Prediction of Early- and Late-Onset Pre-Eclampsia in the Preclinical Stage via Placenta-Specific Extracellular miRNA Profiling.

Pre-eclampsia (PE) is one of the severe complications of pregnancy in 3-8% of all cases and is one of the leading causes of maternal and perinatal mortality. The fundamental role in the pathogenesis of PE is assigned to maternal and/or placental factors, whereby the combination and manifestation of which determines the time of onset of the clinical symptoms of PE (before or after 34 weeks of gestation) and their severity. It is known that the expression level of miRNAs, the regulators of signaling cascades in the cell, depends on gestational age. In the present study, we focused on the identification of the placenta-specific miRNAs that differentiate between early- and late-onset pre-eclampsia (ePE and lPE) throughout pregnancy, from the first to the third trimester. A total of 67 patients were analyzed using small RNA deep sequencing and real-time quantitative PCR, which resulted in a core list of miRNAs (let-7b-5p, let-7d-3p, let-7f-5p, let-7i-5p, miR-22-5p, miR-451a, miR-1246, miR-30e-5p, miR-20a-5p, miR-1307-3p, and miR-320e), which in certain combinations can predict ePE or lPE with 100% sensitivity and 84-100% specificity in the 1st trimester of pregnancy. According to the literature data, these miRNA predictors of PE control trophoblast proliferation, invasion, migration, syncytialization, the endoplasmic reticulum unfolded protein response, immune tolerance, angiogenesis, and vascular integrity. The simultaneous detection of let-7d-3p, miR-451a, and miR-1307-3p, resistant to the repeated freezing/thawing of blood serum samples, in combination with biochemical (b-hCG and PAPP-A) and ultrasound (UAPI) parameters, allowed us to develop a universal model for the prediction of ePE and lPE onset (FPR = 15.7% and FNR = 9.5%), which was validated using a test cohort of 48 patients and demonstrated false-positive results in 26.7% of cases and false negatives in 5.6% of cases. For comparison, the use of the generally accepted Astraia program in the analysis of the test cohort of patients led to worse results: FPR = 62.1% and FNR = 33.3%.

[Nephrotic syndrome during pregnancy. Is it chronic glomerulonephritis or preeclampsia? Case report].

Nephrotic syndrome (NS) during pregnancy is a fairly rare pathology and its descriptions in the literature are few. For a long time, NS was associated only with an exacerbation of chronic glomerulonephritis or de novo nephritis, however, the experience of recent years has shown that NS can be a manifestation of the classical obstetric pathology - preeclampsia (PE). The appearance of massive proteinuria with the development of NS is most typical for early PE, which, of course, makes diagnosis difficult, especially if PE develops at an unusually early time (up to 20 weeks). To describe PE that does not fit into the classical criteria, the term "atypical" PE is now used, the development of which can be promoted by both obstetric and somatic risk factors. The presented clinical observation describes the development of early (within 14 weeks) severe PE with the NS at the onset of the disease in a patient with the first multiple pregnancy and complete hydatidiform mole (HM) of one of the fetuses. The progression of nephropathy with the addition of thrombotic microangiopathy and HELLP syndrome made it possible to assume the diagnosis of PE with a high probability. The rapid relief of all clinical manifestations after delivery confirmed this assumption. The role of HM as the main trigger of unusually early PE is discussed. Apparently, the patient's trophoblast disease in the form of hydatidiform mole caused the formation of a severe angiogenic imbalance already in the early stages of pregnancy, which led to the development of PE, which manifested NS as a consequence of podocytopathy due to VEGF deficiency. Thus, the development of NS in a pregnant patient without a history of kidney disease dictates, first of all, the exclusion of PE, until proven otherwise.

Microarray analysis of preterm preeclampsia.

Premature preeclampsia is the second cause of maternal mortalities around the world. To investigate its potential driving mechanism(s), we constructed a multi-regulatory-mediated preeclampsia dysfunction module. Through combining differential expression analysis, co-expression analysis, and enrichment analysis, we obtained 23 sets of preeclampsia expression disorder modules in the disease, which involve the modular aggregations of 3016 genes. The modules were subjected to be analyzed for GO and KEGG paths for enrichment analysis. Based on these pivotal regulators, it is possible to manipulate the essential parts of the modular subnetwork and study their cooperative acts to mediate the driving mechanism of the preeclampsia. Simultaneously, they mainly cause the onset of the disease through the regulation of the apoptotic signaling pathway, down-regulation of an inflammatory response and retinol metabolism. This may present a potential driving mechanism for the disease. The predictor analysis of the regulators showed a series of non-coding RNAs that have potentially significant regulatory effects on the disease, including miR-182-5p, miR-200b-3p, miR-23a-3p, miR -429, miR-590-3p, and transcription factors. These pivotal regulators might mediate the potential driving processes. Based on a comprehensive multivariate analysis, we found a possible driving mechanism in which significant pivotal regulators were used as distinct functional segments in the preterm preeclampsia-driven process.

Peculiarities of the Expression of TLR4 and Inhibitor of TLR-Cascade Tollip in the Placenta in Earlyand Late-Onset Preeclampsia.

We studied the peculiarities of the expression of TLR4 and its inhibitor Tollip in placentas obtained from women aged 23-40 years with early- and late-onset preeclampsia. Histological examination of placental tissue (hematoxylin and eosin staining) and immunohistochemical analysis with primary monoclonal antibodies to TLR4 and Tollip were performed on serial paraffin sections. It was found that the expression of TLR4 increased with increasing gestation term in both the syncytiotrophoblast and vascular endothelium of the placental villi (p<0.05). The expression of TLR4 in syncytiotrophoblast and in the endothelium in early preeclampsia was also significantly (p<0.00001) higher than in the reference group (preterm birth before 34 weeks gestation). In the vascular endothelium of placental villi, the expression of TLR4 in placentas from women with early-onset preeclampsia was higher than in late-onset preeclampsia (p=0.002), while Tollip was lower in early-onset preeclampsia than in the reference group. In preeclampsia, especially in early-onset preeclampsia, marked changes in the expression of TLR4 and Tollip in the placental tissue were detected; the severity of preeclampsia correlated with the degree of damage to the placental villi.

High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

OBJECTIVE: This study was to evaluate effects of high normal blood pressure (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe preeclampsia. METHODS: We conducted a multicenter, national representative retrospective cohort study. HNBP was defined as systolic blood pressure between 130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used multivariable logistic regression to examine the associations of HNBP and the risks of above three types of preeclampsia. RESULTS: We included 58 054 women who were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group, and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1 217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood pressure, women with HNBP had significantly higher odds of total preeclampsia (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR = 8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the dose-response relationship between continuous blood pressure and the odds ratio of three types of preeclampsia. The fraction of early preeclampsia associated with prehypertension was 58.6%, which was higher than those of total preeclampsia (42.2%) or severe preeclampsia (40.5%). CONCLUSION: Women in early pregnancy with HNBP more likely develop total preeclampsia, early preeclampsia and severe preeclampsia, compared to those with optimal blood pressure. HNBP contribute more to early preeclampsia than severe preeclampsia. Our study provided robust epidemiological evidences for monitoring HNBP in early pregnancy to reduce the risks of preeclampsia.

Value of Placental Volume and Vascular Flow Indices as Predictors of Early and Late Preeclampsia at First Trimester.

INTRODUCTION: We evaluated the utility of placental volume and three-dimensional (3D) vascular flow indices to predict early and late preeclampsia. MATERIAL AND METHODS: In 1,004 pregnancies attending routine care, we recorded first-trimester screening program for aneuploidy (FTSA) parameter and measured uterine artery pulsatility index (uterine-a PI). Placental volume and vascular flow indices were obtained using 3D power Doppler and VOCAL techniques. RESULTS: Placental volume was lower and uterine-a PI was higher in both early and late preeclampsia groups versus nonaffected pregnancies. The prediction rate of placental volume in late preeclampsia was higher than that of uterine-a PI (AUROC 0.707 vs. 0.581, p < 0.011). The inclusion of placental volume improved significantly the prediction rate of total and late preeclampsia in the models constructed with maternal characteristics, FTSA, and uterine-a PI (AUROC 0.745 vs. 0.818, p < 0.004, and 0.740 vs. 0.812, p < 0.012, respectively). The inclusion of vascular indices did not improve the predictive value of these models. DISCUSSION: Placental volume was an independent predictor of total, early, and late preeclampsia and its inclusion in combined predictive models significantly improved prediction rates. Reduced placental volume observed at first trimester in women with early and late preeclampsia suggests that these entities are the clinical expression of a similar pathophysiological process.

Early-onset Preeclampsia in Lupus Pregnancy.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that occurs during childbearing years and has been associated with preeclampsia. However, little is known about preeclampsia of early onset, which is associated with severe adverse maternal and perinatal outcomes. METHODS: Using national population-based Swedish registers we identified women with SLE (≥2 visits with corresponding ICD codes) and a sample without SLE who gave birth to singleton infants 2001-12. Risk ratios (RR) and 95% confidence intervals (CI) for early-onset preeclampsia (defined by ICD codes corresponding to preeclampsia registered at <34 weeks) in SLE women were calculated based on adjusted modified Poisson models for first, subsequent, and all pregnancies. RESULT: Among 742 births to women with SLE and 10 484 births to non-SLE women, there were 32 (4.3%) and 55 (0.5%) diagnoses of early-onset preeclampsia respectively. SLE was associated with an increased risk of early-onset preeclampsia (RR 7.8, 95% CI 4.8, 12.9, all pregnancies). The association remained similar upon restriction to women without pregestational hypertension. Adjustment for antiphospholipid syndrome (APS)-proxy attenuated the association. RRs for early-onset preeclampsia were smaller for subsequent pregnancies (RR 4.7, 95% CI 2.0, 11.2) compared to first and all (see above). CONCLUSION: Women with SLE are at increased risk of early-onset preeclampsia and this increased risk may be independent of the traditional risk factors such as pregestational hypertension, APS, BMI, or smoking. Women with SLE during pregnancy should be closely monitored for early-onset preeclampsia and future research needs to identify the non-traditional preeclampsia factors that might cause this serious outcome.

Placental histological patterns and uterine artery Doppler velocimetry in pregnancies complicated by early or late pre-eclampsia.

OBJECTIVES: To study placental patterns in pregnancies complicated by pre-eclampsia (PE) and to verify whether the findings are related to gestational age (GA) at PE onset and second-trimester uterine artery (UtA) Doppler. METHODS: For all pre-eclamptic women who delivered between January 2010 and December 2013, we collected retrospectively data related to placental findings and UtA Doppler velocimetry performed at PE onset. The study cohort was divided into groups according to early-onset (EO) or late-onset (LO) PE. Regression analysis was performed to test the ability of UtA Doppler velocimetry to predict subsequent development of placental lesions, after correcting for possible confounders. RESULTS: Placental abnormalities occurred with a significantly lower incidence in the LO-PE group (n = 72) than in the EO-PE group (n = 105) (P = 0.02). Irrespective of GA at PE onset, UtA pulsatility index (PI) was able to predict macroscopic infarctions (P = 0.001), distal villous hypoplasia (P = 0.03), decidual arteriolopathy (P = 0.03), villous infarcts (P < 0.001), syncytiotrophoblast 'knots' (P = 0.02), microcalcifications (P = 0.02), perivillous fibrin deposition (P = 0.02) and placental hemorrhage (P = 0.01). CONCLUSIONS: Similar placental abnormalities were present in both EO-PE and LO-PE groups, although with quantitative differences according to GA and UtA Doppler velocimetry at PE onset. Histological patterns were predicted by UtA-PI, independently of GA, supporting the use of UtA Doppler velocimetry as the key criterion in PE classification. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Pathophysiology of Preeclampsia-Induced Vascular Dysfunction and Implications for Subclinical Myocardial Damage and Heart Failure.

Tragically, preeclampsia is a leading cause of pregnancy-related complications and is linked to a heightened risk for morbid and fatal cardiovascular disease (CVD) outcomes. Although the mechanism connecting preeclampsia to CVD risk has yet to be fully elucidated, evidence suggests distinct pathways of early and late preeclampsia with shared CV risk factors but with profound differences in perinatal and postpartum risk to the mother and infant. In early preeclampsia, <34 weeks of gestation, systemic vascular dysfunction contributes to near-term subclinical myocardial damage. Hypertrophy and diastolic abnormalities persist postpartum and contribute to early onset heart failure (HF). This HF risk remains elevated decades later and contributes to premature death. Black women are at the highest risk of preeclampsia and HF. These findings support closer monitoring of women postpartum, especially for those with early and severe preeclampsia to control chronic hypertension and reduce the potentially preventable sequelae of heightened CVD and HF risk.

A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia.

OBJECTIVE: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. METHODS: This retrospective case-control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. RESULTS: 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924-2926) pg/mL vs. 630 (448-4002) pg/mL, p = .026, and late preeclampsia: 1833 (1441-5534) pg/mL vs. 910 (526-6178) pg/mL, p = .021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070-3188) pg/mL vs. without MVM: 888 (812-1781) pg/mL, p = .03; and with MVM vs. control: 630 (448-4002) pg/mL, p = .04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p = .3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392-3135) pg/mL vs. control: 910 (526-6178), p = .045; and without MVM: 2023 (1578-8936) pg/mL vs. control, p = .01]. CONCLUSIONS: MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.

Placental morphology, apoptosis, angiogenesis and epithelial mechanisms in early-onset preeclampsia.

OBJECTIVES: Early-onset preeclampsia is a form of preeclampsia requiring delivery before 34 weeks of gestation. The etiology is unknown, but placental dysfunction appears crucial. We evaluated the immunohistochemical expression of the antiapoptotic protein Bcl-2, the angiogenetic factors VEGF and PlGF, and the epithelial factors HGF, c-Met and STAT3 in placental samples of pregnancies complicated by early-onset preeclampsia. MATERIALS AND METHODS: Placental sections were obtained from 41 women with early-onset preeclampsia (cases) and from 31 uncomplicated pregnancies (controls). A standard haematoxylin and eosin stain was used to assess histological structure. Immunohistochemical expression of Bcl-2, VEGF, PlGF, HGF, c-Met and STAT3 was analyzed. RESULTS: Mean gestational age was 32 weeks in cases and 39 weeks in controls. Microscopically, sections from women with preeclampsia showed a disorder of villous development as a distal villous hypoplasia with placental undergrowth. The immunoistochemical expression of Bcl-2 (p < 0.0001), VEGF (p = 0.0323), PlGF (p = 0.002), HGF (p < 0.0001), c-Met (p < 0.0001) and STAT3 (p = 0.0004) were significantly lower in placentas of complicated pregnancies compared to uncomplicated ones. CONCLUSIONS: Early-onset preeclampsia is associated with a disorder of villous development. Apoptotic, angiogenetic and epithelial mechanisms are simultaneously impaired and contribute to placental dysfunctions.

Rentabilidad de la ratio angiogénica en el seguimiento de gestantes de alto riesgo de preeclampsia precoz tratadas con ácido acetilsalicílico / Profitability of the angiogenic ratio in the follow-up of pregnant women at high risk of early preeclampsia treated with acetylsalicylic acid

Objetivo: Evaluar el valor predictivo negativo de la ratio antigénica y conocer su rentabilidad para descartar preeclampsia precoz en pacientes de alto riesgo de desarrollarla, con profilaxis de ácido acetilsalicílico. Métodos: Se realizó un estudio descriptivo transversal que recogió a las gestantes con cribado de preeclampsia precoz de alto riesgo (384 gestantes) en el Hospital Santa Lucía durante el año 2021, para lo que se usó test Elecsys® tabulado a un riesgo mayor a 1/150 en primer trimestre, y que tomaran ácido acetilsalicílico antes de la semana 16, quedando en 368 gestantes vistas en las semanas 20, 26, 31 y 36. Se realizó biometría, ratio angiogénica y doppler. Resultados: La incidencia de preeclampsia precoz en la población fue 4 casos (incidencia 1,08 %). Son significativos por su alto valor predictivo negativo del 100 % de preeclampsia precoz: la ratio angiogénica mayor a 38 en la semana 26 y el doppler de las uterinas en semana 20 y 26. Conclusión: En gestaciones con cribado de alto riesgo de preeclampsia que tomen ácido acetilsalicílico, una ratio angiogénica menor a 38 en la semana 26, además de un doppler uterino normal en semana 20 y 26 permite reducir el seguimiento gestacional(AU)

Objective: Our main objective was to evaluate the negative predictive value of the angiogenic ratio and to know its profitability to rule out early preeclampsia in patients at high risk of early preeclampsia with acetylsalicylic acid prophylaxis. Methods: A cross-sectional descriptive study was carried out that included pregnant women with high-risk early preeclampsia screening (384 pregnant women) at the Santa Lucía Hospital during the year 2021, for which the Elecsys® test tabulated at a risk >1/ was used. 150 in the first trimester, and who take acetylsalicylic acid before week 16, leaving 368 pregnant women seen in weeks 20, 26, 31 and 36, with biometry, angiogenic ratio and Doppler performed. Results: The incidence of early preeclampsia in the population was 4 cases (incidence 1.08%). They are significant due to their high negative predictive value of 100% of early preeclampsia: Angiogenic ratio > 38 in week 26, uterine Doppler in weeks 20 and 26. Conclusion: Pregnancies with high risk screening for preeclampsia who take acid acetylsalicylic acid, an angiogenic ratio < 38 at week 26 in addition to a normal uterine Doppler at weeks 20 and 26 allows for reduced gestational follow-up(AU)

Lower maternal serum tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in early preeclampsia. A retrospective study.

OBJECTIVE: To determine whether maternal serum concentrations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine with anti-inflammatory activity, also involved in cardiovascular morbidity, differ between women with early preeclampsia (<34 weeks) and those with uncomplicated pregnancies. STUDY DESIGN: This nested case control study included 40 women carrying a single fetus with an uncomplicated pregnancy and 20 women with early preeclampsia (<34 weeks). Data were matched 1:2 for gestational age at the time of venipuncture (28-34 weeks of gestation), converted into multiples of the median and adjusted for maternal weight. The maternal serum TRAIL concentrations were determined using an enzyme immunoassay. RESULTS: The TRAIL concentrations were lower in the patients with early preeclampsia when compared with those of the control group, being 29.64 ±â€¯8.83 pg/dL and 43.8 ±â€¯12.53 pg/dL (p-value < 0.001), respectively. The difference was also present after multiple of median conversion and maternal weight adjustment. The quoted multiple of median values were 1.00 ±â€¯0.27 and 0.82 ±â€¯0.23, respectively (p-value < 0.001). CONCLUSIONS: Serum TRAIL concentrations are significantly reduced in patients with early preeclampsia. This result is in line with the presence of an intravascular inflammation typical of preeclampsia. The lower levels of TRAIL detected in preeclampsia should be useful for a more proper selection of women with long-term cardiovascular risk later in life.

FVIIa-antithrombin levels in early and late preeclampsia.

BACKGROUND: Preeclampsia (PE) is associated with a hypercoagulability state. According to the gestational age (GA) at the onset of the disease, PE has been classified as early (GA<34weeks) and late (GA≥34weeks). It has been admitted that early PE is associated with ischemic placental lesions, while in late PE an adequate or slightly impaired placentation occurs, which suggests that the two clinical forms have distinct etiology. Tissue factor (TF) binds and activates plasma factor VII triggering the coagulation. The inhibitor antithrombin (AT), along with tissue factor pathway inhibitor, acts as an inhibitor of the FVIIa-TF pathway. Once the TF-FVIIa complex is formed, the binding and transfer of FVIIa to AT is facilitated and FVIIa activity is inhibited. OBJECTIVE: We evaluated the FVIIa-AT complex levels in pregnant women with early and late severe PE (sPE), in order to verify if this biomarker can be useful for discriminating the two forms of the disease. METHODS: We evaluated 26 pregnant with severe early PE and 19 pregnant with severe late PE. FVIIa-AT levels were measured by STACLOT® (Diagnostica Stago). Statistical analysis was done by Mann-Whitney test. RESULTS: Increased FVIIa-AT levels were found in early sPE [148.4pM (137.1)] compared to late sPE [95.9pM (66.5)] (P=0.046), which suggests a higher pro-coagulant state when PE onset occurs before 34weeks of gestation. CONCLUSION: These pioneer data allow inferring the relevance of FVIIa-AT as a device for early sPE diagnosis. However, the clinical relevance of FVIIa-AT complex surely needs to be fully clarified.

High dose antithrombin supplementation in early preeclampsia: A randomized, double blind, placebo-controlled study.

INTRODUCTION: Antithrombin levels are often reduced in preeclampsia and infusion of antithrombin concentrates has been reported to prolong gestation in severe preeclampsia. We aimed to evaluate efficacy and safety of high-dose antithrombin (ATIII) supplementation in patients with single pregnancies and preeclampsia occurring before 30 weeks of gestation. MATERIALS AND METHODS: In November 2004 a double-blind, placebo-controlled trial (code KB033) was started in 13 Italian centers. The planned sample size was of 240 patients (intention-to-treat, ITT population) to detect a 30% relative risk reduction of the primary endpoint, composite perinatal morbidity. Eligible patients were randomized to high dose AT (3000 IU/daily, ATIII Kedrion S.p.A., Italy), or placebo (1% glycine) for 7 days or less until delivery, whichever came first. The per-protocol (PP) population was restricted to patients receiving at least two days of treatment. RESULTS: The study was terminated by the sponsor in October 2007 after the enrolment of 38 evaluable patients - 20 randomized to high dose AT and 18 to placebo, 27 treated for 2 days or more - out of 164 screened patients. Enrolment failures were mainly represented by requirement for immediate delivery and consent refusal (91 patients). The primary endpoint occurred in 15 of 38 patients (39.5%), with a relative risk in the AT arm of 0.85 (95% CI 0.42-1.75) and 0.79 (95% CI 0.30-2.11) in the ITT and PP populations, respectively. Living neonates in the two arms had similar weight at birth, Apgar scores, and duration of hospitalization in neonatal ICU. In mothers, AT supplementation was associated with reduced blood loss at delivery and with surrogate laboratory markers (LDH, d-dimer). CONCLUSIONS: The results of this markedly underpowered trial, albeit suggestive of a potential maternal benefit, cannot support high-dose AT supplementation to improve fetal/neonatal outcomes in early preeclampsia.

An analysis of the differences between early and late preeclampsia with severe hypertension.

Preeclampsia is clinically divided into early onset and late onset preeclampsia based on the gestational age at delivery. Although the diagnostic criteria are the same in each subgroup of preeclampsia, it has been suggested that the maternal and perinatal mortalities of early onset and late onset preeclampsia are different. However, studies that compare clinical parameters or laboratory biomarkers between early onset and late onset preeclampsia are limited. Data on 177 women with early or late preeclampsia with severe hypertension were collected from a University Teaching Hospital from January 2010 to January 2011 and analysed. Data included all the clinical parameters and laboratory biomarkers of liver and renal function. 63 women and 114 women were diagnosed with early and late preeclampsia with severe hypertension, respectively. There was no difference in the maternal age and the incidence of clinical symptoms including edema, vision disturbance, severe headache and stillbirth between two groups. There was a decrease in alkaline phosphatase levels in early preeclampsia with severe hypertension but other markers of liver function were not altered. However, renal function including blood urea nitrogen, creatinine and uric acid were significantly higher in early preeclampsia with severe hypertension. Umbilical artery systolic velocity/diastolic velocity ratio was significantly higher in early preeclampsia with severe hypertension. Our data demonstrates that the laboratory biomarkers of renal function differ between early and late preeclampsia with severe hypertension. The severity of renal dysfunction correlated with the time of delivery in preeclampsia with severe hypertension.

Placental perfusion in normal pregnancy and early and late preeclampsia: a magnetic resonance imaging study.

OBJECTIVE: Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy. METHODS: The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥ 34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated. RESULTS: Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001). CONCLUSION: Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.

Study on relationship between serum cystatin C and AOPP with early preeclampsia pregnancy outcome / 中国免疫学杂志

Objective:To discuss the relationship between serum advanced oxidation protein products (AOPP)and cystatin C with the early preeclampsia pregnancy outcome.Methods:Clinical data of 75 patients received treatment and labor at our hospital from 2011 to 2013 was retrospectively analyzed.The control group included 60 normal pregnant women who received prenatal examination in our hospital at the same time.The difference in cystatin C and AOPP level of the patients with preeclampsia and the normal group was compared.The clinical data and the adverse pregnancy outcome of the patients with preeclampsia in different severity and different outcome of pregnancy were compared.Results:A total of 135 patients were retrospective analyzed ,including 75 in observe group and 60 in control group.The SBP level in the patients with preeclampsia is obviously higher than in the normal group .The level of SB,UA,Cr and AOPP in the patients of mild group is obviously lower than in the severe group.The incidence of oligohydramnios , placental abruption,fetal growth restriction and HELLP syndrome in the patients of mild group was obviously lower than in the severe group .The differences were statistically significant.The level of cystatin C,UA,Cr and AOPP in the patients of adverse pregnancy outcome were obviously higher than in the group of good outcome of pregnancy.Conclusion:The cystatin C and AOPP level of the early preeclampsia patients is obviously increased and it has significant correlation with the pregnancy outcome in patients .