Late-onset Preeclampsia Research Articles

Evaluation of maternal serum progesterone-induced blocking factor levels in pregnancies complicated with early- and late-onset preeclampsia

The aim of present study was to evaluate maternal serum progesterone-induced blocking factor (PIBF) levels in pregnancies complicated with early-onset (EO-PE) and late-onset (LO-PE) preeclampsia. Patients with preeclampsia were divided in two groups according to preeclampsia onset and compared to healthy control group: EO-PE and LO-PE defined as being diagnosed before 340/7 and ≥340/7 weeks, respectively. Maternal age, nulliparity, BMI at blood sampling, smoking, history of caesarean section and ethnicity were statistically similar among the groups. Statistically significant differences were found between the eo-PE and lo-PE preeclampsia groups in terms of gestational age at delivery, mean birth-weight percentile and foetal growth restriction rates. The mean serum PIBF level was 528.6 ± 220 ng/mL in the eo-PE and 615.3 ± 269.1 ng/mL in the lo-PE preeclampsia and 782.3 ± 292.4 ng/mL in the control groups; the difference among groups was statistically significant. Our results indicated that decreased PIBF levels play an important immunologic role in preeclampsia onset. IMPACT STATEMENT What is already known on this subject? Maternal lymphocytes secrete PIBF that provides the immunological effects of progesterone during pregnancy by activating T-helper type 2 (Th2) cells and inhibiting any activated uterine natural killer (uNK) cells. The recent studies results have shown that there is disproportion in the Th1/Th2 rate in women with preeclampsia. This purports that Th1-mediated immunity is promoted through Th2-mediated immunity, which can be involved in the pathogenesis of preeclampsia. What do the results of this study add? In this study we found that PIBF levels in maternal serum were significantly lower in the EO-PE group than in LO-PE and control group. Our results indicated that decreased PIBF levels play an important immunologic role in preeclampsia onset. What are the implications of these findings for clinical practice and/or further research? We can speculate that first trimester maternal serum PIBF levels may be a useful biomarker for prediction of EO-PE. Using serum PIBF levels within the first trimester combined with Doppler values for the uterine artery, and some biochemical markers to predict onset and severity of preeclampsia appear to be a new screening method.

Evaluating the predictive value of fetal Doppler indices and neonatal outcome in late-onset preeclampsia with severe features: a cross-sectional study in a resource-limited setting

BackgroundPreeclampsia constitutes a major health problem with substantial maternal and perinatal morbidity and mortality. The aim of this study was to detect the diagnostic efficacy of fetal Doppler in predicting adverse outcomes in severe late onset preeclampsia (LOP).MethodsA prospective study was conducted among childbearing women who presented with severe LOP and matched controls. Umbilical artery (UA) and middle cerebral artery (MCA) Doppler indices including pulsatility index (PI), resistance index (RI), systolic/diastolic ratio (S/D) and cerebroplacental ratio (CPR) were measured.ResultsAll UA indices were significantly higher in the case group compared to the controls (p < 0.001). UA PI and RI were significantly correlated with all neonatal adverse outcomes except cord pH status (p < 0.05). Abnormal CPR was the most sensitive index that positively correlated with intrauterine growth retardation (IUGR), low 5- minute Apgar score and neonatal intensive care unit admission (79, 72.8 and 73.3%, respectively). In the same context, Abnormal UA PI and RI represented the most specific tool for predicting IUGR, low 1- and 5- minutes Apgar score with positive predictive values were 52, 87 and 57%, respectively.ConclusionIn severe LOP, UA Doppler remains the preferential indicator for adverse birth outcomes with CPR is the best index that could be solely used for predicting such outcome.

Risk factors associated with early- and late-onset preeclampsia in a population sample of Bogotá (Colombia)

Risk factors associated with early- and late-onset preeclampsia in a population sample of Bogotá (Colombia)

Identifying preeclampsia-associated genes using a control theory method

Preeclampsia is a pregnancy-specific disease that can have serious effects on the health of both mothers and their offspring. Predicting which women will develop preeclampsia in early pregnancy with high accuracy will allow for improved management. The clinical symptoms of preeclampsia are well recognized, however, the precise molecular mechanisms leading to the disorder are poorly understood. This is compounded by the heterogeneous nature of preeclampsia onset, timing and severity. Indeed a multitude of poorly defined causes including genetic components implicates etiologic factors, such as immune maladaptation, placental ischemia and increased oxidative stress. Large datasets generated by microarray and next-generation sequencing have enabled the comprehensive study of preeclampsia at the molecular level. However, computational approaches to simultaneously analyze the preeclampsia transcriptomic and network data and identify clinically relevant information are currently limited. In this paper, we proposed a control theory method to identify potential preeclampsia-associated genes based on both transcriptomic and network data. First, we built a preeclampsia gene regulatory network and analyzed its controllability. We then defined two types of critical preeclampsia-associated genes that play important roles in the constructed preeclampsia-specific network. Benchmarking against differential expression, betweenness centrality and hub analysis we demonstrated that the proposed method may offer novel insights compared with other standard approaches. Next, we investigated subtype specific genes for early and late onset preeclampsia. This control theory approach could contribute to a further understanding of the molecular mechanisms contributing to preeclampsia.

Red Light Mitigates the Deteriorating Placental Extracellular Matrix in Late Onset of Preeclampsia and Improves the Trophoblast Behavior.

Preeclampsia is a serious pregnancy disorder which in extreme cases may lead to maternal and fetal injury or death. Preexisting conditions which increase oxidative stress, e.g., hypertension and diabetes, increase the mother's risk to develop preeclampsia. Previously, we established that when the extracellular matrix is exposed to oxidative stress, trophoblast function is impaired, and this may lead to improper placentation. We investigated how the oxidative ECM present in preeclampsia alters the behavior of first trimester extravillous trophoblasts. We demonstrate elevated levels of advanced glycation end products (AGE) and lipid oxidation end product 4-hydroxynonenal in preeclamptic ECM (28%, and 32% increase vs control, respectively) accompanied with 35% and 82% more 3-chlorotyrosine and 3-nitrotyrosine vs control, respectively. Furthermore, we hypothesized that 670 nm phototherapy, which has antioxidant properties, reverses the observed trophoblast dysfunction as depicted in the improved migration and reduction in apoptosis. Since NO is critical for placentation, we examined eNOS activity in preeclamptic placentas compared to healthy ones and found no differences; however, 670 nm light treatment triggered enhanced NO availability presumably by using alternative NO sources. Light exposure decreased apoptosis and restored trophoblast migration to levels in trophoblasts cultured on preeclamptic ECM. Moreover, 670 nm irradiation restored expression of Transforming Growth Factor (TGFβ) and Placental Growth Factor (PLGF) to levels observed in trophoblasts cultured on healthy placental ECM. We conclude the application of 670 nm light can successfully mitigate the damaged placental microenvironment of late onset preeclampsia as depicted by the restored trophoblast behavior.

Impairment of mitochondrial respiration in platelets and placentas: a pilot study in preeclamptic pregnancies

Preeclampsia (PE) is a major complication of pregnancy with partially elucidated pathophysiology. Placental mitochondrial dysfunction has been increasingly studied as major pathomechanism in both early- and late-onset PE. Impairment of mitochondrial respiration in platelets has recently emerged as a peripheral biomarker that may mirror organ mitochondrial dysfunction in several acute and chronic pathologies. The present study was purported to assess mitochondrial respiratory dys/function in both platelets and placental mitochondria in PE pregnancies. To this aim, a high-resolution respirometry SUIT (Substrate-Uncoupler-Inhibitor-Titration) protocol was adapted to assess complex I (glutamate + malate)- and complex II (succinate)-supported respiration. A decrease in all respiratory parameters (basal, coupled, and maximal uncoupled respiration) in peripheral platelets was found in preeclamptic as compared to healthy pregnancies. At variance, placental mitochondria showed a dichotomous behavior in preeclampsia in relation to the fetal birth weight. PE pregnancies with fetal growth restriction were associated with decreased in coupled respiration (oxidative phosphorylation/OXPHOS capacity) and maximal uncoupled respiration (electron transfer/ET capacity). At variance, these respiratory parameters were increased for both complex I- and II-supported respiration in PE pregnancies with normal weight fetuses. Large randomized controlled clinical studies are needed in order to advance our understanding of mitochondrial adaptive vs. pathological changes in preeclampsia.

Predictive performance of first trimester serum galectin-13/PP-13 in preeclampsia screening: A systematic review and meta-analysis.

Placental protein-13 (PP-13) is a member of the galectin group involved in placental implantation, maternal artery remodeling, and placental inflammatory processes. Its levels are lower in the first trimester for pregnancies later affected by ischemic placental disease, and slowly increase during the second and third trimesters of pregnancy. The aim of the present meta-analysis is to assess the predictive performance of PP-13 in first trimester preeclampsia screening. PubMed, Web of Science, Scopus, Embase, BIOSIS, and Cochrane databases were used to find relevant studies. All prospective and retrospective observational studies that evaluated the accuracy of PP-13 in predicting preeclampsia were assessed. The investigation revealed that the quantitative synthesis was based on 14 studies with a total number of 8,239 women. The pooled sensitivity of PP-13 for the prediction of preeclampsia was 0.53 [95% (confidence interval (CI), 0.08-0.99], and the pooled specificity was 0.83 (95% CI, 0.38-1.29). Further analysis revealed a higher accuracy of PP-13 for the screening of late-onset preeclampsia [pooled sensitivity of 0.58 [95% CI, -0.17-1.33) with a specificity of 0.85 (95% CI, 0.10-1.60)] when compared with early-onset preeclampsia [pooled sensitivity of 0.51 (95% CI, -0.04-1.05) with a specificity of 0.88 (95% CI, 0.33-1.42)]. In conclusion, PP-13 appears to be a promising biomarker for evaluating the risk of developing preeclampsia during the first trimester of pregnancy. As a result, incorporating it into future predictive models is a viable option.

Inflammasomes in placental explants of women with preeclampsia cultured with monosodium urate may be modulated by vitamin D

ABSTRACT Objectives Preeclampsia (PE) is an important syndrome of gestation characterized by placental and systemic inflammation. High plasma concentration of uric acid are frequently associated with inflammation and endothelial dysfunction and may contribute to PE pathogenesis. This study aimed to evaluate the vitamin D (VD) immunomodulatory effect on the NLRP1/NLRP3 inflammasomes in placental explants from preeclamptic (PE) and normotensive (NT) pregnant women. Study design Placental explants from 10 late-onset PE (LOPE), 10 early-onset PE (EOPE), and 10 NT pregnant women were cultured with or without monosodium urate (MSU) and VD. Main outcome measures Gene and protein expression of NLRP1, NLRP3, HMGB1, caspase-1, interleukin-1 beta (IL-1β), and IL-18 were determined by quantitative PCR and Western blotting/ELISA. Statistical significance was accepted at p < 0.05. Results Basal gene and protein expression of NLRP1/NLRP3 and IL-1β, IL-18 and HMGB1 were significantly higher in explants from EOPE compared to LOPE and NT pregnant women. In addition, culture with MSU increased these inflammatory markers, and concomitant treatment with MSU+VD decreased this effect. Conclusions The results demonstrated that NLRP1 and NLRP3 inflammasomes are upregulated in the placental tissue of EOPE women, associated with high production of inflammatory cytokines. The in vitro treatment with VD downregulated placental inflammasomes induced by MSU, suggesting its immunomodulatory role in the systemic inflammation of PE.

Prediction of pregnancy-related hypertensive disorders using metabolomics: a systematic review

ObjectiveTo determine the accuracy of metabolomics in predicting hypertensive disorders in pregnancy.DesignSystematic review of observational studies.Data sources and study eligibility criteriaAn electronic literature search was performed in June 2019 and...

Evaluation of dyslipidemia in preeclamptic pregnant women and determination of the predictive value of the hemato-lipid profile: A prospective, cross-sectional, case-control study.

Objective:In this study, we examined the serum hematologic and lipid parameters of pregnant women with preeclampsia and an age- and gestational-age matched normotensive control group. We also compared the ratios of hemato-lipid parameters defined as systemic inflammatory markers and determined the predictive value of these values in preeclampsia.Materials and Methods:All patients diagnosed with late-onset preeclampsia or severe preeclampsia between 34 and 40 weeks of gestation at Inonu University Faculty of Medicine between March 2019 and October 2020 were included.Results:A total of 253 pregnant women were included in the study period. When the study groups were compared in terms of hematological and blood lipid profile; while serum lymphocyte, triglyceride, and total cholesterol levels were significantly higher in the preeclampsia group than in the control group (p<0.001, p<0.001, p=0.013, respectively); high-density lipoprotein (HDL)-cholesterol levels were found to be significantly lower (p=0.017). The cut-off value for the monocyte/HDL ratio in predicting severe preeclampsia was 16.65 with 59.0% sensitivity and 85.4% specificity [the area under the receiver operating characteristic 0.756, 95% confidence interval (CI) 0.681-0.821, p<0.001]. Multivariate analysis showed that the monocyte/HDL ratio was independently associated with both preeclampsia and severe preeclampsia [odds ratio (OR): 1.094; 95% CI 1.009-1.185 and OR: 1.731; 95% CI 1.218-2.459, respectively].Conclusion:This study demonstrated that serum triglyceride and total cholesterol levels were significantly higher and serum HDL-cholesterol levels were significantly lower in pregnant women with late-onset preeclampsia compared to normotensive pregnant women. Additionally, this study revealed that the measurement of monocyte/HDL ratio in the pregnant population could be a useful clinical tool for predicting preeclampsia.

Association of Keap1 (rs11085735) polymorphism and lncRNA MEG3 hypermethylation status with the risk of preeclampsia

BackgroundPreeclampsia (PE) is one of the complications of pregnancy. The pathogenesis of PE has not been completely understood. The aims of the present study were to investigate the role of Keap1 (rs11085735) variants and the methylation status of long non-coding RNA (lncRNA) MEG3 in the risk of PE.MethodsIn a case–control study, 150 pregnant women, including 75 PE patients and 75 healthy pregnant women recruited from Western Iran with Kurdish ethnic background, were studied for Keap1 variants using polymerase chain reaction‐restriction fragment length polymorphism (PCR-RFLP). The methylation status of lncRNA MEG3 was investigated using methylation-specific PCR (MSP) among 50 preeclamptic patients and 50 controls.ResultsThe frequency of Keap1 A allele was significantly lower (5.3%) in preeclamptic patients compared to controls (12.7%, p = 0.024). The frequencies of hemimethylated (UM) and full methylated (MM) lncRNA MEG3 were 94 and 6% (p = 0.04), respectively, in all patients, 86.4, and 13.6% (p = 0.04), respectively, in patients with severe preeclampsia and 98 and 0% in controls. The frequency of full methylated lncRNA MEG3 was 14.3% in early-onset preeclampsia and 2.8% in late-onset preeclampsia (p = 0.12). Patients with PE had significantly higher levels of liver biomarkers (including ALT, AST, ALP, and total bilirubin) and lower PLT counts compared to healthy pregnant women.ConclusionThe present study suggests the presence of hypermethylation status of lncRNA MEG3 in preeclampsia that might contribute to the pathogenesis and development of preeclampsia. Also, Keap1 rs11085735 polymorphism might be involved in the risk of preeclampsia.

Comparison of clinical features and pregnancy outcomes in early- and late-onset preeclampsia with HELLP syndrome: a 10-year retrospective study from a tertiary hospital and referral center in China

BackgroundEarly-onset preeclampsia (EO-PE) and late-onset preeclampsia (LO-PE) are different subtypes of preeclampsia. We conducted this study to analyze the similarities and differences in the clinical features and pregnancy outcomes in EO- and LO-PE with HELLP syndrome.MethodsThis was a retrospective study in a tertiary hospital. Eighty-three parturients with HELLP syndrome were allocated into two groups based on the timing of preeclampsia onset: EO-PE with HELLP (n = 47) and LO-PE with HELLP (n = 36).ResultsIn total, 31.9% and 63.9% of women in the EO-PE with HELLP and LO-PE with HELLP groups, respectively, were asymptomatic at diagnosis (P = 0.004, OR = 0.265 (0.106–0.662)). Headache or visual symptoms were more frequent in the EO-PE group than in the LO-PE group (48.9% vs. 25%, P = 0.026, OR = 0.348 (0.135–0.896)). Women in the EO-PE with HELLP group had higher SBP and DBP than those in the LO-PE with HELLP group. Laboratory tests, including platelets, liver function, and hemolysis, which are the main indicators for the diagnosis of HELLP syndrome, showed almost no significant differences between the two groups, with kidney function being the only difference observed. Women in the EO-PE with HELLP group had higher Scr than those in the LO-PE with HELLP group. The degree of proteinuria was higher in the EO-PE group than in the LO-PE with HELLP group. The incidence of severe maternal complications was significantly higher in the EO-PE group than in the LO-PE with HELLP group (25.5% vs. 5.6%, P = 0.016, OR = 0.172 (0.036–0.824)). In total, 57.4% and 8.3% of neonates in the EO-PE and LO-PE with HELLP groups were admitted to the NICU, and the difference was statistically significant, even after adjustment for the delivery week (P = 0.009, OR = 0.830 (0.729–0.944)). Postpartum HELLP syndrome was more common in the LO-PE group than in the EO-PE group (30.6% vs. 4.3%, P = 0.001, OR = 9.9 (2.031–48.256)).ConclusionsCompared with LO-PE with HELLP patients, EO-PE with HELLP patients have more obvious kidney damage, higher blood pressure and a higher risk of adverse maternal and neonatal outcomes. Patients with LO-PE need to be alerted to the occurrence of HELLP syndrome after delivery.

Reduced Abundance of Nitrate-Reducing Bacteria in the Oral Microbiota of Women with Future Preeclampsia.

The oral microbiota can contribute to the regulation of blood pressure by increasing the availability of nitric oxide through the reduction of nitrate to nitrite, which can be converted into nitric oxide in the stomach and then enter the circulation. It is unclear if the composition of the oral microbiota is different between women who do and do not develop preeclampsia. This study aimed to compare the composition of the buccal microbiota just prior to the development of symptoms at 36 weeks gestation in 12 women who developed late-onset preeclampsia and 24 matched women who remained normotensive throughout pregnancy by 16S rRNA gene amplicon sequencing. The abundance of the nitrate-reducing Veillonella spp V. parvula and V. dispar and a subunit of nitrate reductase narH was compared using real-time PCR. The abundance of bacteria was correlated with maternal blood pressure and dietary intake of nitrate-containing vegetables. The results showed that the abundance of nitrate-reducing bacteria including Veillonella, specifically V. parvula, and Prevotella was reduced in women who developed preeclampsia. Veillonella but not Prevotella abundance was negatively correlated with maternal blood pressure. The dietary intake of nitrate-containing vegetables did not differ between the groups and was not correlated with the abundance of Veillonella. There was no difference in the abundance of the nitrate reductase subunit narH between the groups. These results suggest that the abundance of nitrate-reducing bacteria is reduced in the oral microbiota of women who later develop preeclampsia, indicating a potential pathway for prevention.

Predictive ability of serum advanced glycation end products at 11 to 13 weeks of gestation for early-onset preeclampsia

Placental hypoxia and resultant oxidative stress have been associated with the development of preeclampsia. Oxidative stress promotes the formation of advanced glycation end products. This study aimed to assess whether serum levels of advanced glycation end products during the early stage of pregnancy are a predictive biomarker of early-onset and late-onset preeclampsia. This was a nested case-control study that included 6 women with early-onset preeclampsia, 21 women with late-onset preeclampsia, and 50 age- and body mass index-matched healthy female control subjects. All women enrolled in the study had a complete medical history, including mean arterial pressure and uterine artery pulsatility index measurements. Furthermore, the women underwent blood chemistry analysis, including circulating levels of advanced glycation end products, soluble fms-like tyrosine kinase-1, and placental growth factor. Clinical measurements and biochemistry were evaluated at 11 to 13 and 19 to 24 weeks of gestation. The median serum concentrations of advanced glycation end products at 11 to 13 weeks of gestation were significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia and control subjects (6.62 vs 4.10 vs 3.77; P<.05), but no significant difference was found in advanced glycation end products at 19 to 24 weeks of gestation among the 3 groups. The advanced glycation end product-to-placental growth factor ratio in the first trimester of pregnancy was significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia or control subjects (0.78 vs 0.10 vs 0.10; P<.05). The area under the receiver operating characteristic curve values for patients with early-onset preeclampsia were 0.782 (95% confidence interval, 0.522-0.922), 0.855 (95% confidence interval, 0.433-0.978), and 0.925 (95% confidence interval, 0.724-0.983) for the advanced glycation end product and placental growth factor levels and advanced glycation end product-to-placental growth factor ratios, respectively. This population achieved a 100% detection rate for predicting early-onset preeclampsia at a screen-positive rate of 10% by combining the advanced glycation end product-to-placental growth factor ratio and the mean arterial pressure. The study results suggested that an elevated advanced glycation end product-to-placental growth factor ratio and mean arterial pressure at 11 to 13 weeks of gestation could be a potential biomarker for predicting the future development of early-onset preeclampsia.

Serum Vasostatin-1 Level is Increased in Women with Preeclampsia.

To evaluate the serum vasostatin-1 levels in preeclamptic and non-preeclamptic pregnant women. Thirty consecutive women with mild preeclampsia and sixty consecutive women with severe preeclampsia were compared with ninety gestational age-matched (±1 week) non-preeclamptic pregnant women with an appropriate-for-gestational-age (AGA) fetus. Mean serum vasostatin-1 was significantly higher in women with preeclampsia than gestational age-matched controls. Mean serum vasostatin-1 was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group, and in the severe preeclampsia group compared to its gestational age-matched control group. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups, and in severe early- and severe late-onset preeclampsia groups. Serum vasostatin-1 had positive correlations with systolic and diastolic blood pressure. Serum vasostatin-1 was significantly higher in women with preeclampsia compared to those of the gestational age-matched controls. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups and severe early- and severe late-onset preeclampsia groups.

Profiles of circular RNAs in human blood and their potential roles in preeclampsia

IntroductionTo identify circular RNAs (circRNAs) expression profiles in the blood of preeclampsia (PE) and healthy pregnant women, further clarify the possible mechanisms of circRNAs involved in the pathogenesis of PE.Material and methodsMethods: Whole blood samples were collected from 5 paired PE and healthy pregnant women, the differentially expressed circRNAs (DE-circRNAs) were investigated by using high-throughput sequencing. Bioinformatics was performed to evaluate the sequencing results and obtain insights into possible mechanisms, such as GO and KEGG pathway analyses. Then, six DE-circRNAs were chosen and validated by quantitative real-time PCR (RT-qPCR) in an enlarged sample size. Their diagnostic values were analyzed by the receiver operating characteristic (ROC) curve. The establishment and analysis of the circRNA-miRNA-mRNA network were made for the validated DE-circRNAs.ResultsResults: A total of 139 DE-circRNAs between PE and controls were revealed. Of them, 18 circRNAs were upregulated, and 31 circRNAs were downregulated (fold change &gt;2 and P-value &lt; 0.05). Three circRNAs (has-circ-0007717, has-circ-0006460, and has-circ-0093055) were higher in both blood of early-onset and late-onset PE patients. The ROC analysis showed area under the curve values of has-circ-0007717, has-circ-0006460, and has-circ-0093055 were 0.64 (P=0.11), 0.72 (P=0.01), and 0.72 (P=0.01), respectively. Then, the circRNA-miRNA-mRNA competing for endogenous RNAs (ceRNAs) network comprised 2 circRNAs, 154 miRNAs, and 6 mRNAs. KEGG analysis of these mRNAs included immunity response-related pathways and cellular senescence.ConclusionsConclusion: CeRNA regulatory network indicated that the DE-circRNAs might participate in the processes of cell immunity response.

Elevated mid-trimester 4-h postprandial triglycerides for predicting late-onset preeclampsia: a prospective screening study

BackgroundAbnormal maternal lipid concentrations are associated with increased risk of preeclampsia. However, previous studies mainly focused on fasting lipid concentrations, scarce data have been published on the relationship between postprandial triglyceride (TG) concentrations in the second trimester and the risk of preeclampsia. Our aim is to evaluate the potential of triglyceride (TG) concentrations at the time of oral lipid tolerance test (OLTT) measurement in the second trimester to predict preeclampsia and to elucidate the lipid metabolic changes related to these diseases.MethodsThis is a prospective cohort study of Pregnant women at 12–24 weeks of gestation undergone an OLTT in a university affiliated hospital between May 2019 and January 2020. Data were stratified into binaries according to the OLTT results. The receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off points of TG, HDL-C, LDL-C, sd-LDL, FFA, and BG for predicting preeclampsia.Results438 pregnant women were recruited to undergo an OLTT at 12–24 weeks of gestation. Among these, 24 women developed preeclampsia and 414 women remained normotensive. Women who subsequently developed preeclampsia had higher concentrations of 4-h postprandial TG than those who remained normotensive. In the linear logistic regression analyses of potential confounding factors, mid-trimester 4-h postprandial TG concentrations at the time of OLTT measurement were significantly higher in preeclamptic cases than in controls.ConclusionsDyslipidemia in the second trimester of pregnancy, particularly postprandial hypertriglyceridemia, appears to be associated with an increased risk of preeclampsia. Mid-trimester 4-h postprandial TG concentration at the time of OLTT measurement may be a potential predictive marker of preeclampsia.Trial registration Data of registration: 2018/10/15. Date of initial participant enrollment: 2019/05/01. Clinical trial identification number: chiCTR1800018884. URL of the registration site: http://www.chictr.org.cn/showproj.aspx?proj=25526. Data sharing information: The data including individual participant data, detailed study protocols, statistical analysis plans will be shared upon request to the corresponding author.

Expression profiles and functions of ferroptosis-related genes in the placental tissue samples of early- and late-onset preeclampsia patients

BackgroundThe accumulation of reactive oxygen species (ROS) resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation that likely plays an important role in PE pathogenesis. This study aimed to investigate the expression profiles and functions of ferroptosis-related genes (FRGs) in early-onset preeclampsia (EOPE) and late-onset preeclampsia (LOPE).MethodsGene expression data and clinical information were downloaded from the Gene Expression Omnibus (GEO) database. The “limma” R package was used to screen differentially expressed genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to verify the expression of hub FRGs in PE.ResultsA total of 4215 differentially expressed genes (DEGs) were identified between EOPE and preterm cases while 556 DEGs were found between LOPE and term controls. Twenty significantly different FRGs were identified in EOPE subtypes, while only 3 FRGs were identified in LOPE subtypes. Functional enrichment analysis revealed that the differentially expressed FRGs were mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as the response to hypoxia, iron homeostasis and iron ion binding process. PPI network analysis and verification by RT-qPCR resulted in the identification of the following five FRGs of interest: FTH1, HIF1A, FTL, MAPK8 and PLIN2.ConclusionsEOPE and LOPE have distinct underlying molecular mechanisms, and ferroptosis may be mainly implicated in the pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

Uncovering serum placental-related non-coding RNAs as possible biomarkers of preeclampsia risk, onset and severity revealed MALAT-1, miR-363 and miR-17

New predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = − 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = − 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein–protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.

Comparison of the Kisspeptin levels in early onset preeclampsia and late-onset preeclampsia.

Maternal Kisspeptin plays role in cell migration which is responsible for trophoblast invasion. We aimed to investigate the role of Kisspeptin as an invasion marker in the early-onset and late-onset preeclampsia cases. In this case-control study, 125 patients were included: 20 patients with early-onset preeclampsia and 20 gestational-age-matched healthy controls; 45 patients with late-onset preeclampsia and 40 gestational-age-matched controls). Maternal plasma Kisspeptin concentration was measured and compared in groups regarding the presence of early-onset and late-onset preeclampsia. In the late-onset PE group, significantly higher maternal plasma Kisspeptin values were observed compared with the control group at > 34weeks of gestation (68.7 ± 93.4pg/ml vs 68.5 ± 57.9pg/ml; p = 0.004). Before the 34th week of gestation, plasma Kisspeptin levels did not show a significant difference when patients with early-onset PE and gestational-age matched controls were compared (66.8 ± 87.9pg/ml vs 48.5 ± 91.3pg/ml; p = 0.56). Plasma Kisspeptin levels were significantly higher in women with late-onset preeclampsia, while no significant difference was observed in early-onset preeclampsia when compared with healthy gestational age-matched controls. The role of Kisspeptin proteins is still not clearly defined in the pathogenesis of preeclampsia.