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

Measuring heart rate variability using a heart rate monitor in horses (Equus caballus) during groundwork

Measuring physiological parameters of stress in horses during groundwork, for example when involved in equine-assisted interventions, is important to gain insight into the stress levels of the horses. Heart rate and heart rate variability can be used as physiological indicators of stress in horses. Heart rate monitors could be easily incorporated into practice, as they are not expensive and easy to use. However, it is questionable whether heart rate monitors present accurate heart rate variability results in exercising horses, similar to electrocardiograms. The aim of this study was to determine the accuracy of heart rate monitors for the assessment of heart rate variability in horses during groundwork exercise. Simultaneous telemetric electrocardiograms (Televet) and heart rate monitor (Polar H10 transmitter and M430 receiver, Hylofit electrodes) recordings were performed on 28 horses (15 mares and 13 geldings). Results indicate that the heart rate monitor accurately determined heart rate and time-domain heart rate variability parameters when compared to electrocardiograms during both baseline and groundwork conditions. As expected, heart rate significantly increased and the heart rate variability significantly decreased during groundwork compared to baseline conditions. This indicates that the heart rate monitor can be used to accurately determine heart rate variability during groundwork

Long-term neurodevelopmental outcome after intrauterine transfusion for hemolytic disease of the fetus/newborn: the LOTUS study

ObjectiveTo determine the incidence and risk factors for neurodevelopmental impairment (NDI) in children with hemolytic disease of the fetus/newborn treated with intrauterine transfusion (IUT).Study DesignNeurodevelopmental outcome in children at least 2 years of age was assessed using standardized tests, including the Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of Intelligence, and the Wechsler Intelligence Scale for Children, according to the children's age. Primary outcome was the incidence of neurodevelopmental impairment defined as at least one of the following: cerebral palsy, severe developmental delay, bilateral deafness, and/or blindness.ResultsA total of 291 children were evaluated at a median age of 8.2 years (range, 2–17 years). Cerebral palsy was detected in 6 (2.1%) children, severe developmental delay in 9 (3.1%) children, and bilateral deafness in 3 (1.0%) children. The overall incidence of neurodevelopmental impairment was 4.8% (14/291). In a multivariate regression analysis including only preoperative risk factors, severe hydrops was independently associated with neurodevelopmental impairment (odds ratio, 11.2; 95% confidence interval, 1.7–92.7).ConclusionIncidence of neurodevelopmental impairment in children treated with intrauterine transfusion for fetal alloimmune anemia is low (4.8%). Prevention of fetal hydrops, the strongest preoperative predictor for impaired neurodevelopment, by timely detection, referral and treatment may improve long-term outcome

Identification of distinct seminal plasma cytokine profiles associated with male age and lifestyle characteristics in unexplained recurrent pregnancy loss

Background: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may contribute to pregnancy loss. This study investigated cytokine expression profiles in seminal plasma of male partners of couples with unexplained recurrent pregnancy loss (RPL) and the association with clinical and lifestyle characteristics, including smoking, alcohol consumption and body mass index (BMI). Methods: In the seminal plasma of 52 men who visited a specialised RPL clinic the levels of 25 pre-selected cytokines, chemokines and growth factors were measured by Bio-Plex assay or ELISA. Two-way hierarchical cluster analysis was performed. Identified patient clusters were compared on clinical and lifestyle characteristics. Results: Two distinct cytokine expression profiles in the seminal plasma were revealed by cluster analysis. Patient cluster I showed relatively higher levels of pro-inflammatory cytokines, including IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-12, IL-18 and TNF-alpha, compared to Patient cluster II. Men belonging to Patient cluster I were significantly older and had significantly more lifestyle risk factors compared to men in Patient cluster II. Conclusion: Cluster analysis suggested the existence of a less favourable pro-inflammatory cytokine expression profile, being present in part of men affected by RPL and associated with advanced male age and lifestyle risk factors. These findings may serve as a starting point for further research into underlying mechanisms and ultimately lead to novel diagnostic and therapeutic approaches for couples with RPL.Research into fetal development and medicin

Clinical value of early viscoelastometric point-of-care testing during postpartum hemorrhage for the prediction of severity of bleeding: a multicenter prospective cohort study in the Netherlands

Introduction To evaluate rotational fibrin-based thromboelastometry (ROTEM(R) FIBTEM) with amplitude of clot firmness at 5 min (A5) as an early point-of-care parameter for predicting progression to severe postpartum hemorrhage, and compare its predictive value with that of fibrinogen.Material and methods Prospective cohort study in the Netherlands including women with 800-1500 ml of blood loss within 24 h following birth. Blood loss was quantitatively measured by weighing blood-soaked items and using a fluid collector bag in the operating room. Both FIBTEM A5 values and fibrinogen concentrations (Clauss method) were measured between 800 and 1500 ml of blood loss. Predictive accuracy of both biomarkers for the progression to severe postpartum hemorrhage was measured by area under the receiver operating curves (AUC). Severe postpartum hemorrhage was defined as a composite endpoint of (1) total blood loss >2000 ml, (2) transfusion of >= 4 packed cells, and/or (3) need for an invasive intervention to cease bleeding.Results Of the 391 women included, 72 (18%) developed severe postpartum hemorrhage. Median (IQR) volume of blood loss at blood sampling was 1100 ml (1000-1300) with a median (interquartile range [IQR]) fibrinogen concentration of 3.9 g/L (3.4-4.6) and FIBTEM A5 value of 17 mm (13-20). The AUC for progression to severe postpartum hemorrhage was 0.53 (95% confidence interval [CI] 0.46-0.61) for FIBTEM A5 and 0.58 (95% CI 0.50-0.65) for fibrinogen. Positive predictive values for progression to severe postpartum hemorrhage for FIBTEM A5 <= 12 mm was 22.5% (95% CI 14-33) and 50% (95% CI 25-75) for fibrinogen <= 2 g/L.Conclusions The predictive value of FIBTEM A5 compared to fibrinogen concentrations measured between 800 and 1500 ml of blood loss following childbirth was poor to discriminate between women with and without progression towards severe postpartum hemorrhage.Research into fetal development and medicin

Роль страдающей депрессией матери в развитии личности ребенка

С позиций психодинамического подхода показана роль страдающей депрессией матери в формировании личности ребенка на первых этапах его постнатального развития и ее влияние на его психическое здоровье в дальнейшем.The role of the mother with depression in development of the child's personality at the first stages of the postnatal period as well as its influence on his/her mental state in future are shown from the perspective of a psychodynamic approach

Biologically induced mineralization of dypingite by cyanobacteria from an alkaline wetland near Atlin, British Columbia, Canada

Background: This study provides experimental evidence for biologically induced precipitation of magnesium carbonates, specifically dypingite (Mg(CO)(OH) ·5HO), by cyanobacteria from an alkaline wetland near Atlin, British Columbia. This wetland is part of a larger hydromagnesite (Mg(CO)(OH) ·4HO) playa. Abiotic and biotic processes for magnesium carbonate precipitation in this environment are compared. Results: Field observations show that evaporation of wetland water produces carbonate films of nesquehonite (MgCO ·3HO) on the water surface and crusts on exposed surfaces. In contrast, benthic microbial mats possessing filamentous cyanobacteria (Lyngbya sp.) contain platy dypingite (Mg (CO)4(OH)·5HO) and aragonite. Bulk carbonates in the benthic mats (δC avg. = 6.7%, δO avg. = 17.2%) were isotopically distinguishable from abiotically formed nesquehonite (δC avg. = 9.3%, δO avg. = 24.9%). Field and laboratory experiments, which emulated natural conditions, were conducted to provide insight into the processes for magnesium carbonate precipitation in this environment. Field microcosm experiments included an abiotic control and two microbial systems, one containing ambient wetland water and one amended with nutrients to simulate eutrophic conditions. The abiotic control developed an extensive crust of nesquehonite on its bottom surface during which [Mg] decreased by 16.7% relative to the starting concentration. In the microbial systems, precipitation occurred within the mats and was not simply due to the capturing of mineral grains settling out of the water column. Magnesium concentrations decreased by 22.2% and 38.7% in the microbial systems, respectively. Laboratory experiments using natural waters from the Atlin site produced rosettes and flakey globular aggregates of dypingite precipitated in association with filamentous cyanobacteria dominated biofilms cultured from the site, whereas the abiotic control again precipitated nesquehonite. Conclusion: Microbial mats in the Atlin wetland create ideal conditions for biologically induced precipitation of dypingite and have presumably played a significant role in the development of this natural Mg-carbonate playa. This biogeochemical process represents an important link between the biosphere and the inorganic carbon pool

Effectiveness of routine third trimester ultrasonography to reduce adverse perinatal outcomes in low risk pregnancy (the IRIS study): nationwide, pragmatic, multicentre, stepped wedge cluster randomised trial

Objectives To investigate the effectiveness of routine ultrasonography in the third trimester in reducing adverse perinatal outcomes in low risk pregnancies compared with usual care and the effect of this policy on maternal outcomes and obstetric interventions. Design Pragmatic, multicentre, stepped wedge cluster randomised trial. Setting 60 midwifery practices in the Netherlands. Participants 13 046 women aged 16 years or older with a low risk singleton pregnancy. Interventions 60 midwifery practices offered usual care (serial fundal height measurements with clinically indicated ultrasonography). After 3, 7, and 10 months, a third of the practices were randomised to the intervention strategy. As well as receiving usual care, women in the intervention strategy were offered two routine biometry scans at 28-30 and 34-36 weeks’ gestation. The same multidisciplinary protocol for detecting and managing fetal growth restriction was used in both strategies. Main outcome measures The primary outcome measure was a composite of severe adverse perinatal outcomes: perinatal death, Apgar score <4, impaired consciousness, asphyxia, seizures, assisted ventilation, septicaemia, meningitis, bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leucomalacia, or necrotising enterocolitis. Secondary outcomes were two composite measures of severe maternal morbidity, and spontaneous labour and birth. Results Between 1 February 2015 and 29 February 2016, 60 midwifery practices enrolled 13 520 women in mid-pregnancy (mean 22.8 (SD 2.4) weeks’ gestation). 13 046 women (intervention n=7067, usual care n=5979) with data based on the national Dutch perinatal registry or hospital records were included in the analyses. Small for gestational age at birth was significantly more often detected in the intervention group than in the usual care group (179 of 556 (32%) v 78 of 407 (19%), P<0.001). The incidence of severe adverse perinatal outcomes was 1.7% (n=118) for the intervention strategy and 1.8% (n=106) for usual care. After adjustment for confounders, the difference between the groups was not significant (odds ratio 0.88, 95% confidence interval 0.70 to 1.20). The intervention strategy showed a higher incidence of induction of labour (1.16, 1.04 to 1.30) and a lower incidence of augmentation of labour (0.78, 0.71 to 0.85). Maternal outcomes and other obstetric interventions did not differ between the strategies. Conclusion In low risk pregnancies, routine ultrasonography in the third trimester along with clinically indicated ultrasonography was associated with higher antenatal detection of small for gestational age fetuses but not with a reduced incidence of severe adverse perinatal outcomes compared with usual care alone. The findings do not support routine ultrasonography in the third trimester for low risk pregnancies. Trial registration Netherlands Trial Register NTR4367