Late-onset Severe Preeclampsia Research Articles

Clinical application evaluation of serum C1q and other complement factors in the diagnosis and prediction of preeclampsia

Objective To observe the levels of serum complement C1q, C3, C4 and factor B in different phases during normal pregnancy; To evaluate the diagnostic value and the predictive value of serum complement C1q, C3, C4 and factor B in preeclampsia (PE). Methods Three groups of subjectes were enrolled from January 2017 to March 2018 in Department of Obstetrics and Gynecology, Peking University Third Hospital. (1) 30 pregnant women in each group at 8-14 weeks, 20-26 weeks and 28-36 weeks were retrospectively selected, and the serum levels of complement C1q, C3, C4 and B factors were measured and compared. (2)Selecting 17 cases of early-onset mild PE, 47 cases of early-onset severe PE, 24 cases of late-onset mild PE, 27 cases of late-onset severe PE, and 30 normal pregnant cases of the same gestational stage as early-onset / late-onset controls, through ANOVA analysis and comparison between two groups, this study evaluated the diagnostic value of serum complement C1q, C3, C4 and factor B in PE. (3)To evaluate the predictive effect in PE, it analyzed serum C1q and factor B levels of pregnant women at 20-26 gestation weeks through prospective nested case-control study of 214 cases. Results The levels of serum C1q remained stable in the whole pregnancy. The levels of C3 and factor B increased at the early stage of pregnancy and remained stable after the middle stage. C4 increased early in pregnancy and then remained stable. Compared with the control group, the levels of serum C1q in all four types of PE patients were significantly decreased (median: 169 mg/L, 161 mg/L, 165 mg/L, 163 mg/L; early-onset, late-onset control group: 187 mg/L, 194 mg/L; U=130.500, 426.500, 159.500, 130.500, all P 0.05). 33 (15.4%) cases developed PE out of 214 pregnant women with PE risk factors. Compared to those who didn′t develop PE, it showed no statistical difference of serum C1q, C3, C4, and factor B levels at 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 184 mg/L; C3: 1 523 mg/L vs. 1 467 mg/L; C4: 230 mg/L vs. 229 mg/L; FB: 344 mg/L vs. 320 mg/L; U=2 090.000, 1 575.000, 2 058.500, 1 362.000, all P>0.05). Compared to those of the healthy pregnant controls, it showed no statistical difference of serum C1q, C3 and C4 levels of 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 190 mg/L; C3: 1 523 mg/L vs. 1 428 mg/L; C4: 230 mg/L vs. 227 mg/L; U=353.000, 395.000, 493.500, all P>0.05), while it showed statistical difference (344 mg/L vs. 306 mg/L; U= 233.500, P=0.007) for factor B. Conclusions Serum C1q level of PE patients significantly decreased, which can be used as potential indicators of PE diagnosis, but serum C1q, C3, C4 level of 20-26 gestational weeks cannot predict risk of PE. Factor B cannot serve as serum index of PE diagnosis, but its serum levels at 20-26 gestational weeks werer higher than those of normal pregnant controls, factor B may be a potential predictor, but need further verification. (Chin J Lab Med, 2018, 41: 934-942) Key words: Preeclampsia; Complement; C1q; C3; C4; factor B

Placental Factors Affecting Birth Weight of Late Onset Severe Preeclampsia

Objective of the study is to determine the correlation of placenta and birth weight in late onset preeclampsia. A case-control study,analysis prevalence was conducted in Moh Hoesin Hospital Palembang from August 2015 to August 2016. Samples were women who giving birth in Moh Hoesin Hospital Palembang. They were devided into two groups, severe preeclampsia as case group and normotension as control. Data were analyzed by X2, Exact Fisher’s and logistic regression test using SPSS 16.0. There were 180 subjects (90 cases and 90 controls). There was a positive correlation between placental macroscopic and late onset preeclampsia (p=0.009; OR=6.9), in contrast there was only one different placental microvascularisation of 16, between late onset preeclampsia and normotension, the mural or occlusive fibrin thrombi chorion (p=0.005; OR=9.9). Birth weight in late onset preeclampsia tended to be small but still in normal range and it was not statistictly significant (p=0.112; OR=10.4). There was a positive correlation between placental macroscopic and SGA baby on late onset preeclampsia (p=0.026; OR=16.6), but it wasnot proven microscopically. Placenta remains contributed to the pathogenesis of the late onset preeclampsia, but not as dominant as the early one.

Placental Factors Affecting Birth Weight of Late Onset Severe Preeclampsia

Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. Placental insufficiency is considered as the main pathogenesis in the early onset PE. Objective of the study is to determine the correlation of placenta and birth weight in late onset preeclampsia. A case-control study of prevalence was conducted in Moh. Hoesin Hospital Palembang from August 2015 to August 2016. Samples were women who giving birth in Moh.Hoesin Hospital Palembang. They were divided into two groups, severe preeclampsia as case group and normotensionas control. Data were analyzed by X2, Exact Fisher’s and logistic regression test using SPSS 16.0. There were 180 subjects (90 cases and 90 controls). There was a positive correlation between placental macroscopic and late onset preeclampsia (p=0.009; OR=6.9), in contrast there was only one different placental microvascularisation of 16, between late onset preeclampsia and normotension, the mural or occlusive fibrin thrombi chorion (p=0.005; OR=9.9). Birth weight in late onset preeclampsia tended to be small but still in normal range and it was not statistictly significant (p=0.112; OR=10.4). There was a positive correlation between placental macroscopic and SGA baby on late onset preeclampsia (p=0.026; OR=16.6), but it wasnot proven microscopically. Placenta remains contributed to the pathogenesis of the late onset preeclampsia, but not as dominant as the early one.

Maternal folic acid supplementation for the prevention of preeclampsia: A systematic review and meta-analysis.

Preeclampsia is a significant contributor to maternal and neonatal morbidity and mortality. Folic acid supplementation is recommended periconceptionally for the prevention of neural tube defects. Epidemiological evidence suggests that maternal folic acid supplementation may play a role in preventing other adverse birth outcomes. This systematic review aimed to investigate the effect of maternal folic acid supplementation during pregnancy on risk of preeclampsia and gestational hypertension. Multiple scientific databases and grey literature were searched for relevant studies. Studies were reviewed according to pre-specified inclusion and exclusion criteria. Study characteristics were summarised and study quality was assessed. A meta-analysis of observational studies was conducted to examine the effect of maternal folic acid supplementation on preeclampsia risk. Meta-analysis of eight observational studies showed significantly lower odds of preeclampsia with folic acid supplementation in comparison to no folic acid supplementation: OR=0.78 (95% CI 0.63, 0.98), with moderately high heterogeneity between studies. Subgroup analysis showed no significant subgroup difference between folic acid supplementation taken by itself, in comparison to folic acid taken in or alongside a multivitamin. Low level evidence is available for a modest association between maternal folic acid supplementation and reduction in preeclampsia risk. Future studies should differentiate between early and late onset and mild vs severe preeclampsia, and should control for relevant confounders including the presence of multivitamin supplements. The protocol for this systematic review was prospectively registered with PROSPERO (CRD42015029310).

Transcriptomic Profiling in Human Decidua of Severe Preeclampsia Detected by RNA Sequencing.

Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes; is a powerful tool for new transcript discovery, genome annotation, and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n = 3, early-onset severe PE, EOSPE; n = 3, late-onset severe PE, LOSPE) and normal pregnancies (n = 3). We revealed that decidual gene transcription profile was altered in severe PE and identified 293 key PE-related genes involved in 19 differentially regulated pathways relevant for the pathogenesis of PE, among which ENO2, PGK1, and HK2 involved in glycolysis/gluconeogenesis and HIF-1 signaling pathway which are all highly related with tumorigenesis and are significantly upregulated in cancer cells were severely inhibited in the decidua of PE. Moreover, we identified 22 core regulatory genes, including the newly identified pseudogenes BNIP3P1, HK2P1, and PGK1P1 that encode long non-coding RNA (lncRNA); interestingly, BNIP3/BNIP3P1, HK2/HK2P1, and PGK1/PGK1P1 appear in pairs in core genes. Subsequent analyses using quantitative PCR validated a portion of these results. This study may provide further insight into the mechanisms of PE and function as preventive, predictive, and therapeutic measures. Future functional studies are needed in order to accomplish a greater understanding of the mechanisms involved. J. Cell. Biochem. 119: 607-615, 2018. © 2017 Wiley Periodicals, Inc.

Interpretation of laboratory test results in early and late onset severe preeclampsia

Objective To analyze the difference of laboratory test results between early-onset and late-onset severe preeclampsia and to investigate their clinical application values. Methods Totally 108 blood samples were collected from patients with severe preeclampsia who were diagnosed according to the Diagnostic Standard of Obstetrics and Gynecology(7th Edition) published by People′s Medical Publishing House, in Shandong Provincial Hospital affiliated to Shandong University from March to November 2016, which consisted of 64 early-onset severe preeclampsia before 34 weeks gestation(early onset group) and 44 late-onset severe preeclampsia after 34 weeks gestation(late onset group). In addition, 42 women with normal pregnancies as the control group were selected.General clinical data were collected, and the blood sample was analyzed through detecting Hb, PLT, fibrinogen (FIB), D-dimer, AST, ALT, urea, creatinine (Cr), uric acid, CRP, urine protein. The tested results were analyzed and compared. Flow cytometry was used to analyze the proportion of T helper 1 cells(Th1) and T helper 2 cells(Th2), and the ratio of Th1/Th2 was also calculated. All data and F test were performed by use of statistical software SPSS19.0. Results The pre-pregnancy body mass index(29.55±4.49, 30.66±5.13, 26.62±3.17, F=9.829, P<0.05), diastolic blood pressure[(105.17±14.46)mmHg(1 mmHg=0.133 kPa), (99.80±12.56)mmHg, (74.36±8.42)mmHg, F=82.088, P<0.05], Hb[(123.22±14.38)g/L, (117.03±16.48)g/L, (112.62±11.24)g/L, F=7.133, P<0.05], urea[(6.56±2.36)mmol/L, (4.51±1.35)mmol/L, (3.04±0.87)mmol/L, F=51.733, P<0.05], Cr[(68.47±18.05)μmol/L, (61.37±14.37)μmol/L, (48.54±8.73)μmol/L, F=23.737, P<0.05], CRP[(7.68±8.76)mg/L, (5.88±6.03)mg/L, (3.56±2.41)mg/L, F=4.735, P<0.05], urine protein[(3.66±0.76)g/L, (2.20±1.05)g/L, (0.19±0.40)g/L, F=249.714, P<0.05]had a statistically significant difference among the early-onset, late-onset and control groups. The flow cytometry results demonstrated that the proportion of Th1 in early-onset group(19.83±3.04)was higher than that in both late-onset (14.49±2.79)and control groups(11.78±1.17), on the contrary, the result of Th2 was much lower(early-onset : 1.02±0.12, late-onset: 1.11±0.12, control: 1.56±0.11), there was statistical significance among these three groups(Th1: F=135.110, P<0.05; Th2: F=293.687, P<0.05). Conclusions It′s necessary to real-time monitor the laboratory indicators, such as liver and kidney function, especially the immunologic function indicators for evaluating the disease of early-onset and late-onset severe preeclampsia and personal treatment, and for ensuring the health of mother and fetus and improving the prognostic of mother and fetus.(Chin J Lab Med, 2017, 40: 180-185) Key words: Pre-eclampsia; Clinical laboratory techniques; Body mass index; Hemoglobins; Th1 cells; Th2 cells; Proteinuria

Expression and significance of EPCR in plasma and placenta of patients with early onset severe preeclampsia

Objective: To investigate the expression of endothelial protein C receptor(EPCR)and its roles in plasma and placenta of patients with early onset severe preeclampsia. Methods: Sixty cases of severe preeclampsia women who delivered in Xuzhou Maternity and Child Health Care Hospital from March 2014 to February 2016, were recruited, which included 30 cases with early onset severe preeclampsia(early onset group, gestational week <34 weeks)and 30 patients with late onset severe preeclampsia(late onset group, gestational week ≥34 weeks). Thirty cases of healthy late pregnant women at the same period(gestational week ≥34 weeks)were selected as control group. Immunohistochemistry SP method was applied to detect the expression of in EPCR placenta. Reverse transcription(RT)- PCR was used to detect the expression of EPCR mRNA in placenta. ELISA method was used to detect the levels of soluble EPCR(sEPCR)level in plasma of the pregnant women of the three groups. Results: The expression of EPCR in placenta mainly distributed in the membrane and cytoplasm of placental syncytiotrophoblasts and vascular endothelial cells, a few in the cell nucleus. The expression of EPCR in early onset group(57%, 17/30)was significantly lower than that in late onset group(93%, 28/30; χ2=25.165, P=0.001). The expression of EPCR in late onset group had no significant difference from that in control group(97%, 29/30; χ2=0.540, P= 0.910). The expression of EPCR mRNA in placenta of early onset group(0.40±0.07)was significantly lower than that in late onset group(0.91±0.06; t=-30.044, P=0.001), while there was no statistical difference of the expression of EPCR mRNA between the late onset group and the control group(0.92±0.07; t=-0.631, P=0.538). Plasma sEPCR level in early onset group, late onset group and control group were(231 ± 11),(124±6)and(121±4)μg/L respectively, which is higher in early onset group than that in late onset group(t=48.080, P=0.001). There was no statistical difference of plasma sEPCR level between the late onset group and the control group(t=2.534, P=0.100). Conclusions: The pathogenesis of early onset and late onset severe preeclampsia may be different. Decreased expression of EPCR in placenta may be associated with the pathogenesis of early onset severe preeclampsia.

Expression of the complement system's activation factors in plasma of patients with early/late‐onset severe pre‐eclampsia

To investigate the expression of complement activation factors in plasma of patients with early/late-onset severe pre-eclampsia. A case-control study was performed. The study group consisted of 30 cases of early-onset severe pre-eclampsia (EOSPE) and 30 cases of late-onset severe pre-eclampsia (LOSPE). Thirty cases were selected as the early-onset control group (E-control) and 30 as the late-onset control group (L-control). ELISA was used to test C1q, C4d, MBL, Bb, C3a, C5a, and MAC in the maternal peripheral circulation. The complement activation factors Bb, C3a, C5a, and MAC were increased significantly in EOSPE (all P<.01) and LOSPE (P value: .027, <.001, .001, and <.001, respectively) compared with E/L-control. C1q and C4d were increased significantly in LOSPE (P value: .003 and .014, respectively) compared with L-control. Abnormal activation of the complement system exists in the maternal circulation of patients with early- and late-onset severe pre-eclampsia. In patients complicated with LOSPE, the complement system was activated through both the classical and alternative pathways, while in EOSPE, the complement system was activated mainly through the alternative pathway.

127 Hypertension at an early stage of prenatal is a major risk factor for adverse neonatal outcomes

Objective To analyze which of the maternal risk factors for PE is more predictive unfavorable perinatal outcomes between women diagnosed with Severe PE. Methods Over a period of twelve months, (2014–2015), 208 cases of severe preeclampsia were included in a observational and retrospective cohort study. This study was conducted at the Maternity School Assis Chateaubriand in Fortaleza, State of Ceara, Brazil. The maternal risk factors were analized by the Student ’T’ test and logistic regression Results Of the 208 patients analyzed obtained in perinatal outcomes 39 (18%) cases of SGA, 17 (8.17%) cases of intrapartum anoxia and 10 (4.8%) cases of fetal death. Early- and late-onset severe preeclampsia differed from each other remarkably. The increased arterial systolic and diastolic pressure early in the prenatal care was the most important predictive factor to unfavorable perinatal outcomes (OR = 1.13, CI- 1.00 to 1.06; p = 0,03) Conclusion women with Hypertension in the beginning of prenatal care was an important risk factor to early preeclampsia and unfavorable perinatal outcomes; therefore, the Primiparity was protector parameter.

Correlations between complement system’s activation factors and anti-angiogenesis factors in plasma of patients with early/late-onset severe preeclampsia

ABSTRACTObjective: To investigate the expression of complement system’s activation factors in plasma of patients with severe preeclampsia and their correlations with anti-angiogenesis factors.Methods: A case–control study was performed. The study group consisted of 30 cases of early-onset severe preeclampsia (EOSPE) and 30 cases of late-onset severe preeclampsia (LOSPE). Thirty cases were selected as the early-onset control group (E-control) and 30 as the late-onset control group (L-control), with the weeks of gestation matched. Enzyme-linked immunosorbent assay (ELISA) was used to test C3a, C5a, MAC, sEng, and sflt-1 in the maternal peripheral circulation.Results: The complement system’s activation factors C3a, C5a, and MAC were increased significantly in EOSPE and LOSPE (all P < 0.01) compared with E/L-control. Plasma levels of C3a correlated inversely with plasma sEng (r = –0.454, P < 0.001) and sflt-1 (r = –0.326, P = 0.011) in preeclampsia patients, while MAC correlated with soluble endoglin (sEng; r = 0.343, P = 0.007) and soluble fms-like tyrosine kinase-1 (sflt-1; r = 0.318, P = 0.013). There were no significant correlations between complement system’s activation–related factors and the anti-angiogenesis factors in healthy control group.Conclusions: Abnormal activation of the complement system exists in the maternal circulation of patients with E/L-onset severe preeclampsia. There were correlations between the abnormal activation of the complement system and the abnormal expression of anti-angiogenesis factors in patients with severe preeclampsia, but the correlation was not strong.

Placental levels of total oxidative and anti-oxidative status, ADAMTS-12 and decorin in early- and late-onset severe preeclampsia

Objective: Preeclampsia (PE), can be classified according to the timing of disease onset: early-onset PE occurs before the 34th gestational week and late-onset PE occurs in the 34th gestational week or later. The aim of this study was to determine whether total antioxidant status (TAS), and total oxidant status (TOS), ADAMTS-12 and decorin levels differ among early-onset severe PE (EOS-PE), late-onset severe PE (LOS-PE) and uncomplicated pregnancies. Methods: In this case–control study, placental samples obtained from 25 pregnant patients with EOS-PE, 26 pregnant patients with LOS-PE and 28 healthy patients with uncomplicated pregnancies (control group). Results: Placenta levels of decorin and TOS were significantly higher and TAS was significantly lower in the EOS-PE and LOS-PE groups than in the control group. These alterations were more prominent in patients with EOS-PE than in patients with LOS-PE. There were no significant differences in the ADAMTS-12 levels of the groups. Conclusion: The distinctly higher rate of negative perinatal outcomes in both EOS-PE and LOS-PE patients is well evidenced. However, the main questions that need to be answered are whether the only difference between these two diseases is the time of their onset and whether the only difference between them with respect to fetal morbidity and mortality is prematurity.

Circulating ADAMTS-12 levels in early- and late-onset severe preeclampsia

Aim of this study is to determine whether maternal serum ADAMTS-12 levels differ among early-onset (

Early and late onset severe preeclampsia: a clinicopathologic study of 178 placentas

To explore the pathologic features and prognosis of early and late onset severe preeclampsia. An observational study was conducted in 178 cases of severe preeclampsia collected during January 2010 to December 2014 from Haidian Maternal and Child Health Hospital.The cases were divided into two groups according to the onset of gestational age of the severe preeclampsia, with 54 cases of namely early onset (onset ≤ 34 weeks) and 124 cases of late onset (onset >34 weeks). Clinical characteristics of the patients, perinatal outcome and the pathologic characteristics of the placentas in each group were evaluated. Decidual vascular disease, placental infarction, abruptio placentae and placental villi dysplasia were seen in both groups. The incidence of placental villi dysplasia was the highest, followed by placental infarction. Incidence of severe decidual vascular disease of early and late onset severe decidual vascular disease were 16.7% (9/54) and 5.6% (7/124), respectively.Incidence of placental infarction of early and late onset severe preeclampsia were 48.1% (26/54) and 61.3% (76/124). Incidence of placental villi dysplasia of early and late onset severe preeclampsia were 79.6% (43/54) and 50.8% (63/124). Incidence of Severe decidual vascular disease, placental infarction and placental villi dysplasia were significantly different between early and late onset severe preeclampsia cases (P<0.05), while there was no difference in decidual vascular disease and placenta thrombi (P>0.05). Fetal survival rate of every group was 81.5% (44/54) and 93.5% (116/124). Incidence of fetal growth retardation was 55.6% (30/54) and 38.7% (48/124). The fetal survival rate and incidence of fetal growth retardation were different between two groups (P<0.05). The incidence of decidual vascular disease and placental villi dysplasia in early onset severe preeclampsia is higher than those in late onset severe preeclampsia. Neonatal outcome and prognosis in early onset severe preeclampsia are worse than those in late onset severe preeclampsia.

Expression of thrombomodulin in maternal plasma and placental tissue in early onset severe preeclampsia

To explore the thrombomodulin (TM) expression levels changes in plasma and placenta in patients with early onset severe preeclampsia. Sixty cases of severe preeclampsia women who delivered in the affiliated Xuzhou Maternity and Child Health Care Hospital of Xuzhou Medical College were enrolled in the study from June 2012 to February 2014, including 30 patients with early onset severe preeclampsia (early onset group), and 30 patients with late onset severe preeclampsia (late onset group). Healthy pregnant women were divided into two control groups according to gestational weeks at delivery: early control group (n = 23, at 28-33⁺⁶ weeks), and late control group (n = 30, delivered after 34 weeks). ELISA was used to detect the levels of TM in plasma. Immunohistochemistry SP was applied to detect the TM protein expression on placenta. TM mRNA was determined by reverse transcription polymerase chain reaction (RT)-PCR technique. (1) TM level in plasma in early onset group and late onset group were (90.8 ± 6.9) and (87.5 ± 7.0) µg/L, and TM level in plasma in early control group and late control group were (37.7 ± 2.3) and (37.7 ± 2.5) µg/L. Plasma TM level in early onset group was higher than that in late onset group, early control group and late control group. The TM level had no statistically significant compare of early-onset group to late onset group. (P > 0.05). The plasma TM level in early onset group was significantly higher than that in early control group (P < 0.05), and the plasma TM level in late onset group was significantly higher than that in late control group (P < 0.05). (2) TM expressed mainly in the membrane and cytoplasm of placental syncytiotrophoblasts and endothelial cells. The expression of TM protein in early onset group was 47% (14/30), significantly lower than that in late onset group, early control group and late control group (P < 0.05), in which the positive rate were 90% (27/30), 91% (21/23) and 93% (28/30) respectively (P < 0.05). There was no difference between late onset group and late control group (P > 0.05). There was no difference between early control group and late control group (P > 0.05). (3) TM mRNA expression in early onset group, late onset group, early control group and late control group were 0.14 ± 0.06, 0.89 ± 0.23, 0.88 ± 0.22 and 0.93 ± 0.19, respectively. The expression of TM mRNA in early onset group was significantly lower than that in late onset group, early control group and late control group (P < 0.05), and the difference between early control group and late control group was not statistically significant (P > 0.05). There was no difference between late onset group and late control group (P > 0.05). There was no difference between early control group and late control group (P > 0.05). Decreased expression of TM in placenta may be associated with the pathogenesis of early onset severe preeclampsia, there may be different pathogenesis in early onset and late onset severe preeclampsia.

Association between decreased plasma levels of soluble human leukocyte antigen-G and severe pre-eclampsia.

The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late-onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109-0.591, P=0.010), second (OR=0.315, 95% CI=0.158-0.627, P=0.001), and third (OR=0.170, 95% CI=0.054-0.533, P=0.002) trimester was a risk factor for severe preeclampsia. Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia.

Genome-Wide Mapping of 5mC and 5hmC Identified Differentially Modified Genomic Regions in Late-Onset Severe Preeclampsia: A Pilot Study.

Preeclampsia (PE) is a leading cause of perinatal morbidity and mortality. However, as a common form of PE, the etiology of late-onset PE is elusive. We analyzed 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels in the placentas of late-onset severe PE patients (n = 4) and normal controls (n = 4) using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing ([h]MeDIP-seq), and the results were verified by (h)MeDIP-qPCR. The most significant differentially methylated regions (DMRs) were verified by MassARRAY EppiTYPER in an enlarged sample size (n = 20). Bioinformatics analysis identified 714 peaks of 5mC that were associated with 403 genes and 119 peaks of 5hmC that were associated with 61 genes, thus showing significant differences between the PE patients and the controls (>2-fold, p<0.05). Further, only one gene, PTPRN2, had both 5mC and 5hmC changes in patients. The ErbB signaling pathway was enriched in those 403 genes that had significantly different5mC level between the groups. This genome-wide mapping of 5mC and 5hmC in late-onset severe PE and normal controls demonstrates that both 5mC and 5hmC play epigenetic roles in the regulation of the disease, but work independently. We reveal the genome-wide mapping of DNA methylation and DNA hydroxymethylation in late-onset PE placentas for the first time, and the identified ErbB signaling pathway and the gene PTPRN2 may be relevant to the epigenetic pathogenesis of late-onset PE.

P103. Relationship between severe preeclampsia onset with IUGR incidence at Dr. Soetomo General Hospital in 2013

Introduction Intrauterine growth restriction can be a serious problem in neonates because it is associated with increased morbidity and mortality and long-term sequel in the future. One of the main maternal risk factors of intrauterine growth restriction is severe preeclampsia in pregnancy. As we know preeclampsia has two types, first is early onset of severe preeclampsia that caused by failed of trophoblast invasion to the spiral artery and the second is late onset of severe preeclampsia that caused by such as chronic hypertension, diabetes mellitus, obese, tuberculosis, SLE ( systemic lupus erythematosus) and other autoimmune disease. Objectives We are curious about relationship onset of severe preeclampsia with intrauterine growth restriction. This study analyzed the relationship between the onset of severe preeclampsia and the incidence of intrauterine growth restriction in Dr. Soetomo General Hospital Surabaya. The aim of this study was to prove whether early onset severe preeclampsia is a risk factor for intrauterine growth restriction compared with late-onset severe preeclampsia. Methods This was an analytic observational cross-sectional study. Sampling technique we used in this study was random sampling. The data in this study were taken from the medical records at the Department of Obstetrics and Gynecology Dr. Soetomo General Hospital Surabaya in January 2013 until December 2013, which include in these data are gestational age, preeclampsia onset, sex, birth weight, and intrauterine growth restriction incidence. The onset of severe preeclampsia was divided into two categories: first, early onset (⩽34 weeks) and second, late onset (>34 weeks). Data analysis was performed in two stages, the univariate and bivariate analysis. Data analysis used was cross tabulation and chi-square test with level of significance of 95% ( p Results Results showed that prevalence rate of IUGR in early-onset severe preeclampsia was 1.32 times higher compared with late-onset severe preeclampsia. However, there was no statistically significant association between early-onset preeclampsia and the incidence of IUGR. ( p = 0.53; PR=0.71; 95% CI = 0.25–2.07). Late-onset severe preeclampsia also had no effect on the incidence of intrauterine growth restriction ( p = 0.53; PR = 1.40; 95% CI = 0.48–4.08). Conclusion It can be concluded that the onset of severe preeclampsia had no effect on the incidence of intrauterine growth restriction.

Number and distribution of myofibroblasts and α-smooth muscle actin expression levels in fetal membranes with and without gestational complications.

The permeability and tension of fetal membranes (FMs) is associated with extracellular matrix proteins produced largely by myofibroblasts (MFBBs). α-smooth muscle actin (α-SMA) is involved in the contraction of MFBBs and has been implicated as a special biomarker of MFBBs in non-vessel FM. The present study demonstrated, by using immunohistochemistry, reverse-transcription polymerase chain reaction and western blotting, that MFBBs were mainly distributed in chorioamniotic mesoderm at 16-21 weeks and in chorionic mesoderm at 22-40 weeks, respectively, while overlapping with each other at 16-40 weeks. In addition, a quantity of MFBBs were identified in chorionic epithelia at 16-40 weeks. The MFBBs were distributed parallel to the FMs. The quantities of MFBBs and the expression levels of α-SMA were negatively associated with increasing gestational progress and of amniotic fluid indexes in full-term females (those from oligohydramnios were higher than polyhydramnios); however, the thickness of the FM's mesoderm remained unchanged. Of note, the number of MFBBs in early-onset severe pre-eclampsia (EOSP) was significantly decreased in comparison with that in EOSP controls and late-onset severe pre-eclampsia (LOSP), while that in LOSP was higher than that in LOSP controls. The present data indicated that the changes in the quantity and distribution of MFBBs in the FM affects the permeability and tension of the FM. In addition, the findings suggested that the expression levels of α-SMA in the FM also contributed to the properties of the FM. Simultaneously, the number and distribution of MFBBs and the expression levels of α-SMA in the FM may be involved in the mechanisms of development, apoptosis and trophoblast-MFBB transformation of the FM.

Expression of markers of endoplasmic reticulum stress-induced apoptosis in the placenta of women with early and late onset severe pre-eclampsia

ObjectivesEndoplasmic reticulum (ER) stress-induced apoptosis has been implicated in severe pre-eclampsia (SPE) and is characterized by the activation of three signaling pathways: PKR-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring 1 (Ire1). This study was designed to investigate the role of ER stress in the pathogenesis of SPE. Materials and methodsPlacental tissues were collected from 32 women with normal pregnancies and two cohorts of women with early (n = 32) or late onset (n = 32) SPE. The expression of glucose-regulated protein 78 (GRP78), PERK, eukaryotic initiation factor 2 subunit a (eIF2α), activating transcription factor 6 (ATF4), ATF6, Ire1, CHOP (ClEBP homologus protein), and caspase 12 mRNA and protein in the placentas was analyzed using real-time reverse transcription-polymerase chain reaction and Western blotting, respectively. ResultsThe levels of GRP78, PERK, eIF2α, CHOP, ATF6, and caspase 12 mRNA and protein expression were significantly higher in the placentas of women with early and late SPE than in the control women, whereas there were no differences in ATF6 and Ire1 mRNA and protein. ConclusionER stress-induced apoptosis was important in the development of SPE, especially in early onset SPE and was probably due to the activation of the PERK signaling pathway.

Increased expression of prostasin contributes to early-onset severe preeclampsia through inhibiting trophoblast invasion.

To investigate the potential role of prostasin, as an invasion suppressor, in the process of trophoblast invasion in preeclampsia. This case-control study included 19 early-onset severe preeclampsia (⩽ 34 weeks), 20 late-onset severe preeclampsia (>34 weeks) and 20 normal term pregnant women. Immunohistochemistry was conducted to identify the cellular localization of prostasin, as well as the matrix metalloproteinase 2 (MMP2) and MMP9 in the placenta tissues. Enzyme-linked immunosorbent assay was performed to analyze the expression of these three proteins in placental homogenates. The effect of prostasin on the invasive and migratory ability of trophoblast cells was detected by transwell assays. We also examined the regulation of the prostasin antibody in the MMP2 and MMP9 secretion by HTR-8/SVneo cells via blocking the prostasin activity. This study demonstrated that the prostasin, MMP2 and MMP9 were all expressed in the placental syncytiotrophoblasts. Increased expression of prostasin was detected in cases with early-onset severe preeclampsia compared with the late-onset and control groups (P < 0.05), whereas the expression patterns of MMP2 and MMP9 in placental homogenates were opposite to that of prostasin (P < 0.05). Recombinant prostasin inhibited the invasion and migration of trophoblast cells, whereas prostasin antibody enhanced the MMP2 and MMP9 secretion in a dose- and time-dependent manner. These findings suggest that prostasin may suppress the invasion process in preeclampsia by attenuating MMP2 and MMP9 secretion.