NICU) admission ≥24 hours (risk ratio 3.85, 95% CI 2.07-7.17). All fetal deaths (5.0%) recorded after implementation had a positive sFlt-1/PlGF result. Among patients with suspected preeclampsia, sFlt-1/PlGF testing did not decrease the time-to-diagnosis of preeclampsia; it was associated with an earlier gestational age at time of diagnosis, identified patients with increased risk of NICU admission and adverse fetal outcomes, and supports optimization of access to biochemical marker testing in regional centres.

In vitro fertilization (IVF) culminates in embryo transfer into a hormonally primed endometrium, often via a programmed cycle (PC) regimen postulated to influence hypertensive disorders of pregnancy (HDP) risk. We thus generated a single-cell atlas of PC endometrium to define cell type-specific differences relative to natural cycle (NC) endometrium, and evaluated whether PC-associated modulation of the window of implantation (WOI) endometrium influences angiogenic balance in pregnancy. Single-nucleus RNA-seq of prospectively collected PC and NC WOI endometrium. An independent prospective cohort of 548 singleton pregnancies was separately analyzed for maternal serum angiogenic markers (soluble fms-like tyrosine kinase-1; placental growth factor) and HDP incidence in PC- versus NC-conceived pregnancies, adjusting for clinical confounders and IVF use. Prominent transcriptomic differences were observed between PC (n = 7; 48,843 nuclei) and NC (n = 9; 44,230 nuclei) WOI endometrium, particularly in glandular epithelium (682 up- and 979 down-regulated genes; adjusted P < 0.05) and stromal fibroblasts (108 up- and 168 down-regulated). PC endometrium showed reduced uterine natural killer cell abundance, potentially from CXCL14 downregulation. Functional enrichment revealed downregulation of embryo implantation, angiogenesis, and extracellular matrix remodeling pathways in PC. Altered cell-cell signaling in decidualization, angiogenesis, and inflammatory response was also observed. Despite these WOI perturbations, PC-conceived pregnancies were not associated with early gestational angiogenic imbalance or increased HDP risk. PC endometrial preparation induced distinct cellular and signaling alterations in the WOI, but was not associated with subsequent development of angiogenic imbalance or HDP, thereby underscoring the resilience and adaptability of the early maternal-fetal interface. gov NCT03799107. ABOG/AAOGF; NICHD-R01-HD084380; NCTRI-P50-HD055764; NIAMS-P30-AR070155.

Blood-based biomarker testing for Placental Growth Factor (PlGF) for preeclampsia is gaining adoption as diagnostic assays have become increasingly available in Canada. However, guidance on the diagnostic and prognostic thresholds for various PlGF-based tests is not standardized nor interchangeable. The implementation of PlGF-based testing in a clinical setting requires laboratory support to advise on the assay selection due to test configuration, handling, and report interpretation. To support dialogue among clinicians and laboratory stakeholders, this brief review covers the currently available assays in Canada and describes their main studies in preterm preeclampsia, single cut-offs versus gestational age ranges, and technical considerations.

Coronary artery disease (CAD) is a leading global cause of mortality, yet the predictive accuracy of conventional risk models is limited. Here, we integrate conventional risk factors, polygenic risk scores, and large-scale proteomics to develop a unified model for enhanced CAD risk prediction. Using data from UK Biobank, participants with plasma proteomics and genetic risk data were included after excluding prevalent CAD. Participants from England were split into training (n=32 330) and internal validation (n=13 857) sets, and Scotland/Wales participants formed an external validation set (n=5775). Incident CAD was ascertained from linked health records. A 202-protein proteomic risk score was derived by least absolute shrinkage and selection operator Cox regression, and CatBoost models were trained using conventional risk factors alone and with incremental addition of polygenic risk scores and protein proteomic risk scores; Shapley Additive Explanations-guided forward selection identified a compact protein panel. Across cohorts, the median age was 58 years and ∼45% were men. Protein proteomic risk score was dose-dependently associated with CAD risk. Compared with conventional risk factors alone, integrating polygenic risk scores and protein proteomic risk scores improved discrimination, with the area under the curve increasing from 0.750 (95% CI, 0.732-0.767) to 0.789 (95% CI, 0.772-0.805) in internal validation and from 0.717 (95% CI, 0.683-0.750) to 0.762 (95% CI, 0.732-0.791) in external validation. A 9-protein panel (GDF15 [growth differentiation factor 15], MMP12 [matrix metalloproteinase 12], NPPB [natriuretic peptide B], PGF [placental growth factor], REN [renin], ADGRG2 [adhesion G-protein coupled receptor], ACE2 [angiotensin-converting enzyme 2], CDCP1 [CUB domain-containing protein 1], CXCL17 [C-X-C motif chemokine ligand 17)]) captured most proteomic predictive information. Our findings demonstrate that integrating conventional risk factors, polygenic risk scores, and proteomic data improves CAD risk prediction. This study highlights the utility of proteomics in precision cardiovascular medicine and simplified risk stratification tools.

There is an unmet need for biomarkers that can dynamically track maternal vascular health and guide interventions in disordered pregnancies. The retina and choroid provide a window into the systemic vasculature. We aimed to characterize longitudinal trajectories of retinal and choroidal features during healthy pregnancy and explore differences associated with preeclampsia. Overall, 251 pregnant women underwent multimodal retinal imaging with color fundus photography, scanning laser ophthalmoscopy, and optical coherence tomography at multiple antenatal (12±3 or 20±3 weeks' gestation and 36±3 weeks' gestation, n=183) or a single third-trimester (36±3 weeks' gestation, n=68) time point. Retinal and choroidal vascular features were extracted using an automated pipeline. We examined gestational trajectories of these features and their associations with blood pressure change and serum angiogenic factors. Trajectories were compared for women with preeclampsia and those without placental dysfunction. Significant reductions in measurements of retinal vessel caliber and density and of choroidal thickness, and increases in retinal thickness measurements, were seen over healthy pregnancy. These changes were not correlated with maternal blood pressure change. Third-trimester retinal arteriolar caliber and density were weakly correlated with placental growth factor (r=0.32, P<0.001 and r=0.31, P<0.001) and soluble fms-like tyrosine kinase 1 (r=-0.21, P=0.006 and r=-0.33, P<0.001) levels. Preeclampsia was associated with significantly greater reductions in retinal arteriolar caliber (P=0.022 for right eye, P=0.019 for left) and density (P<0.001 for each eye) across gestation. Retinal and choroidal features change throughout pregnancy, and these trajectories are altered in preeclampsia. URL: xxx; Unique identifier: ISRCTN40843826.

Maternal and perinatal placental dysfunction severity in extremely high values of sFlt1/PlGF ratio: A retrospective observational study.

Early pregnancy screening to identify high-risk women for targeted prevention is effective for reducing pregnancy complications. Placental biomarkers, including PlGF and PAPP-A, are linked to adverse outcomes, yet their combined predictive value for pregnancy complications remains unclear. Here, a retrospective cohort study was conducted to assess first-trimester prediction models incorporating PlGF, PAPP-A, and maternal factors for major obstetric complications. This was a retrospective cohort study using data that were prospectively collected during first-trimester screening. A cohort study was conducted at the International Peace Maternity and Child Health Hospital of China Welfare Institution (Shanghai, China) from December 2021 to October 2022. A total of 4046 participants were recruited during the first-trimester screening, excluding those with miscarriages and those without delivery data. In our routine screening, all pregnant women were tested for placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A). The mean arterial pressure (MAP) and uterine artery pulsatility index (UTPI) were also measured in accordance with the Fetal Medicine Foundation guidelines, along with maternal characteristics and medical history collected via face-to-face interviews. Multivariable logistic regression was used for model development. Model performance was evaluated by the area under the receiver operating characteristic curve (AUC). Among 4046 initially recruited participants, data from 3910 participants regarding fetal growth restriction (FGR), gestational diabetes mellitus (GDM), placenta previa and preterm birth (PTB) were analyzed. For the PE analysis, a subgroup of 1,588 women with available UTPI measurements was evaluated. The best models for predicting FGR were the indicator height, PAPP-A levels, and PlGF levels, with an AUC of 0.742 (95% CI: 0.633-0.851). Regarding GDM prediction, the model including BMI and PAPP-A levels had the best AUC (0.667, 95% CI: 0.622-0.713). With respect to placenta previa prediction, the model including age and PlGF levels had the best AUC (0.765, 95% CI: 0.588-0.941). For PTB, indicators such as the PlGF multiples of the median (MoM), PAPP-A, type I diabetes and systemic lupus erythematosus had the best performance, with an AUC of 0.665 (95% CI: 0.553-0.776). For PE screening using the Fetal Medicine Foundation (FMF) competing-risk model (PAPP-A, PIGF, MAP, and UTPI), the model achieved an AUC of 0.847 for preterm PE (< 37 weeks), with a detection rate of 50.00%, and an AUC of 0.777 for term PE (≥ 37 weeks), with a detection rate of 95.12% at the recommended risk cutoff of 1 in 100. First-trimester screening using PlGF, PAPP-A, and maternal factors shows preliminary associations with common obstetric complications, suggesting the potential utility of these biomarkers in early risk stratification, providing a proof-of-concept tool for early risk stratification and improved management of high-risk pregnancies to reduce maternal and fetal morbidity. However, these models require validation in larger, more diverse populations before clinical consideration.

With growing evidence to support the use of placental growth factor (PlGF) testing as a tool to assess suspected preeclampsia, various Canadian tertiary centres have begun integrating biochemical markers for pre-eclampsia diagnosis and risk stratification into clinical care. Most recently, laboratory-based serum PlGF testing was implemented at The Ottawa Hospital, ON, point-of-care PLGF at the Regina General Hospital, SK, and the sFlt-1:PlGF ratio implemented at the London Health Sciences Centre, Victoria Hospital, ON. Here we describe the implementation of PlGF testing across three Canadian tertiary care centres, using a parallel, comparative approach examining key components of implementation: (1) the technical aspects of different PlGF assays and their respective reference value approaches, along with the rationale for assay and reference range selection; (2) differences in reference range interpretation comparing absolute cut-offs versus gestational age-specific centiles; (3) early clinical interpretation and real-world application; (4) implementation processes, operational considerations, and (5) preliminary cost implications. We find that institutions require adoption strategies tailored to their local context.

Placental growth factor (PlGF) is a key biomarker for diagnosing and predicting preeclampsia (PE). While serum-based PlGF assays are well established, urine has emerged as a promising non-invasive alternative matrix. However, the absence of urinary PlGF stability data remains a major preanalytical limitation. This study aimed to assess urinary PlGF stability under common preanalytical conditions, including refrigerated storage and a double freeze-thaw cycle. A prospective study was conducted using urine samples from ten pregnant women. Each sample was processed under standard laboratory conditions and aliquoted into five tubes. One aliquot was immediately frozen at - 80 °C (T0), three were stored at 2-8 °C for 48, 96, and 168 hours before freezing, and one underwent a double freeze-thaw cycle. Urinary PlGF concentrations were measured using the Elecsys PlGF immunoassay on Roche Cobas e801 analyzer. Percent degradation (PD%) was calculated relative to baseline. A linear regression model was applied to estimate the time to exceed a maximum permissible instability (MPI) of ± 10%. Urinary PlGF remained stable at 2-8 °C for up to 48 hours, with a mean PD% of - 6% (95% confidence interval (CI): - 9.1 to - 2.8). The regression model (PD% = - 0.0834 x Time (h)) estimated the - 10% threshold at approximately 120 hours. After a double freeze-thaw cycle, the mean PD% was - 1.5% (95% CI: - 3.4 to 0.4%). Urinary PlGF shows acceptable stability for up to 48 hours under refrigeration and is stable over two freeze-thaw cycles. These findings provide essential preanalytical data supporting its potential use in clinical and research settings.

Trophoblasts are multifunctional cells in the placenta and essential for normal pregnancy. Although trophoblast dysfunction can cause pregnancy complications, the underlying mechanisms remain unclear, and effective treatments are limited, partly because of the scarcity of appropriate experimental models. We previously reported the derivation of human trophoblast stem cells (hTSCs) from 1st-trimester placentas and blastocysts, providing a powerful tool to investigate human trophoblast development and function. However, the difficulty in deriving hTSCs from late-gestation placentas has limited their application to pregnancy complication research. Here we report a robust technique to derive hTSCs from term placentas based on the transient expression of a p53 dominant negative mutant, SALL4, and shRNAs against cyclin-dependent kinase inhibitors. Using this technique, we derived and characterized hTSCs from placentas obtained from patients with early-onset preeclampsia (PE). PE-derived hTSCs exhibit impaired trophoblast invasion and reduced placental growth factor secretion, consistent with trophoblast abnormalities reported in PE. Therefore, this study provides a technological basis for investigating pregnancy complications associated with trophoblast dysfunction.

Antiangiogenic treatment with ramucirumab (RAM) is a standard second-line option in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. However, reliable biomarkers are lacking. The phase II RAMIRIS trial compared RAM plus paclitaxel with RAM plus FOLFIRI (5-fluororuracil, leucovorin and irinotecan) in this setting. We present the exploratory biomarker analysis evaluating placental growth factor (PlGF), carbonic anhydrase IX (CAIX), and tryptase. Plasma samples from 99 patients enrolled in RAMIRIS were collected at predefined timepoints (baseline, Cycle 2 Day 1, and Cycle 4 Day 1). PlGF, CAIX, and tryptase were quantified by ELISA. Associations with progression-free survival (PFS) and overall survival (OS) were analyzed using dichotomized biomarker levels and Cox regression models. PlGF levels increased substantially under treatment, whereas CAIX showed a transient rise, followed by a slight decline, and tryptase remained stable. Elevated PlGF levels at baseline and early-treatment (c2d1) were associated with shorter OS in univariate analysis (baseline HRu = 1.75; p = 0.020; c2d1 HRu = 1.69; p = 0.054). After multivariate adjustment, the association remained directionally consistent; although statistical support was retained only for c2d1 (baseline HRm = 1.41, p = 0.198; c2d1 HRm = 1.85, p = 0.030). CAIX and tryptase showed no consistent associations with survival. Elevated PlGF-particularly its early increase during RAM-based therapy-was associated with shortened survival and may represent a dynamic marker of unfavorable prognosis in advanced gastric/GEJ adenocarcinoma. Given the exploratory nature of this analysis, these findings should be considered hypothesis-generating and require validation in independent biomarker-driven studies.

Hypertensive disorders of pregnancy (HDP) are a significant global health concern requiring effective strategies for risk stratification. We hypothesized that integrating quantitative retinal vascular features with the soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio and clinical data would significantly improve the prediction of delivery within 2 weeks due to HDP progression. This prospective cohort study enrolled 54 hospitalized patients with HDP who underwent simultaneous sFlt-1/PlGF testing and fundus photography. Retinal vascular parameters (density, fractal dimension, tortuosity) were automatically quantified from images using the deep-learning-based AutoMorph pipeline, with separate analyses performed for arteries and veins. The primary outcome was delivery for maternal or fetal indications within 2 weeks. Predictive models were developed and compared using logistic regression with feature selection. Patients with an sFlt-1/PlGF ratio at least 38 exhibited significant retinal microvascular alterations, including reduced vessel density and fractal dimension, compared to those with a lower ratio. These changes were more pronounced in patients who progressed to preeclampsia. The full multimodal model, incorporating retinal features, the sFlt-1/PlGF ratio, and clinical data, achieved an area under the curve (AUC) of 0.85 [95% conflicts of interest (CI), 0.75-0.96)] for predicting delivery within 2 weeks. This significantly outperformed models based on the sFlt-1/PlGF ratio alone (AUC = 0.64) or the ratio combined with clinical data (AUC = 0.72). The integration of retinal vascular features with clinical and biochemical data may improve predictive performance of short-term risk stratification in HDP. This non-invasive, multimodal approach warrants validation in larger prospective studies to determine its potential for improving clinical decision-making.

Cadmium exposure activates ferroptosis through downregulated PPARγ expression in preeclampsia placenta.

DHODH regulates trophoblast fusion via IFITM-reduced plasma membrane fluidity: Implications for hypertensive disorders of pregnancy

To evaluate the association between low placental growth factor (PlGF) levels and adverse maternal and neonatal outcomes, and to assess whether rural residence modifies these associations in a high-risk obstetric population. A retrospective cohort study was conducted, including 189 high-risk pregnant individuals who underwent second-trimester PlGF testing between December 2021 and December 2025. PlGF was categorized as low (<10th centile) or normal (≥10th centile). Outcomes included preeclampsia, preterm birth, low birthweight, small for gestational age (SGA), and neonatal intensive care unit (NICU) admission. Multivariable logistic regression models were used to estimate adjusted odds ratios (aOR). Rural residence was included as an exposure of interest in all models, and interaction terms between low PlGF and rural residence were assessed to evaluate effect modification. Low PlGF was strongly associated with increased odds of preeclampsia, preterm birth and low birthweight. No association was observed with SGA. Rural residence did not modify the relationship between PlGF and adverse outcomes. An initial interaction between PlGF and rural residence was observed for NICU admission; however, this interaction was attenuated and no longer statistically significant after adjustment for gestational age. Gestational age was a strong independent predictor of NICU admission. Low PlGF is a robust marker of placental dysfunction and is strongly associated with adverse perinatal outcomes across both rural and urban populations. While rural residence influences baseline risk, it does not modify the biological effect of PlGF. These findings support the clinical utility of PlGF for risk stratification across diverse geographic settings.