HLA-C antibodies in women with recurrent miscarriage suggests that antibody mediated rejection is one of the mechanisms leading to recurrent miscarriage

AbstractHLA-C is the only polymorphic classical HLA I antigen expressed on trophoblast cells. It is known that higher incidence of C4d deposition on trophoblast cells is present in women with recurrent miscarriage. C4d is a footprint of antibody-mediated classical complement activation. Therefore, this study hypothesize that antibodies against HLA-C may play a role in the occurrence of unexplained consecutive recurrent miscarriage.Present case control study compared the incidence of HLA-C specific antibodies in 95 women with at least three consecutive miscarriages and 105 women with uneventful pregnancy. In the first trimester of the next pregnancy, presence and specificity of HLA antibodies were determined and their complement fixing ability. The incidence of HLA antibodies was compared with uni- and multivariate logistic regression models adjusting for possible confounders.Although in general a higher incidence of HLA antibodies was found in women with recurrent miscarriage 31.6% vs. in control subjects 9.5% (adjusted OR 4.3, 95% CI 2.0–9.5), the contribution of antibodies against HLA-C was significantly higher in women with recurrent miscarriage (9.5%) compared to women with uneventful pregnancy (1%) (adjusted OR 11.0, 95% CI 1.3–89.0). In contrast to the control group, HLA-C antibodies in the recurrent miscarriage group were more often able to bind complement.The higher incidence of antibodies specific for HLA-C in women with recurrent miscarriage suggests that HLA-C antibodies may be involved in the aetiology of unexplained consecutive recurrent miscarriage

Гігієнічні аспекти відновлення відкритих техногенних бедлендів із застосуванням осадів міських стічних вод

Зростання індивідуального водоспоживання у великих містах породжує проблему утворення і розміщення на території населених пунктів значної кількості осадів стічних вод. Часто вони представляють епідемічну небезпеку для людини і с джерелом потрапляння у довкілля техногенних хімічних речовин. На основі санітарно-гігієнічної оцінки осадів комунальних стічних вод м. Кривого Рогу розглядається можливість і даються рекомендації для її безпечного використання при створенні вторинних природних ландшафтів у місцях «місячних поверхонь» після відкритого видобутку залізної руди.Рост индивидуального водопотребления в крупных городах порождает проблему образования и размещения на территории населенных пунктов значительного количества осадков сточных вод. Часто они представляют эпидемическую опасность для человека и являются источником поступления в окружающую среду техногенных химических веществ. На основе санитарно-гигиенической оценки осадков коммунальных сточных вод г. Кривого Рога рассматривается возможность и даются рекомендации для их безопасного использования при создании вторичных природных ландшафтов в местах «лунных поверхностей» после открытой добычи железной руды.Growth of individual water consumption in large cities generates a problem of formation and placing of a considerable quantity of deposits of sewage. Often they represent epidemic danger to the person and are a receipt source in environment of technogenic chemical substances. On the basis of a sanitary-and-hygienic estimation of deposits of sewage in a city* of Krivoi Rig consider possibility and definition of the recommendation for safe use of deposits at creation of secondary natural landscapes in places of open-pit mining of iron ore

Genetic Variants in Pre-Eclampsia: A Meta-Analysis EDITORIAL COMMENT

Clinical epidemiolog

Regional differences in severe postpartum hemorrhage: A nationwide comparative study of 1.6 million deliveries

Background: The incidence of severe postpartum hemorrhage (PPH) is increasing. Regional variation may be attributed to variation in provision of care, and as such contribute to this increasing incidence. We assessed reasons for regional variation in severe PPH in the Netherlands. Methods: We used the Netherlands Perinatal Registry and the Dutch Maternal Mortality Committee to study severe PPH incidences (defined as blood loss ≥ 1000 mL) across both regions and neighborhoods of cities among all deliveries between 2000 and 2008. We first calculated crude incidences. We then used logistic multilevel regression analyses, with hospital or midwife practice as second level to explore further reasons for the regional variation. Results: We analyzed 1599867 deliveries in which the incidence of severe PPH was 4.5%. Crude incidences of severe PPH varied with factor three between regions while between neighborhoods variation was even larger. We could not explain regional variation by maternal characteristics (age, parity, ethnicity, socioeconomic status), pregnancy characteristics (singleton, gestational age, birth weight, pre-eclampsia, perinatal death), medical interventions (induction of labor, mode of delivery, perineal laceration, placental removal) and health care setting. Conclusions: In a nationwide study in The Netherlands, we observed wide practice variation in PPH. This variation could not be explained by maternal characteristics, pregnancy characteristics, medical interventions or health care setting. Regional variation is either unavoidable or subsequent to regional variation of a yet unregistered variable

Towards standardized criteria for diagnosing chronic intervillositis of unknown etiology: A systematic review

Research into fetal development and medicin

One-sided chronic intervillositis of unknown etiology in dizygotic twins: a description of 3 cases

Chronic intervillositis of unknown etiology (CIUE) is a rare, poorly understood, histopathological diagnosis of the placenta that is frequently accompanied by adverse pregnancy outcomes including miscarriage, fetal growth restriction, and intrauterine fetal death. CIUE is thought to have an immunologically driven pathophysiology and may be related to human leukocyte antigen mismatches between the mother and the fetus. Dizygotic twins with one-sided CIUE provide an interesting context to study the influence of immunogenetic differences in such cases. The main immune-cell subsets were investigated using immunohistochemistry. We identified three dizygotic twin pregnancies in which CIUE was present in only one of the two placentas. Two of the pregnancies ended in term delivery and one ended in preterm delivery. Presence of CIUE was correlated with lower placental weight and lower birthweight. Relative number of CD68, CD56, CD20, and CD3 positive cells were comparable between co-twins. The presence of one-sided CIUE in dizygotic twin pregnancy was associated with selective growth restriction in the affected twin. This suggests a unique fetal immunogenetic contribution to the pathogenesis of CIUE. Further study of dizygotic and monozygotic placentas affected by CIUE could identify new insights into its pathophysiology and into the field of reproductive immunology.Research into fetal development and medicin

Clinical value of early assessment of hyperfibrinolysis by rotational thromboelastometry during postpartum hemorrhage for the prediction of severity of bleeding: a multicenter prospective cohort study in the Netherlands

Introduction: Coagulopathy may be the result of hyperfibrinolysis and could exacerbate bleeding following childbirth. Timely recognition of hyperfibrinolysis during the earliest stages of postpartum hemorrhage could identify women at risk of more severe blood loss who may benefit from targeted anti-fibrinolytic therapy. Rotational thromboelastometry (ROTEM (R)) is a point-of-care test that could detect hyperfibrinolysis. The aim of this study was to evaluate whether early assessment of hyperfibrinolysis by ROTEM during postpartum hemorrhage could predict progression to severe postpartum hemorrhage.Material and methods: During a prospective cohort study in the Netherlands among women with postpartum hemorrhage (total blood loss at least 1000 ml within 24 h after childbirth) ROTEM measurements were performed following 800-1500 ml of blood loss. Hyperfibrinolysis was defined as an enzymatic fibrinolysis index (ROTEM EXTEM maximum clot lysis [ML] minus the ROTEM APTEM ML) above 15%. Severe postpartum hemorrhage was defined as a composite end point of total blood loss greater than 2000 ml, transfusion of four or more units of packed cells, and/or need for an invasive intervention. The predictive value of hyperfibrinolysis for progression to severe postpartum hemorrhage was assessed by area under the receiver operating curve ( AUC) and positive and negative predictive values.Trial registration: ClinicalTrials. gov (NCT02149472).Results: Of 390 women included, 82 (21%) had severe postpartum hemorrhage. Four (1%) women had thromboelastometric evidence of hyperfibrinolysis, of whom two developed severe postpartum hemorrhage. The AUC for enzymatic fibrinolysis index more than 15% for progression to severe postpartum hemorrhage was 0.47 (95% CI 0.40-0.54). Positive and negative predictive values for this index were 50.0% (95% CI 6.8-93.2) and 79.3% (95% CI 74.9-83.2), respectively.Conclusions: Thromboelastometric evidence of hyperfibrinolysis was rare in women with postpartum hemorrhage when assessed between 800 and 1500 ml of blood loss. The clinical predictive value of viscoelastometric point-of-care testing for hyperfibrinolysis for progression to severe postpartum hemorrhage during early postpartum hemorrhage is limited.Clinical epidemiolog

Induction of labor with a Foley catheter and the risk of subsequent preterm birth: A follow-up study of two randomized controlled trials (PROBAAT-1 and -2)

OBJECTIVE:The objective of this study was to evaluate the preterm birth rate in a subsequent pregnancy in women who had undergone term induction with a Foley catheter in comparison to induction with prostaglandins. METHODS:This was a follow-up study of two large randomized controlled trials. In the original trials (PROBAAT-1 and PROBAAT-2), women with a term, singleton pregnancy in cephalic presentation with an indication for labor induction were randomized to either a 30cc Foley catheter or prostaglandins (i.e. vaginal prostaglandin E2 in PROBAAT 1 and oral misoprostol in PROBAAT 2). The main outcome measures were preterm birth <37 weeks gestation and preterm birth <34 weeks gestation. Data were collected from hospital charts on subsequent pregnancies from hospitals participating in this follow-up study. RESULTS:14 hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 162 women (14%) were lost to follow-up. Of the 572 women randomized to a Foley catheter, 251 women had a subsequent pregnancy beyond 16 weeks gestation, versus 258 women of the 570 women who received prostaglandins. There were no differences in baseline characteristics. The overall preterm birth rate was 9/251 (3.6%) in the Foley catheter group versus 10/258 (3.9%) in the prostaglandin group (RR 0.93; 95%CI 0.38-2.24), with spontaneous preterm birth rates of 5/251 (2.0%) versus 5/258 (1.9%) respectively (RR 1.03, 95%CI 0.30-3.51). CONCLUSIONS:In women with a singleton term pregnancy, induction of labor with a 30cc Foley catheter is not associated with an increased risk of preterm birth in a subsequent pregnancy as compared to induction of labor with prostaglandins. This article is protected by copyright. All rights reserved.M. D. T. de Vaan, D. Blel, K. W. M. Bloemenkamp, M. Jozwiak, M. L. G. ten Eikelder ... B. W. Mol ... et al

Coagulation parameters during the course of severe postpartum hemorrhage: a nationwide retrospective cohort study

Research into fetal development and medicin