Risk Of Preeclampsia Research Articles

Normally Developing Pregnancy and Hydatidiform Mole: A Case Report

Introduction: Hydatidiform mole with a normally developing fetus is a rare case associated with an increased risk of bleeding, preterm birth, preeclampsia, congenital anomalies, and intrauterine fetal death.Case report: We report a case of a twin pregnancy with a hydatidiform mole and a normal fetus. The pregnancy was conceived via in vitro fertilization. The complete hydatidiform mole was diagnosed during the first screening. We extended the pregnancy until 38 weeks’ gestation. Thanks to the control of beta-human chorionic gonadotropin levels and dynamic ultrasound monitoring, the woman successfully gave birth.

Chronic hypertension diagnosed before or during pregnancy and its effects on pregnancy outcomes.

Chronic hypertension (CH) during pregnancy, identified before or within the first 20 weeks, presents varying risks depending on the timing of diagnosis. This real-world study was conducted from January 2018 to June 2023 and included singleton pregnancies with CH to compare pre-pregnancy CH (Group 1) and newly diagnosed CH (Group 2). There were 565 women in the final analysis, with 307 in Group 1 with pre-pregnancy CH and 258 in Group 2 with new-onset CH. Those in Group 1 more frequently had pre-gestational diabetes and a history of hypertensive disorders in pregnancy, whereas Group 2 had a higher incidence of excessive gestational weight gain. Notably, 56.2% of Group 2 patients did not receive antihypertensive treatment before 20 weeks, while the proportion was 36.2% in Group 1, resulting in a significant difference in baseline blood pressure. The study revealed higher incidences of preterm preeclampsia (44.2% vs. 34.9%) and placental abruption (5.4% vs. 2.0%) in Group 2 compared to Group 1. After adjustment, logistic regression indicated that Group 2 had a 1.8-fold higher risk of preterm preeclampsia than Group 1. These findings suggest that pregnant women newly diagnosed with CH in the first 20 weeks face increased adverse outcomes compared to those diagnosed before pregnancy. Intense monitoring and earlier intervention may help manage women with new-onset CH.

Placental growth factor at 24-28 weeks for aspirin discontinuation in pregnancies at high risk for preterm preeclampsia: Post hoc analysis of StopPRE trial.

This study aims to evaluate the safety of discontinuing aspirin treatment at 24-28 weeks in women at high risk after first-trimester combined screening for preeclampsia (PE) and normal placental growth factor (PlGF) levels at 24-28 weeks of gestation. This is a post hoc analysis of the StopPRE trial, conducted at nine Spanish maternity hospitals from September 2019 to September 2021. In the StopPRE trial, all high-risk single pregnancies identified during first-trimester screening for PE were treated with 150 mg of daily aspirin. Out of 1604 eligible women with a soluble fms-like tyrosine kinase-1 to PlGF ratio (sFlt-1/PlGF) ≤38 at 24-28 weeks, 968 were randomly assigned in a 1:1 ratio to either continue aspirin until 36 weeks (control group) or discontinue it (intervention group). In this secondary analysis, only women with PlGF ≥100 pg/mL at 24-28 weeks were included. As in the StopPRE trial, the non-inferiority margin was set at a 1.9% difference in preterm PE incidence between the groups. Among the 13 983 screened pregnant women, 1984 (14.2%) were deemed high-risk for preterm PE, of which 397 (20.0%) were ineligible, 636 declined participation, and 32 were excluded. Ultimately, 919 women with PlGF >100 pg/mL were randomized and included in this analysis. Preterm PE occurred in 0.9% of the intervention group (4 out of 465) and 1.5% of the control group (7 out of 454), indicating non-inferiority of aspirin discontinuation. There were no significant differences between the groups in adverse pregnancy outcomes before 37 weeks, at <34 weeks, or ≥37 weeks. Minor antepartum hemorrhage incidence was significantly lower in the intervention group (absolute difference, -5.96; 95% CI, -10.10 to -1.82). Discontinuation of aspirin treatment at 24-28 weeks in women with PlGF levels ≥100 pg/mL was non-inferior to continuing until 36 weeks for preventing preterm PE. However, these findings should be interpreted with caution, as they originate from a subanalysis of the StopPRE trial.

Association of obesity and overweight with the risk of preeclampsia in pregnant women: an observational cohort study.

According to the World Health Organization, obesity is considered a pervasive global epidemic with significant medical and social implications. In antenatal mothers, the prevalence varies from 40% in Western countries to 12% in India which leads to life-threatening complications-preeclampsia and eclampsia. This study delves into the association between body mass index (BMI) and preeclampsia, among primi antenatal mothers with pregnancy-induced hypertension (PIH). An observational cohort (prospective) study was conducted among 150 primi antenatal mothers with pregnancy-induced hypertension in Government Headquarters Hospital, Tamil Nadu, India. Demographic data, body mass index, and pregnancy outcomes were assessed. Statistical analysis was performed using the SPSS 28.0 version. Among 150 pregnant women, 63 (42%) were overweight, and 13 (8.7%) were obese. Higher BMI was significantly associated with maternal complications, especially preeclampsia (P < 0.001). Moreover, other complications such as abruptio placenta, pulmonary edema, eclampsia, and postpartum hemorrhage were not significantly associated with BMI. The study calls attention to the persistent link between BMI and preeclampsia, emphasizing the need for comprehensive strategies aligned with the Sustainable Development Goal. Despite ongoing efforts, the study suggests a lack of substantial change in the prevalence of preeclampsia associated with increased BMI, prompting the exploration of innovative interventions to address weight-related factors during pregnancy for improved maternal and neonatal well-being.

Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a common pregnancy disorder associated with an increased risk of pre-eclampsia and macrosomia. Recent research has shown that the buildup of excess lipids within the placental trophoblast impairs mitochondrial function. However, the exact lipids that impact the placental trophoblast and the underlying mechanism remain unclear. GDM cases and healthy controls were recruited at Kaohsiung Medical University Hospital. The placenta and cord blood were taken during birth. Confocal and electron microscopy were utilized to examine the morphology of the placenta and mitochondria. We determined the lipid composition using liquid chromatography-mass spectrometry in data-independent analysis mode (LC/MSE). In vitro studies were carried out on choriocarcinoma cells (JEG3) to investigate the mechanism of trophoblast mitochondrial dysfunction. Results showed that the GDM placenta was distinguished by increased syncytial knots, chorangiosis, lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) overexpression, and mitochondrial dysfunction. Lysophosphatidylcholine (LPC) 16:0 was significantly elevated in the cord blood LDL of GDM patients. In vitro, we demonstrated that LPC dose-dependently disrupts mitochondrial function by increasing reactive oxygen species (ROS) levels and HIF-1α signaling. In conclusion, highly elevated LPC in cord blood plays a pivotal role in GDM, contributing to trophoblast impairment and pregnancy complications.

Role of chronic kidney disease and risk factors in preeclampsia

BackgroundOur goal was to identify what impact chronic kidney disease (CKD) and its associated risk factors, such as body mass index (BMI), diabetes and hypertension, have on preeclampsia and other adverse pregnancy outcomes in the CKD population. MethodsThis was a population-based cohort study of women with CKD who had a pregnancy from 2010 to 2022 (n = 95). At the time of the woman’s pregnancy, data was collected on demographics, clinical measures, BMI, CKD etiology and other renal parameters. Outcomes included preeclampsia, pre-term delivery, and low birth weight. ResultsPre-pregnancy BMI increased over time in patients with CKD, with a median (interquartile range) BMI of 25 (22–29) prior to 2016 and 29 (25–34) after 2016 (p = 0.01). There were significant trends of increasing age at delivery and decreasing pre-pregnancy estimated glomerular filtration rate (eGFR) by delivery year. Preeclampsia affected nearly half of pregnancies in this cohort. In multivariate analyses, BMI and chronic hypertension did not impact the odds of preeclampsia, preterm delivery or low birth weight, though a CKD etiology of diabetes (19/20 with type I diabetes), was associated with a significant increase in preeclampsia risk (odds ratio (OR) 7.41 (95 % CI 2.1–26.1)). Higher pre-pregnancy eGFR was associated with a lower odds of preterm delivery (OR 0.81 (95 % CI 0.67–0.98)) per 10 ml/min/1.73 m2). ConclusionPre-pregnancy BMI significantly increased over time, similar to the general population. While preeclampsia was common in CKD patients, outcomes were associated with eGFR and CKD etiology as opposed to BMI and chronic hypertension.

Association between pregnancy-related changes in serum creatinine and preeclampsia diagnosis

BackgroundPreeclampsia is a leading cause of maternal and neonatal morbidity and mortality, affecting 2–8% of all pregnancies. Typically, the increased glomerular filtration rate of pregnancy results in a decrease in serum creatinine. It is unknown if women without the expected decrease in serum creatinine during pregnancy are more likely to be diagnosed with preeclampsia.ObjectiveWe sought to determine if the absence of a pregnancy-related decrease in serum creatinine was associated with the development of preeclampsia in patients deemed to be at high risk for developing preeclampsia. We hypothesized that the absence of the expected decrease in serum creatinine may be a marker of impaired renal function and therefore may be associated with increased risk of preeclampsia in this cohort.Study designWe conducted a retrospective cohort study of deliveries between November 2, 2017 and June 30, 2020 at a single institution. Pregnancies were included if a baseline serum creatinine (measured between one year prior to conception through 6 weeks gestation), and another serum creatinine value prior to 20 weeks of gestation were measured. Decrease in serum creatinine was defined as any decrease (at least 0.01 mg/dL) from baseline. The primary outcome was diagnosis of preeclampsia. Exclusion criteria included fetal anomalies, fetal demise, multiple gestation, or delivery prior to 20 weeks. Bivariable analyses were performed using Chi-square, ANOVA, and Student’s t test. Logistic regression was used to determine odds of developing preeclampsia controlling for confounders.ResultsWe identified 392 pregnancies that met inclusion criteria. Preeclampsia was diagnosed in 56 (14.3%) pregnancies. Patients diagnosed with preeclampsia were more likely to have a history of preeclampsia in a prior pregnancy, chronic hypertension (HTN), and diabetes. They were also more likely to have aspirin prescribed in the current pregnancy. Prevalence of advanced maternal age, multiparity, obesity, smoking, history of autoimmune disease, history of CKD, gestational HTN, or multiple pregnancy were not significantly different between patients with and without a diagnosis of preeclampsia. After controlling for confounders, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia (OR 0.76, CI 0.32–1.78).ConclusionAfter controlling for risk factors associated with preeclampsia, a decrease in serum creatinine from baseline was not significantly associated with a diagnosis of preeclampsia in this high-risk cohort.

Pregnancy outcome predictors in systemic lupus erythematosus: a systematic review and meta-analysis

To enhance patient-tailored preconception risk assessment for women with systemic lupus erythematosus (SLE), knowledge on risk factors associated with adverse pregnancy outcomes is required. Therefore, we did a systematic review and meta-analysis to identify and provide unambiguous effect sizes of preconception predictors of pregnancy outcomes in women with SLE. In this systematic review and meta-analysis, we searched PubMed and Embase for studies reporting preconception predictors of pregnancy outcomes in women with SLE, from database inception to Aug 22, 2023. Studies were included if they presented original, quantitative data on pregnant women with SLE and reported on preconception risk factors on at least one of the outcomes as defined in the protocol. Studies were excluded if they had a sample size of less than 20 patients, were restricted to multiple pregnancies, had unclear timing of prognostication, or exclusively reported a composite outcome. Literature screening, data extraction, and risk-of-bias assessment (quality in prognostic studies tool) were done by two reviewers independently, in a blinded, standardised manner. The reported outcomes included livebirth, pre-eclampsia, small for gestational age, preterm birth, pregnancy loss before and after 20 weeks of gestation, and SLE flares. We computed pooled univariate odds ratios (ORs) and 95% CIs using a random effects model. We assessed heterogeneity using the I2 statistic and prediction intervals. This study is registered with PROSPERO, CRD42022344732. Of the 6705 unique articles identified, 72 (1·1%) were included in the meta-analysis, comprising 10 355 pregnancies in 8065 women with SLE. One potentially eligible study was retracted and therefore removed from our analysis. Previous lupus nephritis was associated with decreased livebirth probability (OR 0·62 [95% CI 0·47-0·81]; I2=0%), increased risk of preterm birth (2·00 [1·55-2·57]; I2=17%), and increased risk of pre-eclampsia (3·11 [2·35-4·12]; I2=0%). Chronic hypertension was associated with increased risk of disease flare (2·50 [1·74-3·58]; I2=0%), preterm birth (2·65 [1·87-3·77]; I2=0%), and pre-eclampsia (5·86 [3·41-10·06]; I2=33%). SLE disease activity at conception or preconception was associated with increased risk of preterm birth (2·91 [1·96-4·33]; I2=21%) and pre-eclampsia (2·32 [1·40-3·83]; I2=0%). Secondary antiphospholipid syndrome was associated with decreased livebirth probability (0·40 [0·27-0·58]; I2=0%), increased risk of pregnancy loss after 20 weeks of gestation (2·77 [1·44-5·31]; I2=0%), and increased risk of preterm birth (1·65 [1·29-2·11]; I2=0%). Across studies, risk-of-bias assessment suggested considerable bias in study attrition and confounding. We identified previous lupus nephritis, chronic hypertension, SLE disease activity before and at conception, and secondary antiphospholipid syndrome as predictors of adverse pregnancy outcomes in women with SLE. These findings contribute to an optimal patient-tailored risk assessment in preconception counselling. None.

Evaluation of the effect of vitamin D on the placenta, kidney, and growth of developing fetuses in preeclamptic mice

Background Preeclampsia (PE) is a complicated syndrome that leads to maternal and fetal morbidity and mortality. PE is defined by the elevation of the mother’s blood pressure (hypertension) and the presence of proteinuria. Objective This study aimed to evaluate the effect of vitamin D on 18-day-old mice fetuses in which the PE syndrome was induced in the mother by L-NG-nitro arginine methyl ester (L-NAME). Materials and methods The mice grouping was divided as: (a) the control group (group I), (b) the female pregnant mice of the second group intraperitoneally injected with 50 mg/kg/day of L-NAME (group II), (c) the female pregnant mice of the third group were administered orally with 50 IU/kg/day of vitamin D (group III), and (d) the female pregnant mice of the fourth group were intraperitoneally injected with 50 mg/kg/day L-NAME and then orally, with 50 IU/kg/day vitamin D (group IV). All groups were treated daily from 7 to 14 days of gestation. Results and conclusion The placenta of mice injected with L-NAME showed different phases of histopathological changes in the basal and labyrinth zone. Meanwhile, the kidney in 18-day-old fetuses maternally injected with L-NAME showed an apparent enlargement in the glomerular area and the presence of hemorrhages among the tubules. However, the 18-day-old fetuses maternally treated with L-NAME and vitamin D (group IV) showed mild injury. This study concluded that induced PE-like symptoms in pregnant mice by L-NAME caused increased fetal growth restriction, impairment of placental histology, and histopathology of the kidneys of fetuses. On the other hand, vitamin D ameliorated the effect of L-NAME and reduced the risk of PE.

Pilot association of common NOS3 variants with Preeclampsia risk in Russian pregnant women from Rostov region

Preeclampsia (PE) is a severe medical condition affecting pregnant women, often developing after 20 weeks, and is the most common serious disorder during pregnancy, contributing to 2%-8% of pregnancy-related complications worldwide. The goal of this study is to investigate the association of two genetic variants in NOS3 (-786T&gt;C; rs2070744) and (894G&gt;T; rs1799983) with the risk of developing PE in Russian pregnant women from Rostov region. The case–control study involved 106 pregnant women (46 pregnant women with PE and 60 healthy controls). Genotyping of the selected NOS3 genetic variants (-786T&gt;C) and (894G&gt;T) was done using allele specific RT-PCR. Multifactor dimensionality reduction (MDR) was used to assess the relationship between the SNP-SNP interaction and risk of developing PE. In addition, we analyzed the linkage disequilibrium (LD), and haplotypes association for the selected SNPs in the studied population. According to our results, both NOS3 polymorphisms were statistically significant (P=0.004 and P=0.045, respectively). The NOS3 -786(TT) genotype (OR=0.25 95% CI [0.11- 0.58]) and the NOS3 894(GG) genotype (OR=0.38 95% CI [0.17- 0.84]) were associated with low risk of developing PE. While -786(TC) genotype (OR=4.17 95% CI [1.76-9.85]), 894(GT) (OR=2.48 95% CI [1.10-5.63]) and dominant model of NOS3 (-786T&gt;C) TC+CC (OR=3.97 95% CI [1.72-9.14]) as well as the dominant model GT+TT of NOS3 (894G&gt;T) (OR=2.64 95% CI [1.20-5.82]) were associated with increased risk of PE. In addition, the polymorphism -786(C) allele (OR=2.21 95% CI [1.23-3.98]) and polymorphism 894(T) allele (OR=2.14 95% CI [1.15-4.01]) were both associated with an increased risk of PE. According to the MDR results, the SNP-SNP interaction was statistically significant (P=0.0003). Moreover, two haplotypes of NOS3 gene variants -786C*894G (OR=3.01 95% CI [1.15- 7.86]; P=0.027) and -786C*894T (OR=3.03 95% CI [1.27-7.23]; P=0.014) were shown to be statistically related with an elevated risk of PE. Преэклампсия (ПЭ) − тяжелое заболевание, поражающее беременных женщин, часто развивается после 20 недель гестации, и является наиболее распространенным серьезным расстройством, составляя 2-8% осложнений, связанных с беременностью, во всем мире. Цель исследования: изучить ассоциацию двух вариантов в гене NOS3 (-786T&gt;C; rs2070744) и (894G&gt;T; rs1799983) с риском развития ПЭ у российских беременных женщин из Ростовской области. В исследование типа «случай-контроль» были включены 106 беременных женщин (46 с ПЭ и 60 здоровых, составивших контрольную группу). Генотипирование выбранных генетических вариантов NOS3 (-786T&gt;C) и (894G&gt;T) проводилось методом аллель-специфической RT-PCR. Для оценки взаимодействия SNP-SNP с риском развития ПЭ использовали многофакторное снижение размерности (MDR). Кроме того, мы проанализировали неравновесие по сцеплению (LD) и ассоциацию гаплотипов выбранных SNP в исследуемой популяции. Согласно нашим результатам, оба полиморфизма NOS3 были статистически значимы (р=0,004 и р=0,045, соответственно). Генотип NOS3 -786(TT) (OR=0,25 95% CI [0,11- 0,58]) и генотип NOS3 894(GG) (OR=0,38 95% CI [0,17- 0,84]) были ассоциированы с низким риском развития ПЭ. Генотипы -786(TC) (OR=4,17 95% CI [1,76-9,85]), 894(GT) (OR=2,48 95% CI [1,10-5,63]) и доминантная модель NOS3 (-786T&gt;C) TC+CC (OR=3. 97 95% CI [1,72-9,14]), а также доминантная модель GT+TT NOS3 (894G&gt;T) (OR=2,64 95% CI [1,20- 5,82]) были связаны с повышенным риском развития ПЭ. Кроме того, аллели -786(C) (OR=2,21 95% CI [1,23-3,98]) и 894(T) (OR=2,14 95% CI [1,15-4,01]) были ассоциированы с повышенным риском ПЭ. Взаимодействие SNP-SNP было статистически значимым (р=0,0003). Кроме того, было показано, что два гаплотипа вариантов гена NOS3 -786C*894G (OR=3,01 95% CI [1,15-7,86]; р=0,027) и -786C*894T (OR=3,03 95% CI [1,27-7,23]; р=0,014) статистически значимо ассоциированы с повышенным риском ПЭ.

Ambient air pollutants exposure during gestation and incidence risk of hypertensive disorders of pregnancy or preeclampsia in China

The relationships between the exposure to ambient air pollutants during gestation and the incidence of hypertensive disorders in pregnancy (HDPs) or preeclampsia are contradictory. This prospective cohort study enrolled the participants between January 2020 and December 2021 from the Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology. The exposure to ambient air pollutants and daily temperatures were obtained from the ChinaHighAirPollutants dataset and the Big Earth Data Platform for Three Poles, respectively. Logistic regression models were used as single- and two-pollutant models. Restricted cubic splines were applied to each ambient air pollutant exposure to further evaluate the exposure-response relationships. Quantile G-computation approaches were employed to evaluate the cumulative impact of mixed ambient air pollutants on the incidence risk HDPs and preeclampsia. Among 19,325 participants (median age: 30.2 years), 1669 (8.64%) were diagnosed with HDPs and 180 (0.94%) with preeclampsia. While mostly null risk estimates were observed, exposure to PM1, PM2.5, PM10, and NO2 correlated with a decreased incidence risk for HDPs and preeclampsia during most gestational periods. Additionally, our multi-pollutant model presented that an increase by one quartile in the cumulative effect of ambient air pollutants was associated with a significantly decreased incidence risk for HDPs in the trimester before gestation and in the third trimester during gestation, as well as for preeclampsia in the third trimester during gestation. These findings warrant further investigation into the mechanisms underlying these associations.

Racial/ethnic differences in pre-pregnancy conditions and adverse maternal outcomes in the nuMoM2b cohort: A population-based cohort study.

To determine how pre-existing conditions contribute to racial disparities in adverse maternal outcomes and incorporate these conditions into models to improve risk prediction for racial minority subgroups. We used data from the "Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b)" observational cohort study. We defined multimorbidity as the co-occurrence of two or more pre-pregnancy conditions. The primary outcomes of interest were severe preeclampsia, postpartum readmission, and blood transfusion during pregnancy or up to 14 days postpartum. We used weighted Poisson regression with robust variance to estimate adjusted risk ratios and 95% confidence intervals, and we used mediation analysis to evaluate the contribution of the combined effects of pre-pregnancy conditions to racial/ethnic disparities. We also evaluated the predictive performance of our regression models by racial subgroup using the area under the receiver operating characteristic curve (AUC) metric. In the nuMoM2b cohort (n = 8729), accounting for pre-existing conditions attenuated the association between non-Hispanic Black race/ethnicity and risk of severe preeclampsia. Cardiovascular and kidney conditions were associated with risk for severe preeclampsia among all women (aRR, 1.77; CI, 1.61-1.96, and aRR, 1.27; CI, 1.03-1.56 respectively). The mediation analysis results were not statistically significant; however, cardiovascular conditions explained 36.6% of the association between non-Hispanic Black race/ethnicity and severe preeclampsia (p = 0.07). The addition of pre-pregnancy conditions increased model performance for the prediction of severe preeclampsia. Pre-existing conditions may explain some of the association between non-Hispanic Black race/ethnicity and severe preeclampsia. Specific pre-pregnancy conditions were associated with adverse maternal outcomes and the incorporation of comorbidities improved the performance of most risk prediction models.

Hsa_circ_0088196 Predicts Adverse Pregnancy Outcomes in Preeclampsia Patients and Contributes to Endothelial Cell Injury Via Modulating the miR-145-5p/FLT1 Axis.

Preeclampsia (PE) is a specific hypertension-related disease in pregnancies, causing adverse pregnancy outcomes. Endothelial cell dysfunction is a major etiology of PE, of which the regulation could affect disease progression. This study focused on hsa_circ_0088196, evaluating its clinical significance in PE and its effect on endothelial cell injury, aiming to identify a novel biomarker for PE and complete its regulating mechanism in disease development. The study enrolled 165 normal pregnancies and 165 pregnancies with gestational hypertension. The significance of hsa_circ_0088196 in discriminating gestational hypertension, predicting PE, and predicting adverse pregnancy outcomes was evaluated based on its serum expression. The effect and mechanism of hsa_circ_0088196 in HUVEC injury were assessed by CCK8, Transwell, ELISA, and western blotting. Significant downregulation of hsa_circ_0088196 could distinguish gestational hypertension pregnancies and predict the risk of PE. Gestational hypertension pregnancies developed PE showed a lower serum hsa_circ_0088196 level, which also discriminated PE patients, predicted severe conditions and adverse pregnancy outcomes. Overexpressing hsa_circ_0088196 alleviated the enhanced proliferation, migration, inflammation, and angiogenesis by hypoxia/reoxygenation (H/R), which was reversed by miR-145-5p. Silencing miR-145-5p showed similar effects on H/R-induced endothelial cell injury, which was reversed by FLT1. Moreover, FLT1 was positively regulated by hsa_circ_0088196, indicating its involvement in the regulation of HUVEC injury by hsa_circ_0088196. Reduced serum hsa_circ_0088196 served as a biomarker for the diagnosis of gestational hypertension, risk evaluation of PE, and the prediction of adverse pregnancy outcomes. hsa_circ_0088196 suppressed endothelial cell injury induced by H/R through modulating the miR-145-5p/FLT1 axis.

Epicardial adipose tissue thickness associated with preeclampsia and birth weight in early pregnancy

ABSTRACT Objective Preeclampsia (PE) increases the risk of many adverse maternal and fetal outcomes. This study was to investigate the correlation between epicardial adipose tissue (EAT) thickness and PE and birth weight. Methods This was a single-center retrospective study, 221 patients with PE were selected, and 81 women without hypertension and proteinuria were selected as a comparison. Echocardiogram was performed in their first prenatal examinations at 11–13 gestational weeks, and the thickness of EAT was measured. At the subsequent follow-up, the birth weight was recorded. Results EAT thickness was significantly elevated (6.60 ± 1.34 vs. 5.71 ± 1.79 mm, p < 0.001) in severe PE compared to mild PE. In the multivariate analysis, EAT thickness (OR 5.671, 95% CI, 1.991–16.150, p = 0.001), and C reactive protein (OR 4.097, 95% CI, 2.323–7.224, p < 0.001) were found as significant independent predictors of severe PE after adjusting for other risk factors. Linear regression analysis showed that hs-CRP, EAT thickness, and severe PE significantly negatively affected birth weight. Conclusion EAT thickness can be used to identify pregnant women with severe PE risks and low birth weight. It is an independent risk factor for severe PE but is not a valuable sign of mild PE.

Hydroxychloroquine and Pre-eclampsia in a Diverse Cohort of Women With Systemic Lupus Erythematosus.

Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as pre-eclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality, and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce pre-eclampsia risk in lupus pregnancy. Using a cohort of pregnant patients with prevalent SLE at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ treatment in early pregnancy reduced the risk of pre-eclampsia or eclampsia. Among pregnant patients with SLE from 2011 to 2020, we assessed HCQ treatment from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of treatment. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RRs) and 95% confidence intervals of the association between HCQ treatment and pre-eclampsia or eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody (aPL) status was investigated through stratified analysis. There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and pre-eclampsia or eclampsia. The RRs were consistently lower among nullipara patients, and RRs were consistently protective but not statistically significant among the high-risk subgroup of patients with a history of nephritis, aPL positivity, or pregestational hypertension (for both nullipara and multipara patients). Although this study found no reduced risk of HCQ on pre-eclampsia or eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data.

Time in therapeutic range and risk of preeclampsia in chronic hypertensive pregnant women.

Pregnancy Hypertensive Disorders (PHD), particularly Preeclampsia (PE), are significant contributors to maternal-fetal morbidity and mortality, with chronic arterial hypertension (CH) being a major risk factor. The prevalence of CH has risen alongside obesity and advanced maternal age. While antihypertensive treatment mitigates adverse pregnancy outcomes, the duration of effective blood pressure (BP) control, termed Time in Therapeutic Range (TTR), has not been extensively studied in pregnant women. TTR, reflecting the proportion of time BP remains within target ranges, predicts long-term cardiovascular and renal events in the general population but remains unexplored in pregnancy. This study investigates the association between TTR, assessed through office BP (OBP) and ambulatory BP monitoring (ABPM), and PE development in pregnant women with CH. In a retrospective longitudinal study, data from 166 pregnant women with HA referred to our hospital analyzed. BP was measured using OBP and ABPM from 10 weeks of gestation, with TTR calculated as the percentage of visits where BP remained within target ranges. The study defined four TTR control groups: 0%, 33%, 50-66%, and 100%. Results showed that 28% of the participants developed PE, with a higher incidence correlating with lower TTR in ABPM. TTR in ABPM was a significant predictor of PE risk, with the best-controlled group (100% TTR) demonstrating a 92% reduced risk compared to those with 0% TTR. The agreement between OBP and ABPM TTR was low, emphasizing the importance of ABPM for accurate BP monitoring in pregnancy. This study indicates that integrating ABPM for TTR assessment in high-risk pregnancies has the potential to reduce maternal and fetal complications.

GSTP1-A313G genetic polymorphism and the risk of preeclampsia in pregnant women: A study in the northern population of Iran

Preeclampsia or high blood pressure in pregnancy is one of the special disorders during pregnancy. It seems that oxidative stress plays an important role in the occurrence of this disease. The purpose of this study is to investigate the relationship between the A313G polymorphism in exon five of the glutathione S-transferase gene (GSTP1) and the risk of preeclampsia in a case-control study. In this study, blood samples were collected from 70 healthy pregnant women and 70 women with preeclampsia. After genomic DNA extraction, the PCR-RFLP method was performed to check the genotype in GSTP1-A313G and the genotypic frequencies of AA, AG, and GG were determined in all samples. Also, using bioinformatics software, the effect of the above polymorphism on the protein structure was investigated. Statistical analysis for A313G polymorphism showed that AG (OR: 1.1684, 95 % CI: 0.5877–2.3228, p = 0.657) and GG (OR: 1.3793, 95 % CI: 0.3376–5.6359, p = 0.654) genotypes were not associated with risk of preeclampsia in the population of northern Iran. However, bioinformatic analyzes have shown that this polymorphism does have a destructive effect on the protein structure. However, more studies with larger sample sizes are needed to draw firm conclusions.

Insights into preeclampsia: a bioinformatics approach to deciphering genetic and immune contributions.

Preeclampsia (PE) is a global pregnancy concern, characterized by hypertension with an unclear etiology. This study employs Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to clarify its genetic and molecular roots, offering insights into diagnosis and treatment avenues. We integrated PE-specific genome-wide association study (GWAS) data, expression and protein quantitative trait loci (eQTL and pQTL) data, and single-cell data from peripheral blood mononuclear cells (PBMCs). We identified highly variable genes using single-cell information and employed MR to determine potential causality. We also combined pQTL and GWAS data, discerned genes positively associated with PE through scRNA-seq, and leveraged the Enrichr platform to unearth drug-gene interactions. Our scRNA-seq pinpointed notable cell type distribution variances, especially in T helper cells (Th cells), between PE and control groups. We unveiled 591 highly variable genes and 6 directly PE-associated genes. Although MR revealed correlations with PE risk, pQTL analysis was inconclusive due to data constraints. Using DSigDB, 93 potential therapeutic agents, like Retinoic acid targeting core genes (IFITM3, NINJ1, COTL1, CD69, and YWHAZ), emerged as prospective multi-target treatments. Utilizing MR and scRNA-seq, this study underscores significant cellular disparities, particularly in Th cells, and identifies crucial genes related to PE. Despite some limitations, these genes have been revealed in PE's underlying mechanism. Potential therapeutic agents, such as Retinoic acid, suggest promising treatment pathways.

Risk assessment of preeclampsia

Introduction and purpose: Preeclampsia (PE) is a complication during pregnancy characterized by high blood pressure (≥140/90 mmHg) and signs of organ involvement appearing after 20 weeks’ of gestation. Various factors are known to increase the risk of this condition as well as clinical factors. The pathogenesis of the disease is complex and not fully understood. State of Knowledge: The main roles play two angiogenic factors: soluble fms-like tyrosine kinase 1 (sFlt-1), which is an antiangiogenic protein, and placental growth factor (PlGF), which is a pro-angiogenic protein. Elevated sFlt-1 and reduced PlGF levels in the mother’s blood can predict the future development of preeclampsia during pregnancy. The imbalance between these two angiogenic biomarkers indicates de new-onset preeclampsia, distinct from chronic hypertension. Both MAP and UTA-PI are essential components of first-trimester screening protocols, which, combined with maternal history and other biochemical markers, allow for accurate preeclampsia risk assessment and early intervention to improve maternal and fetal outcomes. Conclusions: Preeclampsia is a major cause of maternal and perinatal morbidity and mortality. The integration of multiple biomarkers, such as PlGF and sFlt-1, along with advanced analytical techniques, enhances early detection and accurate risk stratification, improving maternal and fetal outcomes. Aspirin prophylaxis before 16 weeks’ gestation has been shown to reduce the risk of preeclampsia.

Maternal hypothyroidism and the risk of preeclampsia: a Danish national and regional study

BackgroundMaternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se.MethodsWe conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity.ResultsIn the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1–5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)).ConclusionsIn two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia.