Venous thromboembolism in obese pregnant women: approach to diagnosis and management

Venous thromboembolism (VTE) remains among the leading causes of maternal mortality in the developed world, presenting variably as deep vein thrombosis (DVT), pulmonary embolism (PE) or cerebral vein thrombosis (CVT), among others. Obesity in particular has been recognized as the principal contributing factor to the risk of VTE in pregnancy and with the global increase in the rates of obesity affecting reproductive age women, heightened awareness of the risk and consequences of VTE in this population are vital. Thus, prophylaxis, diagnosis and treatment of VTE in the obese gravida are discussed

The Ontario Mother and Infant Study (TOMIS) III: A multi-site cohort study of the impact of delivery method on health, service use, and costs of care in the first postpartum year

Abstract Background The caesarean section rate continues to rise globally. A caesarean section is inarguably the preferred method of delivery when there is good evidence that a vaginal delivery may unduly risk the health of a woman or her infant. Any decisions about delivery method in the absence of clear medical indication should be based on knowledge of outcomes associated with different childbirth methods. However, there is lack of sold evidence of the short-term and long-term risks and benefits of a planned caesarean delivery compared to a planned vaginal delivery. It also is important to consider the economic aspects of caesarean sections, but very little attention has been given to health care system costs that take into account services used by women for themselves and their infants following hospital discharge. Methods and design The Ontario Mother and Infant Study III is a prospective cohort study to examine relationships between method of delivery and maternal and infant health, service utilization, and cost of care at three time points during the year following postpartum hospital discharge. Over 2500 women were recruited from 11 hospitals across the province of Ontario, Canada, with data collection occurring between April 2006 and October 2008. Participants completed a self-report questionnaire in hospital and structured telephone interviews at 6 weeks, 6 months, and 12 months after discharge. Data will be analyzed using generalized estimating equation, a special generalized linear models technique. A qualitative descriptive component supplements the survey approach, with the goal of assisting in interpretation of data and providing explanations for trends in the findings. Discussion The findings can be incorporated into patient counselling and discussions about the advantages and disadvantages of different delivery methods, potentially leading to changes in preferences and practices. In addition, the findings will be useful to hospital- and community-based postpartum care providers, managers, and administrators in guiding risk assessment and early intervention strategies. Finally, the research findings can provide the basis for policy modification and implementation strategies to improve outcomes and reduce costs of care

Intrapartum sonography for fetal head asynclitism and transverse position: sonographic signs and comparison of diagnostic performance between transvaginal and digital examination

Objective: The primary goal of this study was to determine the ultrasonographic signs of asynclitic and transverse head positioning. In addition, we compared the performance of intrapartum ultrasound to vaginal digital examination. Material & Methods: 150 women were evaluated by 2D transabdominal and translabial ultrasound (US) to detect the asynclitic and deep transverse positions. Transvaginal sterile digital examinations were performed immediately after each intrapartum US assessments, the examinations were repeated at intervals of 45-90 minutes. Examiners were blinded to each other's findings (clinical or sonographic). Data were reviewed and analyzed by an independent reviewer. Results: The efficacy of digital examination was significantly lower than US evaluation for the detection of either transverse position or asynclitism. The most frequent transverse position was the left one, while the most frequent asynclitism was the anterior one. Conclusions: Digital pelvic examination for detection of fetal head transverse position during labor is inferior to US, especially in the deep transverse positioning, where caput succedaneum occurs and reduces the diagnostic accuracy of vaginal digital examination. The US examination leads to early detection of persistent transverse position allowing for earlier timing and optimal technique for the operative vaginal delivery. We describe two signs for diagnosing asynclitism. The "squint sign" and the "sunset of thalamus and cerebellum signs" are two simple US signs allowing detection of anterior and posterior asynclitis

Quantification of increased biologically active CXCL12α plasma concentrations after ACKR3 antagonist treatment in humans

Abstract CXCL12 acts as a chemoattractant by binding to the receptor CXCR4. The (atypical) chemokine receptor ACKR3 (CXCR7) scavenges CXCL12. Antagonism of ACKR3 thus leads to an increase in CXCL12 concentrations that has been used as a pharmacodynamic biomarker in healthy adults. Increased CXCL12 concentrations have also been linked to repair mechanisms in human diseases and mouse models. To date, CXCL12 concentrations have typically been quantified using antibody‐based assays with overlapping or unclear specificity for the various CXCL12 isoforms (α, β, and γ) and proteoforms. Only the N‐terminal full‐length CXCL12 proteoform is biologically active and can engage CXCR4 and ACKR3, but this proteoform could so far not be quantified in healthy adults. Here, we describe a new and fit‐for‐purpose validated immunoaffinity mass spectrometry (IA‐MS) assay for specific measurement of five CXCL12α proteoforms in human plasma, including the biologically active CXCL12α proteoform. This biomarker assay was used in a phase I clinical study with the ACKR3 antagonist ACT‐1004‐1239. In placebo‐treated healthy adults, 1.0 nM total CXCL12α and 0.1 nM biologically active CXCL12α was quantified. The concentrations of both proteoforms increased up to two‐fold in healthy adults compared to placebo following drug administration. At all dose levels, 10% of the CXCL12α was the biologically active proteoform and the simultaneous increase of all proteoforms suggests that a new steady state has been reached 24 h following dosing. Hence, this IA‐MS biomarker assay can be used to specifically measure active CXCL12 proteoform concentrations in clinical trials to demonstrate target engagement and correlate with clinical outcomes