Trajectories of maternal D-dimer are associated with the risk of developing adverse maternal and perinatal outcomes: A prospective birth cohort study

Identifying and monitoring multiple disease biomarkers and other clinically important factors affecting the course of a disease, behavior or health status is of great clinical relevance. Yet conventional statistical practice generally falls far short of taking full advantage of the information available in multivariate longitudinal data for tracking the course of the outcome of interest. We demonstrate a method called multi-trajectory modeling that is designed to overcome this limitation. The method is a generalization of group-based trajectory modeling. Group-based trajectory modeling is designed to identify clusters of individuals who are following similar trajectories of a single indicator of interest such as post-operative fever or body mass index. Multi-trajectory modeling identifies latent clusters of individuals following similar trajectories across multiple indicators of an outcome of interest (e.g., the health status of chronic kidney disease patients as measured by their eGFR, hemoglobin, blood CO2 levels). Multi-trajectory modeling is an application of finite mixture modeling. We lay out the underlying likelihood function of the multi-trajectory model and demonstrate its use with two examples.

Placenta previa, placenta accreta, and vasa previa are important causes of bleeding in the second half of pregnancy and in labor. Risk factors for placenta previa include prior cesarean delivery, pregnancy termination, intrauterine surgery, smoking, multifetal gestation, increasing parity, and maternal age. The diagnostic modality of choice for placenta previa is transvaginal ultrasonography, and women with a complete placenta previa should be delivered by cesarean. Small studies suggest that, when the placenta to cervical os distance is greater than 2 cm, women may safely have a vaginal delivery. Regional anesthesia for cesarean delivery in women with placenta previa is safe. Delivery should take place at an institution with adequate blood banking facilities. The incidence of placenta accreta is rising, primarily because of the rise in cesarean delivery rates. This condition can be associated with massive blood loss at delivery. Prenatal diagnosis by imaging, followed by planning of peripartum management by a multidisciplinary team, may help reduce morbidity and mortality. Women known to have placenta accreta should be delivered by cesarean, and no attempt should be made to separate the placenta at the time of delivery. The majority of women with significant degrees of placenta accreta will require a hysterectomy. Although successful conservative management has been described, there are currently insufficient data to recommend this approach to management routinely. Vasa previa carries a risk of fetal exsanguination and death when the membranes rupture. The condition can be diagnosed prenatally by ultrasound examination. Good outcomes depend on prenatal diagnosis and cesarean delivery before the membranes rupture.

In normal pregnancy, there is a marked increase in the procoagulant activity in maternal blood characterized by elevation of factors VII, X, VIII, fibrinogen and von Willebrand factor, which is maximal around term. This is associated with an increase in prothrombin fragments (PF1+2) and thrombin-antithrombin complexes. There is a decrease in physiological anticoagulants manifested by a significant reduction in protein S activity and by acquired activated protein C (APC) resistance. The overall fibrinolytic activity is impaired during pregnancy, but returns rapidly to normal following delivery. This is largely due to placental derived plasminogen activator inhibitor type 2 (PAI-2), which is present in substantial quantities during pregnancy. D-dimer, a specific marker of fibrinolysis resulting from breakdown of cross-linked fibrin polymer by plasmin, increases as pregnancy progresses. Overall, there is a 4- to 10-fold increased thrombotic risk throughout gestation and the postpartum period. Local haemostasis at the placental throphoblast level is characterized by increased tissue factor (TF) expression and low expression of the inhibitor TFPI. Microparticles derived from maternal endothelial cells and platelets, and from placental throphoblasts may contribute to the procoagulant effect. Local anticoagulant mechanisms on placental throphoblasts are important for counterbalance of the procoagulant milieu. Disruption of anticoagulant mechanisms, for example, autoantibodies, to annexin V may increase pregnancy complications in patients with antiphospholipid antibodies (APLA).