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    MYPP trial

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    Data underlying the MYPP trial: Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial

    Do patients with a history of pre-eclampsia have elevated levels of coagulation and angiogenic markers postpartum?

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    Background: Pre-eclampsia (P-EC) is a pregnancy-specific disorder, characterised by placental insufficiency and endothelial dysfunction. It is a significant cause of maternal and fetal morbidity. Women with a history of P-EC have heightened risks of future cardiovascular and thromboembolic disease. In addition, pre-eclamptic patients have elevated levels of clotting and angiogenic factors; however it is unclear whether these changes persist postpartum. Aims: The aim of this study was to investigate the relationship between haemostatic as well as angiogenic and anti-angiogenic factors in women with a past-history of P-EC, including vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), in combination with tissue factor (TF) and TF pathway inhibitor (TFPI), also whether these factors were altered postpartum in women with a history of P-EC. Methods: The study followed a case-control design. Blood samples were obtained at 6-12 months postpartum from 21 primiparous women after a pregnancy affected by P-EC, and 21 women with a previously unaffected pregnancy. Plasma concentrations of each of the factors were determined using enzyme-linked immunosorbent assay. Results: Significant differences were not observed in levels of VEGF (p=0.068), PlGF (p=0.333), sFlt-1 (p=0.910), sEng (p=0.612), TF (p=0.260) or TFPI (p=0.786) between women with and without a history of pre-eclampsia. Additionally, no significant difference was found in the TF: TFPI ratio between case and control groups (p=0.734). Conclusion: This study does not support the hypothesis that levels of VEGF, PlGF, sFlt-1, sEng, TF or TFPI are altered in women with a history of P-EC compared to controls. However, we observed a weak positive association between all parameters measured. While we acknowledge that this is a pilot study and that the sample sizes is relatively small, our results suggest that circulating haemostatic, angiogenic and anti-angiogenic factors are not significantly altered in women with a past-history of P-E

    Additional file 1: of H3K27 acetylation and gene expression analysis reveals differences in placental chromatin activity in fetal growth restriction

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    Table S1. Differentially acetylated regions in FGR compared to controls. Table S2. Genes annotated to hyper- and hypoacetylated sites in placenta of FGR using a 20-kb window. Table S3. Functional pathways related to hypo- and hyperacetylated in placenta of FGR identified by GREAT. Table S4. Up- and downregulated gene transcripts in placenta of FGR compared to controls. Table S5. RNA-seq pathways TOPPfunn. Table S6. Functional pathways related to overlapping genes in CHIP-seq and RNA-seq. Table S7. AME output: differentially acetylated TFBM&acirc; s in placenta of FGR vs. controls and functional pathways related to differentially acetylated TFBM (XLSX 694 kb)</span

    Inflammatory and haemostatic changes following pre-eclampsia: potential link with development of subsequent cardiovascular events?

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    Pre-eclampsia (P-EC) is a major cause of maternal and neonatal mortality and morbidity. Despite intensive research, its aetiology remains poorly understood. However, underlying maternal cardiovascular risk factors are thought to be implicated. Changes in the maternal vasculature and coagulation profile may predispose women with P-EC to subsequent adverse cardiovascular consequences. Here we investigate the relationship between circulating levels of haemostatic factors and inflammatory cytokines in women with a previous history of P-EC. The participents included 26 women who had had P-EC within the last three years and were more than 6 months postpartum and 14 age-matched healthy women with no past history of P-EC. Blood was collected and assayed for plasma IL-6, IL-8, TNF-α and IL-10, Tissue Factor (TF) and TF-Pathway Inhibitor (TFPI), using Enzyme-Linked Immunosorbent Assays. Individually, plasma TF, IL-6, IL-8 and IL-10 levels increased in the P-EC group compared with their normal counterparts, whereas plasma TFPI and TNF-α level were reduced. Plasma TF/TFPI ratios and IL-10 values were significantly increased in the P-EC group compared with controls (p&lt;0.05, p&lt;0.01, respectively). There were positive and significant correlations between TFPI and IL-10 (r= 0.5; p&lt;0.01) and TF/TFPI ratio and IL-10 (r= 0.31; p&lt;0.041), and between IL-6 and TNF-α (r=0.71; p&lt;0.001) and IL-6 and IL-10 (r=0.42; p&lt;0.01). In conclusion, our results suggest the presence of elevated inflammatory cytokines and an imbalance of the haemostatic system in women with a past-history of P-EC, which may contribute to the known increased risk of cardiovascular disease in these women later in life

    Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case–control plasma proteomics study

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    Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case–control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann–Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE

    Salivary uric acid as a predictive test of pre‐eclampsia, pregnancy‐induced hypertension and preterm delivery: a pilot study

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    Introduction: There remains a need for a non-invasive, low-cost and easily accessible way of identifying women at risk of developing hypertensive disorders in pregnancy. This study evaluated the predictive value of longitudinal salivary uric acid measurement. Material and methods: Pregnant women (n = 137) from 20 weeks of gestation were recruited at St Richards Hospital, Chichester, UK, for this prospective cohort study. Weekly samples of salivary uric acid were analyzed until delivery. Information regarding pregnancy and labor were obtained from the patient’s record after delivery. Independent t tests were used to compare mean levels of salivary uric acid in women with hypertensive complications and adverse fetal outcomes with women with normal pregnancies. Main outcome measures were preeclampsia, pregnancy-induced hypertension, spontaneous preterm delivery and small-for-gestational-age babies. Results: From 21 weeks of gestation until delivery, levels of salivary uric acid increased significantly in women who subsequently developed preeclampsia and pregnancy-induced hypertension compared with women with normal pregnancies (preeclampsia—mean at gestational age 21-24, 95% confidence interval [95% CI] [mean GA21-24): 108 [63-185] vs 47 (39-55) µmol/L; P =.005; pregnancy-induced hypertension—mean GA21-24: 118 [54–258] vs 47 [39-55] µmol/L; P =.004). In women who had spontaneous preterm delivery, salivary uric acid levels increased significantly from 29 to 32 weeks of gestation compared with women with normal pregnancies (mean GA29-32: 112 (57-221) vs 59 (50-71) µmol/L; P =.04). In women who had babies small-for-gestational-age &lt;10th percentile and small-for-gestational-age &lt;3rd percentile, differences in salivary uric acid levels were insignificant. Conclusions: Elevated levels of salivary uric acid precede the onset of preeclampsia, pregnancy-induced hypertension and preterm delivery. Salivary uric acid may prove to be an early biomarker of hypertensive complications of pregnancy and spontaneous preterm delivery. </p

    Evaluation of 7 serum biomarkers and uterine artery Doppler ultrasound for first-trimester prediction of preeclampsia: a systematic review

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    Preeclampsia (PE) affects 1% to 2% of pregnant women and is a leading cause of maternal and perinatal morbidity and mortality worldwide. The clinical syndrome of PE arises in the second half of pregnancy. However, many underlying factors including defective placentation may already be apparent in the first and early second trimester in many patients. In clinical practice, there is currently no reliable screening method in the first trimester of pregnancy with sufficient accuracy to identify women at high risk to develop PE. Early identification of high-risk pregnancy may facilitate the development of new strategies for antenatal surveillance or prevention and thus improve maternal and perinatal outcome. The aim of this systematic review was to study the literature on the predictive potential of first-trimester serum markers and of uterine artery Doppler velocity waveform assessment (Ut-A Doppler). Literature on the 7 most studied serum markers (ADAM12, f?-hCG, Inhibin A, Activin A, PP13, PlGF, and PAPP-A) and Ut-A Doppler was primarily selected. In the selected literature, a combination of these markers was analyzed, and where relevant, the value of maternal characteristics was added. Measurements of serum markers and Ut-A Doppler were performed between week 8 + 0 and 14 + 0 GA. Low levels of PP13, PlGF, and PAPP-A and elevated level of Inhibin A have been found to be significantly associated with the development of PE later in pregnancy. The detection rates of single markers, fixed at 10% false-positive rate, in the prediction of early-onset PE were relatively low, and ranged from 22% to 83%. Detection rates for combinations of multiple markers varied between 38% and 100%. Therefore, a combination of multiple markers yields high detection rates and is promising to identify patients at high risk of developing PE. However, large scale prospective studies are required to evaluate the power of this integrated approach in clinical practice. Target Audience: Obstetricians and Gynecologists, Family physicians Learning Objectives: After completion of this article, the reader should be better able to appraise the recent literature on the development of preeclampsia in the first-trimester, evaluate the predictive value of first-trimester markers and use first-trimester markers, either individually or in combination, to assess the risk of preeclampsia

    Cardiovascular disease risk factors in women with a history of early-onset preeclampsia

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    Objective: to assess the prevalence of established cardiovascular disease risk factors and to estimate 10-year absolute risk of cardiovascular disease after early-onset preeclampsia.Methods: we assessed major cardiovascular disease risk factors in 243 primiparous women with a history of early-onset preeclampsia (delivery at less than 34 weeks of gestation) at least 6 months after delivery; 374 healthy nonpregnant women of similar age served as a reference group.Results: after adjustment for age, we observed significantly higher means for body mass index, blood pressure, total and low-density lipoprotein cholesterol, triglycerides, glucose, and lower mean high-density lipoprotein cholesterol (all P&lt;.01) in women with previous early-onset preeclampsia compared with the reference group. Prevalence of the metabolic syndrome was 15.2% compared with 4.3% (P&lt;.001), two or more major cardiovascular disease risk factors were present in 51.0% compared with 26.5%, and three or more risk factors were present in 18.9% compared with 6.4%, respectively. Mean estimated 10-year cardiovascular disease risks by the Framingham Risk Score were 1.08% (95% confidence interval 1.04–1.12) and 1.01% (95% CI 1.00–1.01; P&lt;.001) for the difference.Conclusionn: women with a history of early-onset preeclampsia have a high prevalence of several major cardiovascular disease risk factors. Although the estimated 10-year cardiovascular disease risk is low (less than 5%) after delivery, cardiovascular disease risk is expected to increase rapidly with increasing age
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