Late-onset Preeclampsia Group Research Articles

Body mass index, lipid profile, and endothelial dysfunction gene polymorphism in women with early-onset and late-onset preeclampsia

The aim: to investigate and analyze clinical parameters, laboratory biomarkers of lipid metabolism and endothelial dysfunction gene polymorphisms in early-onset and late-onset preeclampsia and to identify potential risk factor(s) for the development of early-onset preeclampsia.
 Materials and methods: a prospective case-control study included 133 women in the second half of pregnancy, including 46 with early-onset (EOP) and 87 with late-onset preeclampsia (LOP) and 34 conditionally healthy pregnant women with an uncomplicated obstetric history and no risk factors for preeclampsia. Concentrations of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides in blood plasma were determined. Genetic polymorphisms of endothelial dysfunction (192 Q→R PON-1, 677 C→ T MTHFR) were studied using allele-specific polymerase chain reaction.
 Results: Early-onset preeclampsia is associated with an increased relative risk: preterm delivery by 2.08 times (95 % CI 1.48-2.93), operative delivery by 2.2 times (95 % CI 1.46-3.33), early operative delivery by 2.9 times (95 % CI 1.5-5.5), fetal distress during delivery by 3.78 times (95 % CI 1.2-11.9), a low score on the Apgar scale on the 1st minute, less than 6 points, by 2.59 times (95 % CI 1.84-3.66), on the 5th minute – 5.04 times (95 % CI 1.41-18.11), Grade III prematurity – 13.24 times (95 % CI 3.14-55.78) compared to women with late-onset preeclampsia. The study found that overweight was more often observed in patients with EOP (34.8 %) than in those with normal pregnancy (15.9 %) (p=0.02; OR=2.8; 95 % CI 1.03-7.7), obesity (BMI > 30 kg/m2) was more often recorded in those with LOP (33.33 %) than in the control group (3 (6.8 %)) (p=0.02; OR=6.8; 95 % CI 1.9-23.9). Patients in both groups with preeclampsia showed signs of dyslipidemia, but its significance in the development of early-onset or late-onset preeclampsia has not been separately proven. The study found that the number of carriers of MTHFR 677 TT in the group with EOP prevailed over the indicator of C group where there were no carriers of the pathological homozygote 677TT (p<0.05, OR= 20.73 95 % CI 1.16-371.28), and the T allele in the EOP group occurs 1.78 times more often than in the LOP group (p<0.05, OR=2.22; 95 % CI 1.26-3.88) and 2.43 times more often than in the C group (P<0.05, or= 3.15; 95 % CI 1.54-6.45).
 Conclusions: Factors of early onset of PE include pre-pregnancy, overweight, first pregnancy, a history of preeclampsia, and carrier of the 677T allele of the MTHFR gene

Diagnostic Role of Cell-Free miRNAs in Identifying Placenta Accreta Spectrum during First-Trimester Screening.

Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, there is a high need for an additional non-invasive test to improve the diagnostic accuracy and to select the real PAS from the suspected ones in the first-trimester screening. miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profiles in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or pre-eclampsia, were obtained using deep sequencing. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p, quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset pre-eclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to data from the literature, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for first-trimester screening of pregnant women, subject to validation with independent test samples.

Altered Placental Insulin Signaling in the Absence of Systemic Insulin Resistance in Hypertensive Disorders of Pregnancy among South Indian Tamil Population

A cross sectional study was conducted to explore the possible derangements in placental insulin signaling and also to investigate the presence or absence of maternal systemic insulin resistance in different types of hypertensive disorders of pregnancy (HDP). Study Design: Healthy pregnant women (n=32) and pregnant women with gestational hypertension (GH) (n=18), late onset Pre-eclampsia (LP) (n=18) and early onset Pre-eclampsia (EP) (n=19) were recruited for the study. Maternal venous blood and placental samples were collected from the study subjects at 35±7 weeks of gestation. Insulin resistance parameters such as fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, beta cell function and insulin sensitivity and glycated hemoglobin were estimated in the maternal venous blood samples. Placental protein expressions of insulin signaling molecules were analyzed by western blotting method. Results: Maternal venous blood insulin resistance parameters were not significantly different between the study groups. However, placental content of phospho insulin receptor beta was significantly decreased in GH, LP and EP groups in comparison to controls. We also found a significant decrease in placental protein expression of phosphatidyl inositol 3-kinase p85 alpha in LP group when compared to other groups.

The Risk of Persistent Hypertension and Chronic Kidney Disease in Early- and Late-Onset Preeclampsia: A Report From Developing Country.

Preeclampsia (PE) has been disproportionately prevalent in developing countries and constitutes a leading cause of maternal mortality, and also has long-term impacts, including renal consequences.This study aimed to explore the risk of persistent hypertension and kidney failure in early-onset PE (EOP) and late-onset PE (LOP) in the five years after delivery. This retrospective cohort study included women with a prior history of severe PEor normotensive pregnancy admitted to tertiary hospitals in Indonesia. The blood pressure, body mass index (BMI), urea, creatinine serum, and protein urine were analyzed, and the risk of chronic kidney disease (CKD) after five years was performed using theKidney Disease Improvement Global Outcomes (KDIGO) classification. Twenty-seven EOP, 35 LOP, and 30 normotensive cases were included. Mean blood pressure after five years was recorded as 115.6 ± 14.25 mmHg in the normotensive group, 131.82 ± 19.34 mmHg in the LOP group, and 154.96 ± 23.48 mmHg in the EOP group. According to the KDIGO classification, the normotensive group had an average 10% risk of CKD, but severe PE had a risk of CKD greater than 90%. In the severe PE group, the risk of CKD was 20.94 times higher compared to normotensive women (OR 20.94; 95% CI 2.67-163.72, p = 0.004). The risk of CKD in the EOP group was 6.75 times higher than in the LOP group (OR 6.75; 95% CI 2.19-20.76, p = 0.001), whereas persistent hypertension in the EOP group was 5.78 times higher than in the LOP group (OR 5.78; 95% CI 1.91-17.395, p = 0.002). PE women have a higher risk of CKD than normotensive women. Women with a history of EOP are more likely to develop persistent hypertension and CKD than women with a prior LOP history.

Placental progesterone and its receptor in HIV-infected pre-eclamptic women

Given the high prevalence of HIV infection and pre-eclampsia (PE) in South Africa, this study evaluated and compared the placental immunostaining of progesterone (P) and progesterone receptors (PR) in the synergy of HIV-infected PE compared to normotensive pregnant women using immunohistochemistry interfaced with morphometric image analysis. Progesterone immunostaining was expressed widely across exchange and conducting villi within mesenchymal, endothelial, and trophoblast cells. In contrast, PR was expressed within syncytiotrophoblasts and was absent within endothelial cells. In exchange villi, P and PR immuno-expression was significantly lower in PE compared to the normotensive group (p = < 0.0001 and p = < 0.0001, respectively) and within the early-onset pre-eclampsia (EOPE) compared to the late-onset pre-eclampsia (LOPE) group (p = < 0.0001 and p = < 0.0001, respectively). Progesterone immuno-expression was significantly lower in the HIV+ compared to the HIV− group (p = < 0.0001), whilst PR was non-significant. In conducting villi, P and PR immuno-expression was significantly lower in the EOPE compared to the LOPE group (p = < 0.0001 and p = < 0.0001, respectively) and in the HIV+ compared to the HIV− group (p = < 0.0001 and p = 0.0009, respectively). Progesterone immuno-expression was slightly higher in the PE compared to normotensive group, and PR immuno-expression was non-significant. There was a significant difference between P and PR within exchange versus conducting villi regardless of pregnancy type, with villi type accounting for 34.47% and 15.28% of total variance for P and PR, respectively. Placental P and PR immuno-expression is downregulated in the duality of PE and HIV+ infection. The use of combined antiretroviral therapy (cART) may result in defective P synthesis, which causes insufficient binding to its receptors. Consequently, PI3K/AKT, JAK-STAT, and MAPK signalling pathways are affected, impairing trophoblast invasion and leading to pre-eclampsia development. Notably, the decrease in P and PR immuno-expression in EOPE validates their effect on placentation.

Genome-wide association study reveals HSF2, GJA1 and TRIM36 as susceptibility genes for preeclampsia: a community-based population study in Tianjin, China

ABSTRACT Background Preeclampsia (PE) mainly occurs in pregnant women and is hereditary. Several genome-wide association studies (GWAS) on Caucasian samples have reported some gene loci that are associated with preeclampsia. However, these studies have not reached consistent conclusions. No previous GWAS has examined preeclampsia in the Chinese Han population. Method This study aimed to identify common genetic variations associated with preeclampsia in the Chinese Han population through two-stage case‒control studies. The discovery cohort included 92 patients with severe preeclampsia and 187 healthy controls. The validation cohort included 52 patients with preeclampsia and 104 controls. A genome-wide association study was performed to identify putative preeclampsia genes in the discovery cohort, with validation in the validation cohort. Results In the discovery cohort, GWAS demonstrated that 19 single-nucleotide polymorphisms (SNPs) were associated with preeclampsia (P < 10−5). The pathway analysis revealed that these 19 SNP representative genes were mainly enriched in the adenylyl cyclase-inhibiting G-protein coupled receptor signaling pathway. After validation in the validation cohort, rs13176432 and rs13210237 remained closely related to preeclampsia (P<0.05). In the combined data set, the frequency of the G allele in rs13176432 was significantly higher in cases with preeclampsia than in controls (P = 5 × 10−6). The frequency of the A allele in rs13210237 was higher in the preeclampsia group (P = 8 × 10−6). The rs13210237 representative genes include HSF2 and GJA1, while the rs13176432 representative gene is TRIM36. There were no differences in genotype distribution between the early-onset and late-onset preeclampsia groups (P > 0.05). Furthermore, rs13210237 and rs13176432 were related to preeclampsia in the adjusted regression model (P < 0.000). Conclusion In this study of two independent cohorts, we found that rs13210237 and rs13176432 might be novel preeclampsia-susceptible genetic factors in the Han population in China. However, there was no association between the onset of preeclampsia and these genotypes.

Immunohistochemical Expression of Placental Vitamin D Receptors in Pregnancies Complicated by Early and Late-Onset Preeclampsia.

The aim of our study was to determine whether the immunohistochemical expression of placental vitamin D receptors is altered in pregnancies complicated by preeclampsia. Vitamin D receptor expression was immunohistochemically analysed in the placentas of three groups: a control group, and early- and late-onset preeclampsia groups. Total immunohistochemical intensity staining of placentas showed that the control group had a median vitamin D receptor (VDR) expression significantly higher than the placentas of mothers with early- and late-onset preeclampsia. There was no difference among the three groups in a semiquantitative analysis of VDR staining of the stroma only. Vitamin D receptors showed lower median expression in preeclampsia-affected pregnancies, especially early-onset preeclampsia. Therefore, Vitamin D receptor expression may be an important marker for normal placentation and preeclampsia onset.

Bax mRNA Expression as A Potential Biomarker of Placental Apoptosis in Early-onset Preeclampsia

BACKGROUND: Early-onset preeclampsia is characterized by higher oxidative stress and apoptosis level than late-onset one. Studies comparing the expression of the Bcl-2 family protein in early and late-onset preeclampsia are still lacking and show inconclusive evidence. This study aimed to compare the expression of Bax and Bcl-2 messenger RNA (mRNA) as a biomarker of placental apoptosis between early-onset and late-onset preeclampsia.METHODS: A cross-sectional study was conducted using formalin-fixed, paraffin-embedded preeclamptic placental samples and dividing them into early-onset and late-onset preeclampsia groups. Bax and Bcl-2 mRNA expressions were assessed using the quantitative real-time polymerase chain reaction method. Apoptosis was assessed through DNA fragmentation examination by the ligation-mediated real-time polymerase chain reaction method.RESULTS: Thirty early-onset and 30 late-onset preeclamptic placental samples were included. The mean fold change Bax mRNA in early-onset was higher than in late-onset preeclampsia (6.02±3.59 vs. 2.82±1.97; p=0.00). The mean fold change Bcl-2 mRNA early-onset was not different from late-onset preeclampsia (31.20±17.94 vs. 31.01±27.60; p=0.98). The mean DNA fragmentation cycle threshold in early-onset preeclampsia was lower than in late-onset preeclampsia (28.07±0.64 vs. 30.63±0.96; p=0.00). A weak negative correlation exists between fold change Bax mRNA and DNA fragmentation cycle threshold (r=-0.30; p=0.02).CONCLUSION: Bax mRNA showed significant correlation in DNA fragmentation compared to Bcl-2 mRNA; hence, might show more role in apoptotic pathway. Early-onset preeclampsia has higher Bax mRNA relative expression and apoptosis than late-onset preeclampsia. Therefore, Bax mRNA can be potential biomarker in early-onset preeclampsia.KEYWORDS: mRNA, Bax, Bcl-2, apoptosis, DNA fragmentation, early-onset, preeclampsia

Evaluation of first- and third-trimester afamin levels in preeclampsia.

The aim of this study was to investigate serum afamin levels in the first and third trimesters in preeclampsia. Serum samples from 118 patients in the first and third trimesters were analyzed. Serum samples were collected from pregnant women who had enrolled in the first trimester. Blood was then collected from pregnant women who had developed preeclampsia and from healthy controls in the third trimester. The collected blood samples were resolved for analysis, and serum afamin concentrations were measured in the first and third trimesters. Preeclampsia and healthy controls were compared. There was no significant difference between the control and preeclampsia groups in terms of age, body mass index, and smoking. Afamin levels in the first and third trimesters were higher in the preeclampsia group than in the control group (p<0.05). In the subgroup analysis of the preeclampsia group, afamin levels were higher in the early-onset preeclampsia group than in the late-onset preeclampsia group in the first and third trimesters (p<0.05). In the receiver operating characteristic analysis afamin levels were 96.23 ng/mL in the first trimester and 123.57 ng/mL in the third trimester as cut-off values for preeclampsia. Serum afamin levels are useful for predicting preeclampsia in the first trimester in pregnant women and can be used in clinical practice as a supportive biomarker for the diagnosis of preeclampsia in the third trimester. Meta-analyzes are needed to investigate the effect of afamin levels in the prediction and diagnosis of preeclampsia and to determine the cut-off value.

Integrated Proteomic and N-Glycoproteomic Profiling of Placental Tissues of Patients with Preeclampsia.

Preeclampsia (PE) is a multi-system disorder of pregnancy that poses a serious threat to maternal and perinatal health worldwide. This study aims to evaluate the global alterations of protein expression and N-glycosylations that are crucial for PE pathogenesis. Here, tandem mass tag labeling combined with LC-MS/MS was employed to determine the global expression of all proteins and intact glycopeptide in placentas from three healthy pregnant women, three patients with early-onset severe PE, and three patients with late-onset severe PE. A total of 2260 proteins were quantified across 9 placental tissues, of which 37 and 23 were differentially expressed in the early-onset and late-onset PE groups, compared to the controls. A total of 789 glycopeptides were accurately quantified, which were derived from 204 glycosylated sites in 159 glycoproteins and were modified by 59 N-Linked glycans. A total of 123 differently expressed glycopeptides, which were from 47 glycoproteins were identified among three groups. Through a combined analysis of proteomic and glycoproteomic data, it was found that the changes in 10 glycoproteins were caused by the difference in glycosylation level but not in the protein abundance level. This is the first study to conduct an integrated proteomic and glycoproteomic characterization of placental tissues of PE patients. Our findings suggest that glycosylation modification may affect the molecular function of proteins through changes in the glycosylation structure or the occupancy of glycosylation, which will provide new insights to help elucidating the pathogenic mechanism of PE.

LC-MS/MS based untargeted lipidomics uncovers lipid signatures of late-onset preeclampsia

The mechanisms underlying late-onset preeclampsia (LOPE) remain unknown. Metabolic disturbances have been implicated as a primary factor in LOPE development. Lipids have been shown to have great clinical value in recent years. This study aimed to use lipidomics to provide evidence for the etiology and potential therapeutic approaches for LOPE. Twenty patients with LOPE and 20 healthy controls were enrolled in this study. Placental lipidomic data were acquired using liquid chromatographymass spectrometry (LC-MS/MS), and the data were analyzed by weighted gene correlation network analysis (WGCNA) and statistical methods. Of 1508 identified lipids, 226 were differentially expressed between the LOPE and control groups. In the LOPE group, the abundance of most unsaturated triglycerides (TG) increased, whereas that of other lipids, including phosphatidylcholine (PC), sphingomyelin, and phosphatidylserine (PS) increased. The WGCNA implied that the correlation network module of lipids was highly related to clinical traits. Pathway analysis revealed that these dysregulated lipids are closely related to glycerophospholipid metabolism. Lipidomics may help identify the pathogenesis underlying placental dysfunction in LOPE patients and provide potential therapeutic targets in the future.

[Glucose Metabolism-Derived Nicotinamide Adenine Dinucleotide Phosphate in Late-Onset Preeclampsia Placenta Tissue and Its Correlation with Oxidative Stress].

To study the changes in the expression of nicotinamide adenine dinucleotide phosphate (NADPH), a glucose metabolism-derived antioxidant, in late-onset preeclampsia (LOPE) placenta tissue and the correlation with oxidative stress. A total of 13 normal pregnant women and 13 pregnant women with LOPE who were hospitalized in the Obstetrics Department, the First Affiliated Hospital of Chongqing Medical University and who underwent elective cesarean section between November 2020 and October 2021 were included in the study. Placenta tissues were collected from the subjects. Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay was done to determine the ROS levels in the placenta tissues of the LOPE group and the normal control group. Spectrophotometric analysis was conducted to determine the levels of NADPH, glutathione (GSH), and glucose, and the expressions and activities of glucose-6-phosphate dehydrogenase (G6PD) and phospho-gluconate dehydrogenase (PGD), key rate-limiting enzymes of the pentose phosphate pathway (PPP), in the placenta tissues of the LOPE group and the normal control group. Western blot was done to determine changes in the protein expressions of phosphofructokinase 1 (PFK1), a key rate-limiting enzyme of the glycolytic pathway, G6PD, and PGD in the placenta tissues from the two groups. ROS levels in the placenta tissue of the LOPE group were significantly higher than those of the control group ( P<0.05). The levels of NADPH and GSH, two antioxidants, and glucose in the LOPE placenta were significantly higher than those of the control group ( P<0.05). The expression of PFK1 was significantly elevated in the LOPE group ( P<0.05). However, there were no significant differences in the activities and protein expression of G6PD and PGD between the two groups. Glucose metabolism reprogramming takes place in LOPE placenta tissue, which may be one of the causes of the abnormal elevation of NADPH and GSH.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted. Impact statement What is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

Evaluation of placental growth potential and placental bed perfusion by 3D ultrasound for early second-trimester prediction of preeclampsia.

This study aimed to investigate whether placental parameters measured by three-dimensional ultrasound are associated with preeclampsia (PE) and small-for-gestational-age (SGA). In total, 1163 pregnancies at 11-14weeks of gestation were recruited between October 8, 2020, and April 30, 2021. Placenta volume (PV), placental bed vascularization flow index (PBVFI), and uterine arteries pulse index (UtA-PI) were measured. Placental quotient (PQ = PV/weeks of gestation) was calculated. All participants were re-examined 4weeks later. The placental volume growth rate (PVGR = placental volume difference between the two examinations/interval days) was also calculated. Patients were divided into four groups by the gestational age at the onset of PE and birth weight: early-onset PE (E-PE, n = 18), late-onset PE (L-PE, n = 36), isolated SGA5 (birth weight less than the fifth percentile for gestational age without PE, n = 9), and unaffected (n = 1100) groups. A predictive model for E-PE was established, which consisted of unnatural conception, chronic hypertension, PBVFI (of second examination), and PVGR for E-PE; 94.4% sensitivity and 96.7% specificity by receiver operating characteristic curve analysis. Overall, decreased placental growth potential and low placental bed perfusion in the early second trimester have potential in predicting E-PE.

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.

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.

Iron metabolism disorder and oxidative damage levels in placenta are involved in preeclampsia

IntroductionTo explore the role of ferritin in placenta, serum and umbilical cord blood of pregnant women and the changes of oxidative stress injury as well as cell apoptosis in placenta in the pathogenesis of preeclampsia (PE).Material and methodsSixty pregnant women with severe PE were assigned into early-onset and late-onset PE group. Another 60 cases of normal late pregnant women with similar gestational weeks were divided into early-onset and late-onset control group. Maternal serum and fetal umbilical cord blood ferritin content was determined by automatic biochemical immunoassay system; mRNA expression levels of ferritin and ferritin heavy chain (FTH) were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Western Blot was used to detect the relative expression level of ferritin and apoptosis; the contents of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) were detected by colorimetry.ResultsSerum uric acid (UA) and creatinine (Cr) levels of PE groups were significantly higher when compared to the controls. The serum ferritin levels in blood sample and umbilical cord blood sample were significantly higher relative to the controls. However, the mRNA and protein levels of ferritin levels in placenta samples were significantly lower compared with the controls. The placental cleaved caspase-3, Bcl-2 levels were significantly lower than the early onset PE group. The levels of GSH-Px and MDA in placenta were significantly higher.ConclusionsThese results may assist understanding the pathogenesis of PE and provide potential biomarkers for diagnosis of PE.

Predictive Value of Second-Trimester Maternal Lipid Profiling in Early-Onset Pre-eclampsia: A Prospective Cohort Study and Nomogram.

Purpose: Maternal lipid profile in second trimester has rarely been investigated in the risk assessment for pre-eclampsia (PE). Since early-onset PE often companied by much worse clinical outcomes, thus, we aimed to evaluate the predictive value of second-trimester maternal lipid profiling for early-onset PE.Methods: A prospective cohort study was conducted to measure the second-trimester maternal lipid profile of pregnant women from January to December 2019. The pairwise association between maternal lipid profile and PE onset or pregnancy termination time was quantified. Multiple logistic regression was preformed to define risk factors for early-onset PE, and a nomogram for early-onset PE was developed. The net benefit of our model was evaluated by calibration curve and decision curve analyses.Results: We enrolled 5,908 pregnant women and they were divided into healthy (n = 5,789), late-onset PE (n = 64), and early-onset PE (n = 55) groups. Total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c) were elevated in patients with PE, while high-density lipoprotein cholesterol (HDL-c) was decreased in patients with PE. TC, TG, and LDL-c were negatively correlated with PE onset time or gestational week at delivery. Receiver operating characteristic curves (ROC) defined the cutoff values of TG and HDL-c, and the final regression model included five statistically significant risk predictors for early-onset PE (maternal age of ≥35 years, multipara, pre-pregnancy body mass index (BMI) ≥25 kg/m2, second trimester TG ≥ 2.59 mmol/L and second trimester HDL-c ≤ 2.03 mmol/L. The nomogram had an excellent diagnostic performance (area under the curve = 0.912, sensitivity = 92.7%, and specificity = 76%) and was further validated with good calibration and positive net benefits in a decision curve analysis.Conclusions: An abnormally increased TG concentration and a decreased HDL-c concentration might serve as predictors of early-onset PE. Whether blood lipid-lowering measures can improve severe PE prognosis require further clarification.

Differential expression of markers of oxidative stress and apoptosis in relation to serum ferritin levels in patients with pre-eclampsia

&lt;p&gt;&lt;strong&gt;Background and Objective:&lt;/strong&gt; Pre-eclampsia (PE) is a hypertensive gestational disease appearing during second trimester of pregnancy. Free radicals are released by the placenta in this condition that may cause oxidative damage. This study was designed to determine the serum ferritin (SF) levels in maternal blood, fetal umbilical cord blood and placenta and the changes associated with oxidative stress as well as cell apoptosis to understand the pathogenesis of PE.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; This cross-sectional analytical study recruited 60 pregnant females with severe PE and assigned into early and late onset PE groups. Another n = 60 cases of normal pregnant females with similar gestational weeks were selected in the control group. Maternal serum and fetal umbilical cord blood ferritin levels were determined by automatic biochemical immunoassay system. Reverse transcription real-time fluorescence, Western blot and colorimetry were used to determine mRNA expression levels of ferritin and ferritin heavy chain, relative expression of ferritin and superoxide dismutase, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels, respectively.&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Mean age was 30.89 &amp;plusmn; 5.65 and 31.79 &amp;plusmn; 5.06 years in early and late onset PE groups respectively. Serum uric acid and creatinine levels of both PE groups were significantly higher than the normal pregnant females. SF levels were also higher in the participants of PE groups. However, the mRNA and ferritin protein levels in placental tissue were significantly lower in PE groups while comparing to controls. The cleaved caspase-3 protein, GSH-Px and MDA levels were significantly higher in both PE groups (p &amp;lt; 0.05).&lt;/p&gt;&#x0D; &lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; The alterations in factors related to oxidative stress and cell apoptosis in placental tissue may be helpful to understand the pathogenesis of PE and may provide potential biomarkers for the diagnosis of PE.&lt;/p&gt;

Expression levels of MiRNA-16, SURVIVIN and TP53 in Preeclamptic and Normotensive women.

To measure and compare micro ribonucleic acid-16, survivin and tumour protein p53-regulated apoptosis-inducing protein 1 expression levels in preeclamptic and normotensive pregnancies, and to check the correlation of micro ribonucleic acid-16 with messenger ribonucleic acid expression of survivin and tumour protein p53. The observational cross-sectional comparative study was conducted at the Department of Physiology and Cell Biology, University of Health Sciences, Lahore, Pakistan, from 2016 to 2018, and comprised preeclamptic women in group A and normotensive women in group B. The preeclamptic patients were further categorised into early-onset preeclampsia subgroup A1and late-onset preeclampsia group A2. Expression of micro ribonucleic acid-16, messenger ribonucleic acid expression of survivin and tumour protein p53 in preeclamptic and normotensive pregnancies were analysed using real time polymerase chain reaction. Data was analysed using SPSS 22. Of the 54 patients, 27(50%) were in each of the two groups. Within group A, 14(52%) patients were in group A1 and 13(48%) in group A2. The expression of micro ribonucleic acid 16 showed significant increase in group A compared to group B (p<0.05). The difference was not significant between the subgroups A1 and A2. The levels of messenger ribonucleic acid expression of survivin and tumour protein p53 were deregulated in group A, with a decrease in survivin and an increase in tumour protein p53. The messenger ribonucleic acid expression of survivin and tumour protein p53 showed statistically significant differences across subgroups A1 and A2 (p<0.05). The micro ribonucleic acid-16 expression correlated negatively with messenger ribonucleic acid expression of survivin, but exhibited a positive correlation with tumour protein p53. Deregulated micro ribonucleic acid-16 along with differentially expressed apoptotic genes, survivin and tumour protein p53 might result in altered apoptosis implicated in the pathogenesis of preeclampsia.