Late-onset Severe Preeclampsia Research Articles

Association of pre-pregnancy body mass index with early- and late-onset severe preeclampsia.

To determine whether maternal pre-pregnancy body mass index is associated with preeclampsia with severe features, categorized as early- or late-onset. This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, Rajavithi Hospital. The inclusion criteria were singleton pregnant women who gave birth at Rajavithi Hospital between January 1, 2015 and October 31, 2019. The study group was pregnant women diagnosed with preeclampsia with severe features while the control group was those without preeclampsia. Body mass index was classified based on The Regional Office for the Western Pacific Region of the World Health Organization criteria. The primary outcome was association of pre-pregnancy body mass index and risk of preeclampsia with severe features, classified by gestational age into early- (<34 weeks) and late- (≥34 weeks) onset preeclampsia. Comparisons were made using the Student's t-test, Chi-square, or Fisher's exact tests, as appropriate. Logistic regression was used to assess associations. There were 589 pregnant women in the control group and 519 women with preeclampsia in the study group. The study group was subdivided into early-onset (32.4%, 168/519) and late-onset (67.6%, 351/519) preeclampsia. Women who had preeclampsia with severe features had higher mean pre-pregnancy BMI than those without preeclampsia. Women with class I (63.6%, 136/214) and II (81.0%, 111/137) obesity (body mass index, 25.0-29.9 and ≥30.0kg/m2, respectively) had significantly increased risk of preeclampsia with severe features (adjusted odds ratio 2.71, 95% confidence interval 1.85-4.00 and adjusted odds ratio 3.84, 95% confidence interval 2.22-6.64, respectively). In preeclampsia subgroup analysis, class I obesity was significantly associated with late-onset severe preeclampsia (adjusted odds ratio 2.02, 95% confidence interval 1.40-2.93), while class II obesity was significantly associated with both early- and late-onset severe preeclampsia (adjusted odds ratio 1.69, 95% confidence interval 1.01-2.84 and adjusted odds ratio 2.13, 95% confidence interval 1.36-3.33, respectively). Class I and II obesity are significantly associated with preeclampsia with severe features. Class I obesity is significantly related to late-onset severe preeclampsia with, whereas class II obesity is associated with both early- and late-onset severe preeclampsia.

Neuroserpin: A potential biomarker for early-onset severe preeclampsia

Preeclampsia is a hypertensive disease of pregnancy associated with intense inflammatory and pro-coagulant responses. Neuroserpin is a serine protease inhibitor that has been involved in neurological and immune processes and has not yet been investigated in preeclampsia. Herein, we evaluated neuroserpin levels in association with other inflammatory mediators (IL-17A, IL-33, and CXCL-16) during severe preeclampsia. The mediators’ plasma levels were measured by immunoassays in 24 pregnant women with severe preeclampsia (early preeclampsia: N = 17, late preeclampsia: N = 7), 34 normotensive pregnant women, and 32 non-pregnant women. In general, pregnancy was associated with higher levels of neuroserpin, IL-17A, IL-33, and CXCL-16 than the non-pregnant state. However, this increase was attenuated in pregnancies complicated by severe preeclampsia. Although neuroserpin levels did not differ between normotensive pregnant women and pregnant women with severe preeclampsia, neuroserpin levels tended to be lower in early-onset than in late-onset severe preeclampsia. There were positive correlations between neuroserpin and IL-17A, neuroserpin and CXCL-16, and IL-17A and CXCL-16 levels in women with severe preeclampsia. In addition, although the risk for developing severe preeclampsia was higher in older women in this study, maternal age did not significantly influence the mediators’ levels, nor their correlations in the preeclampsia group. In summary, our data suggest that neuroserpin might be a potential biomarker for early-onset severe preeclampsia and, that the imbalance among neuroserpin, IL-17A, IL-33, and CXCL-16 levels may be associated with the pathogenesis of preeclampsia, regardless of the maternal age.

Association between polymorphisms rs2228001 and rs2228000 in XPC and genetic susceptibility to preeclampsia: a case control study

BackgroundXeroderma pigmentosum complementation group C (XPC) is a DNA damage recognition protein that plays an important role in nucleotide excision repair and can reduce oxidative stress, which may be involved in the development of preeclampsia (PE). Therefore, the aim of this study was to explore whether XPC polymorphisms were relevant to the genetic susceptibility to PE in Chinese Han women.MethodA total of 1276 healthy pregnant women were included as the control group and 958 pregnant women with PE as the case group. DNA was extracted from peripheral blood samples to perform genotyping of loci rs2228001 and rs2228000 in XPC through real-time quantitative polymerase chain reaction (PCR). The relationship between XPC and susceptibility to PE was evaluated by comparing the genotypic and allelic frequencies between the two groups of pregnant women.ResultsPolymorphism of rs2228000 may be associated with PE risk and allele T may play a protective role (genotype, χ2 = 38.961, P < 0.001 and allele χ2 = 21.746 P < 0.001, odds ratio (OR) = 0.885, 95% confidence interval (CI) = 0.840-0.932). No significant difference was found between the two groups in rs2228001,(genotype χ2 = 3.148, P = 0.207 and allele χ2 = 0.59, P = 0.442, OR = 1.017, 95% CI = 0.974–1.062). When the frequencies of genotypes and alleles for early- and late-onset PE, mild PE and severe PE were compared with those of controls, the results were consistent with the large clinical sample.ConclusionOur data suggest that the genetic variant rs2228000 in XPC may be associated with PE risk in Chinese Han women, and that pregnant women with the TT genotype have a reduced risk of PE. Further investigations are needed to confirm these findings in other regions or larger prospective populations.

The expression of ATP-sensitive potassium channels in human umbilical arteries with severe pre-eclampsia

The aim of this study is to establish the expression of ATP-sensitive potassium channels(KATP) in human umbilical arteries with severe pre-eclampsia. Real-time quantitative PCR and western blotting were used to detect the mRNA and protein expression levels of KATP channel subunits Kir6.1 and SUR2B in human umbilical arteries from normal pregnant and those with severe pre-eclampsia, early onset severe pre-eclampsia and late onset severe pre-eclampsia. The mRNA and protein levels of SUR2B in the severe pre-eclampsia group were lower than those in the normal group (P < 0.001), and the expression of Kir6.1 was not statistically significant between the two groups (P > 0.05). The mRNA and protein levels of SUR2B in early onset severe pre-eclampsia group were lower than those in late onset severe pre-eclampsia group (P < 0.001). There was no significant difference in expression of Kir6.1 between the two groups (P > 0.05). The mRNA and protein expression levels of SUR2B in pregnant women with severe pre-eclampsia were lower than those in normal pregnant women, suggesting that the expression of the SUR2B of the KATP channel may be related to the occurrence and development of severe pre-eclampsia. Compared with late onset severe pre-eclampsia, the mRNA and protein expression levels of SUR2B were lower in the umbilical arteries of women with early onset severe pre-eclampsia, suggesting that the occurrence time of severe pre-eclampsia may be related to the extent reduced expression of the SUR2B of the KATP channel.

The Difference in Average of Maternal Serum Hypoxia-Inducible Factors-1α Levels between Early Onset and Late-Onset Severe Preeclampsia

The purpose of this study is to know the difference average of maternal serum levels of HIF-1α between early-onset and late-onset severe preeclampsia. This study used a cross sectional comparative study design that conducted in Februari 2020 - Agustus 2020 in the SMF / Obstetrics and Gynecology department of RSUP dr. M. Djamil Padang, RSUD Achmad Mochtar, RSUD Pariaman, RSUD M Zein Painan. We used consecutive sampling method which consists of 60 pregnant women who fulfill the inclusion and exclusion criteria. They were divided into two groups early-onset severe preeclampsia and late-onset severe preeclampsia. HIF-1α tests were done using ELISA method. The average of maternal serum levels of HIF-1α in late-onset severe preeclampsia is found to be the highest when compared to the early-onset severe preeclampsia, 1,37 ± 1,08 ng/ml vs 0,69 ± 0,11 ng/ml. This difference is significant with the Mann-whitney non parametrical statistical test (p &lt;0.05). There is a significant difference average of maternal serum levels of HIF-1α between early-onset and late-onset severe preeclampsiaKeywords: early onset severe preeclampsia, late onset preeclampsia late onset, maternal serum levels of HIF-1α

Distinct placental molecular processes associated with early-onset and late-onset preeclampsia.

Background: Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes.Methods: We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in.Results: We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients.Conclusion: These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.

Involvement of WNT2 in trophoblast cell behavior in preeclampsia development

ABSTRACT This study aimed to determine the WNT2 expression in patients with severe preeclampsia and to explore the function of WNT2 dysregulation on the biological behaviors of trophoblast cells. The WNT2 and β-catenin expression in the patients with early-onset and late-onset severe preeclampsia and normal controls was determined. Subsequently, WNT2 was overexpressed and knocked down in HTR8 cells and WNT2 signaling pathway in regulating trophoblast cell proliferation, migration, invasion, and apoptosis were evaluated in vitro. The mRNA and protein expression levels of WNT2 and β-catenin were decreased in patients with preeclampsia, especially early-onset severe preeclampsia. Overexpression of WNT2 promoted trophoblast cell proliferation, migration, and invasion and inhibited apoptosis in vitro, whereas knockdown of WNT2 had opposite effects. The findings of this study reveal that WNT2 and β-catenin were decreased expressed in patients with preeclampsia. Decreased expression of WNT2 may inhibit trophoblast cell proliferation, migration, and invasion but induced apoptosis. WNT2 may serve as a promising biomarker for early detection of preeclampsia.

Decorin levels in early- and late-onset preeclampsia

Preeclampsia (PE) is a pregnancy complication caused by typically limited proliferation, apoptosis, migration, and invasion of extra-trophoblast cells. Decorin (DCN) is a decidua-derived transforming growth factor (TGF)-binding proteoglycan which exerts multiple physiological functions such as collagen fibrillogenesis, myogenesis, angiostasis, and restraining placental invasiveness by adversely regulate proliferation, migration, and invasiveness of human extravillous trophoblast cells. Preeclampsia is mainly classified as early- and late-onset PE according to the timing of the disease onset. In the present study, we aimed to investigate the DCN levels in early-onset PE (EOPE, < 34 weeks) and late-onset severe PE (LOPE, ≥ 34 weeks) and uncomplicated pregnancies. In this case-control study, serum samples were obtained from 21 pregnant women with EOPE and 29 pregnant women with LOPE, as well as from 38 healthy controls (n = 12 early-onset controls and n = 26 late-onset controls) with uncomplicated pregnancies. The mean DCN level was statistically significantly higher in the early-onset PE controls than late-onset PE controls (p = 0.040). Although the mean DCN level was higher in the early-onset PE controls than EOPE and LOPE groups, it did not reach statistical significance (p = 0.119 and p = 0.117, respectively). Although DCN has been thought to play a role in the pathophysiology of PE, our study results show that DCN is not a useful predictive marker of EOPE and LOPE. Further large-scale studies are needed to draw a definitive conclusion.

Preeclampsia severa de aparición temprana: características clínico epidemiológicas en la unidad de cuidados intensivos materno del INMP agosto del 2014 a setiembre del 2018

Objetivo: conocer las características epidemiológicas clínicas y patológicas de la Preeclampsia severa (PES) de aparición temprana y la PES de aparición tardía de pacientes admitidas a la Unidad de Cuidados Intensivos Maternos (UCIM) del Instituto Nacional Materno Perinatal (INMP). Material y métodos: se realizó un estudio descriptivo transversal comparativo en el que se revisaron las historias clínicas desde EL primero de agosto del 2014 hasta el 30 de Setiembre del 2018 obteniendo 332 registros de pacientes con PES de aparición Temprana y 325 registros de pacientes con PES de aparición tardía.Resultados: La edad promedio de las pacientes con diagnóstico de PES de aparición temprana fue 27.84 años [IC 26.88- 28.81 (p: 0.72)], el promedio de estancia hospitalaria fue mayor en las pacientes con PES de aparición temprana (p 0.006). Los recién nacidos mostraron diferencias significativas con respecto al peso (p= 0.000), la talla (p= 0.000); el APGAR al minuto fue significativamente menor en el grupo de aparición temprana (p=0.000). No se encuentra diferencia significativa entre la PES de aparición temprana y la eclampsia (p=0.481). Conclusión: No observamos diferencias significativas entre PES de aparición temprana y eclampsia. Los recién nacidos, presentan peso, talla y APGAR menores en el grupo de aparición temprana que el grupo de aparición tardía.

Relationship between polymorphisms of CXCL3 gene and preeclampsia

Background Preeclampsia (PE), a pregnancy-specific disease, is a main cause of maternal and perinatal mortality in the world, the exact pathogenesis of which is still unknown. Recent studies have found it is a disorder caused by multiple factors and genes. Previously, we found a significantly abnormal expression of CXCL3 in plasma and placenta of severe preeclampsia. Here, we intend to explore the association of polymorphisms in CXCL3 gene with preeclampsia susceptibility in women from western China. Methods Four hundred eighty-one pregnant women were involved in this case-control study, including 83 early-onset severe preeclampsia cases, 114 late-onset severe preeclampsia cases, 41 mild preeclampsia cases and 243 normal pregnancies. The rs370655 variant in CXCL3 was detected by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results No significantly reduced risk of preeclampsia is observed in the rs370655 AA genotype compared with other genotypes (AG versus AA: OR = .82, 95%CI = .54–1.26; GG versus AA: OR = .95, 95%CI = .56–1.61). After subgroup analysis, there are still no significant differences among various genotypes in the mild preeclampsia, early-onset severe preeclampsia and late-onset sever preeclampsia. Conclusion Our study suggests that rs370655 polymorphism in CXCL3 gene may be not the risk factor of preeclampsia, exploring other consequential SNPs in CXCL3 gene may help to predict the preeclampsia.

Serum Levels of Complement Factors C1q, Bb, and H in Normal Pregnancy and Severe Pre-Eclampsia.

BackgroundThis study aimed to determine the diagnostic role of serum levels of complement C1q, Bb, and H in nonpregnant women, women with normal pregnancy, and women with severe pre-eclampsia.Material/MethodsHealthy nonpregnant women (n=30), women with early, middle, and late normal pregnancy (n=30, respectively), and women with severe pre-eclampsia (n=73) were studied. The pre-eclampsia study group included early-onset cases (n=43) and late-onset cases (n=30). Serum levels of Bb were determined by enzyme-linked immunosorbent assay (ELISA), and C1q and H were tested by a turbidimetric immunoassay method.ResultsIn the pre-eclampsia study group, compared with women with normal pregnancy, serum levels of C1q remained stable throughout pregnancy, and Bb levels declined from mid-pregnancy (p=0.250). Serum levels of factor H increased in the middle and late stages of pregnancy, and C1q and H were lower in early-onset severe pre-eclampsia (p<0.001, p=0.009, respectively) and late-onset severe pre-eclampsia (p<0.001, p=0.031, respectively) compared with the early-onset control and late-onset control groups. Serum levels of Bb increased in early-onset severe pre-eclampsia (p=0.001) and late-onset severe pre-eclampsia (p=0.003) compared with early-onset control and late-onset control groups. The area under the receiver operator curve (ROC) for serum C1q, Bb, and H for the diagnosis of early-onset severe pre-eclampsia were 0.814 (95% CI, 0.712–0.917), 0.743 (95% CI, 0.638–0.859), and 0.681(95% CI, 0.556–0.806), and late-onset severe pre-eclampsia were 0.805 (95% CI, 0.694–0.913), 0.796 (95% CI, 0.680–0.911), and 0.662 (95% CI, 0.524–0.800).ConclusionsThe classical and alternative pathways of complement were activated in patients with severe pre-eclampsia. Serum levels of C1q, Bb, and H should be studied further as potential diagnostic markers for severe pre-eclampsia.

Expression and significance of TNF-α and M-CSF in placenta tissue of early severe preeclampsia

Objective To investigate the expression and clinical significance of macrophage colony stimulating factor (M-CSF) and tumor necrosis factor α (TNF-α) in placenta of early onset severe preeclampsia (PE). Methods Immunohistochemical SP method was used to detect the expression of M-CSF and TNF-α in 77 cases paraffin specimens from Department of Pathology, First Affiliated Hospital of Henan University of Science and Technology from September 2015 to September 2017, including 35 cases of early-onset severe PE, 42 cases of late-onset severe PE and 30 cases of normal pregnant women. Results (1)The positive expression rates of M-CSF in control group, late-onset severe PE group and early-onset severe PE group were 30% (9/30), 61.90% (26/42), 82.86% (29/35), respectively.The difference was statistically significant (χ2=18.90, P<0.05). The positive expression rates of early-onset severe PE group were significantly higher than those in control group (χ2=18.59, P<0.05), and the difference was statistically significant..The positive expression of early-onset severe PE group was higher than that of late-onset severe PE group, and the difference was statistically significant (χ2=4.017, P<0.05). (2) The positive expression rates of TNF-α in control group, late-onset severe PE group and early-onset severe PE group were 33.33% (10/30), 69.05% (29/42), 91.43% (32/35), respectively.The difference was statistically significant (χ2=30.21, P<0.05). The positive expression of TNF-α in early-onset severe PE group was significantly higher than that in control group (χ2=21.37, P<0.05), and the difference was statistically significant.The positive expression of M-CSF and TNF-a in early-onset severe PE group was higher than that in late-onset severe PE group, and the difference was statistically significant (χ2=4.529, P<0.05); (3) The expression of M-CSF and TNF-α was positively correlated in PE (r=0.441, P=0.000). Conclusion Placental damage is higher in early-onset severe PE, and is related to the severity of the disease.The levels of M-CSF and TNF-alpha in placenta of PE patients may play a synergistic role in the occurrence and development of PE. Key words: Preeclampsia; Early onset severe preeclampsia; Placental tissue; Macrophage colony-stimulating factor; Tumor necrosis factor α

Point-of-Care Ultrasound Abnormalities in Late-Onset Severe Preeclampsia: Prevalence and Association With Serum Albumin and Brain Natriuretic Peptide.

Pilot studies applying point-of-care ultrasound (POCUS) in preeclampsia indicate the presence of pulmonary interstitial edema, cerebral edema, and cardiac dysfunction. Laboratory markers of oncotic pressure (albumin) and cardiac dysfunction (brain natriuretic peptide [BNP]) may be abnormal, but the clinical application remains unclear. We investigated the prevalence of pulmonary interstitial syndrome (PIS), cardiac dysfunction, and increased optic nerve sheath diameter (ONSD) in late-onset preeclampsia with severe features. The primary aim was to examine the association between PIS or ONSD and maternal serum albumin level. The secondary aims were to explore the association between cardiac dysfunction and PIS, ONSD, BNP, and serum albumin level and between POCUS-derived parameters and a suspicious or pathological cardiotocograph. Ninety-five women were enrolled in this prospective observational cohort study. A POCUS examination of lungs, heart, and ONSD was performed. PIS was defined as a bilateral B-line pattern on lung ultrasound and diastolic dysfunction according to an algorithm of the American Society of Echocardiography. ONSD >5.8 mm was interpreted as compatible with raised intracranial pressure (>20 mm Hg). Serum BNP and albumin levels were also measured. PIS, diastolic dysfunction, systolic dysfunction, and raised left ventricular end-diastolic pressure (LVEDP) were present in 23 (24%), 31 (33%), 9 (10%), and 20 (25%) women, respectively. ONSD was increased in 27 (28%) women. Concerning the primary outcome, there was no association between albumin level and PIS (P = .4) or ONSD (P = .63). With respect to secondary outcomes, there was no association between albumin level and systolic dysfunction (P = .21) or raised LVEDP (P = .44). PIS was associated with diastolic dysfunction (P = .02) and raised LVEDP (P = .009; negative predictive value, 85%). BNP level was associated with systolic (P < .001) and diastolic dysfunction (P = .003) and LVEDP (P = .007). No association was found between POCUS abnormalities and a suspicious/pathological cardiotocograph (P = .07). PIS, diastolic dysfunction, and increased ONSD were common in preeclampsia with severe features. Cardiac ultrasound abnormalities may be more useful than albumin levels in predicting PIS. The absence of PIS may exclude raised LVEDP. The further clinical relevance of PIS and raised ONSD remains to be established. BNP level was associated with cardiac ultrasound abnormalities. Although this study was not designed to directly influence clinical management, the findings suggest that POCUS may serve as a useful adjunct to clinical examination for the obstetric anesthesiologist managing these complex patients.

Downregulation of receptor tyrosine kinase-like orphan receptor 1 in preeclampsia placenta inhibits human trophoblast cell proliferation, migration, and invasion by PI3K/AKT/mTOR pathway accommodation

IntroductionInvasive deficiency of the trophoblast and poor remodeling of the uterine spiral arteries were probably the primary pathogenesis causes of preeclampsia (PE). The expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) during embryogenesis had been previously confirmed and was closely related to the function of tumor cells, which was similar to the characteristics of trophoblasts. In this work, we investigated the expression profile of ROR1 in preeclampsia placentas and the functional role of ROR1 in trophoblast cells, as well as the associated molecular mechanisms. MethodsThe localization expression of ROR1 in the placenta was detected by immunohistochemistry in 20 cases of normal term pregnancy, preterm delivery, late-onset severe PE, and early-onset severe PE, respectively. The expression levels were determined by fluorescence quantitative PCR and Western blot. The influence of ROR1 on trophoblast proliferation, migration, invasion, and potential regulatory pathways was evaluated in HTR-8/SVneo cell lines by transient transfection methods. ResultsThe levels of ROR1 in the placental tissues in PE were significantly lower than those in normal term pregnancy and preterm delivery. Moreover, the expression levels of ROR1 in early-onset severe PE were significantly lower than those in its late counterparts. ROR1 overexpression increased cell proliferation, migration, and invasion of HTR-8/SVneo cells, whereas its silencing had the opposite effect. Meanwhile, the phosphorylation levels of critical kinases in the PI3K/AKT/mTOR pathways were increased by ROR1 overexpression, whereas they were decreased by the silencing of ROR1. ConclusionROR1 might be involved in the development of PE through regulating trophoblast viability, migration, and invasion by PI3K/AKT/mTOR signaling pathway.

Neurological manifestations and neuroimaging presentations in patients with severe preeclampsia: predisposing factors and clinical implications.

Neurological manifestations and neuroimaging abnormalities are common in patients with severe preeclampsia; however, the differences between these abnormal features occurring during early- and late-onset severe preeclampsia are unclear, and the factors associated with abnormal imaging changes in patients with neurological manifestations have not yet been fully elucidated. A retrospective study was conducted on 172 patients with severe preeclampsia from January 2017 to June 2018 in the Department of Neurology and Obstetrics, Shengjing Hospital of China Medical University. The neurological manifestations, clinical parameters, laboratory, and neuroimaging findings were analyzed. Early- and late-onset preeclampsia were diagnosed in 83 and 89 patients, respectively. Headache and dizziness were more common in patients with early-onset preeclampsia than in patients with late-onset preeclampsia (p= 0.013, p= 0.004, respectively). Serum uric acid, creatinine, and urea nitrogen were significantly elevated in the patients with early-onset preeclampsia (p< 0.001, p= 0.004, and p= 0.005, respectively). Neuroimaging was performed in 81 patients, of which 57 were positive. Findings indicating cerebral edema were the most common neuroimaging abnormality. Gestational weeks (p= 0.014), headache (p< 0.001), and blood urea nitrogen level (p= 0.027) may be associated with positive imaging findings. By multiple logistic regression, headache (OR = 10.2, 95% CI, 2.4-42.7; p= 0.002) proved to be an independent factor associated with neuroimaging abnormality. Neurological symptoms such as headache and dizziness were more common in patients with early-onset preeclampsia. Renal dysfunction may also associate with early-onset severe preeclampsia. Cerebral edema was the most common neuroimaging abnormality, and headache might be independently associated with abnormal imagine changes.

Plasma Level of Umbilical Cord Hemeoxygenase-1 (HO-1) and Neonatal Outcome in Early Onset and Late Onset Severe Preeclampsia

Background: Many studies had discovered that early onset severe preeclampsia (EO-PE) has worst maternal and neonatal outcome compared to late-onset type (LO-PE), related to its placental involvement. Severe preeclampsia was defined as newly onset severe hypertension developed after 20 weeks gestation in previously normal blood pressure women, with coexistence of proteinuria, or maternal organ or uteroplacental dysfunction. Hemeoxygenase-1 (HO-1) is an enzyme with multiple effect which is protective to pregnancy.Materials and Methods: The total study subjects were 40 pregnant women consisted of 10 EO-PE, 10 normal early onset pregnancy (EO-NP), 10 LO-PE, and 10 normal late onset pregnancy (LO-NP). As much as 5 cc of plasma from umbilical cord was taken as soon as the baby was born, and the HO-1 level was examined by enzyme-linked immunosorbent assay (ELISA). The primary outcome were umbilical cord HO-1 level and neonatal composite morbidity (low Apgar score, low birthweight, length of stay &gt;5 day, respiratory distress syndrome, jaundice and neonatal death).Results: The plasma level of HO-1 in EO-PE subjects were lower than EO-NP (0.96±0.37 ng/mL vs. 2.43±0.58 ng/mL, p&lt;0.001). There were no significant differences in the level of HO-1 in LO-PE and LO-NP (2.18±1.07 ng/mL vs. 3.02±0.64 ng/mL, p=0.277). Plasma level of umbilical cord HO-1 of EO-PE patients was lower compared to LO-PE (0.96±0.37 ng/mL vs. 2.18±1.07 ng/mL, p=0.034). Neonatal outcome of EO-PE was worse than EO-NP (p=0.033), and LO-PE (p=0.003), while in LO-PE did not different with LO-NP (p=0.211).Conclusion: EO-PE is associated with lower plasma umbilical cord level of HO-1 and worse neonatal outcome compared to LO-PE. This indicating abnormal placental blood vessel development, placental ischemia in EO-PE, lead to reduced uteroplacental perfusion and significantly worse neonatal outcome compared to LO-PE.Keywords: severe preeclampsia, early onset preeclampsia, late onset preeclampsia, hemeoxygenase-1

Association between polymorphisms in CXCR2 gene and preeclampsia.

BackgroundPreeclampsia is a serious pregnancy‐specific syndrome with incompletely understood pathogenesis. Previous study has demonstrated that the decreased CXCR2 in preeclamptic placentas may contribute to the development of preeclampsia. The role of single nucleotide polymorphisms (SNPs) of CXCR2 gene in the pathogenesis of preeclampsia remains largely unexplored. Thus, we aimed to investigate the association between polymorphisms of CXCR2 gene and preeclampsia in Han Chinese women.MethodsTotally 481 pregnant women, including 243 controls and 238 patients with preeclampsia were recruited. The rs1126579 and rs2230054 polymorphisms in CXCR2 gene were tested using polymerase chain reaction‐restriction fragment length polymorphism method.ResultsSignificantly increased risk of preeclampsia was observed in the rs1126579 CC or TC/CC genotypes when compared with TT genotype (CC vs. TT: odss ratio [OR] = 2.11, 95% confidence interval [CI] = 1.18–3.76, p = 0.039; TC/CC vs. TT: OR = 1.89, 95% CI = 1.29–2.78, p = 0.001). Markedly higher risk of preeclampsia was found to be associated with rs1126579 TC genotype (TC vs. TT/CC: OR = 1.48, 95% CI = 1.04–2.12, p = 0.031). After stratification analysis, the different distribution of TC/CC genotypes was particularly significant in the severe preeclampsia group (OR = 2.15, 95% CI = 1.42–3.24, p < 0.01), the early‐onset severe preeclampsia group (OR = 1.97, 95% CI = 1.14–3.42, p = 0.013), and the late‐onset severe preeclampsia group (OR = 2.29, 95% CI = 1.39–3.78, p < 0.01). Besides, TC genotype carriers had a 1.55 fold increased risk of severe preeclampsia (95% CI = 1.06–2.27, p = 0.022) and a 1.80 fold increased risk of late onset severe preeclampsia (95% CI = 1.14–2.83, p = 0.01) than those of TT/CC genotype carriers.ConclusionsOur study suggests a genetic association between rs1126579 polymorphism in CXCR2 gene and increased risk of preeclampsia. These data provide a new clue for future investigation.

Expression of S100 calcium-binding protein A8 in peripheral blood of patients with preeclampsia during pregnancy

A total of 30 late onset severe preeclampsia (LS-PE) patients and 30 early onset severe preeclampsia (ES-PE) patients were selected as Experimental group, and 30 normal pregnant were selected as Control group. Expression of S100 calcium-binding protein A8 (S100A8) mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect expression of S100A8 protein and inflammatory factors. Levels of uric acid (UA) and creatinine (CRE) were measured using an automatic biochemical analyzer. Urinary protein (UPRO) content was measured using biuret colorimetry. S100A8 levels were significantly higher in experimental groups than in control groups at mRNA and protein levels ( P &lt; 0.05). Significantly increased contents of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-12, UA, CRE, and UPRO, and decreased level of IL-10 were found in experimental groups than in control groups ( P &lt; 0.05). Compared with patients with ES-PE, significantly higher levels of TNF-α, IL-12, IL-6, UA, CRE, and UPRO, and lower level of IL-10 were found in patients with LS-PE. S100A8 plays pivotal roles in the development of preeclampsia through the interactions with other inflammatory factors.

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.