Leptin is a well-known metabolic hormone that plays diverse roles in various body functions, including growth, reproduction, and blood pressure regulation. In pregnancy, leptin produced from the placenta is crucial for ensuring proper fetal development and angiogenesis; however, pathological increases in leptin in maternal circulation are strongly associated with vascular endothelial dysfunction and preeclampsia. Leptin has a strong role in fertility and healthy pregnancy; however, numerous clinical reports over the last 2 decades show that leptin levels pathologically increase in patients with preeclampsia independent of metabolic status (ie, obesity). Despite this strong correlation, the role of leptin in preeclampsia is largely unexplored compared with other biomarkers likely due to differences in placental leptin production among mammals. Emerging literature has recently begun to shed light on this hormone in preeclampsia pathogenesis and uncovered some key mechanisms whereby pathologically elevated leptin production leads to cardiovascular complications for pregnant women.

The aim of this study was to investigate the role of low molecular weight heparin in the prevention of preeclampsia and/or fetal growth restriction in pregnant women with chronic hypertension.

Women diagnosed with chronic hypertension were retrospectively selected from our electronic database from January 2019 to January 2024. The primary endpoint was the occurrence of adverse pregnancy outcomes described as the onset of preeclampsia and/or fetal growth restriction.

A total of 219 pregnant women with chronic hypertension were included. BMI before pregnancy was 27.8 ± 6.4 kg/m 2 and age 36.1 ± 5.4 years. Preeclampsia and fetal growth restriction occurred in 22.9 and 9.6% of patients, respectively. As concerns prophylaxis in the first trimester, 80.1% of patients were administered low-dose aspirin (100 mg), while 16.7% low molecular weight heparin (at prophylactic doses according to BMI), of which 86.1% aspirin + heparin. The rate of preeclampsia was similar in patients taking aspirin or not (21.3 vs. 25%), while it significantly differed in those administered with heparin as thromboprophylaxis (8.8 vs. 25%, P  = 0.04). Fetal growth restriction occurrence did not differ according to the use of prophylaxis. High resistance at uterine arteries Doppler velocimetry at 24-25 weeks of gestation was confirmed to be associated with the onset of preeclampsia (51 vs. 11.9%; P  < 0.001) and fetal growth restriction (18.2 vs. 6.9%; P  = 0.04).

Thromboprophylaxis with low molecular weight heparin reduces the onset of superimposed preeclampsia, independently from aspirin intake.

The microvascular system is essential for delivering oxygen and nutrients to tissues while removing metabolic waste. During pregnancy, the uteroplacental microvascular system undergoes extensive remodeling to meet the increased demands of the fetus. Key adaptations include vessel dilation and increases in vascular volume, density, and permeability, all of which ensure adequate placental perfusion while maintaining stable maternal blood pressure. Structural and functional abnormalities in the uteroplacental microvasculature are associated with various gestational complications, posing both immediate and long-term risks to the health of both mother and infant. In this review, we describe the changes in uteroplacental microvessels during pregnancy, discuss the pathogenic mechanisms underlying diseases such as preeclampsia, fetal growth restriction, and gestational diabetes, and summarize current clinical and research approaches for monitoring microvascular health. We also provide an update on research models for gestational microvascular complications and explore solutions to several unresolved challenges. With advancements in research techniques, we anticipate significant progress in understanding and managing these diseases, ultimately leading to new therapeutic strategies to improve maternal and fetal health.

Inflammatory bowel disease (IBD) often presents during the fertile age and may affect pregnancy outcomes. Both IBD and selected pregnancy complications involve oxidative stress. Soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) serve as biomarkers of placental insufficiency, while free thiols (FT) reflect systemic oxidative stress. This study aimed to assess the dynamics of FT, sFlt-1, and PlGF before, during, and shortly after pregnancy, and their relationships with disease- and pregnancy outcomes in patients with IBD.

This retrospective cohort study included pregnant women with and without IBD. FTs were measured with colorimetric detection; sFlt-1 and PlGF were measured using immunofluorescent assays. Extensive clinical data were collected, including pregnancy complications and IBD parameters.

A total of 40 patients and 14 non-IBD controls participated, covering 57 IBD and 14 control pregnancies. Serum FT levels were significantly lower in patients with ulcerative colitis during pregnancy (p = 0.007) and decreased compared to pre-conceptional levels (p = 0.005), indicating increased oxidative stress. sFlt-1/PlGF ratios were higher in patients with small-for-gestational-age infants (p = 0.015). Post-pregnancy FT levels were lower in patients experiencing disease exacerbations during pregnancy (p = 0.046), whereas sFlt-1/PlGF ratios were numerically higher (p = 0.063). IBD severity correlated with lower FT levels regarding surgical history (p = 0.066) and biologic use (p = 0.033).

This study demonstrates increased systemic oxidative stress in patients with IBD during pregnancy, as reflected by lower FT levels compared to pre-conceptional values and non-IBD controls. Prospective validation is required to evaluate the utility of these biomarkers in predicting pregnancy complications and informing clinical decisions.

The objective of this study was to evaluate total circulating PlGF (placental growth factor) and free PlGF concentrations to provide insights into the mechanisms of decreased PlGF noted in preeclampsia and fetal growth restriction.

We conducted a retrospective single-center study in pregnant women receiving care for suspected preeclampsia or fetal growth restriction. Serum angiogenic proteins (sFLT1 [soluble fms-like tyrosine kinase] and free PlGF) were measured on an automated platform as part of standard-of-care. Total PlGF concentrations in the serum were directly measured using a validated biochemical procedure that dissociated circulating sFLT1 and PlGF complexes. Small for gestational age (SGA) was defined by birthweight ≤10th percentile.

Of the 407 women studied, 155 women did not develop preeclampsia or SGA (control group), 111 women developed SGA without preeclampsia (SGA group), 71 women developed preeclampsia without SGA (preeclampsia group), and 70 developed preeclampsia and SGA (preeclampsia+SGA group). Despite reductions in free PlGF levels (229 [158-321] pg/mL), total PlGF levels were not reduced in the preeclampsia group (1020 [738-1444] pg/mL) compared with the control group (1077 [763-1595] pg/mL). In contrast, the total PlGF levels were significantly reduced in the SGA group (744 [462-1161] pg/mL; P<0.0001) and the preeclampsia +SGA group (616 [349-917] pg/mL; P<0.0001) compared with the control group (1077 [763-1595] pg/mL).

Placental dysfunction associated with preeclampsia, characterized by reduced free PlGF levels but unchanged total PlGF, is driven by excessive placental production of sFLT1. Placental dysfunction associated with SGA, marked by reductions in both free and total PlGF, is mediated by decreased placental PlGF production.

We characterize rat placenta microstructure in the context of the reduced uterine perfusion pressure (RUPP) model of preeclampsia using the homodyned K-distribution to parameterize envelope-detected signals of ultrasound radiofrequency echo frames obtained in vivo. Preeclampsia is a life-threatening pregnancy syndrome related to abnormal placental tissue microstructure which motivated the quantitative ultrasound-based tissue characterization approach used in this study.

Ultrasound radiofrequency echo frames against time (or videos) were obtained on 30 and 38 in vivo placentae at gestation day (GD) 14 and 18 respectively, using 9 Sprague-Dawley rats. Preeclampsia-like effects were induced by surgical modification (post GD 14) following the RUPP model, giving a total of 20 RUPP and 18 control placentae at GD 18. The homodyned K-distribution was fit to value distributions of envelope-detected signals of ultrasound radiofrequency echo frames against time, yielding temporal α (scatterer number per resolution cell) and κ (ratio of coherent to diffuse signal power) parameters used to characterize the placental tissue microstructure.

Visualization of GD 18 α values as a color overlay on B-mode ultrasound video suggested higher values of control compared with RUPP. The mean kurtosis for RUPP was 4.07 ± 0.71 in comparison to 5.08 ± 1.28 for the control using placenta-level kurtosis values (p = 0.0044). There were no significant differences observed in GD 14 placentae, consistent with expectations. Further, we visualized and quantified temporal changes in GD 18 α values with frame-level statistics that support earlier findings.

This study quantitatively characterizes rat placenta microstructure using the homodyned K-distribution and temporal α and κ parameters.

Preeclampsia, one of the great obstetrical syndromes, manifests through diverse maternal and fetal complications and remains a leading contributor to adverse perinatal outcomes. In this review, we describe our work on single-cell and single-nuclei RNA sequencing to elucidate the molecular mechanisms that underlie early- and late-onset preeclampsia. Analysis of 46 cell types, encompassing approximately 90,000 cells from placental tissues collected after delivery, demonstrated cellular dysregulation in early-onset preeclampsia, whereas late-onset preeclampsia showed comparatively subtle changes. These findings were observed in all cell lines, including all types of trophoblast, lymphoid, myeloid, stromal, and endothelial cells. Key findings in early-onset preeclampsia included disrupted syncytiotrophoblast and extravillous trophoblast angiogenic signaling, characterized by an up-regulation of FLT1 and down-regulation of PGF, consistent with an angiogenic imbalance. The stromal and vascular compartments exhibited stress-induced transcriptomic shifts. Both endothelial cells and pericytes showed evidence of stress, including up-regulation of heat shock proteins and markers of apoptosis. In addition, the inflammation- and stress-responsive states were more abundant in early-onset preeclampsia than in matched controls. Inflammatory pathways were markedly up-regulated in both the maternal and fetal immune cells; for example, we observed a marked increase in pro-inflammatory cytokines, including secreted phosphoprotein 1 and C-X-C motif chemokine ligand 2 and 3. Conversely, late-onset preeclampsia retained adaptive placental features with localized dysregulation of extracellular matrix remodeling and angiogenic markers, underscoring its possible maternal cardiovascular etiology. Single-cell and single-nuclei RNA sequencing investigations of placental tissues support the proposed classification of preeclampsia into a placental dysfunction type, primarily presenting early in pregnancy, and a maternal cardiovascular maladaptation type, primarily presenting later in pregnancy, each with distinct biomarkers, risk factors, and therapeutic targets. The early-onset preeclampsia findings advocate for interventions that target angiogenic pathways, such as RNA-based therapies that target specific cells of the placenta, to modulate soluble fms-like tyrosine kinase-1 levels. In contrast, late-onset preeclampsia management may benefit from maternal cardiovascular optimization, including individualized antihypertensive and metabolic treatments. These results underscore the heterogeneity of preeclampsia, emphasizing the need for individualized diagnostic and therapeutic strategies. This molecular atlas of preeclampsia advances our understanding of the complex interplay among elements of the maternal-placental-fetal array, thereby bridging clinical phenotypes and cellular mechanisms. Future research should focus on integrating these insights into longitudinal studies to develop precision medicine approaches for preeclampsia to enhance outcomes for mothers and neonates.

A soluble fms-like tyrosine kinase-1 (sFlt-1)-to-placental growth factor (PlGF) ratio cut-off of 38 is currently considered optimal for ruling out pre-eclampsia (PE); however, implementation of this ratio in clinical practice is limited. N-terminal pro B-type natriuretic peptide (NT-proBNP) is elevated in PE owing to the cardiovascular effects of this disease. This study aimed to identify the predictive performance of NT-proBNP to detect PE and placental complications within 1 week after assessment, and compare it with the predictive performance of the sFlt-1/PlGF ratio. High-sensitivity troponin T (hs-TnT) and uric acid were also evaluated.

This was a prospective nested case-control study conducted in five Spanish centers between March 2018 and December 2020, and comprised women with a singleton pregnancy and suspected PE between 24 + 0 and 41 + 0 weeks' gestation. We evaluated the ability of the sFlt-1/PlGF ratio, NT-proBNP, hs-TnT and uric acid to predict the development of any-onset (at any gestational age), early-onset (before 34 weeks) or term (at or after 37 weeks) PE within 1 week or 4 weeks after assessment. Predictive performance was assessed by estimating negative predictive values, positive predictive values, sensitivity, specificity and areas under the receiver-operating-characteristics curves (AUCs) for these biomarkers, with corresponding 95% CIs. We performed post-hoc exploratory analyses of associations between the sFlt-1/PlGF ratio, NT-proBNP, hs-TnT and uric acid in women who developed PE, as well as in women who developed complicated PE (PE plus fetal growth restriction, stillbirth or placental abruption) within 1 week and 4 weeks after assessment.

A total of 323 women with suspected PE at or before 41 + 0 weeks were enrolled in the study, of whom seven were lost to follow-up. The final analysis included 316 eligible participants, with 424 samples. The overall incidence of PE was 23.4% (n = 74) and early-onset PE developed in 8.5% (n = 27) of cases. The sFlt-1/PlGF ratio and NT-proBNP exhibited similar abilities to predict early-onset PE within 1 week after assessment (AUC, 0.970 (95% CI, 0.932-1.000) and 0.971 (95% CI, 0.942-1.000), respectively). hs-TnT and uric acid demonstrated inferior predictive capability compared with the sFlt-1/PlGF ratio for the prediction of any-onset PE, early-onset PE and term PE within 1 week and 4 weeks after assessment. The optimal cut-off for NT-proBNP was 116 pg/mL. At this cut-off, NT-proBNP showed a sensitivity of 90.9% (95% CI, 70.8-98.9%) and a specificity of 94.3% (95% CI, 91.2-96.5%), with a positive predictive value of 5.7% (95% CI, 3.7-8.7%) and a negative predictive value of 99.9% (95% CI, 99.9-100%) in predicting early-onset PE within 1 week of assessment, which was comparable with that of the sFlt-1/PlGF ratio. Participants with PE-related complications had higher levels of all biomarkers, but only NT-proBNP showed a similar predictive ability to the sFlt-1/PlGF ratio for complicated PE within 1 week after assessment (AUC, 0.818 (95% CI, 0.706-0.930) vs 0.822 (95% CI, 0.723-0.921), respectively).

An NT-proBNP cut-off value of 116 pg/mL has a similar diagnostic performance to that of the sFlt-1/PlGF ratio in predicting the diagnosis of early-onset PE within 1 week after assessment. Thus, NT-proBNP could be used in clinical practice for the early identification and management of PE, particularly in cases for which the sFlt-1/PlGF ratio is not available. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.

Placentation is a key process that is tightly regulated that ensures the normal placenta and fetal development. Preeclampsia (PE) is a hypertensive pregnancy‑associated disorder characterized by increased oxidative stress and inflammation. STAT3 signaling plays a key role in modulating important processes such as cell proliferation, differentiation, invasion and apoptosis. The present review aimed to analyse the role of STAT3 signaling in PE pregnancies, discuss the main natural and synthetic compounds involved in modulation of this signaling both in vivo and in vitro and summarize the main cellular modulators of this signaling to identify possible therapeutic targets and treatments to improve the outcome of PE pregnancies.

Although twin pregnancies are known to have higher rates of preeclampsia, the association between twin pregnancy and Hemolysis, Elevated Liver Enzymes, and Low Platelet Count (HELLP) syndrome has not been adequately studied. We assessed the association between twin pregnancy and HELLP syndrome, and also examined gestational age-specific rates of HELLP syndrome in twin and singleton pregnancies.

We conducted a retrospective cohort study of women with singleton or twin live births or stillbirths between 200 and 436 weeks gestation in British Columbia, Canada, from 2008/09 to 2019/20. Data on the demographic and clinical characteristics were obtained from the British Columbia Perinatal Database Registry. Logistic regression was used to estimate adjusted odds ratios and 95% CIs, adjusted for maternal age, body mass index, smoking, and other potential confounders.

Among 524 236 women (515 953 singleton and 8283 twin pregnancies), 1510 were diagnosed with HELLP syndrome (2.9 per 1000 women). HELLP syndrome occurred in 181 twin pregnancies (21.9 per 1000 women), while 1329 cases occurred in singleton pregnancies (2.6 per 1000 women) (rate ratio 8.5 [95% CI 7.3-9.9]). The adjusted odds ratio for the associations between HELLP syndrome and twin versus singleton pregnancies was 7.1 (CI 6.0-8.5). In twin pregnancies, the incidence of HELLP syndrome increased markedly from 260 to 286 weeks gestation until 370 to 396 weeks. In contrast, the incidence of HELLP syndrome increased more gradually from 230 to 406 weeks gestation in singleton pregnancies.

Twin pregnancy is strongly associated with HELLP syndrome. HELLP syndrome risk in twin pregnancies increases markedly from 260 weeks gestation onwards.

An imbalance of the antiangiogenic factor, soluble fms-like tyrosine kinase-1, and proangiogenic factor, placental growth factor, in the circulation is a reliable predictor for the development of preeclampsia with severe features and related adverse outcomes. In 2023, the US Food and Drug Administration approved a serum soluble fms-like tyrosine kinase-1/placental growth factor test at a cutoff of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy for the progression to preeclampsia with severe features between 23 and 35 weeks.

This study aimed to generate real-world evidence for clinical utility for serum soluble fms-like tyrosine kinase-1/placental growth factor test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within 2 weeks of testing among hospitalized patients with hypertensive disorders of pregnancy.

Hospitalized patients with hypertensive disorders of pregnancy between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to January 2024 after the implementation of serum soluble fms-like tyrosine kinase-1/placental growth factor testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (placental growth factor and soluble fms-like tyrosine kinase-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines on the basis of biomarkers but made pragmatic management decisions independently. Results of soluble fms-like tyrosine kinase-1/placental growth factor tests were available to clinicians within 24 hours of venipuncture. The association between soluble fms-like tyrosine kinase-1/placental growth factor ≥40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed.

Of the 65 patient encounters, 36 had a soluble fms-like tyrosine kinase-1/placental growth factor <40 (55.4%). The rate of delivery for indications related to hypertensive disorders of pregnancy within 2 weeks was significantly lower among encounters with a low ratio vs high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted hazard ratio, 7.52; 95% confidence interval, 3.05-18.54; P<.001). A diagnosis of preeclampsia with severe features within 2 weeks of testing was also less likely among the encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 when compared with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (2/36 [5.6%] vs 23/29 [79.3%], P<.001; positive predictive value of 79% [95% confidence interval, 0.65-0.94] and negative predictive value of 0.94 [95% confidence interval, 0.87-1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within 2 weeks of testing were 6.13 and 0.09, respectively. Encounters with a soluble fms-like tyrosine kinase-1/placental growth factor ratio <40 were less likely to experience a maternal or fetal adverse event as compared with encounters with soluble fms-like tyrosine kinase-1/placental growth factor ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], P=.01). Among 36 encounters involving low soluble fms-like tyrosine kinase-1/placental growth factor values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed on the basis of biomarkers, and none developed preeclampsia with severe features or adverse outcomes at 2 weeks. The median latency defined as days between biomarker measurement and delivery in patients with a low biomarker ratio was 33 (interquartile ratio, 23-47) vs 7 (interquartile ratio, 4-14) days among patients with a high ratio (P<.001). Corticosteroid use within 2 weeks was also significantly reduced in the low biomarker group when compared with the high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], P<.001).

In this study, the incorporation of soluble fms-like tyrosine kinase-1/placental growth factor ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with hypertensive disorders of pregnancy in the United States. Among patients with a low ratio, pregnancy may be prolonged, which results in better neonatal outcomes without harm to the mother.

This retrospective study evaluated diagnostic and prognostic values of sFlt-1/PlGF ratio combined with serum endocan-1 for preeclampsia (PE). This study included 105 patients with PE admitted at Xiamen University Affiliated Xiang'an Hospital from January 2020 to September 2023, with 90 healthy pregnant women receiving routine check-ups during the same period as controls. sFlt-1, PlGF, and endocan-1 levels were measured, and sFlt-1/PlGF ratio was calculated. The correlation of sFlt-1/PlGF ratio with serum endocan-1 levels was analysed, and influencing factors for poor prognosis of PE patients were screened. Diagnostic and prognostic values of sFlt-1/PlGF ratio combined with serum endocan-1 were assessed. Results showed an increase in sFlt-1/PlGF ratio and serum endocan-1 levels in PE patients and a positive correlation between them. For assisting in the diagnosis of PE, the AUC of the sFlt-1/PlGF ratio combined with serum endocan-1 was 0.874 (95%CI: 0.819 - 0.917; sensitivity, 75.24%; specificity, 100.00%), which was superior over that of sFlt-1/PlGF ratio (P = 0.025) and endocan-1 (P = 0.047) alone. Elevated sFlt-1/PlGF ratio and serum endocan-1 levels were independent risk factors for poor prognosis of PE patients. For assisting in predicting poor prognosis of PE, the AUC of sFlt-1/PlGF ratio with serum endocan-1 was 0.955 (95%CI: 0.896 - 0.986; sensitivity, 82.61%; specificity, 100.00%), which was higher than that of sFlt-1/PlGF ratio (P = 0.023) or serum endocan-1 (P = 0.010) alone. Altogether, sFlt-1/PlGF ratio combined with serum endocan-1 is advantageous over sFlt-1/PlGF ratio and serum endocan-1 alone for predicting PE occurrence and prognosis.

Central precocious puberty (CPP) is one of the common endocrine diseases in pediatrics. However, the molecular mechanisms regulating development of CPP have remained unclear. The purpose of this study was to discover the key pathways and hub genes related to CPP.

We analyzed two public datasets (GSE7142 and GSE8310) to identify differentially expressed genes in the progression of CPP. Then, we screened out overlapping differential genes from these two datasets and performed a series of bioinformatics analyses to explore promising targets and molecule mechanism of CPP.

We identified 30 down-regulated overlapping DEGs between GSE7142 (CPP/no CPP) and GSE8130 (EP/JUV) datasets and 17 down-regulated overlapping DEGs between GSE7142 (CPP/no CPP) and GSE8130 (LP/JUV) datasets. KEGG signaling pathway shows that calcium signaling pathway is suppressed continuously in early and late pubertal of CPP patients. MAPK signaling pathway also plays an important role in the occurrence and development of CPP. Eventually, we screened out 2 hub genes (FGFR2 and FLT1) highly related to CPP, which may provide a new directions for the diagnosis and treatment of CPP.

While further validation is needed, we provide useful and novel information to explore potential signaling pathways and candidate genes for CPP diagnosis and treatment options.

Preeclampsia is a common and severe pregnancy complication. The syndrome is highly heterogeneous, making accurate classification difficult, which is not conductive to find ways to predict and prevent this syndrome. Recently, we reported that high placental miR-155 defined a new subtype of preeclampsia. Here, we aimed to examine whether high maternal sero-miR-155 could be a marker to identify this subtype.

To explore whether the patients with high sero-miR-155 no matter in first and third trimester, we conducted a case-control and a longitudinal cohort study. We measured the sero-miR-155 levels at first, second and third trimesters in all pregnant women. Then, using the 95th percentile (P95) of sero-miR-155 in controls as the cut-off value, we divided the preeclamptic patients into high sero-miR-155 group (≥ P95) and normal sero-miR-155 group (< P95). We compared the difference of clinical manifestations between two groups and used t-distributed stochastic neighbor embedding (t-SNE) to evaluate whether the patients with high sero-miR-155 could be clustered as a subtype. Finally, we evaluated the predictive value of sero-miR-155 in the subtype.

The case-control study included 525 subjects (350 controls and 175 preeclampsia) and the longitudinal cohort study included 411 subjects (274 controls and 137 preeclampsia). Sero-miR-155 was significantly elevated in preeclampsia. Compared with preeclamptic patients with normal sero-miR-155 levels, the cases with high sero-miR-155 had significantly higher blood pressure and other severe preeclampsia-related complications. The incidences of HELLP syndrome [5.2% (5/96) vs. 0.9% (2/216), p < 0.01], visual disturbance [15.6% (15/96) vs. 4.6% (10/216), p < 0.01], hypertensive retinopathy [13.5% (13/96) vs. 3.2% (7/216), p < 0.01], and placenta abruption [7.3% (7/96) vs. 0.9% (2/216), p < 0.01] in patients with high miR-155 level were significantly increased. T-SNE analysis showed the patients with high sero-miR-155 were predominantly clustered on the left of the plot.

The patients with high sero-miR-155 exhibited more severe clinical manifestations and sero-miR-155 could be a biomarker to identify a subtype of preeclampsia with high sero-miR-155.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the relative benefits and harms of statins for preeclampsia prevention in pregnant women.

Exposure to suboptimal temperatures during pregnancy has been associated with adverse pregnancy and birth outcomes related to placental development disorders. No prior studies have examined the potential impacts of temperature on placental markers. We conducted an investigation into the cumulative impact of daily ambient temperature on critical clinical placental perfusion and function markers during the placentation period, utilizing data from a prospective birth cohort in Nanjing, China.

We collected UtA-PI data and blood samples during the first follow-up (11-13.5 weeks of gestation) and measured PlGF and PAPP-A concentrations in plasma. We estimated individual daily temperature exposure over the 30 days preceding the follow-up and applied a Distributed Lag Nonlinear Model to evaluate its associations with UtA-PI, PlGF, and PAPP-A levels.

We included 3403, 3407, and 3427 women in the UtA-PI, PlGF, and PAPP-A analyses, respectively. Cold exposure was associated with higher UtA-PI measurements, with the strongest estimated percent change being 14.80% (95% CI: 3.32, 27.55). Both cold and heat exposures were associated with decreased PlGF concentrations, with the strongest estimated percent changes being -44.23% (95% CI: 63.28, -15.30) and -48.27% (95% CI: 64.33, -24.98), respectively. Temperature effects on UtA-PI were immediate, whereas changes in PlGF concentrations manifested after a cumulative lag of 24 days.

Both cold and heat exposures were associated with changes in placental markers, providing new insights into the potential mechanisms connecting ambient temperature to adverse pregnancy and birth outcomes through disorders of placental development.

Pre-eclampsia is a significant contributor to maternal and neonatal morbidity and mortality. However, its etiology remains elusive. More and more studies have highlighted the potential involvement of folic acid metabolism in the development of pre-eclampsia. Folic acid is known to be important for DNA synthesis and methylation processes, which are crucial during pregnancy. Disruptions in these pathways may contribute to the pathogenesis of pre-eclampsia. Clinical studies investigating associations between folic acid supplementation and pre-eclampsia produced inconsistent results. The research aims to explore the potential link between folic acid deficiency and the development of pre-eclampsia-like symptoms in rat models, shedding light on the possible role of one-carbon metabolic pathways in the etiology of pre-eclampsia.

Establishing a rat model with severe and moderate folate deficiency by providing female rats with a folate-deficient diet from birth or weaning, respectively. The effects on folate and homocysteine levels during pregnancy were then studied.

Both groups exposed to folate deficiency exhibited decreased levels of 5-methyltetrahydrofolic acid in both plasma and red blood cells, along with increased levels of homocysteine in plasma, compared to the control group. Consistent high blood pressure and urinary protein excretion were not significantly different among the three groups. However, fetuses from the folate-deficient group exhibited noticeably lower body weight compared to those from the folate-replete group.

Folate deficiency alone may not be sufficient to cause pre-eclampsia in rats, but it does increase the risk of offspring being small for their gestational age at birth.

Does trophectoderm biopsy for preimplantation genetic testing for aneuploidies (PGT-A) affect maternal serum first-trimester pregnancy biomarkers (pregnancy-associated plasma protein A [PAPP-A], free β-HCG and placental growth factor [PIGF])?

Retrospective cohort study of all singleton pregnancies (n = 9794) after naturally conceived (n = 8005) IVF and fresh embryo transfers (n = 478), frozen embryo transfer of non PGT-A (FET) (n = 963) or PGT-A tested embryos (FET + PGT-A) (n = 348). Serum levels of free β-HCG and PAPP-A were measured in all women with a viable pregnancy at 8-13.6 weeks of pregnancy; PIGF was measured in 3784 women. Biomarkers were converted to a multiple of the expected normal median (MOM) for a pregnancy of the same gestational day. The medians for the multiple of the median were calculated and compared.

Free β-HCG did not differ according to mode of conception. The PAPP-A concentrations were significantly lower in IVF and fresh embryo transfers (-0.1 Log10 MOM raw PAPP-A) compared with FET + PGT-A (-0.04 Log 10 MOM raw PAPP-A, P = 0.009) and natural conceptions (-0.0187 Log 10 MOM raw PAPP-A) (P < 0.001). The PIGF levels were significantly lower in the FET + PGTA group versus natural conception (P = 0.001). Difference in means adjusted by crown rump length was 4.6 pg/ml (95% CI 2.7 to 6.6) for natural conceptions, 3.5 pg/ml (95% CI 0.34 to 6.6) for IVF and 2.2 pg/ml (95% CI 0.06 to 4.4) for FET.

Trophectoderm biopsy for PGT-A has a significant effect on first-trimester maternal serum PAPP-A and PIGF. This needs to be further validated, as it may mislead the estimation of the first-trimester risk of aneuploidies and pre-eclampsia.

Preeclampsia is a key cause of prematurity in the U.S. and incurs significant healthcare costs. An imbalance between soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) predicts severe preeclampsia and aids in its management.

This study aimed to assess the cost-effectiveness of the sFlt-1/PlGF test as an addition to standard care for patients at risk of developing preeclampsia.

A decision tree analysis was conducted to assess the cost effectiveness of the ratio test in the United States, using data from Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification [PRAECIS] and from a real-world evidence study conducted after the implementation of sFlt-1/PlGF testing into routine clinical practice (Biomarker Examination and Analysis for Clinical Obstetrical Navigation Study [BEACON]). The model compared standard of care alone versus a biomarker-based approach utilizing the sFlt-1/PlGF test for managing patients at risk of preeclampsia with severe features. Published data was used to estimate theoretical cost values of infants for their first six months of life.

The analysis indicated potential total neonatal cost savings of nearly $10,595,332 (95% CI: $6,555,439 to $14,730,536) per 1,000 patients using the sFlt-1/PlGF ratio test, translating to about $10,595 saved per patient. The incremental cost-effectiveness ratio (ICER) analysis showed a mean cost savings of $62,572 for each pregnancy prolonged by two weeks.

The sFlt-1/PlGF test, when used alongside standard care, enhances risk stratification for severe preeclampsia and may lead to significant neonatal cost savings by reducing preterm deliveries and neonatal intensive care admissions.

sFLT-1 has been implicated in the pathogenesis of HDP. We aimed to examine the role of maternal and fetal polymorphisms in risk of HDP and severe-spectrum disease.

Cases of HDP (143) and controls (169) from mother-baby dyads were recruited at the Los Angeles County Women's and Children's Hospital (WCH). Cases of severe disease (99) and controls (31) from mother-father-baby triads were recruited through HELLP syndrome websites. Four sFLT-1 SNPs (rs7993594, rs3751395, rs7983774, and rs664393) were genotyped. Data was analyzed using a log-linear regression model in the Haplin package in R.

Maternal double dose of the A allele (rs7993594) exhibited a nominally significant increased risk of HDP (RR = 3.52, 95% CI 1.08, 11.20). In the severe-spectrum cohort, a marginally significant protective effect among mothers carrying infants with a single dose of the A allele (rs7993594) was observed (RR = 0.59, 95% CI 0.36, 0.98) and double-dose maternal carriage of the G-t-G-G haplotype increased risk of severe disease (RR = 4.13, 95% CI 1.22, 13.80).

The maternal rs7993594 A allele appears to be associated with increased risk of HDP. Double-dose maternal carriage of the G-t-G-G haplotype increased risk of severe disease whereas the fetal rs7983774 A allele appears to be associated with decreased risk.

The ratio of soluble fms-like tyrosine kinase 1 to placental growth factor is a useful biomarker for preeclampsia. Since it is a measure of placental dysfunction, it could also be a predictor of clinical deterioration and fetal tolerance to intrapartum stress.

We tested the hypothesis that soluble fms-like tyrosine kinase 1 to placental growth factor ratio predicts time to delivery. Secondary objectives were to examine associations between the soluble fms-like tyrosine kinase 1 to placental growth factor ratio and mode of birth, fetal distress, need for labor induction, and birthweight z score.

Secondary analysis of the INSPIRE trial, a randomized interventional study on prediction of preeclampsia/eclampsia in which women with suspected preeclampsia were recruited and their blood soluble fms-like tyrosine kinase 1 to placental growth factor ratio was assessed. We stratified participants into 3 groups according to the ratio result: category 1 (soluble fms-like tyrosine kinase 1 to placental growth factor ≤38); category 2 (soluble fms-like tyrosine kinase 1 to placental growth factor >38 and <85); and category 3 (soluble fms-like tyrosine kinase 1 to placental growth factor ≥85). We modeled time from soluble fms-like tyrosine kinase 1 to placental growth factor determination to delivery using Kaplan-Meier curves and compared the 3 ratio categories adjusting for gestational age at soluble fms-like tyrosine kinase 1 to placental growth factor determination and trial arm with Cox regression. The association between ratio category and mode of delivery, induction of labor, and fetal distress was assessed using a multivariable logistic regression adjusting for gestational age at sampling and trial arm. The association between birthweight z score and soluble fms-like tyrosine kinase 1 to placental growth factor ratio was evaluated using multiple linear regression. Subgroup analysis was conducted in women with no preeclampsia and spontaneous onset of labor; women with preeclampsia; and participants in the nonreveal arm.

Higher ratio categories were associated with a shorter latency from soluble fms-like tyrosine kinase 1 to placental growth factor determination to delivery (37 vs 13 vs 10 days for ratios categories 1-3 respectively), hazards ratio for category 3 ratio of 5.64 (95% confidence interval 4.06-7.84, P<.001). A soluble fms-like tyrosine kinase 1 to placental growth factor ratio ≥85 had specificity of 92.7% (95% confidence interval 89.0%-95.1%) and sensitivity of 54.72% (95% confidence interval, 41.3-69.5) for prediction of preeclampsia indicated delivery within 2 weeks. A ratio category 3 was also associated with decreased odds of spontaneous vaginal delivery (Odds ratio [OR] 0.47, 95% confidence interval 0.25-0.89); an almost 6-fold increased risk of emergency cesarean section (OR 5.89, 95% confidence interval 3.05-11.21); and a 2-fold increased risk for intrapartum fetal distress requiring operative delivery or cesarean section (OR 3.04, 95% confidence interval 1.53-6.05) when compared to patients with ratios ≤38. Higher ratio categories were also associated with higher odds of induction of labor when compared to ratios category 1 (category 2, OR 2.20, 95% confidence interval 1.02-4.76; category 3, OR 6.0, 95% confidence interval 2.01-17.93); and lower median birthweight z score. Within subgroups of women a) without preeclampsia and with spontaneous onset of labor and b) women with preeclampsia, the log ratio was significantly higher in patients requiring intervention for fetal distress or failure to progress compared to those who delivered vaginaly without intervention. In the subset of women with no preeclampsia and spontaneous onset of labor, those who required intervention for fetal distress or failure to progress had a significantly higher log ratio than those who delivered vaginaly without needing intervention.

The soluble fms-like tyrosine kinase 1 to placental growth factor ratio might be helpful in risk stratification of patients who present with suspected preeclampsia regarding clinical deterioration, intrapartum fetal distress, and mode of birth (including the need for intervention in labor).

Small fetuses, with estimated fetal weight (EFW) below the tenth percentile, are classified as fetal growth restriction (FGR) or small for gestational age (SGA) based on prenatal ultrasound. FGR fetuses have a greater risk of stillbirth and perinatal complications and may benefit from serial ultrasound scans to guide early delivery. Abnormal serum angiogenic factors, such as the soluble fms-like tyrosine kinase-1 (sFlt-1):placental growth factor (PlGF) ratio, have shown potential to more accurately distinguish FGR from SGA, with fewer false positives. This randomized controlled trial compared a management protocol based on the sFlt-1:PlGF with EFW and Doppler ultrasound in avoiding adverse perinatal outcomes in small fetuses after 36 weeks of gestation. A total of 1,088 pregnant women with singleton pregnancies were randomized to either the Doppler-based (control) or the sFlt-1:PlGF-based (intervention) protocol. The primary outcome, neonatal acidosis or Cesarean delivery as a result of abnormal cardiotocography, was assessed in 1,013 participants. The incidence was 10.5% in the intervention group and 10.0% in the control group (absolute difference, 0.53 (-3.21 to 4.26)), with the upper limit of the confidence interval <8.5%, confirming noninferiority. Thus, the sFlt-1:PlGF was noninferior to EFW and Doppler ultrasound in avoiding neonatal acidosis or Cesarean delivery owing to nonreassuring fetal status in small fetuses after 36 weeks (ClinicalTrials.gov registration: NCT04502823 ).

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy.

Retrospective cohort study.

Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy.

Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test.

Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1).

In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Placental growth factor (PlGF) has been reported as a good biomaker for the prediction of preeclampsia occurring in the short term in singleton pregnancies, in women presenting with clinical suspicion of preeclampsia. This study aims to evaluate the predictive value of the PlGF in twin pregnancies.

Twin pregnancies with clinically suspected preeclampsia (24 weeks 0 days-36 weeks 6 days of gestation) were enrolled in this study. The threshold of PlGF for predicting preeclampsia was determined on the basis of a receiver-operating characteristic curve to predict preeclampsia and the short-term occurrence of preeclampsia.

Within 1 week, 2 weeks, and 4 weeks of testing respectively, a cutoff value of 215 pg/mL for PlGF to predict preeclamsia in twin pregnancies suspected to have preeclampsia has a specificity of 100 %[51.7 %, 100 %], 100 %[62.9 %, 100 %], 93.8 %[667.6 %, 99.7 %], and a negative predictive value of 100 %[94.8 %, 100 %], 100 %[95.0 %, 100 %], and 98.9 %[93.0 %, 99.9 %].

A cutoff value of 215 pg/mL for PlGF is a useful tool to exclude the development of preeclampsia within 4 weeks of measurement.

The use of assisted reproductive technology (ART) is growing, both to assist individuals with infertility and for fertility preservation. Individuals with cardiovascular disease (CVD), or risk factors for CVD, are increasingly using ART. Thus, knowing how to care for patients undergoing ART is important for the cardiovascular clinician. In this scientific statement, we review the ART process and known short-term and long-term risks associated with ART that can adversely affect patients with CVD. We review current knowledge on risks from ART for specific cardiac conditions and provide a suggested approach to evaluating and counseling patients with CVD contemplating ART as well as suggested management before and during the ART process. Individuals with CVD are at increased risk for pregnancy complications, and management of this unique population has been discussed previously. The focus of this scientific statement is on ART. Therefore, discussions on risk assessment, counseling, and management of individuals with CVD during pregnancy are limited, and established guidelines are referenced.

Preeclampsia (PE) is a gestational complication affecting 5% to 10% of all pregnancies. PE is characterized by hypertension and endothelial dysfunction, whose etiology involves, among other factors, alterations in the extracellular matrix (ECM) that can compromise vascular remodeling and trophoblast invasion, ie, processes essential for placental development. Endothelial dysfunction is caused by release of antiangiogenic factors, mainly a soluble fms-like tyrosine kinase-1 (sFlt-1), which antagonizes two endothelial angiogenic factors, the vascular endothelial growth factor (VEGF) and placental growth factor (PLGF). This angiogenic imbalance contributes to clinical symptoms including hypertension and multisystem dysfunction. This review aims to summarize recent advances in understanding PE, particularly with altered ECM components such as heparan sulfate proteoglycans, the glycosidase heparanase, fibronectin, collagen XVIII (endostatin), and metalloproteases. This comprehensive narrative review was conducted on PubMed from 1994 to 2024, focusing on articles on the pathophysiology of PE, particularly endothelial dysfunction caused by ECM modifications. The data shows a reduced expression of matrix metalloproteinases, increased collagen fragment XVIII, and significant changes in fibronectin associated with PE. Furthermore, endothelial dysfunction was associated with increased degradation of heparan sulfate chains from proteoglycans and increased sFlt-1. Understanding these ECM modifications is crucial for developing potential new therapeutic interventions that improve maternal and fetal outcome in PE.

Preeclampsia (PE) is a complex pregnancy-specific disorder characterized by hypertension, proteinuria, and systemic inflammation, posing significant risks to maternal and fetal health. This study investigates the role of growth arrest-specific protein 6 (Gas6) in PE pathogenesis using a rat model. Gas6 administration induces hallmark PE features, including hypertension, proteinuria, and significant alterations in placental gene expression. Transcriptomic analysis revealed changes in pathways related to extracellular matrix remodeling, interleukin signaling, and oxidative stress, highlighting their contribution to PE pathology. Key findings include the upregulation of Fam111a, linked to oxidative stress and DNA replication, and the downregulation of Clca4, associated with ion transport and cellular homeostasis. Protein-level validation through immunofluorescence confirmed these alterations, reinforcing their mechanistic roles in placental dysfunction. Enrichment analysis further identified significant disruptions in extracellular matrix organization and intercellular signaling. These results underscore the pivotal role of Gas6 in exacerbating placental oxidative stress and systemic inflammation. Importantly, therapeutic inhibition of the Gas6/AXL axis using small-molecule inhibitors mitigated PE-like symptoms, highlighting its potential as a therapeutic target. This study provides novel insights into the molecular underpinnings of Gas6-mediated placental dysfunction and supports the development of targeted therapies to improve PE outcomes.

Preeclampsia (PE) is a major cause of maternal mortality and morbidity, affecting 3-6% of pregnancies worldwide and ranking among the top six causes of maternal deaths in the U.S. PE typically develops after 20 weeks of gestation and is characterized by new-onset hypertension and/or end-organ dysfunction, with or without proteinuria. Current management strategies for PE emphasize early diagnosis, blood pressure control, and timely delivery. For prevention, low-dose aspirin (81 mg/day) is recommended for high-risk women between 12 and 28 weeks of gestation. Magnesium sulfate is also advised to prevent seizures in preeclamptic women at risk of eclampsia. Emerging management approaches include antiangiogenic therapies, hypoxia-inducible factor suppression, statins, and supplementation with CoQ10, nitric oxide, and hydrogen sulfide donors. Black women are at particularly high risk for PE, potentially due to higher rates of hypertension and cholesterol, compounded by healthcare disparities and possible genetic factors, such as the APOL1 gene. This review explores current and emerging strategies for managing PE and addresses the underlying causes of health disparities, offering potential solutions to improve outcomes.

Preeclampsia (PE) is the primary cause of maternal and neonatal morbidity and mortality. However, comprehensive studies on the related risk factors with PE and its effects on adverse perinatal outcomes are limited. This study aimed to evaluate the prevalence, risk factors, and adverse perinatal outcomes in Chinese women with preeclampsia.

We conducted a retrospective cohort study from January 1, 2018, to December 31, 2019, which enrolled 38,496 women without preeclampsia (non-PE) and 1130 women with PE. Univariate and multivariate logistic regression models were used to determine the risk factors and adverse perinatal outcomes of PE.

Multivariate logistic regression models showed that maternal age > 35 years, pp-BMI overweight/obesity, excessive gestational weight gain, multiparity, twin pregnancy, IVF, cesarean section history, times of abortion history ≥ 2, GDM, and ICP were significantly associated with the risk of PE (all P < 0.05). Women with PE in singleton pregnancies were associated with an increased risk of maternal outcomes of cesarean section, and preterm birth, and a higher risk of neonatal outcomes of stillbirth, low birth weight, fetal distress, neonatal asphyxia, and neonatal unit admission, which were also observed in women with PE in twin pregnancies, except for stillbirth and neonatal asphyxia.

This study identified the risk factors and associated adverse perinatal outcomes of PE, which providing comprehensive evidence for clinicians to manage women at risk of PE.

We report a case of confusingly high soluble fms-like tyrosine kinase 1/placental growth factor (sFlt1/PlGF) ratio in a pregnant patient with underlying systemic lupus erythematosus and antiphospholipid syndrome without superimposed pre-eclampsia.

Preeclampsia is a complex pregnancy condition marked by hypertension and organ dysfunction, posing significant risks to maternal and fetal health. This study investigates the role of energy metabolism-associated genes in preeclampsia development and identifies potential early diagnostic biomarkers.

Preeclampsia datasets from Gene Expression Omnibus were analyzed for batch correction, normalization, and differential expression. Enrichment analyses using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment were performed. Protein-protein interaction networks were constructed to identify key genes, and regulatory networks involving transcription factors, miRNAs, and RNA-binding proteins were established. Differential expression was validated with receiver operating characteristic curve analyses, and immune infiltration was assessed.

Six energy metabolism-related genes were identified. Enrichment analyses revealed their involvement in glycolysis, gluconeogenesis, lipid transport, bone remodeling, and glucagon secretion. Key differentially expressed genes included CRH(Corticotropin-Releasing Hormone), LEP(Leptin), PDK4(Pyruvate Dehydrogenase Kinase Isozyme 4), SPP1(Secreted Phosphoprotein 1), and SST(Somatostatin). PDK4 exhibited moderate accuracy in receiver operating characteristic analysis. Immune infiltration analysis indicated significant differences between preeclampsia and control samples. qRT-PCR confirmed LEP and CRH increased, while SPP1 expression in preeclampsia samples.

Dysregulated energy metabolism-related genes may contribute to preeclampsia through metabolic and immune changes. Identifying these genes aids in understanding preeclampsia's molecular basis and early diagnosis. Future studies should validate these markers in larger cohorts and explore targeted treatments.

Pre-eclampsia is a condition associated with significant maternal and neonatal morbidity and mortality. The prediction of pre-eclampsia in high-risk populations using angiogenic markers, such as serum placental growth factor (PlGF) assessment, has been shown to improve maternal outcomes and is recommended by the National Institute for Health and Care Excellence (NICE). However, such tests are not yet available at the point of care (POC). Glycosylated fibronectin (GlyFn) level for the prediction of pre-eclampsia development is available as a POC test (Lumella) and has the potential to aid rapid clinical decision making. This study aimed to test the hypothesis that the sensitivity of the GlyFn test is not inferior to that of the current gold standard of soluble fms-like tyrosine kinase (sFlt)/PlGF-based laboratory testing for pre-eclampsia.

This is a multicentre prospective study. Women at risk for pre-eclampsia based on predefined clinical and/or obstetric risk factors will be invited to participate in the study. The recruitment target is 400 participants. Consenting participants will have paired samples for sFlt/PlGF together with POC GlyFn testing. Two follow-up visits are planned at 2 and 4 weeks after the initial recruitment where repeat testing with both tests will be performed. The clinical team will be blinded to the results of the GlyFn test but not that of the sFlt/PlGF test. Clinical care will be based on established protocols incorporating maternal/fetal evaluation and the results of sFlt/PlGF levels. Maternal and neonatal outcome data will be collected to compare the sensitivity and specificity of the tests, with the primary outcome being delivery for pre-eclampsia within 4 weeks.

Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales Ethics Committee. The results of this study will be published in peer-reviewed journals and presented at scientific conferences.

ISRCTN13430018.

Oocyte donation (OD) pregnancies show a higher fetal-maternal incompatibility and a higher risk of developing pre-eclampsia (PE) than autologous pregnancies. As maternal monocytes play a role in the tolerization of the allogeneic fetus, the aim of this study was to analyse monocyte phenotypes in healthy and PE OD pregnancies. We collected maternal peripheral blood at different gestational time points in healthy (n = 10) and PE (n = 5) OD pregnancies. Fetal-maternal human leukocyte antigen (HLA) mismatches were calculated. We used a 35-colour antibody panel for Aurora spectral flow cytometry to analyse the composition and surface marker expression of monocyte subsets. Expression of CD38 on intermediate monocytes significantly increased throughout gestation in healthy OD pregnancies. Compared with the healthy group, the PE group exhibited even higher CD38 expression on monocyte subsets, with statistical significance. Immune inhibiting receptors CD85j (LILRB1) and CD85d (LILRB2), as well as monocyte recruitment regulating molecules CCR2 and CD91, also showed significantly enhanced expression on monocyte subsets during PE. When comparing healthy and PE OD only in pregnancies with high HLA mismatches, the different CD38 and CD85j expression in monocyte subsets was still significant. In conclusion, in healthy OD pregnancies, the upregulated CD38 expression might reflect a proinflammatory condition specifically at the third trimester. In PE OD pregnancies, expression of both inflammatory and immune regulatory markers is increased in maternal peripheral monocyte subsets. The elevated expression of CCR2 and CD91 on these subsets might reflect monocyte chemotaxis and the effect from systemic vascular dysfunction at the late stage of PE.

Prompt diagnosis of preeclampsia is key to ensure appropriate management and reduce associated adverse outcomes. Placental growth factor (PlGF)-based biomarkers have been shown to be safe and effective diagnostic tools for preterm preeclampsia, and their use is recommended by most recent Canadian guidelines. The present report summarizes an expert panel discussion that led to the development of a proposed utilization algorithm for PlGF-based diagnostic testing for suspected preeclampsia in Québec. In addition to recommendations on who, why, when to test and how to interpret and respond to the test, considerations for optimizing clinical testing relevance were suggested.

It is still difficult to predict the outcome of preeclampsia and determine the individual procedure with regards to the time of birth. Cut-offs of the sFlt-1/PlGF ratio with a high risk for imminent delivery have been previously published and analyzed by our study group, but could not be confirmed. The aim of the current study is to re-evaluate the described cut-off values again in a new period of time.

We performed a retrospective analysis (IRB 1279/2020) including all preeclampsia patients delivering in our department over a 3-year period. Patients were divided into 2 groups - gestational week 24+0-33+6 with an s-Flt1/PlGF > 655.2 and 34+0-37+0 weeks with an sFlt-1/PlGF > 201 and were compared with preeclampsia patients of the same weeks with sFlt-1/PlGF values below the described cut-offs. Correlation between sFlt-1/PlGF ratio and time to delivery was assessed.

The association between sFlt-1/PlGF above the threshold and delivery within 48 h is significant for the high ratio early group (p < 0.01) but not for the high ratio late group (p = 0.62). In the early group, 60% of patients with sFlt-1/PlGF > 655.2 but only 8% in the low ratio group delivered within 48 h. In both the early and the late preeclampsia group, a high number of patients remained pregnant even though they showed elevated ratios.

High sFlt-1/PlGF ratios seem to correlate with a shorter pregnancy duration to some extent. Nevertheless, not all patients need to be delivered within 48 h, so the decision should never be based on the laboratory test alone.

Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia.

Venous ECs were isolated from postpartum patients with severe preeclampsia and those with normotensive pregnancy using a J wire-based technique in the antecubital vein followed by CD144 (vascular endothelial cadherin) magnetic bead isolation. Venous EC transcriptomes were compared between preeclamptic and normotensive individuals. Differentially expressed genes were carried forward for genetic validation using expression quantitative trait loci from the Genotype-Tissue Expression project as exposures for vascular-specific Mendelian randomization. Functional validation of the top candidate was performed in human umbilical vein ECs using gain- and loss-of-function genetic approaches.

Seventeen individuals with preeclampsia and 7 normotensive controls were included. Pairwise analysis yielded 14 protein-coding genes nominally differentially expressed in participants with preeclampsia. Mendelian randomization revealed a significant association between higher genetically predicted METAP1 (methionyl aminopeptidase 1) expression in aortic and tibial arterial tissues and greater risk of preeclampsia. METAP1 overexpression in human umbilical vein ECs decreased angiogenesis, with a 66% decrease in tube formation (P=7.9×10-3) and 72% decrease in cell proliferation (P=2.9×10-2). Furthermore, METAP1 overexpression decreased VEGFA expression and increased expression of multiple preeclampsia-related genes, for example, FLT1, INHBA, and IL1B. Conversely, METAP1 knockdown produced opposite effects on tube formation, cell proliferation, and inflammation-related gene expression.

In a cohort of early postpartum individuals, we observed greater METAP1 expression in venous ECs of women with preeclampsia versus normotensive delivery. Mendelian randomization supported a causal relationship between greater vascular METAP1 expression and higher preeclampsia risk, and functional experiments demonstrated antiangiogenic and proinflammatory effects of METAP1 in human ECs consistent with alterations observed in preeclampsia. Ex vivo EC transcriptomics can identify novel mechanisms underlying preeclampsia pathophysiology, with implications for prevention and treatment.