Factors In Preeclampsia Research Articles

Genetic polymorphisms associated with preeclampsia risk in Nigerian women

BackgroundPreeclampsia, a complex hypertensive disorder unique to pregnancy, significantly impacts maternal and fetal health worldwide, with a prevalence of 2–8%. This condition results from a complex interplay of genetic, environmental, and immunological factors.Aim and objectivesThis study aims to investigate the genetic predispositions to preeclampsia, focusing on specific gene polymorphisms among pregnant women at Central Hospital Auchi, Nigeria.Materials and methodsWe examined the endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), angiotensin-converting enzyme (ACE), and tumor necrosis factor-alpha (TNF-α) genes in 200 pregnant women, equally divided between preeclamptic patients and normotensive controls.ResultsThe eNOS G894T polymorphism was significantly associated with preeclampsia, with the T allele nearly doubling the risk. The VEGF C936T polymorphism's T allele also indicated a higher risk. The D allele in the ACE gene's insertion/deletion (I/D) polymorphism significantly increased the risk, as did the A allele in the TNF-α G308A polymorphism.ConclusionsThese findings highlight the importance of genetic factors in preeclampsia and suggest that genetic screening could improve risk stratification and early detection. Future research should integrate genetic, epigenetic, and environmental data to understand preeclampsia's multifaceted nature and develop targeted therapies. This study underscores the potential of personalized medicine in managing and reducing the risks associated with preeclampsia.

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.

Clinical Analysis of Serum Soluble Tyrosine Kinase Receptor-1 and Placental Growth Factor in Pre-eclampsia

Objective: To study the clinical application effect of using serum soluble tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) in pre-eclampsia. Methods: From September 2021 to September 2023, 58 cases of pre-eclampsia patients who underwent physical examination during pregnancy and eventually gave birth in Xinghua People’s Hospital were the observation group of this study and 795 cases of healthy pregnant women who underwent pregnancy examination in this hospital during the same period of time were the control group of this study; 38 cases of mild pre-eclampsia in the observation group were treated as the mild group and 20 cases of severe pre-eclampsia patients were treated as the severe group and the serum sFlt-1 and PlGF were used to compare the results of the observation group and the control group. Compare the serum sFlt-1 and PlGF levels between the observation and control groups; compare the serum sFlt-1 and PlGF levels between the mild and severe groups. Results: The serum PlGF level of the observation group was lower than that of the control group, and the sFlt-1 level was higher than that of the control group, P < 0.05; the serum PlGF level of the mild group was higher than that of the severe group, and the sFlt-1 level was lower than that of the control group, P < 0.05; the results showed that the serum and urine sFlt-1 and PlGF levels of pregnant women of all the three groups were elevated with the aggravation of the condition of pre-eclampsia, and the sFlt-1/PlGF ratio also increased. The differences of sFlt-1/PlGF in serum and urine of the three groups were compared, with P < 0.05; the above ratios of the patients in the mild group were higher than those of the control group and those of the severe group were higher than those of the mild group, with P < 0.05. Conclusion: Serum sFlt-1 level was high in preeclamptic patients, while serum PlGF was low in preeclamptic patients.

Bowtie Nanoantenna LSPR Biosensor for Early Prediction of Preeclampsia.

The concentration of the placental circulating factor in early pregnancy is often extremely low, and the traditional prediction method cannot meet the clinical demand for early detection preeclampsia in high-risk gravida. It is of prime importance to seek an ultra-sensitive early prediction method. In this study, finite-different time-domain (FDTD) and Discrete Dipole Approximation (DDA) simulation, and electron beam lithography (EBL) methods were used to develop a bowtie nanoantenna (BNA) with the best field enhancement and maximum coupling efficiency. Bio-modification of the placental circulating factor (sFlt-1, PLGF) to the noble nanoparticles based on the amino coupling method were explored. A BNA LSPR biosensor which can specifically identify the placental circulating factor in preeclampsia was constructed. The BNA LSPR biosensor can detect serum placental circulating factors without toxic labeling. Serum sFlt-1 extinction signal (Δλmax) in the preeclampsia group was higher than that in the normal pregnancy group (14.37 ± 2.56 nm vs. 4.21 ± 1.36 nm), p = 0.008, while the serum PLGF extinction signal in the preeclampsia group was lower than that in the normal pregnancy group (5.36 ± 3.15 nm vs. 11.47 ± 4.92 nm), p = 0.013. The LSPR biosensor detection results were linearly consistent with the ELISA kit. LSPR biosensor based on BNA can identify the serum placental circulating factor of preeclampsia with high sensitivity, without toxic labeling and with simple operation, and it is expected to be an early detection method for preeclampsia.

MicroRNA-223-3p downregulates the inflammatory response in preeclampsia placenta via targeting NLRP3

ObjectiveTo investigate the regulatory role of miR-223-3p in the inflammatory response of PE placenta.MethodsPE and normal placental tissues were collected to measure the expression of NLRP3 and miR-223-3p. The targeting relationship between NLRP3 and miR-223-3P was verified by bioinformatics analysis and classical double-luciferase reporter gene assay. Lipopolysaccharide (LPS) was used to induce HTR8/SVneo cells as PE placental cell inflammation model. Then we transfected miR-223-3p overexpression/miR-223-3p negative control plasmid into the LPS-induced HTR8/SVneo cells. Next, the expressions of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 were evaluated to elucidate the regulatory effect of miR-223-3p on the inflammatory response mediated by NLRP3 in PE placenta.ResultsCompared with normal controls, NLRP3 was significantly up-regulated in PE placenta, while miR-223-3p was down-regulated. In addition, NLRP3 was a direct target of miR-223-3p. Further research revealed that the expression of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 could be obviously promoted in HTR8/SVneo cells treated with LPS (500 ng/ml) for 24 h, nevertheless it could be significantly suppressesed under the overexpression of miR-223-3p.ConclusionMiR-223-3p suppressed NLRP3 inflamariomes activation, downstream inflammatory factors secretion and pyroptosis in LPS-induced HTR8/SVneo cells indicating that miR-223-3p could serve as an anti-inflammatory factor in preeclampsia.

SFRP2 suppresses trophoblast cell migration by inhibiting the Wnt/β‑catenin pathway.

The present study investigates the role of Secreted Frizzled‑Related Protein 2 (SFRP2) in trophoblast cells, a key factor in preeclampsia (PE) progression. Elevated levels of Secreted Frizzled‑Related Protein 1/3/4/5 (SFRP1/3/4/5) are associated with PE, but the role of SFRP2 is unclear. We analyzed SFRP2 expression in PE placental tissue using the GSE10588 dataset and overexpressed SFRP2 in JEG‑3 cells via lentiviral transfection. The viability, migration, apoptosis, and proliferation of SFRP2‑overexpressing JEG‑3 cells were assessed using Cell Counting Kit‑8, Transwell assays, flow cytometry, and EdU staining. Additionally, we evaluated the impact of SFRP2 overexpression on key proteins in the Wnt/β‑catenin pathway and apoptosis markers (Bax, cleaved‑caspase 3, BCL‑2, MMP9, E‑cadherin, Wnt3a, Axin2, CyclinD1, c‑Myc, p‑β‑catenin, β‑catenin, phosphorylated Glycogen Synthase Kinase 3 beta (p‑GSK3β), and GSK3β) through western blotting. Results showed high SFRP2 mRNA and protein expression in PE placenta and JEG‑3 cells post‑transfection. SFRP2 overexpression significantly reduced JEG‑3 cell viability, proliferation, and migration, while increasing apoptosis. It also altered expression levels of Wnt pathway proteins, suggesting SFRP2's potential as a therapeutic target for PE by inhibiting trophoblast cell migration through the Wnt/β‑catenin signaling cascade.

Modeling risk factors in preeclampsia for late pregnancies using fuzzy cognitive maps

As women delay motherhood, concerns arise about the risks associated with pregnancy at advanced ages. Pregnant women aged 35 and older face an increased likelihood of complications, such as spontaneous abortions and preexisting conditions that can complicate pregnancy, such as hypertension and diabetes. The incidence of hypertensive disorders, such as preeclampsia, also significantly increases in this age group, which can lead to a higher use of cesarean sections and instrumental deliveries, as well as an increase in neonatal morbidity and mortality. This study aims to model the risk factors for preeclampsia in late pregnancies using fuzzy cognitive maps, seeking a better understanding of the complexity of this condition and facilitating the early identification of women at risk. Data collection will be conducted through the review of clinical records and structured interviews with participants, which will complement the existing clinical information. The identification of risk factors, such as obesity and a history of hypertension, is crucial for optimizing prenatal care and improving maternal-fetal outcomes. Additionally, prevention strategies are proposed that include education about the risks, promoting healthy lifestyle habits, and ensuring access to adequate prenatal care, in order to reduce the incidence of preeclampsia and its associated complications in pregnant women aged 35 and older

The significance of mitochondrial haplogroups in preeclampsia risk

ObjectiveTo determine whether mitochondrial haplogroups function as disease-modifiers or as susceptibility factors in preeclampsia using a traditional haplogroup association model. MethodsThis retrospective study haplotyped 235 control and 78 preeclamptic pregnancies from Denmark using either real-time PCR or Sanger sequencing depending on the rarity of the haplogroup. ResultsNo significant association between haplogroups and the risk of preeclampsia was found, nor was any role for haplogroups in disease severity uncovered. ConclusionMitochondrial haplogroups are not associated with preeclampsia or the severity of preeclampsia in the Danish population. However, this study cannot exclude a role for less common mtDNA variation. Models that can examine these should be applied in preeclamptic patients.

Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia.

Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial decidualization and spiral artery remodeling are important contributing factors in preeclampsia, a major disorder in pregnancy. Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood volume and pressure. ANP is also generated in non-cardiac tissues, such as the uterus and placenta. In recent human genome-wide association studies, multiple loci with genes involved in natriuretic peptide signaling are associated with gestational hypertension and preeclampsia. In cellular experiments and mouse models, uterine ANP has been shown to stimulate endometrial decidualization, increase TNF-related apoptosis-inducing ligand expression and secretion, and enhance apoptosis in arterial smooth muscle cells and endothelial cells. In placental trophoblasts, ANP stimulates adenosine 5'-monophosphate-activated protein kinase and the mammalian target of rapamycin complex 1 signaling, leading to autophagy inhibition and protein kinase N3 upregulation, thereby increasing trophoblast invasiveness. ANP deficiency impairs endometrial decidualization and spiral artery remodeling, causing a preeclampsia-like phenotype in mice. These findings indicate the importance of natriuretic peptide signaling in pregnancy. This review discusses the role of ANP in uterine biology and potential implications of impaired ANP signaling in preeclampsia.

Extended combined screening for preeclampsia prediction in women with diabetes mellitus

BACKGROUND:Early screening for preeclampsia has shown high efficiency for low-risk groups, however, the presence of systemic vascular disease in patients with diabetes mellitus complicates their use and requires the development of additional approaches to predicting preeclampsia in this group of patients.
 AIM:The aim of this study was to evaluate the effectiveness of early prediction of preeclampsia with extended combined screening in patients with pregestational types of diabetes mellitus.
 MATERIALS AND METHODS:This study included 75 pregnant women: 40 patients with type 1 diabetes mellitus, and 35 patients with type 2 diabetes mellitus. To determine the risk of further preeclampsia development, we evaluated biochemical, biophysical and anamnestic factors, along with the serum levels of placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin at 11+0to 13+6gestational weeks. The main outcome assessed was the development of preeclampsia.
 RESULTS:In patients with further development of preeclampsia (35% in type 1 and 40 % in type 2 diabetic women), we observed higher soluble fms-like tyrosine kinase 1 / placental growth factor ratios, as well as elevated serum soluble endoglin (type 1 diabetes mellitus) and soluble fms-like tyrosine kinase 1 (type 2 diabetes mellitus) levels. Isolated determination of placental growth factor showed no significant differences in the levels of this angiogenic factor in preeclampsia. A multivariate predictive model for preeclampsia demonstrated high prognostic parameters: for patients with type 1 diabetes mellitus, area under the curve was 0.96 (95% confidence interval 0.931.00), with positive predictive value 76.7% and negative predictive value 90.1%; for patients with type 2 diabetes mellitus, area under the curve was 0.94 (95% confidence interval 0.861.00), with positive predictive value 88.5% and negative predictive value 97.1%.
 CONCLUSIONS:Specific biochemical and biophysical markers of preeclampsia combined with maternal risk factors and assessment of carbohydrate metabolism can increase the predictive value of early screening studies for preeclampsia in women with pregestational diabetes mellitus.

Identification of vascular endothelial growth factor in preeclampsia in Iraqi women.

Preeclampsia (PE) is a major obstetric syndrome and represents a pregnancy hypertensive disease affecting about 2-8% of pregnancies. Typically, it occurs after 20 weeks of pregnancy, being classified as early or late in accordance with the gestational age at diagnosis or delivery. An imbalance between angiogenic and antiangiogenic factors has an important role in the pathophysiology of PE. It was hypothesized that the dysfunctional endothelium contributes to the pathogenesis of PE. A change in the production of Vascular endothelial growth factor (VEGR), a biomarker of endothelial dysfunction, is associated with this disease, whether presenting an increase, decrease, or being at a normal level. This study examined the associations between VEGF and preeclampsia and the importance of this VEGF as a predictor of its severity. This case-control study included 50 patients with preeclampsia and 50 normotensive pregnant women in the control group. Venous blood was aspirated from each patient, and VEGF levels were measured from sera. The mean VEGF for patients with mild PE was 29.410±18.976 pg/ml, for those with severe PE it was 36.188±36.98 pg/ml, and for normotensive women it was 92.104±154.715 pg/ml. There were significant differences in VEGF levels between the studied groups (P=0.024). This study showed that serum VEGF levels were significantly reduced in patients with preeclampsia compared with normotensive pregnant women, suggesting marked endothelial dysfunction. This led to widespread vasoconstriction and, in turn, caused hypertension and proteinuria.

Decidual dendritic cells 10 and CD4+CD25+FOXP3 regulatory T cell in preeclampsia and their correlation with nutritional factors in pathomechanism of immune rejection in pregnancy

BackgroundImmune intolerance is thought to be the underlying cause of immune rejection to fetus in preeclampsia. Decidual dendritic cell-10 (DC-10) and T regulator cell (Treg) play important role to create tolerogenic environment during pregnancy. However, their roles on the specific pathomechanism of preeclampsia along with various nutritional factors have not been widely studied. AimTo determine the number of DC-10 and Treg in preeclampsia and their correlations with decidual nutritional factors. MethodThis was a cross-sectional study among early onset preeclampsia (EOPE), late onset preeclampsia (LOPE), and normotensive (NT) pregnancies. Decidual specimens were obtained by curettage after caesarean section. The number of DC-10 and Treg cells were counted using flow cytometry. The levels of nutritional factors (zinc, retinol, all-trans retinoic acid, vitamin D) were determined using ICP-MS and LC-MS method. ResultA total of 14 subjects for each group were included in the study. The DC-10 was significantly lower in both EOPE and LOPE compared to NT (p < 0.001). Treg cells were significantly higher in EOPE compare to NT (p = 0.015). There was a moderate correlation between zinc level and DC-10 (p = 0.011) and a strong correlation between retinol level and DC-10 (p = 0.002) in the NT group. A moderate correlation was found between vitamin D level and Treg cells in the NT group (p = 0.026). ConclusionThere was a lower number of DC-10 and higher number of Treg cells in early preeclampsia. There was no correlation between DC-10 and Treg number with decidual nutritional factors in preeclampsia.

Characterization of the MG828507 lncRNA Located Upstream of the FLT1 Gene as an Etiology for Pre-Eclampsia.

Background: FLT1 is one of the significantly overexpressed genes found in a pre-eclamptic placenta and is involved with the etiology of this disease. Methods: We conducted genome-wide expression profiling by RNA-seq of placentas from women with pre-eclampsia and those with normotensive pregnancy. Results: We identified a lncRNA gene, MG828507, located ~80 kb upstream of the FLT1 gene in a head-to-head orientation, which was overexpressed in the pre-eclamptic placenta. MG828507 and FLT1 are located within the same topologically associated domain in the genome. The MG828507 mRNA level correlated with that of the FLT1 in placentas from pre-eclamptic women as well as in samples from uncomplicated pregnancies. However, neither the overexpression nor knockdown of MG828507 affected the expression of FLT1. Analysis of pre-eclampsia-linking genetic variants at this locus suggested that the placental genotype of one variant was associated with the expression of MG828507. The MG828507 transcript level was not found to be associated with maternal blood pressure, but showed a relationship with birth and placental weights, suggesting that this lncRNA might be one of the pivotal placental factors in pre-eclampsia. Conclusion: Further characterization of the MG828507 gene may elucidate the etiological roles of the MG828507 and FLT1 genes in pre-eclampsia in a genomic context.

Expression level of immune checkpoint inhibitory factors in preeclampsia

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation.

P-381 A novel natural cycle proliferative phase/progesterone replacement(NC/PR) protocol for endometrial preparation for frozen-thawed embryo transfer(FET) Can it improve pregnancy outcomes : a prospective comparative study

Abstract Study question Can a novel protocol for endometrial preparation- NC/PR-FET, lead to better pregnancy outcomes than artificial cycle (AC)-FET, with similar ease of cycle monitoring and scheduling? Summary answer NC/PR-FET protocol gave comparable clinical pregnancy rates (CPR), significantly less early miscarriage rates (MR) and significantly more live birth rates (LBR) compared to AC-FET protocol. What is known already AC-FET is the most common protocol for endometrial preparation due to flexibility, easy monitoring, and high pregnancy rates albeit with evidence of higher obstetrical risks e.g., miscarriage, pre-eclampsia versus NC-FET. This risk could be due to suboptimal hormonal administration in AC-FET leading to impaired endometrial maturation, predecidualization, and altered endometrial function. Studies indicate, estradiol may have a stronger negative effect(versus progesterone) on the endometrial transcriptome. Hence, we studied a novel protocol with NC-estrogen (but with progesterone similar to AC-FET), for better endometrial maturation, predecidualization along with simple monitoring and flexible ET scheduling. Previously, a proof-of-concept case-series has been reported. Study design, size, duration The prospective comparative study was conducted at a tertiary center (Jan2019-Dec2021) with 126 patients (both autologous [AO] and donor oocytes [DO]):79 (AC-FET) and 47 (NC/PR-FET) with similar ICSI, vitrification, ET protocols. 2 or 3 Grade A cleavage stage embryos were transferred. CPR, implantation rates(IR), early MR (≤13 weeks, miscarriages/clinical pregnancies) and LBR (≥28 weeks, LBs/ETs) were compared. Serum progesterone was studied on day 5 post-ET. Antenatal care and most deliveries were at the same institute. Participants/materials, setting, methods Patients were non-smokers with normal hysteroscopy. In AC-FET, oral estradiol (6-8mg) was initiated from day 1-2 (for 10-17 days). In both groups, when endometrium ≥7mm and S.progesterone&amp;lt;1ng/ml, intramuscular progesterone was initiated(daily till day 4 post-ET, then every 3rd day till week 8). ET was scheduled on day 4 of intramuscular progesterone, and concurrently, vaginal progesterone was added (till week 10). Chi-square, t-tests, and multiple regression was used for statistical analysis and 2-tailed P &amp;lt;.05 indicated statistical significance. Main results and the role of chance Mean age and BMI were comparable in NC/PR-FET and AC-FET groups: 34.48±4.69 years vs. 33.58 ± 5.62 years (P =.35) and 26.27 ± 3.62 kg/m2 vs. 27.34 ± 4.61kg/m2 (P =.18) respectively. Similarly, the source of oocytes (%AO) and % singletons were also comparable in NC/PR-FET and AC-FET groups: 57.4% vs. 46.8% (P = .25), and 78.1% vs. 75% (P= .75) respectively. There were 3 ectopic pregnancies overall. The CPRs and IRs were comparable: 68.09% (NC/PR-FET) vs. 60.76% (AC-FET) (P=.41) and 32.30% (NC/PR-FET) vs. 28.96% (AC-FET) (P=.45) respectively. The early MR was significantly more in AC-FET vs. NC/PR-FET: 29.17% vs. 6.25% (P =.012). Consequently, LBRs were significantly more in NC/PR-FET vs. AC-FET: 59.57% vs. 39.24% (P =.028). After adjusting for age, BMI, AO/DO, this difference remained significant (AOR 2.66; 95% CI 1.21-5.81; P =.014) Mean serum progesterone was comparable in all patients in both groups: 38.50 ± 13.6ng/ml (NC/PR-FET) vs. 40.98 ± 28.64 ng/ml (AC-FET) (P =.57). Serum progesterone levels were also comparable in patients who were pregnant in both groups: 38.51 ± 14.79 (NC/PR-FET) vs. 42.25 ± 32.63 (AC-FET) (P =.53).Also, in the AC-FET group serum progesterone was comparable in patients who aborted,44.23 ± 31.60 vs. those who didn’t, 41.48 ± 33.44 (P =.79). Limitations, reasons for caution This was a single center study. Due to limited sample size, we could not control for many potential confounders (e.g., multiple pregnancies). For the same reason, we could not compare obstetrical risks as a study outcome. Wider implications of the findings This study shows significantly better pregnancy outcomes with a novel NC/PR-FET protocol vs. AC-FET. This needs to be validated in larger studies. Since suboptimal hormone administration in AC-FET could be causal factor for pre-eclampsia, larger studies can test if the NC/PR-FET protocol can lead to better obstetrical outcomes. Trial registration number not applicable

The association between chronic liver diseases and preeclampsia

BackgroundPreeclampsia is a multisystem disorder characterized by an abnormal vascular response to placentation associated with increased systemic vascular resistance. As liver involvement is one of the main clinical features of preeclampsia, we sought to determine if there is an association between chronic liver diseases and preeclampsia.MethodsA retrospective matched case–control analysis was conducted in a tertiary medical center. Three hundred eleven (311) pregnant women with preexisting chronic liver disease (study group), including viral and autoimmune hepatitis, non-alcoholic fatty liver, Wilson disease, and cirrhosis, were match for age, parity, and number of fetuses to 933 healthy pregnant women (control group). The primary outcome measure was the incidence of preeclampsia in each group. Secondary outcome measures were obstetrical and neonatal complications. Confounders found to be significant on univariate analysis were evaluated using logistic regression models, and odds ratios (OR) and confidence intervals (CI) were calculated.ResultsPreeclampsia was diagnosed in 28 women (9.0%) in the study group and 33 women (3.54%) in the control group (p < 0.001).On multivariate analysis adjusted for maternal age, parity, previous preeclampsia, chronic hypertension, gestational diabetes mellitus, pregestational diabetes mellitus, antiphospholipid syndrome, and mode of conception, chronic liver disease was found to be an independent risk factor for preeclampsia (aOR 2.631, 95% CI 1.518–4.561). Although there was no difference in the gestational week at delivery between the groups (38.6 ± 2.13 vs. 38.8 ± 2.17 for study and control group, respectively, p = 0.410), the study group had a lower mean neonatal birthweight (3088 ± 551 vs. 3182 ± 566 g, p = 0.011). There were no between-group differences in the other parameters evaluated.ConclusionIn our study, preexisting chronic liver disease was associated with a 2.6-fold increased risk of preeclampsia.

MO080: Pre-Eclampsia in Patients With Chronic Kidney Disease (CKD)

Abstract BACKGROUND AND AIMS CKD is a significant risk factor for preeclampsia (PE). However, the features of PE in this cohort of patients (pts) have not been previously studied in detail. In this regard, the analysis of PE in pts with CKD is of great clinical and social importance. The aim of the study is to analyze the incidence and characteristics of PE in pts with CKD METHOD A retrospective analysis of 60 case histories of pregnant women with CKD (1–4 stages) was carried out, 27 of which had CKD st. 3a-4, followed in the dedicated center from 2018 to 2021. About 10 (37%) women with CKD 3a-4 developed PE, then the course of their pregnancy was analyzed. Indicators of creatinine, proteinuria and blood pressure were assessed at the time of the first visit to the center and further at the time of PE. The physiological response of the kidneys to pregnancy was assessed in six women in whom the value of creatinine before pregnancy was known as a decrease in creatinine concentration by 10% from the initial (before pregnancy). In 6 out of 10 women, the baseline pre-gestational SCr was available, and the physiological kidney response to pregnancy, which was considered as a persistent decrease in SCr by at least 10% from the baseline level, was assessed. In four pts, there was no information about blood creatinine before pregnancy. RESULTS In the group of pts with PE and advanced CKD, the mean age was 32.3 (±4.8) years (from 28 to 42 years). The most common cause of CKD was GN—6 (60%) and one each—tubulointerstitial nephritis, diabetic nephropathy, aHUS, APS-associated nephropathy. CKD C3a: 4 (40%) pts, C3b: 3 (30%) and C4: 3 (30%) pts. Complicated obstetric history (PE, antenatal fetal death) had 3 (30%) of 10 pts. The mean term of gestation at the time of first visit to nephrologist was 15.6 weeks. At the first measurement during pregnancy, the mean Scr was 157 (±69) μmol/L; the physiological response of the kidneys to pregnancy was noted only in 1 out of 6 pts. The mean proteinuria was 1.2 (±0.8) g/L. Arterial hypertension had 3 (30%) pts and only 1 woman received antihypertensive therapy before pregnancy with the achievement of target BP values. The mean blood pressure at the first visit was: SBP 131 (±11.5)/DBP 84 (±7.3) mm. Hg. Aspirin for the prevention of PE was prescribed in a timely manner in six cases (60%); in 4 pts (40%) aspirin was either not prescribed or was added to therapy after 12 weeks of pregnancy. Anticoagulant therapy with LMWH was prescribed before 28 weeks of gestation for patients with PU &amp;gt;1 g/day (seven cases). Combined antiplatelet and anticoagulant therapy was performed in 4 (40%) cases. PE before 34 weeks of gestation (early PE), developed in 7 (70%) pts, and the mean term for the development of PE was 31.3 weeks [27; 36.5]. The mean blood pressure at the moment of PE was 142 (±17)/90 (±10.6) mm Hg. The majority of women showed an increase in proteinuria (Table 1). The development of AKI was noted in six cases (Table 1). Another sign of a severe course of PE was thrombocytopenia in two cases (less than 100 thousand in 1 μL), in one of them as the part of HELLP syndrome. The markers of PE (sFLT1, PLGF, sFLT1/PLGF) were analyzed in five (50%) cases. The mean value of the ratio at the moment of PE was: sFLT1/PLGF: 157.6 that for a given gestational term (31.3 weeks) corresponds to severe ischemic damage to the placenta. The mean delivery term was 32.4 weeks of gestation; all newborns were alive and viable with the mean weight 1514 g (978–2250 g). CONCLUSION According to our data, the main features of PE in pts with advanced CKD are its early onset (up to 34 weeks), severe course with AKI in 60% of cases, with relatively low BP values.

Effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of GDM

To investigate the effects of pre-pregnancy BMI and gestational weight gain on adverse pregnancy outcomes and complications of gestational diabetes mellitus. 3966 pregnant women were enrolled in this study. Multivariate logistic regression analysis was conducted to estimate the relative risk between pre-pregnancy BMI, gestational weight gain, and adverse pregnancy outcome. Pre-pregnancy BMI was found to be a risk factor for preeclampsia (OR = 1.159), gestational diabetes mellitus (OR = 1.191), gestational hypertension (OR = 1.221), and macrosomia (OR = 1.165). Gestational weight gain was a risk factor for preeclampsia (OR = 1.783), placental abruption (OR = 2.209), and macrosomia (OR = 1.506). Total weight gain during pregnancy cannot be used as a predictor of GDM. Pre-pregnancy BMI is a risk factor for gestational diabetes mellitus complicated with preeclampsia, preterm delivery, gestational hypertension, and macrosomia. Impact statement What is already known on this subject? Obesity during pregnancy includes pre-pregnancy obesity and excessive weight gain during pregnancy. Obese pregnant women have a higher risk of pregnancy complications. What do the results of this study add? We focus on the effects of pre-pregnancy BMI on pregnancy outcomes, classified by Asian criteria. Our findings suggest for the first time that excessive weight gain during pregnancy is a risk factor for placental abruption and we specifically point out that total weight gain during pregnancy cannot be used as a predictor of GDM. What are the implications of these findings for clinical practice and/or further research? This study is helpful to monitor the risk of adverse pregnancy outcomes in the Asian population and suggest the risk of pregnancy complications, such as gestational diabetes mellitus and placental abruption.

Association Of Socioeconomic Status With Preeclampsia In Pakistani Females

Introduction: To identify whether there is an association between maternal socioeconomic status as in living style, and preeclampsia in women from Pakistan, and if so, to what extent it increases the risk of developing preeclampsia. Methods: This is a case-control study, consisting of 74 normal pregnant and 76 already diagnosed preeclamptic Pakistani females, recruited from various hospitals in Karachi. Their socioeconomic status was assessed through the standard of living index (SLI) using the National Family Health Surveys (NFHS) criteria, which considers different living facilities as an indicator of socioeconomic status. Odds ratios of preeclampsia were calculated for low, middle and high socioeconomic status and other maternal anthropometric parameters. Results: Based on their groups, it appeared that the highest percentage of preeclamptic females (n= 65; 43.3%) and the lowest of control patients (n=14; 9.3%) lie in lower socioeconomic groups and the results were highly significantly different. Study observed that having lower socioeconomic status (P&lt;0.001) significantly increase risk of having preeclampsia by 9% and middle socioeconomic status has no role in prevalence of preeclampsia shown by 0.0 odds ratio. In addition, odds ratio of age and PreBMI for the preeclamptic females were found as 1.37 (P&lt;0.001) and 1.55 (P&lt;0.001) respectively, which shows that each year increase in age, increases risk of preeclampsia by 1.37 times and 1.55 times with each increased in BMI. Conclusion: Living facilities are indications of socioeconomic status and are strong risk factors of preeclampsia

The effect of tumor necrosis factor alpha on human trophoblast cells

Impaired trophoblast cell invasion is believed to be an inciting factor in preeclampsia. Factors driving trophoblast invasion are incompletely understood. Maternal serum tumor necrosis factor alpha (TNFα) levels are elevated in preeclampsia. We hypothesized that elevated TNFα influences human trophoblast cells.