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ObjectivesTo evaluate the impact of aspirin resistance on the incidence of preeclampsia and maternal serum biomarker levels in pregnant individuals at high-risk of preeclampsia receiving low dose aspirin (LDA).Study designWe performed a secondary analysis of a randomized, placebo-controlled trial of LDA (60 mg daily) for preeclampsia prevention in high-risk individuals (N = 524) on pregnancy outcomes and concentrations of PLGF, IL-2, IL-6, thromboxane B2 (TXB2), sTNF-R1 and sTNF-R2 from maternal serum.Main outcome measuresLDA-resistant individuals were defined as those having a TXB2 concentration >10 ng/ml or

BackgroundChildhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks.ObjectiveThis population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring.MethodsData on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers.ResultsOffspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth.ConclusionsIn this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

Preeclampsia (PE) is a serious pregnancy complication that contributes to maternal and perinatal morbidity and mortality. Understanding its pathogenesis and revealing predictive biomarkers are essential for guiding treatment decisions. In order to explore the global changes of serum metabolites in PE patients and identify potential predictive biomarkers for suspected PE patients (pregnant women who had already shown PE-related symptoms in the middle to late stages of pregnancy, but were not yet confirmatively diagnosed as PE.), a large-scale serum metabolomic analysis was conducted in this study with a prospective cohort of 328 suspected PE patients in the middle or late pregnancy stages, as well as a retrospective cohort of 30 healthy pregnant women and 30 PE patients. Using liquid chromatography mass spectrometry (LC − MS), serum metabolomic profiling revealed that the development of PE was closely associated with disturbed amino acid metabolism. Moreover, a panel of seven predictive biomarkers including 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, gamma-glutamyl-leucine, 2-hydroxyvaleric acid, LysoPC(16:1(9Z)/0:0), PC(DiMe(13,5)/MonoMe(13,5)), ADP-D-glycero-beta-D-manno-heptose and phenylalanyl-tryptophan were identified for PE development by performing multiple statistical analysis and LASSO regression analysis. The combination of these biomarkers showed promise in the prediction of PE development for suspected PE patients, with an AUC of 0.753 and 0.885 for the discovery and validation cohorts, respectively. These findings highlight the potential of large-scale prospective metabolomic studies combined with machine learning algorithms in identifying key biomarkers for predicting PE development, while retrospective metabolomics studies provide insights into the pathogenesis of PE. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a challenge in maternal healthcare due to its complex nature, characterized by high blood pressure, protein in the urine, and damage to various organs. There is evidence linking PE to endothelial dysfunction (ED), triggered by substances released from an oxygen-deprived placenta. Previous in vitro studies have not considered the impact of in vivo elements, such as the different patterns of blood flow, and laminar (LSS) vs. oscillatory (OSS) shear stress, on the development of ED. We investigated the impact of plasma from healthy pregnant women (HP), subjects with gestational hypertension (GH), and PE patients on global gene expression of human coronary endothelial cells (HCAECs) under LSS and OSS. Our findings revealed a unique transcriptional profile of endothelial cells induced by plasma incubation in LSS. Notably, OSS resulted in similar transcriptomes irrespective of plasma treatment. Under LSS, GH plasma resulted in a proliferative profile, whereas PE plasma was linked to pro-inflammatory and antioxidant profiles compared to HP plasma. Our findings demonstrate that shear stress levels influence the endothelial cell transcriptome in response to plasma from hypertensive pregnancy patients. Both PE and GH can induce endothelial dysfunction under atheroprotective LSS, with a more significant effect observed with PE-derived plasma. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia is a potentially life-threatening pregnancy complication. Among women whose pregnancies are complicated by preeclampsia, the Preeclampsia Integrated Estimate of RiSk (PIERS) models (i.e., the PIERS Machine Learning [PIERS-ML] model, and the logistic regression-based fullPIERS model) accurately identify individuals at greatest or least risk of adverse maternal outcomes within 48 h following admission. Both models were developed and validated to be used as part of initial assessment. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) recommends repeated use of such static models for ongoing assessment beyond the first 48 h. This study evaluated the models' performance during such consecutive prediction. Methods and findings: This multicountry prospective study used data of 8,843 women (32% white, 30% black, and 26% Asian) with a median age of 31 years. These women, admitted to maternity units in the Americas, sub-Saharan Africa, South Asia, Europe, and Oceania, were diagnosed with preeclampsia at a median gestational age of 35.79 weeks between year 2003 and 2016. The risk differentiation performance of the PIERS-ML and fullPIERS models were assessed for each day within a 2-week post-admission window. The PIERS adverse maternal outcome includes one or more of: death, end-organ complication (cardiorespiratory, renal, hepatic, etc.), or uteroplacental dysfunction (e.g., placental abruption). The main outcome measures were: trajectories of mean risk of each of the uncomplicated course and adverse outcome groups; daily area under the precision-recall curve (AUC-PRC); potential clinical impact (i.e., net benefit in decision curve analysis); dynamic shifts of multiple risk groups; and daily likelihood ratios. In the 2 weeks window, the number of daily outcome events decreased from over 200 to around 10. For both PIERS-ML and fullPIERS models, we observed consistently higher mean risk in the adverse outcome (versus uncomplicated course) group. The AUC-PRC values (0.2–0.4) of the fullPIERS model remained low (i.e., close to the daily fraction of adverse outcomes, indicating low discriminative capacity). The PIERS-ML model's AUC-PRC peaked on day 0 (0.65), and notably decreased thereafter. When categorizing women into multiple risk groups, the PIERS-ML model generally showed good rule-in capacity for the "very high" risk group, with positive likelihood ratio values ranging from 70.99 to infinity, and good rule-out capacity for the "very low" risk group where most negative likelihood ratio values were 0. However, performance declined notably for other risk groups beyond 48 h. Decision curve analysis revealed a diminishing advantage for treatment guided by both models over time. The main limitation of this study is that the baseline performance of the PIERS-ML model was assessed on its development data; however, its baseline performance has also undergone external evaluation. Conclusions: In this study, we have evaluated the performance of the fullPIERS and PIERS-ML models for consecutive prediction. We observed deteriorating performance of both models over time. We recommend using the models for consecutive prediction with greater caution and interpreting predictions with increasing uncertainty as the pregnancy progresses. For clinical practice, models should be adapted to retain accuracy when deployed serially. The performance of future models can be compared with the results of this study to quantify their added value. Guiyou Yang, Tünde Montgomery-Csobán and colleagues assess the performance of the PIERS-ML and fullPIERS models for serial prediction of adverse outcomes of pre-eclampsia. Author summary: Why was this study done?: The fullPIERS model was considered to be the best model for predicting the adverse outcomes of preeclampsia within 2 days following first admission, until recently when the PIERS-ML model was introduced. The National Institute of Health and Care Excellence guideline in the United Kingdom recommends using the fullPIERS model to make serial predictions; however, to the best of our knowledge, this model has never been verified for this use. What did the researchers do and find?: Using the largest available data set in this field (to the best of our knowledge), we quantified the performance of both the fullPIERS and PIERS-ML models (as PIERS-ML has even higher predictive accuracy) when they are used for serial predictions. We found that the performance of both models deteriorated considerably over time in the first 2 weeks following admission to hospital. What do these findings mean?: In the absence of models that have been validated for serial predictions of adverse maternal outcomes of preeclampsia, clinicians may still use fullPIERS and PIERS-ML models for ongoing assessments after the first admission with preeclampsia, but the predictions should be treated with increasing caution as the pregnancy progresses. More research is needed to develop models that perform well over time when used for repeated predictions. The main limitation of this study is that we assessed the initial performance of the PIERS-ML model on the same data used to create it. However, the model's initial performance has also been tested on data from outside sources. [ABSTRACT FROM AUTHOR]

Aging and pregnancy are often considered opposites in a woman's biological timeline. Aging is defined by a gradual decline in the functional capabilities of an organism over its lifetime, while pregnancy is characterized by the presence of the transient placenta, which fosters the cellular fitness necessary to support fetal growth. However, in the context of preeclampsia, pregnancy and aging share common hallmarks, including clinical complications, altered cellular phenotypes, and heightened oxidative stress. Furthermore, women with pregnancies complicated by preeclampsia tend to experience age-related disorders earlier than those with healthy pregnancies. Klotho, a gene discovered fortuitously in 1997 by researchers studying aging mechanisms, is primarily expressed in the kidneys but also to a lesser extent in several other tissues, including the placenta. The Klotho protein is a membrane-bound protein that, upon cleavage by ADAM10/17, is released into the circulation as soluble Klotho (sKlotho) where it plays a role in modulating oxidative stress. This review focuses on the involvement of sKlotho in the development of preeclampsia and age-related disorders, as well as the expression of the recently discovered Mytho gene, which has been associated with skeletal muscle atrophy. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a form of hypertension that manifests in the later stages of pregnancy. Since Kaempferol (Ka) has remedial potential hence this research was conducted to examine its therapeutic effect on Preeclampsia rats by regulating Wingless-related integration site/β-catenin (Wnt/B-catenin) pathway. To achieve this, thirty-two SD female rats were randomly allocated into four groups: control, preeclampsia (PE, LPS, 1 mg/kg), preeclampsia with kaempferol (PE + Ka), and preeclampsia with Dickkopf − 1 (DKK-1) and kaempferol (PE + DKK-1 + Ka). Rats in the PE + Ka and PE + DKK-1 + Ka groups received intraperitoneal injections at 50 mg/kg/d of kaempferol, whereas the PE + DKK-1 + Ka group was administered with 60 µg/kg/d of recombinant rat DKK-1 protein, an inhibitor of the Wnt/β-catenin signaling pathway. Our findings revealed that systolic blood pressure (SBP) in the PE + Ka group was significantly reduced in comparison to PE group (P < 0.05). The urine albumin levels in the PE + Ka group decreased noticeably (P < 0.05), whereas serum concentrations of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6) in the PE + Ka group were reduced (P < 0.05) in comparison to PE group. Although PE + Ka group exhibited elevated levels of superoxide dismutases (SOD), glutathione (GSH), and catalase (CAT) in placental tissue relative to the PE group, whilst levels of malondialdehyde (MDA), alkaline phosphatase (ALP), serum glutamic-pyruvic transaminase (SGPT), and serum glutamic-oxaloacetic transaminase (SGOT) considerably decreased (P < 0.05). Comparatively mRNA levels of Wnt1 and β-catenin in the PE + Ka group were elevated, whereas mRNA level of DKK-1 was diminished (P < 0.05). Administration of DKK-1 counteracted kaempferol effects on these parameters in Preeclampsia rats (P < 0.05). Devastatingly, ovarian and kidney histomorphology in the PE group exhibited significant degenerative alterations, whereas kaempferol groups demonstrated normal histomorphology in comparison to the PE group. Conclusively, Kaempferol can significantly lower systolic blood pressure and urine albumin in PE female rats while mitigating excessive oxidative stress. The therapeutic efficacy of kaempferol on Preeclampsia may be mediatated via Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia, characterized by hypertension and proteinuria during pregnancy, poses significant risks to both mother and fetus. The complement system’s aberrant activation, notably the C3AR1, is important to the pathogenesis of preeclampsia, although the precise mechanisms are not fully understood. Materials and methods: Utilizing the Comparative Toxicogenomics Database (CTD) and Molecular Signatures Database (MSigDB), we identified complement system targets associated with preeclampsia and environmental pollutants. Expression validation was conducted through the Gene Expression Omnibus (GEO) database. Molecular docking predicted interactions between BPA, PFOS, and C3AR1. Immunohistochemical staining of 80 placental tissues (40 early-onset preeclampsia and 40 healthy controls) confirmed C3AR1 expression and its clinical correlation. Integrated bioinformatics analyses revealed C3AR1’s role in preeclampsia’s molecular mechanisms. Functional verification was assessed by knocking down C3AR1 in HTR-8/Svneo cells, including cell proliferation, invasion, and apoptosis. Results: Network pharmacology established connections between pollutants and preeclampsia, with C3AR1 as a key target. Molecular docking confirmed BPA and PFOS binding to C3AR1. Reduced C3AR1 in preeclamptic placentas correlated with maternal blood pressure, and showed high diagnostic potential (AUC = 0.95). C3AR1’s involvement in preeclampsia was linked to Jak-STAT, TGF-β, and HIF-1 pathways, and associated with NK cell and M1 macrophage activity. C3AR1 knockdown in HTR-8/Svneo cells decreased proliferation and invasion, and increased apoptosis. Conclusion: C3AR1 expression is diminished in preeclampsia placental tissues, correlating with disease severity, suggesting its potential as a biomarker. It is crucial for cellular functions and inflammation, with future studies aiming to leverage this for novel preeclampsia treatments. Clinical trial: Not applicable. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the efficacy of low-dose aspirin (LDA) in preventing preeclampsia among pregnant women with polycystic ovary syndrome (PCOS), given the increased susceptibility of this population to preeclampsia development. Methods: A retrospective cohort study was conducted on pregnant women with PCOS who delivered between January 1, 2018 and February 10, 2024 at our institution. Clinical characteristics and obstetric data were extracted from medical records. Propensity score matching (PSM) was employed to analyze the association between LDA use and PE incidence. Results: The study cohort comprised 1522 pregnant women with PCOS. Among 395 pregnant women identified as high-risk for preeclampsia, 98 were administered LDA for preeclampsia prevention, while 297 did not receive LDA. Following PSM, no statistically significant difference was observed in preeclampsia risk between the LDA and non-LDA groups. Additionally, maternal and neonatal outcomes were comparable between the two groups. Conclusions: This cohort analysis did not provide sufficient evidence to support the efficacy of LDA in preventing preeclampsia among PCOS patients at high risk for preeclampsia. [ABSTRACT FROM AUTHOR]

Aim: Our study aimed to evaluate the predictive value of Placental growth factor (PlGF), Vitamin D, and systemic inflammatory index for assessing preeclampsia risk and severity. Materials and methods: This retrospective cohort study included 457 pregnant individuals who delivered at our hospital between March 2023 and October 2024. Participants were divided into three groups: control (n = 217), mild preeclampsia (n = 101), and severe preeclampsia (n = 67). A separate validation cohort (n = 72) was used to test model performance. Data on demographic, clinical, and laboratory characteristics, including PlGF, Vitamin D, neutrophil, lymphocyte, and monocyte counts, were collected between 16 and 20 weeks of gestation. Logistic regression analysis was performed to identify independent risk factors, and receiver operating characteristic (ROC) curve analysis was used to assess the predictive power of PlGF, Vitamin D, lymphocyte count, and Pan-immune-inflammation value (PIV). The regression models adjusted for potential confounders, including maternal age, body mass index (BMI), and parity. Results: In the training cohort, significant differences were observed among control, mild, and severe preeclampsia groups, with severe cases showing elevated PIV (515.8 ± 126.7) and reduced levels of PlGF (12.5 ± 5.8 pg/mL) and Vitamin D (8.4 ± 1.9 ng/mL) compared to controls (P < 0.001). Logistic regression identified lower levels of PlGF (P < 0.001) and Vitamin D (P < 0.001) as significant independent risk factors for severe preeclampsia. PIV was also a strong predictor, showing a high hazard ratio (P < 0.001). In the training and validation cohorts, ROC analysis showed AUC values of 0.774 and 0.751 for PlGF, 0.805 and 0.796 for Vitamin D, 0.688 and 0.675 for Lymphocyte, and 0.724 and 0.752 for PIV, respectively, indicating strong predictive value for PlGF, Vitamin D, and PIV in assessing preeclampsia risk. Conclusion: Lower levels of PlGF and Vitamin D, along with higher PIV, were independently associated with an increased risk of severe preeclampsia. These findings suggest that PlGF, Vitamin D, and PIV are valuable biomarkers for early identification of high-risk preeclampsia patients, potentially aiding in timely intervention and improved outcomes. [ABSTRACT FROM AUTHOR]

Efferocytosis is a mechanism by which phagocytes efficiently clear apoptotic cells, averting their secondary necrosis and the subsequent release of potentially immunogenic or cytotoxic substances that can trigger strong immune and inflammatory responses. During efferocytosis, the metabolic pathways of phagocytes are transformed, which, along with the catabolism of apoptotic cargo, can affect their function and inflammatory state. Extensive apoptosis occurs during placental development, and some studies reported the immunomodulatory effects of efferocytosis at the maternal–fetal interface. The dysregulation of efferocytosis is strongly linked to pregnancy complications such as preeclampsia and recurrent spontaneous abortion. In this review, we discuss the mechanisms of efferocytosis and its relationships with metabolism and inflammation. We also highlight the roles of professional and non-professional phagocytes in efferocytosis at the maternal–fetal interface and their impact on pregnancy outcomes and explore relevant regulatory factors. These insights are expected to guide future basic research and clinical strategies for identifying efferocytosis-related molecules as potential predictors or therapeutic targets in obstetric diseases. [ABSTRACT FROM AUTHOR]

Background: Women with previous hypertensive disorders of pregnancy (HDP) have increased risk of cardiovascular disease (CVD). Overweight is a modifiable risk factor for both conditions. Anthropometric indices such as waist circumference, hip circumference, waist-to-hip ratio, estimated total body fat, a body shape index, waist-to-hip-to-height ratio, and index of central obesity improve estimation of cardiovascular death risk in the general population as compared to body mass index (BMI). Objectives: We aimed to assess whether alternative body mass composition indices associate more strongly with postpartum blood lipid levels, as a proxy for CVD risk, than BMI. We also aimed to investigate whether associations differ between women with previous normotensive or hypertensive index pregnancies. Design: In this cross-sectional study, we examined 296 women 1 or 3 years after an index pregnancy that was normotensive (n = 116) or complicated by a hypertensive pregnancy disorder, including preeclampsia (n = 133) or gestational hypertension (n = 47). Methods: Uni- and multivariable regression analyses, adjusted for age and smoking, were conducted to evaluate associations between postpartum body mass composition indices and blood lipids. p < 0.05 was considered statistically significant. Results: Median BMI and overweight rates were higher in women with previous HDP than in controls (23.9 kg/m2 versus 22.8 kg/m2 and 44.4% versus 30.2%, both p ⩽ 0.03). No body mass composition indices in any pregnancy complication group showed stronger associations with adverse lipid levels than BMI. However, women with previous HDP more often displayed significant associations between adverse body mass composition indices and adverse lipid levels, compared with controls. Conclusion: Alternative anthropometric measurements are not better suited to evaluate circulating lipids as proxy for CVD risk after HDP, compared to BMI. We hence recommend using BMI in CVD risk assessment after HDP due to its current widespread use and feasibility. Plain language summary: Cardiovascular disease risk evaluation in women after hypertensive pregnancy disorders: A study of the role of traditional and nontraditional body mass composition indices Why was the study done ? Women who have experienced hypertensive disorders of pregnancy have increased risk of developing cardiovascular disease later in life. Overweight is a well-known risk factor for both cardiovascular disease and hypertensive disorders of pregnancy. Body mass index (BMI) is the most common used tool to evaluate overweight, but other indices to evaluate body mass composition may be better suited to evaluate cardiovascular death risk in the general population. Lipids are among several modifiable risk factors for cardiovascular disease. We therefore aimed to investigate associations between alternative body mass composition indices and risk of cardiovascular disease, using blood lipids as a marker for cardiovascular disease, in women with previous hypertensive disorders of pregnancy and women with previous uncomplicated pregnancies. What did the researchers do ? We examined 296 women one or three years after pregnancy. Our study group included 180 women with previous hypertensive pregnancy disorder and 116 women with previous uncomplicated pregnancies as controls. We analyzed associations between different body mass composition indices and blood lipid levels, to evaluate the risk of cardiovascular disease after pregnancy. What did the researchers find ? Women with previous hypertensive pregnancy disorders were more often overweight, compared with women with previous uncomplicated pregnancies, and showed in general higher BMIs. We found no differences between the different body mass composition indices and their associations with blood lipids. Women with previous hypertensive pregnancy disorders did however display more frequent associations between body mass composition indices and circulating lipids, compared with the control group. What do the findings mean ? Following hypertensive disorders of pregnancy, women more often have elevated BMI. Their BMI is comparable to alternative body mass composition indices in association with circulating lipids. This supports using BMI in the assessment of cardiovascular disease risk in this group at high risk of cardiovascular disease development. [ABSTRACT FROM AUTHOR]

Background: Gestational hypertension and preeclampsia are potentially linked to similar pathophysiological processes. Maternal preeclampsia increases the occurrence of early-onset neonatal thrombocytopenia. We hypothesized that maternal gestational hypertension may impact the incident early-onset neonatal thrombocytopenia. Methods: We included 538 neonates, comprising 318 and 220 neonates born to healthy mothers and those with pregnancy-induced hypertension. The minimum platelet count within 72 h of birth was recorded for these neonates. The incidence of early-onset thrombocytopenia in neonates in relation to maternal gestational hypertension, preeclampsia, and health status was evaluated. Logistic regression analysis was conducted to assess the relationship between maternal gestational hypertension and the risk of early-onset neonatal thrombocytopenia. Results: The incidence of early-onset thrombocytopenia was significantly higher in neonates born to mothers with preeclampsia than in those born to mothers with gestational hypertension or healthy mothers. Significant differences were observed among the three groups (30.0% vs. 13.3% vs. 7.9%, p < 0.001). Maternal gestational hypertension (OR = 2.79, 95%CI 1.19–6.54) increased the risk of early-onset neonatal thrombocytopenia when compared to healthy mothers. Conclusions: Maternal gestational hypertension increases the occurrence of early-onset neonatal thrombocytopenia. Therefore, we recommend conducting platelet count screening at the early stages of neonates of mothers with gestational hypertension. [ABSTRACT FROM AUTHOR]

Background: Epidural labor analgesia (ELA) is widely and safely used for labor pain relief. However, it remains unclear whether ELA affects maternal and neonatal outcomes in women suffering from preeclampsia. Methods: This study reviewed the medical records of women with preeclampsia at ≥ 28 weeks of gestation between January 2015 and December 2020. The medical records of women were divided into ELA and no analgesia (NA) groups. The primary endpoint was the cesarean section (CS) rate. Secondary endpoints included hypotension, operative vaginal delivery, fetal distress, neonatal intensive care unit admission, and complications. Using multivariate logistic regression analysis and propensity score matching (PSM), the association between ELA and maternal and neonatal outcomes was examined. Results: A total of medical records of 686 women were enrolled, with 242 (35.3%) receiving ELA. Of these, 126 (18.4%) had a higher incidence of CS in the ELA group than in the NA group (22.7% vs. 16.0%, P = 0.020). Multivariable analysis indicated greater risks of CS [adjusted Odds Ratio (aOR) = 1.71; 95% CI, 1.07–2.74; P = 0.025] and operative vaginal delivery (aOR = 2.810; 95% CI, 1.379–5.725; P = 0.004) in the ELA group than that of NA group. In the PSM, ELA did not increase the risk of CS (aOR = 1.56; 95% CI, 0.97–2.52; P = 0.067) and OVD (aOR = 2.048; 95% CI, 0.936–4.484; P = 0.073). The secondary endpoints showed no significant differences between the two groups. Conclusion: The study indicates an association between ELA and maternal and neonatal outcomes, supporting the safety of ELA in this population. [ABSTRACT FROM AUTHOR]

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 have been detected at the materno-embryonic interface in both human and murine pregnancy models. However, research regarding the PD-1/PD-L1 signal in preeclampsia (PE) is limited. In the present investigation, 30 normal pregnant females and 30 PE patients were enrolled. Cellular functional experiments were performed in two trophoblast cell lines by transfection with lentiviral vectors for overexpression and down-regulation of PD-L1. The placental expressions of PD-1, PD-L1, and granulocyte macrophage colony-stimulating factor (GM-CSF) exhibited a notable reduction in PE cases compared with healthy pregnancies. Cellular functional experiments indicated that excessive PD-L1 expression significantly enhanced trophoblast migratory, invasive, and proliferative capabilities while inhibiting cell apoptosis. Additionally, the administration of lentivirus-mediated PD-L1 overexpression could alleviate clinical symptoms (hypertension, proteinuria) of PE-like rats. Therefore, decreased PD-L1 may contribute to PE by inhibiting GM-CSF via activating the JAK2/STAT5 pathway. Our study provides a novel pathway that can be targeted for the therapy of this disease. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a pregnancy-specific complication and there remains no effective treatment. Given the limitations on medication use during pregnancy, exploring natural, safe, and effective drugs for PE is worthwhile. We investigate the causal relationship between ferroptosis, inflammation, and PE, and determine the protective effects of quercetin (QCT), a representative compound that is classified as a flavanol, against endothelial dysfunction. Then, the target of QCT is predicted and verified. The prophylactic addition of a low dose of QCT rescues endothelial dysfunction, aiding in endothelial repair. Furthermore, QCT alleviates PE-like maternal manifestations and endothelial dysfunction in the placenta of the selective reduced uteroplacental perfusion (sRUPP) rat model through binding to the epidermal growth factor receptor (EGFR). The potential applications of QCT are expanded, offering the possibility of further development as a safe and effective preventive molecule for PE. The flavanol quercetin rescues endothelial dysfunction and preeclampsia-like manifestations in a pre-clinical model via inhibition of ferroptosis and inflammation. [ABSTRACT FROM AUTHOR]

Background: Placental syndrome, mainly composed of preeclampsia and fetal growth restriction, has an impact on the health of mother and baby dyads. While impaired placentation is central to their pathophysiology, the underlying molecular mechanisms remain incompletely understood. This study investigates the association between placental syndrome and metabolic alterations in 1-deoxysphingolipids (1-deoxySLs) and polyamines, along with their regulatory enzymes. Methods: This prospective case-control study involved 26 healthy pregnant women and 17 with placental syndrome. Blood samples were collected from maternal, uterine venous, and umbilical cord veins. Levels of 1-deoxySL, spermine, and spermidine, as well as related enzymes of polyamine metabolism such as ornithine decarboxylase (ODC), spermidine/spermine N1-acetyltransferase (SSAT), polyamine oxidase (PAO), and spermine oxidase (SMO), were measured using the techniques of LC-MS and ELISA, respectively. Results: Women with placental syndrome had significantly higher levels of 1-deoxySL, spermine, and spermidine in all blood samples compared to the healthy pregnancy group. Additionally, ODC and SSAT levels were reduced significantly in the placental syndrome group, while PAO and SMO levels showed no significant differences. Strong positive correlations were found between the studied enzymes and biomolecules in healthy pregnancies, which were notably weaker in the placental syndrome group. Conclusion: This study demonstrates significantly altered levels of 1-deoxySL and polyamines, with corresponding enzyme activity changes, in placental syndrome compared to healthy pregnancies. The disrupted correlations between these biomolecules suggest alterations in their metabolic pathways and potential utility as biomarkers. Further mechanistic studies are warranted to elucidate their role in placental syndrome pathophysiology. [ABSTRACT FROM AUTHOR]

Preeclampsia (PE) is a pregnancy complication characterized by high blood pressure and organ damage. This study investigates the differences in the gut microbiota between preterm neonates born to mothers with PE and those born to mothers without PE (PR), aiming to understand how maternal health conditions like PE influence neonatal gut microbiota. The early gut microbiota plays a crucial role in neonatal health, and disturbances in its development can have long-term consequences. Fecal samples were collected from preterm neonates of PE and PR mothers at 2 and 6 weeks postpartum and analyzed using shotgun metagenomic sequencing. We found that PE significantly affected the gut microbial composition of preterm neonates, particularly at 2 weeks postpartum. The gut microbial diversity in the PE_2 group was notably lower compared to the PR_2 group, with no significant difference observed between the PR_6 and PE_6 groups. At the phylum level, Firmicutes and Proteobacteria were predominant, with significant differences observed, particularly a lower abundance of Actinobacteria in the PE_2 group. At the genus level, Escherichia, Enterococcus, and Klebsiella were more prevalent in the PE_2 group, whereas Bifidobacterium and Cutibacterium dominated the PR_2 group. The gut virome analysis showed no significant differences among the groups. Functional analysis revealed distinct metabolic pathway activities across the groups, suggesting that early disturbances due to PE impact the establishment of healthy gut microbiota. These findings underscore the substantial influence of maternal health on the early development of the neonatal gut microbiota and highlight the potential long-term health consequences. Additionally, the differences in metabolic pathways further emphasize the impact of preeclampsia on gut microbiota functionality. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to examine the relationship between conventional and novel Doppler parameters, including cerebroplacental ratio (CPR), cerebral–placental–uterine ratio (CPUR), umbilical-to-cerebral ratio (UCR), and amniotic-to-umbilical-cerebral ratio (AUCR), with the diagnosis of preeclampsia (PE) and adverse neonatal outcomes in PE cases. Methods: This prospective case-control study was conducted at the Ankara Etlik City Hospital Perinatology Clinic between November 2023 and May 2024. The study population was divided into two groups: Group 1, consisting of 74 patients diagnosed with preeclampsia, and Group 2, consisting of 80 healthy control patients. Composite adverse perinatal outcomes (CANOs) include presence of at least one adverse outcome: 5th-minute APGAR score < 7, transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), need for continuous positive airway pressure (CPAP), need for mechanical ventilation, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia, need for phototherapy, intraventricular hemorrhage (IVH), and neonatal sepsis. Results: The CPR, CPUR, and AUCR were significantly lower in the PE group compared to the control group, while the UCR was notably higher in the PE group. Among the combined ratios, the CPUR exhibited the highest diagnostic performance for both PE diagnosis and the prediction of CANOs. Additionally, while the UCR, CPR, and AUCR were significant for PE diagnosis, only AUCR demonstrated a significant association with the prediction of CANOs. Conclusions: Combined Doppler parameters, especially CPUR and AUCR, offer valuable insights into diagnosing PE and predicting CANOs. CPUR demonstrated the highest diagnostic accuracy, underscoring its potential utility in clinical settings. [ABSTRACT FROM AUTHOR]

Background: Despite considerable research on pregnancy outcomes affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the consequences for infants exposed to the virus in utero remain unclear. Methods: A retrospective cohort study was conducted, encompassing 392 mother–infant pairs delivered between April 2020 and July 2021 at a community hospital network in northeastern Pennsylvania, USA. Of these, 198 mothers had a confirmed SARS-CoV-2 infection during pregnancy, while 194 did not. Infant outcomes were compared between the two groups. Results: Pregnant women with a SARS-CoV-2 infection during their gestation exhibited higher rates of obesity (p = 0.04) with higher body mass indices (BMI) (p = 0.01), were more likely to be of Hispanic ethnicity (p = 0.01), and had a history of chronic hypertension (p = 0.05), as well as higher occurrences of postpartum depression (p = 0.01), gestational diabetes (p = 0.05), cesarean section (CS) rates (p< 0.001), and preeclampsia (p = 0.04). Among the infants reviewed, there was no statistical significance difference in developmental milestones at 2, 4, 6, 9, and 12 months of age between infants of parturients who tested positive for coronavirus disease 2019 (COVID-19) and infants of parturients without a positive COVID-19 test result. There was no statistically significant difference between the two groups in developmental outcomes, as measured by Ages and Stages Questionnaire (ASQ) scores at 9 months (p = 0.76) and at 18 months (p = 0.89). Conclusions: This study corroborates the adverse impact of SARS-CoV-2 infection on pregnant women, characterized by increased maternal comorbidities and adverse birth outcomes. No significant disparities in neonatal developmental milestones or growth outcomes were observed at birth; first office visit, or at 1, 2, 4, 6, 9, and 12 months of age. [ABSTRACT FROM AUTHOR]

Background/Objectives: Although preeclampsia (PE) and small for gestational age (SGA) are known to come from impaired placentation during the first trimester, prior studies have focused mostly on Doppler findings in the second trimester. Methods: In this retrospective pilot study, we enrolled 628 singleton pregnant women who underwent ultrasound in both the first and second trimesters and blood test. For SGA correlation, we further excluded 12 subjects with PE because PE may be the cause of SGA. We first presented the reference range of parameters of uterine artery Doppler in the first trimester and then grouped the subjects according to the presence of SGA (presence = 104, absence = 512) or PE (presence = 12, absence = 616) and investigated the association of uterine artery Doppler findings and serum markers in the first trimester with the occurrence of SGA or PE. Results: The uterine artery pulsatility index and the resistance index and the proportion of uterine artery notch decreased progressively in the first trimester. A lower serum beta-hCG level in the first trimester predicted the occurrence of SGA (adjusted odds ratio [AOR] = 0.53, p = 0.019), while the presence of the uterine artery notch in the first trimester predicted the development of PE (notch at least on one side: AOR = 8.65, p = 0.045 and notch on both sides: AOR = 8.91, p = 0.047). Regardless of whether a notch was present in the second trimester, a uterine artery notch in the first trimester was associated with an excellent negative predictive value (99.6%) for PE. Conclusions: This study suggests the clinical importance of assessing serum beta-hCG and the uterine artery notch in the first trimester to predict SGA and PE. [ABSTRACT FROM AUTHOR]