Preeclampsia Pregnancy Research Articles

Association of MTHFR gene polymorphism in preeclampsia and recurrent pregnancy loss: A case-control study from South India

BackgroundPreeclampsia (PE) and recurrent pregnancy loss (RPL), both of which affect maternal and reproductive health, are obstetrical-gynecological issues. Pregnancies that meet one or more of these criteria are considered high risk. This study aims to examine and understand how specific methylation within the MTHFR gene (rs 1,801,131 and rs 1,801,133) polymorphisms may contribute to preeclampsia and recurrent miscarriages in the South Indian population. MethodsA combination of recurrent pregnancy loss and preeclampsia were taken as a case (146), and healthy controls (152) were enrolled in the study. 5 ml of human blood was taken after getting consent from the participants. The DNA was isolated from the peripheral blood lymphocytes and genotyped using ARMS-PCR. ResultThe findings of this study suggest that the MTHFR gene (rs1801131) is not associated with PE and RPL risk. A significant association has been observed between rs1801133 and the derived allele T (OR = 0.6, 95% CI -0.4-0.8, p = 0.001). Furthermore, a p-value of 0.01 was calculated for the homozygous recessive genotype TT (OR = 0.5, 95% CI - 0.29-0.1). ConclusionsThe results of this study suggest that preeclampsia and recurrent pregnancies are more common among South Indian women who carry a variant of the MTHFR gene 1,801,133. According to the conclusion, higher sample sizes and a wider study are necessary to verify these findings. More diverse and valuable information can be obtained through large sample sizes and combined studies, allowing the results to be applied to a wide population.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism.

P-319 Transcriptomic analysis reveals deregulated molecular mechanisms related to miscarriage, preeclampsia, and pregnancy complications during gestational endometrial phase in adenomyosis

Abstract Study question Is there any molecular deregulation in the gestational endometrium of women with adenomyosis responsible for adenomyosis-related pregnancy disorders? Summary answer Women with adenomyosis show deregulated molecular mechanisms in their gestational phase endometrium involved in miscarriage, preeclampsia, and pregnancy complications, causing adenomyosis-related infertility. What is known already Women with adenomyosis are characterized by having defective decidualization, altered endometrial receptivity, impaired embryo-maternal communication, implantation failure and higher risk of preeclampsia and miscarriage. However, molecular mechanisms underlying these infertility-related conditions remain unknown, mainly due to the inaccessibility of obtaining and maintaining these endometrial tissues. We have previously established adenomyosis endometrial organoids and differentiated them into gestational phase, demonstrating the maintenance of disease-specific traits. For this reason, here we use the already established adenomyosis organoid platform to describe the molecular mechanisms deregulated during gestational phase involved in adenomyosis-associated pregnancy disorders, which could be possible infertility therapeutical targets. Study design, size, duration Endometrial organoids from eutopic endometrium of adenomyosis and non-disease (control) women (n = 15/group) were established and differentiated into gestational phase (ADENO-GESTorg and CONTROL-GESTorg) by supplementation with ovarian and pregnancy hormones. An RNA-sequencing was performed. DESeq2 was used to identify differentially expressed genes (DEGs), FDR < 0.05. GO and KEGG analysis were performed to study DEGs implication at biologically functional level. QIAGEN Ingenuity Pathway Analysis (IPA) was used to further identify upregulated and downregulated pathways. Participants/materials, setting, methods Endometrial biopsies were obtained by hysteroscopy from adenomyosis and control patients (n = 15/group) at IVI Valencia Clinics. Patients between 18≤45 years old and BMI≤28 kg/m2 diagnosed with adenomyosis (adenomyosis group) or without adenomyosis nor other uterine pathologies (control group) were included in the study. Main results and the role of chance We identified 1999 DEGs (153 upregulated and 1846 downregulated) in ADENO- compared to CONTROL-GESTorg. Between upregulated genes, CXCL14 restricts trophoblast invasion and outgrowth, CYP24A1 is increased in spontaneous miscarriage and preeclamptic placentas, and PTAFR induces preterm delivery in mice (log2 Fold Change [log2FC] = 1.6, 2.4, 0.8). Among downregulated genes, deregulated PGR expression has been related to severe preeclampsia and recurrent pregnancy loss, whereas defects on ZWINT, ESCO2 and MCM6 expression are associated with high incidence of aneuploidy, leading to miscarriage, infertility, and newborn disorders (log2FC = −2.21, -2.57, -2.53, -2.48). Functional analysis showed deregulated functions as blastocyst growth, in utero embryonic development, developmental maturation and response to oxidative stress, standing out for their possible involvement in pregnancy disorders. IPA predicted a significant inhibition of D-myo-inositol metabolism (z score [z] = −0.7) affecting oocyte and embryo quality, VEGF signaling (z = −1.5) disturbing trophoblast adaptation to hypoxia, ERK/MAPK signaling (z = −4.0) causing embryonic lethality due to placental alterations; and significant activation of PPARα/RXRα (z = 0.5) that gives rise to recurrent miscarriage and preeclampsia, p53 signaling (z = 1.1) related with preeclampsia-complicated pregnancies, and RHOGDI and PTEN signaling (z = 3.6, 3.4) both promoting preeclampsia. Limitations, reasons for caution Although organoid platforms faithfully recapitulate tissue of origin characteristics as well as disease-specific traits, they are still in vitro models that need to be translated into in vivo studies to further corroborate the results obtained. Wider implications of the findings Molecular mechanisms involved in impaired embryo development, pregnancy loss, preeclampsia and placental defects are deregulated in gestational phase endometrium of women with adenomyosis. These deregulated mechanisms could be therapeutic target to develop pharmacological treatments to ameliorate adenomyosis-related infertility. Trial registration number not applicable

Evaluating the characteristics of myocardial work by two-dimensional echocardiography during pre-eclampsia pregnancy.

This study aimed to analyze the changes in myocardial work (MyW) properties and the correlation of MyW with cardiovascular and clinical indices during the pre-eclampsia (PE) pregnancy. Standard two-dimensional and speckle-tracking echocardiography were sequentially performed on 77 women with PE and 89 with normal pregnancy. Four components of MyW: global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were measured. The significant increased GWI, GCW and GWW were observed, while GWW elevated more than GCW with consequently resulting the decline in GWE among PE cases. Although there was a diverse relationship between MyW components and LV morphological as well as functional indices, MyW parameters were significantly correlated with the grades of arterial hypertension and the incidence of adverse outcome of PE. With the hypertension stages, GWI, GCW and GWW gradually increased but GWE decreased. Meanwhile, the higher GWI and GCW and the lower GWE, the more adverse events occurred in PE group. In conclusion, during the PE pregnancy, GWI, GCW and GWW increase, while GWW elevates more than GCW, which leads to the decrease in GWE. Moreover, the changes in MyW are associated with the hypertension grades and the poor prognosis in PE. The non-invasive manner for MyW assessment provides a new perspective on the myocardial biomechanics, cardio-metabolic conditions and pathophysiological changes in the condition of PE.

Differences in Average Serum Cortisol Levels and Serum 25 Hydroxyvitamin D Levels in Preeclampsia and Normal Pregnancy

According to the World Health Organization, hypertension ranks second as the direct cause of maternal death in pregnancy; namely gestational hypertension (14%). Causes of maternal death in 2021 related to hypertension in pregnancy totaling 1,077 cases. Preeclampsia involves a number of biological processes that affect immune dysfunction, placental implantation, abnormal angiogenesis, excessive inflammation and high oxidative stress reactions and diseases related to maternal vascularization or blood vessels are possible contributing causes. Research with a case-control design was conducted at RSUP Dr. M. Djamil, RSIA Siti Hawa, and RSIA Cicik Padang from February 2021–August 2022. Preeclampsia and normal pregnancy research samples consisted of 27 case samples and 27 control samples. Serum cortisol levels and serum 25-hydroxyvitamin D levels were examined by the ELISA method. The Independent Sample T-Test was used to analyze the data. The mean difference in serum cortisol levels in preeclampsia was 48.70 ± 15.23 µg/dL, higher than that in normal pregnancy, 38.62 ± 8.27 µg/dL (p-value = 0.004, p <0.05). Differences The mean serum level of 25 Hydroxyvitamin D in preeclampsia was 13.63 ± 6.12 ng/ml, lower than that in normal pregnancy, 14.49 ± 3.94 ng/ml (p-value =0.539, p>0.05). The study concluded that there were differences in cortisol levels in preeclamptic pregnancies with normal pregnancies and there were no differences in serum levels of 25 Hydroxyvitamin D in preeclamptic pregnancies with normal pregnancies

Differential expression of the angiotensin receptors (AT1, AT2, and AT4) in the placental bed of HIV-infected preeclamptic women of African ancestry

The Renin-Angiotensin-Aldosterone System (RAAS) is implicated in the pathophysiology of preeclampsia (PE). There is a paucity of data on uteroplacental angiotensin receptors AT1-2 and 4. We evaluated the immunoexpression of AT1R, AT2R, and AT4R within the placental bed of PE vs. normotensive (N) pregnancies stratified by HIV status. Placental bed (PB) biopsies (n = 180) were obtained from N and PE women. Both groups were stratified by HIV status and gestational age into early-and late onset-PE. Immuno-labeling of AT1R, AT2R, and AT4R was quantified using morphometric image analysis. Immunostaining of PB endothelial cells (EC) and smooth muscle cells of spiral arteries (VSMC) displayed an upregulation of AT1R expression compared to the N group (p < 0.0001). Downregulation of AT2R and AT4R expression was observed in PE vs. N group (p = 0.0042 and p < 0.0001), respectively. AT2R immunoexpression declined between HIV+ve and HIV−ve groups, while AT1R and AT4R displayed an increase. An increase in AT1R expression was noted in the EOPE−ve/+ve and LOPE−ve/+ve compared to N−ve/N+ve. In contrast, AT2R and AT4R expression decreased in EOPE−ve/+ve and LOPE-ve/+ve compared to N−ve/N+ve. We demonstrate a significant downregulation of AT2R and AT4R with a concomitant elevated AT1R immunoexpression within PB of HIV-infected PE women. In addition, a decline in AT2R and AT4R with an increase in AT1R immunoexpression in PE, EOPE, and LOPE vs. normotensive pregnancies, irrespective of HIV status. Thus highlighting differential immunoexpression of uteroplacental RAAS receptors based on pregnancy type, HIV status, and gestational age.

Genetic Risk Factors Associated With Preeclampsia and Hypertensive Disorders of Pregnancy

A genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood. To disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy. This GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023. The association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes. A total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP). The findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.

Serum uric acid to creatinine ratio and risk of preeclampsia and adverse pregnancy outcomes.

Preeclampsia is one of the most severe diseases among the hypertensive disorders of pregnancy (HDP) and the leading cause of maternal and fetal morbidity and mortality. It is of crucial importance to early identify women at a high risk for preeclampsia to implement appropriate preventive strategies. In our study, we aimed to test the hypothesis that serum uric acid to creatinine ratio (SUA/sCr) is related to the development of preeclampsia and maternal and neonatal complications. We searched for uric acid and creatine values in the medical records of 269 women who consecutively attended our HDP Clinic from December 2018 to December 2022. We compared the baseline characteristics of participants with normotensive pregnancy ( n = 57), to those with HDP without preeclampsia (HDP-non-PE) ( n = 100) and those with preeclampsia ( n = 112), and we performed adjusted logistic regression analysis to test the associations between SUA/sCr and the development of preeclampsia and maternal and neonatal complications. SUA/sCr was consistently higher in women with preeclampsia in all trimesters of pregnancy. Higher SUA/sCr at the third trimester was associated with an increased odd of developing preeclampsia [odds ratio (OR) 1.29, confidence interval (CI) 1.15-1.50, P = 0.001], preterm birth (OR 1.23, CI 1.05-1.45, P = 0.011), and composite neonatal outcome (OR 1.33, CI 1.12-1.59, P = 0.001), after adjustment for age, BMI before pregnancy, nulliparity, antihypertensive therapy, and acetylsalicylic acid therapy during pregnancy. Having higher SUA/sCr during pregnancy is associated with the development of PE and adverse pregnancy outcomes. Controlled prospective studies are warranted to clarify the predictive power of this novel marker during pregnancy.

Modulation of NRF2/KEAP1 Signaling in Preeclampsia.

Placentation is a key and tightly regulated process that ensures the normal development of the placenta and fetal growth. Preeclampsia (PE) is a hypertensive pregnancy-related disorder involving about 5-8% of all pregnancies and clinically characterized by de novo maternal hypertension and proteinuria. In addition, PE pregnancies are also characterized by increased oxidative stress and inflammation. The NRF2/KEAP1 signaling pathway plays an important role in protecting cells against oxidative damage due to increased reactive oxygen species (ROS) levels. ROS activate NRF2, allowing its binding to the antioxidant response element (ARE) region present in the promoter of several antioxidant genes such as heme oxygenase, catalase, glutathione peroxidase and superoxide dismutase that neutralize ROS, protecting cells against oxidative stress damages. In this review, we analyze the current literature regarding the role of the NRF2/KEAP1 pathway in preeclamptic pregnancies, discussing the main cellular modulators of this pathway. Moreover, we also discuss the main natural and synthetic compounds that can regulate this pathway in in vivo and in vitro models.

MTHFR and ERVFRD-1 polymorphisms and preeclampsia risk in Iran population: A case-control study

Background and aimsPreeclampsia (PE) is a complicated disease during pregnancy that could be a risk factor for the mother's health and fetus. The mechanisms of PE pathogenesis might associate with some candidate gene polymorphisms. This study is aimed to evaluate the relation between MTHFR (C677T) MTHFR (A1298C) and ERVFRD-1 (rs9393931) single nucleotide polymorphisms (SNPs) and PE in our patients. Material and methodsThe present study was a case-control study carried out between January 2019 and January 2021, in the Kamali hospital, Karaj, Iran. A total of 104 pregnant women who were diagnosed with Preeclampsia clinically as a case, and 100 healthy pregnant women as a control group were compared for the study. ResultsThere was not a 39 T allele of the ERVFRD-1 gene was observed in this studied population. There was a significant difference in frequency of 677CT genotype in PE pregnant women compared to controls (P = 0.002). Also, our result indicated that the frequency of the MTHFR 1298C allele was found to be significantly higher in the control group than in the case group (P = 0.021). ConclusionOur results suggested that C677T polymorphism in MTHFR might be related to an increased risk of Preeclampsia in pregnancy.

Can M-30, M-65, and IL-6 serum levels be useful markers in the diagnosis of preeclampsia and gestational diabetes?

We aimed to evaluate the maternal and fetal serum M-30, M-65 and IL-6 levels in preeclampsia and gestational diabetes mellitus (GDM) in both maternal and cord blood. Women with preeclampsia (n=30), GDM (n=30), and uncomplicated pregnancy (n=28) were evaluated in a cross-sectional study. After clamping during delivery, the serum M-30, M-65, and IL-6 levels were measured in both maternal venous blood and cord blood. The serum M-30, M-65, and IL-6 levels were significantly higher in preeclampsia and GDM patients' maternal blood and cord blood samples compared to the control group. In the preeclampsia group, M-65 was significantly higher in cord blood compared with the level in maternal serum, but there was no significant difference between the GDM and control groups. The control group's IL-6 level in cord blood was statistically significantly lower than the other groups. Although the M-30 value in both maternal and cord blood was statistically lower in the control group than in the GDM group, there was no significant difference between the two groups when compared to the preeclampsia group. M-30 and M-65 molecules appear to have the potential to serve as biochemical markers in placental diseases, particularly preeclampsia and gestational diabetes. Due to the insufficient sample sizes, more research is needed.

The role of inflammatory biomarkers in the development and progression of pre-eclampsia: a systematic review and meta-analysis.

Pre-eclampsia (PE) is a pregnancy complication associated with maternal and fetal morbidity and mortality. Among the potential pathogenesis discussed, inflammation is considered an essential initiator of PE. Previous studies have compared the levels of various inflammatory biomarkers that indicate the existence of PE; however, the relative levels of pro-inflammatory and anti-inflammatory biomarkers and their dynamic changes during PE progression remain unclear. This knowledge is essential to explain the occurrence and progression of the disease. We aimed to identify the relationship between inflammatory status and PE using inflammatory biomarkers as indicators. We also discussed the underlying mechanism by which inflammatory imbalance contributes to PE by comparing the relative levels of pro-inflammatory and anti-inflammatory biomarkers. Furthermore, we identified additional risk factors for PE. We reviewed PubMed, Embase, and the Cochrane Library for articles published until 15th September 2022. Original articles that investigated inflammatory biomarkers in PE and normal pregnancy were included. We selected healthy pregnant women as controls. The inflammatory biomarkers in the case and control groups were expressed as standardized mean differences and 95% confidence intervals using a random-effects model. Study quality was assessed using the Newcastle-Ottawa Scale. Publication bias was assessed using Egger's test. Thirteen articles that investigated 2,549 participants were included in this meta-analysis. Patients with PE had significantly higher levels of C-reactive protein (CRP), interleukin (IL)-4, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF) than the controls. CRP and pro-inflammatory cytokine levels were higher than those of anti-inflammatory cytokines. Patients with gestational age > 34 weeks had significantly higher IL-6 and TNF levels. Patients with higher systolic blood pressure had significantly higher IL-8, IL-10, and CRP levels. Inflammatory imbalance is an independent risk factor for PE development. Impairment of the anti-inflammatory system is a crucial initiating factor for PE development. Failed autoregulation, manifested as prolonged exposure to pro-inflammatory cytokines, leads to PE progression. Higher levels of inflammatory biomarkers suggest more severe symptoms, and pregnant women after 34 weeks of gestation are more susceptible to PE.

ExoCounter Assays Identify Women Who May Develop Early-Onset Preeclampsia From 12.5 μL First-Trimester Serum by Characterizing Placental Small Extracellular Vesicles.

Preeclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. Identifying women with high risk of developing preeclampsia in early pregnancy remains challenging. Extracellular vesicles released from the placenta offer an attractive biomarker but have been elusive to quantify. Here, we tested ExoCounter, a novel device that immunophenotypes size-selected small extracellular vesicles <160 nm, for its ability to perform qualitative and quantitative placental small extracellular vesicles (psEV) analysis. To investigate disease-specific and gestational age-specific changes, we analyzed psEV counts in maternal plasma samples taken at each of the 3 trimesters from women who had (1) normal pregnancy (n=3); (2) women who developed early-onset preeclampsia (EOPE; n=3); and (3) women who developed late-onset preeclampsia (n=4) using 3 antibody pairs, CD10-placental alkaline phosphatase (PLAP), CD10-CD63, and CD63-PLAP. We further validated the findings in first-trimester serum samples among normal pregnancy (n=9), women who developed EOPE (n=7), and women who developed late-onset preeclampsia (n=8). We confirmed that CD63 was the major tetraspanin molecule coexpressed with PLAP-a known placental extracellular vesicles marker on psEV. Higher psEV counts for all 3 antibody pairs were detected in the plasma of women who developed EOPE than the other 2 groups in the first trimester, which persisted through the second and third trimesters. Significantly higher CD10-PLAP (P<0.01) and CD63-PLAP (P<0.01) psEV counts were validated in the serum of the first trimester of women who developed EOPE compared with normal pregnancy. Application of the ExoCounter assay developed here could identify patients at risk of developing EOPE in the first trimester, thereby providing a window of opportunity for early intervention.

The first-trimester serum high-temperature requirement protease A4 and uterine artery Doppler for the prediction of preeclampsia

The objective of this study was to investigate the predictive value of serum high-temperature requirement protease A4 (HtrA4) and the first-trimester uterine artery in predicting preeclampsia in singleton pregnancy. Pregnant women at gestational age 11–13+6 weeks, who visited the antenatal clinic at King Chulalongkorn Memorial Hospital, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University during April 2020–July 2021 were included. Serum HtrA4 levels and transabdominal uterine artery Doppler ultrasound were performed to evaluate this combination for calculating the predictive value of preeclampsia. While 371 singleton pregnant women enrolled in this study, 366 completed it. Thirty-four (9.3%) women had preeclampsia. Mean serum HtrA4 levels were higher in the preeclampsia group than in the control group (9.4 ± 3.9 vs 4.6 ± 2.2 ng/ml, p < 0.001). The mean uterine artery pulsatility index (UtA-PI) was higher in the group with early onset preeclampsia than in the control group (2.3 ± 0.5 vs 1.7 ± 0.5, p = 0.002). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 76.5%, 90.7%, 45.6%, and 97.4%, respectively, when using serum HtrA4 levels above 1.8 multiples of the median for the gestational age as a cut-off value for predicting preeclampsia. A combination of serum HtrA4 levels and UtA-PI > 95th percentile yielded sensitivity, specificity, PPV, and NPV of 79.4%, 86.1%, 37% and 97.6%, respectively, for the prediction of preeclampsia. A combination of serum HtrA4 levels and uterine artery Doppler in the first trimester had good sensitivity for predicting preeclampsia.

The role of serum markers PAPP-A β-hCG, AFP, and uE3 in predicting the risk of preeclampsia in early, middle, and late pregnancy.

Preeclampsia (PE) has adverse effects on pregnant women, fetuses, and newborns [1], and accounts for 3%-10% of pregnancy-related diseases globally. This study aimed to screen a series of prenatal markers (pregnancy-associated plasma protein [PAPP-A], β-human chorionic gonadotropin [β-hCG], alpha fetoprotein [AFP], and estriol [uE3]) to establish a risk model and evaluate the diagnostic values of the markers for predicting PE. Sixty-five pregnant women were enrolled in this study. They were divided into two groups containing healthy pregnant women (n= 51, the non-PE group) and pregnant women with PE (n= 14, the PE group). According to the stage of pregnancy, the pregnant women in each group were divided into early, middle, and late pregnancy groups for statistical analysis. The levels of PAPPA-A β-hCG, AFP, and uE3 were compared among these groups. Then, a risk model was established, and PE was diagnosed using receiver operating characteristic (ROC) curve results. In the early pregnancy group, the differences in the levels of PAPP-A, AFP, and uE3 between the PE and non-PE groups were statistically significant (P< 0.001, P= 0.029, and P= 0.033, respectively), while the difference in the single remaining marker was not statistically significant. A ROC curve analysis revealed that in early pregnancy, the sensitivity and specificity of PAPP-A were 76.5% and 71.4%, respectively, and the sensitivity and specificity of β-hCG were 82.4% and 57.1%, respectively. The sensitivity and specificity of the combination of the two markers for diagnosing PE were 86.3% and 57.1%, respectively. This study demonstrated that the combination of PAPP-A and β-hCG has diagnostic value for PE in pregnant women. Accordingly, we should formulate innovative PE screening strategies to target the prevention of PE and create important conditions for predictive and preventive personalized medical treatments.

Diffusion-Derived Vessel Density Computed From a Simplified Intravoxel Incoherent Motion Imaging Protocol in Pregnancies Complicated by Early Preeclampsia: A Novel Biomarker of Placental Dysfunction.

Early preeclampsia is associated with significant placental hypoperfusion. We explore the diagnostic value of placental diffusion-derived vessel density (DDVD), a biomarker derived from diffusion-weighted magnetic resonance imaging, which measures in vivo vessel microperfusion, in the differential diagnosis of normal and early preeclampsia pregnancies. This was a prospective study involving 29 controls and 17 singleton pregnancies affected by early preeclampsia. Nineteen pregnancies from 28 to 34 weeks of gestational age were included from the normal group for a comparison with the early preeclampsia group. Using a 3.0 T magnetic resonance imaging scanner, diffusion-weighted images were obtained with the diffusion weighting b values of 0, 20, and 40 s/mm2. DDVDmean was the mean of DDVDb0b20 and DDVDb0b40, while DDVDb0b20 and DDVDb0b40 refer to the diffusion-derived vessel density values computed from b=0 and 20 s/mm2 images, and from b=0 and 40 s/mm2 images, respectively. The correlation between DDVDmean and gestational age was examined using a linear regression model. The area under the curve of the DDVDmean for early preeclampsia pregnancies detection was calculated by the receiver operating characteristic analysis. As gestational age increased, DDVDmean linearly decreased. DDVDmean was significantly decreased in the early preeclampsia pregnancies compared with the normal pregnancies (52.72±46.73 versus 213.34±93.50 au/pixel; P<0.001). The area under the curve (DDVDmean) for discriminating between normal and early preeclampsia pregnancies regardless of fetal growth restriction was 0.954, and the area under the curve was 1.000 when early preeclampsia pregnancies without fetal growth restriction were excluded. DDVDmean, an in vivo vessel microperfusion measure, allowed total separation of normal and early preeclampsia pregnancies.

Relationship between Detection of Preeclampsia High-Risk by Pregnant Women and Health Workers with the Success of the Preeclampsia Eradication Program at the Nogosari Health Center

The background of Preeclampsia Eradication Program is a program that seeks to accelerate the reduction in the incidence of preeclampsia in pregnancy, delivery and postpartum as well as comprehensive management of preeclampsia events, so that it is expected to reduce the number of maternal mortality rates (MMR). In Boyolali, Indonesia, the number of MMR in 2020 was 17 cases, where one of the causes of death was preeclampsia. Efforts are being made by the government to reduce MMR and infant mortality due to preeclampsia in pregnancy with the preeclampsia eradication program which began in 2018. The purpose of the study was to determine the relationship between detection of preeclampsia high-risk by pregnant women and health workers with increasing the success of the Eradication Program at the Nogosari Health Center. Research design Quantitative research that uses correlation analysis by using the approach retrospective. The results of data analysis using chi-square obtained results of detection of preeclampsia high-risk by pregnant women obtained the value of p-value 0.00 while for FIGO screening by health workers obtained a value of p-values 0.00. The results of the study showed that the variable detection of preeclampsia by pregnant women, FIGO screening by health workers had a significant relationship with the success of the preeclampsia eradication program with p value = 0.000, p = 0.000. where most of the respondents had poor knowledge as many as 40 respondents (66.7%), while for FIGO screening by health workers the score was obtained p-value 0.00 &lt; 0.05 where most of the respondents, namely 41 respondents (68.3%) received incomplete FIGO screening.

Long Non-Coding RNA Nuclear Paraspeckle Assembly Transcript 1: A Regulator of Trophoblast Cells in the Progression of Gestational Diabetes Mellitus

The potential function of NEAT1 in the progression of Gestational diabetes mellitus (GDM) and the molecular mechanisms are explored. NEAT1 levels in multiple types of cell lines and placental tissues collected from healthy, GDM and preeclampsia pregnancies were detected by quantitative real-time polymerase chain reaction (qRT-PCR). After intervening NEAT1 level in HTR-8/SVneo cells, proliferative, migratory and apoptotic potentials were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU), transwell assay and flow cytometry. The regulatory effect of NEAT1 on the transcriptional activity of NSD1 was predicted by bioinformatic analysis and further confirmed by dual-luciferase reporter assay. In addition, histone modifications of NEAT1 on NSD1 transcription were examined by chromatin immunoprecipitation (ChIP). NEAT1 was upregulated in placental tissues collected from GDM patients. Overexpression of NEAT1 stimulated proliferative and migratory potentials, but inhibited apoptosis in HTR-8/SVneo cells. Knockdown of NEAT1 had the opposite outcomes. NEAT1 was able to regulate the transcriptional activity of NSD1 through histone modifications on H3K27Me3 and H3K27Cro. NEAT1 is upregulated in GDM cases, which triggers proliferative and migratory potentials in trophoblast cells mainly through regulating transcriptional activity of NSD1 via histone modification.

Adverse Maternal Outcomes Associated With Gestational Weight Gain in Women With Polycystic Ovarian Syndrome [ID: 1377702

INTRODUCTION: The objective of this study was to investigate maternal complications associated with gestational weight gain (GWG) in women with a history of polycystic ovarian syndrome (PCOS). METHODS: This was a retrospective cohort analysis using data abstracted from the California Office of Statewide Health Planning and Development (OSHPD) Linked Birth File with hospital discharge International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnoses between 2007 and 2012. Pregnancies in women with a history of PCOS were stratified based on the Institute of Medicine 2009 recommendations for GWG as follows: appropriate weight gain, excessive weight gain, inadequate weight gain, or weight loss. The maternal outcomes of interest included preeclampsia, cesarean delivery, blood transfusion, and intensive care admission. Logistic regression analysis was performed to estimate the odd ratio of the outcomes of interest for each GWG stratum in pregnancies with and without PCOS, with adjustments for confounding variables. RESULTS: There were 3,161,821 pregnancies, with 4,233 women with history of PCOS. The risk of cesarean delivery for women in the excessive weight gain cohort without PCOS was 1.35% versus 1.68% in the PCOS group (P&lt;.001, 95% CI [1.38–2.04]). There were no significant differences in cesarean delivery rate for women with PCOS in the inadequate weight gain or weight loss groups. There were no statistically significant differences for preeclampsia, blood transfusion, and intensive care admission in pregnancies with and without PCOS based on GWG. CONCLUSION: In pregnancies affected by PCOS, excessive weight gain is associated with increased risk of cesarean delivery compared to women without PCOS.

Diastolic deceleration area in the fetal MCA: a new Doppler parameter

Objective Doppler velocimetry has been widely used throughout the years as a valuable tool in the follow-up and prognosis of various pregnancy complications. Numerous Doppler indices have been introduced to qualitatively describe fetal blood flow. Currently, the Pulsatility index (PI) is the most widely used index for this purpose. In current clinical practice, middle cerebral artery (MCA) PI measurement is commonly used to assess fetal well-being, especially in late-onset fetal growth restriction (FGR). However, existing evidence suggests that MCA PI alone is inferior to the ratio between MCA and umbilical artery (UA) pulsatility indices in predicting adverse perinatal and neonatal outcomes. When comparing normal and abnormal MCA Doppler waveforms, it is evident that most changes appear in the diastolic part of the heart cycle. Therefore, the PI, which contains elements from both systole (peak systolic velocity–PSV) and diastole (end-diastolic velocity), may not be the most effective tool for quantifying fetal brain sparing (BS). Methods We hypothesize that another measurement modality that focuses predominantly on the diastole could be more efficient for evaluating the amount of vasodilatation. In ultrasound velocimetry of larger blood vessels, there is a well-known phenomenon called “dicrotic notch” (DN), which appears on the declining part of each Doppler waveform and can be used to precisely pinpoint the end of systole and the start of diastole. We hypothesized that the extent of cerebral vasodilation can be more accurately assessed by measuring the area between the dicrotic notch (DN) and the end-diastolic velocity (which we refer to as the “diastolic deceleration area–DDA”). In this study, we introduced a new Doppler parameter along with a rationale for DDA measurement in the fetal MCA. We also defined third-trimester nomograms and provided a preliminary assessment of the correlation between DDA and fetal oxygen deficiency. Results Our findings suggest that the DDA may serve as an independent instrument for identifying hypoxia during late pregnancy, either on its own or in conjunction with other Doppler and cardiotocography modalities. Conclusion However, before incorporating DDA into clinical practice, it is crucial to conduct further research and validation studies with larger sample sizes and more diverse populations. This would help assess the generalizability of the results and establish optimal cutoff points for DDA in various clinical settings. It is also important to prospectively study the role of DDA in early- and late-onset fetal growth restriction (FGR), Rh-isoimmunization/anemia, preeclampsia, gestational diabetes, and other pregnancy complications. In fact, we believe that the concept of measuring specific areas in arterial Doppler velocimetry indices could have significant implications not only in fetal medicine and obstetrics, but also in other areas of human and veterinary medicine.