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Results for “pre-eclampsia”

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PubMed2025

Polygenic Risk Scores for Preeclampsia Prediction Beyond Gold-Standard Clinical Models in Multiethnic Populations.

BACKGROUND: Preeclampsia is a major cause of maternal and fetal mortality and morbidity. Early risk stratification enables timely preventative therapy in high-risk women. Polygenic risk scores (PGS) improve prediction in complex diseases, but their added value for preeclampsia remains unclear, particularly in comparison to gold-standard first-trimester prediction models and across non-European ancestries. METHODS: We evaluated the performance of both a preeclampsia and systolic blood pressure PGS in 2 prospective pregnancy cohorts with detailed phenotyping: the Fetal Medicine Foundation study (n=5207; 2127 cases) and the Pregnancy Outcome Prediction study (n=3659; 228 cases). Risk models included (1) clinical factors; (2) clinical factors plus PGS; (3) advanced model including first-trimester mean arterial pressure, PAPP-A (pregnancy-associated plasma protein-A), and uterine artery pulsatility index; and (4) advanced model plus PGS. Discriminative performance, measured by the area under the receiver operating characteristic curve, was assessed overall and by ancestry. RESULTS: The preeclampsia PGS was independently associated with preeclampsia (odds ratio per SD, 1.24 [95% CI, 1.17-1.31]; P<0.001). It modestly improved prediction over clinical models (area under the receiver operating characteristic curve 0.746 versus 0.750; P=0.017) but not over the advanced model (area under the receiver operating characteristic curve 0.817 versus 0.818; P=0.326). The systolic blood pressure PGS showed stronger performance, improving prediction over both models in women of European ancestry. No improvement was observed with either score in women of African ancestry. CONCLUSIONS: PGSs for preeclampsia and SBP provide modest added predictive value beyond clinical risk factors in European ancestry women. Limited utility in African ancestry women reflects underrepresentation in the genome-wide association studies used to develop current scores. As cohort sizes grow and models are refined, PGSs may become important tools for equitable risk stratification in maternal health.

Adult↗
PubMed2025

Methylome profiling of cell-free DNA during the early life course in (un)complicated pregnancies using MeD-seq: Protocol for a cohort study embedded in the prospective Rotterdam periconception cohort.

INTRODUCTION: Placental DNA methylation differences have been associated with timing in gestation and pregnancy complications. Maternal cell-free DNA (cfDNA) partly originates from the placenta and could enable the minimally invasive study of placental DNA methylation dynamics. We will for the first time longitudinally investigate cfDNA methylation during pregnancy by using Methylated DNA Sequencing (MeD-seq), which is compatible with low cfDNA levels and has an extensive genome-wide coverage. We aim to investigate DNA methylation in placental tissues and cfDNA during different trimesters in uncomplicated pregnancies, and in pregnancies with placental-related complications, including preeclampsia and fetal growth restriction. Identified gestational-age and disease-specific differentially methylated regions (DMRs) could lead to numerous applications including biomarker development. METHODS AND ANALYSIS: Our study design involves three sub-studies. Sub-study 1 is a single-centre prospective, observational subcohort embedded within the Rotterdam Periconception cohort (Predict study). We will longitudinally collect maternal plasma in each trimester and during delivery, and sample postpartum placentas (n = 300). In sub-study 2, we will prospectively collect first and second trimester placental tissues (n = 10 per trimester). In sub-study 3 we will retrospectively collect plasma after non-invasive prenatal testing (NIPT) in an independent validation case-control cohort (n = 30-60). A methylation-dependent restriction enzyme (LpnPI) will be used to generate DNA fragments followed by sequencing on the Illumina NextSeq2000 platform. DMRs will be identified in placental tissues and cell types, and in cfDNA related to gestational-age or placental-related complications. (Paired) placental methylation profiles will be correlated to DMRs in cfDNA to aid tissue-of-origin analysis. We will establish a methylation score to predict associated diseases. DISCUSSION: This study will provide insights in placental DNA methylation dynamics in health and disease, and could lead to clinical relevant biomarkers.

Humans↗
PubMed2026

MiR-26a-5p/EZH2 Mediates Wnt2 Promoter Methylation to Regulate Trophoblast Dysfunction.

INTRODUCTION: Preeclampsia (PE) is a common complication of pregnancy, with a concomitant incidence rate of up to 10% among pregnant women worldwide. METHODS: In the current research, we explored the role and mechanism of miR-26a-5p in trophoblast function using CCK-8, colony formation assay, and flow cytometry. The interaction between miR-26a-5p and EZH2 was analyzed using a luciferase reporter assay. Methylationspecific PCR was performed to detect the methylation level of Wnt2 in HTR8 cells. RESULTS: Wnt2 and miR-26a-5p promoted the proliferation and inhibited the apoptosis in trophoblasts (P<0.05). The secretion of inflammatory cytokines was suppressed by Wnt2 and miR-26a-5p (P<0.05). EZH2 was identified as a regulatory target of miR-26a-5p using HTR8 cells and bioinformatic tools. miR-26a-5p inhibited expression through direct binding to EZH2. Importantly, miR- 26a-5p mediated DNA methylation of Wnt2 to regulate Wnt2 expression in HTR8 cells. DISCUSSION: This study elucidates a novel regulatory axis that alleviates trophoblast dysfunction by promoting proliferation and suppressing inflammation and apoptosis. The findings reveal that the miR-26a-5p/EZH2/Wnt2 pathway, potentially involving promoter methylation, is crucial for maintaining trophoblast function. This work identifies a promising therapeutic target for PE, although further in vivo validation is required to confirm its clinical potential. CONCLUSION: It was found that miR-26a-5p increased the expression of Wnt2 by downregulating EZH2. Moreover, miR-26a-5p/EZH2/Wnt2 promoted the proliferation and inhibited the inflammation and apoptosis in trophoblasts. This research provides insight into the role of miR-26a- 5p/EZH2/Wnt2 as a novel indicator for the prevention and treatment of PE.

MicroRNAs↗
PubMed2026

Discovery and validation of GNA12circle as a first-trimester plasma eccDNA marker for early-onset preeclampsia.

BACKGROUND: Early-onset preeclampsia (EOPE) is a major cause of maternal and perinatal morbidity and is characterized by placental dysfunction, systemic endothelial injury, and hypertensive vascular stress. Because hypertensive disorders of pregnancy may also signal later maternal cardiovascular and cerebrovascular vulnerability, effective biomarkers for first-trimester risk assessment remain clinically important. Extrachromosomal circular DNA (eccDNA), a stable form of circulating cell-free DNA, has emerged as a potential source of disease-associated biomarkers. This study aimed to characterize first-trimester plasma eccDNA alterations associated with subsequent EOPE and to identify and validate a candidate circulating eccDNA marker for early risk assessment. METHODS: A two-stage nested case-control study was conducted within a prospective birth cohort. In the discovery stage, plasma samples collected at 11-13&#x202f;weeks of gestation from 5 women who subsequently developed EOPE and 5 matched normotensive controls were profiled by Circle-Seq to characterize genome-wide eccDNA alterations. Candidate eccDNAs were prioritized through differential abundance analysis and were further confirmed by outward PCR and Sanger sequencing. In the validation stage, the candidate selected marker was quantified by junction-specific qPCR in an independent cohort of 109 EOPE cases and 109 controls. Its potential predictive value was further evaluated alone and in combination with routine first-trimester clinical variables. RESULTS: In the exploratory discovery analysis, 410 nominally differentially abundant candidate eccDNAs were identified as a hypothesis-generating pool. Among these, GNA12circle (chr7:2876332-2,876,692) was prioritized and experimentally validated at the circular junction. In the independent validation cohort, plasma GNA12circle levels were significantly higher in women who later developed EOPE than in controls. When combined with routine first-trimester variables, GNA12circle improved predictive performance. The RF model showed the best overall cross-validated performance among the evaluated classifiers, with a mean held-out test-fold AUC of 0.843. CONCLUSION: First-trimester plasma eccDNA profiling revealed distinct alterations associated with subsequent EOPE, from which GNA12circle was identified and validated as a candidate circulating marker. These findings support further investigation of circulating eccDNA for early EOPE risk assessment in larger multicenter populations.

Humans↗
PubMed1976

[Glucose infusions in suspected chronic placental insufficiency caused by gestosis].

In this study glucose load and its possible therapeutical efficiency in chronic nutritive insufficiency of the placenta is investigated. Following a definite regime glucose infusions were applied to the mother prepartually as well as subpartually in order to substitute the carbohydrate metabolism of hypotrophic fetuses. Glucose values and the parameters of the acid-base-balance were taken and calculated. The microblood analyses were performed subpartually on the mother and the fetus and postpartually on the newborn. The results gained are discussed and explained with regard to metabolism. The glucose infusion therapy in the form mentioned is suited to influence favourably the fetal hypoglucosemia.

Blood Glucose↗
PubMed1977

[New aspects in diagnosis and therapy of placental insufficiency. Placental perfusion measurements; placental perfusion test (PPT) and betamimetic long term treatment (clinical and experimental data (authors transl)].

The rate of utero-placental blood flow depends on functional components (perfusion pressure and flow resistance within the area of the vascular bed of the placenta), as well as on morphological factors (regressive changes in the placenta). Different primary maternal conditions and diseases may lower the rate of placental flow, leading to placental insufficiency; the highest percentage, by far, of placental dysfunction is found in patients suffering from gestosis. Hypocirculation initially present in cases of EPH gestosis and caused by arteriolar spasms triggers off a vicious circle involving placental infarction and severe reduction in the utero-placental perfusion rate. This in turn leads to fetal hypotrophy, a high rate of premature births and perinatal mortality. Verification of HPL, HCG, alpha-Fetoprotein or E3 in maternal serum and amniotic fluid or urine greatly improved the recording of partial placental functions. Along with ultrasonic biometry, cardiotocography and amnioscopy, these hormonal parameters allow only indirect assessment of the placental function. On the other hand, measurements of the utero-placental flow offers a direct approach. In order to evaluate the placental flow measurements it is imperative to obtain a curve indicating the course over the last third of the pregnancy-in addition to establishing a general normal range. In case of placental insufficiency, it is necessary to determine whether this is due to functional disorders alone, or to more extenisve morphological changes. A placental perfusion test (PPT) was developed in order to make this distinction. Beta2-mimetic treatment is indicated if functional factors predominate, whereby it appears essential to obtain the requisite experimental data for precise quantification of beta-mimetic action.

Adrenergic beta-Agonists↗
PubMed1976

Effects of ritodrine hydrochloride on uterine activity and the cardiovascular system in toxemic patients.

The effects of ritodrine hydrochloride were evaluated in 25 toxemic patients in active labor utilizing continuous electronic monitoring of fetal and maternal cardiovascular systems and uterine activity. Fetal scalp blood and free flowing maternal antecubital venous blood was obtained for pH, Po2, Pco2, base deficit and blood glucose determinations prior to and immediately following the study period. The initial ritodrine dose was 50 mug/min for 15 minutes. The dose was increased by 50 mug/min each 15 minutes until there was a clinically apparent reduction in uterine activity. Once this was accomplished, the infusion was maintained for 30 minutes. There was a consistent increase in the maternal heart rate (MHR) and a significant rise in fetal heart rate (FHR) late in the infusion and in the postinfusion period. There was a widening of the maternal pulse pressure mainly due to a reduction in diastolic pressure with little change in the mean blood pressure. Maternal and fetal pH decreased and base deficit increased during the study although the PO2 and PCO2 remained unchanged. Maternal and fetal blood glucose rose significantly following ritodrine infusion.

Blood Glucose↗
PubMed1978

Some clinical aspects of caprine reproduction.

Several clinical reproductive problems in the female dairy goat are considered, including estrus detection, artificial insemination, pregnancy diagnosis, abortions, and periparturient difficulties. Sexual behavior of the buck, onset of puberty, techniques for semen collection and evaluation, the production of teaser animals, and methods of castration are also discussed. Recognition of the intersex goat, which may have a masculine, feminine, or intermediate phenotype, is necessary in herds where naturally polled animals are bred.

Abortion, Veterinary↗