Family history of postpartum hemorrhage is a risk factor for postpartum hemorrhage after vaginal delivery: results from the French prospective multicenter Haemorrhages and Thromboembolic Venous Disease of the Postpartum cohort study.

BACKGROUND: Postpartum hemorrhage is a major component of perinatal morbidity and mortality that affects young women worldwide and is still often unpredictable. Reducing the incidence of postpartum hemorrhage is a major health issue and identifying women at risk for postpartum hemorrhage is a key element in preventing this complication. OBJECTIVE: This study aimed to estimate postpartum hemorrhage prevalence after vaginal delivery and to identify postpartum hemorrhage risk factors. STUDY DESIGN: Unselected pregnant women ≥16 years of age admitted to 1 of 6 maternity wards in Brittany (France) for vaginal birth after 15 weeks of gestation were recruited in this prospective, multicenter cohort study between June 1, 2015, and January 31, 2019. Postpartum hemorrhage was defined as blood loss ≥500 mL in the 24 hours following delivery. Independent risk factors for postpartum hemorrhage were determined using logistic regression. Missing data were imputed using the Multivariate Imputation by Chained Equations method. RESULTS: Among 16,382 included women, the postpartum hemorrhage prevalence was 5.37%. A first-degree family history of postpartum hemorrhage (adjusted odds ratio, 1.63; 95% confidence interval, 1.24-2.14) and a personal transfusion history (adjusted odds ratio, 1.90; 95% confidence interval, 1.23-2.92) were significantly associated with postpartum hemorrhage. The use of oxytocin during labor was also a risk factor for postpartum hemorrhage (adjusted odds ratio, 1.24; 95% confidence interval, 1.06-1.44). Inversely, smoking during pregnancy and intrauterine growth restriction were associated with a reduced risk for postpartum hemorrhage (adjusted odds ratio, 0.76; 95% confidence interval, 0.63-0.91, and 0.34; 95% confidence interval, 0.13-0.87, respectively). CONCLUSION: In addition to classical risk factors, this study identified a family history of postpartum hemorrhage and personal transfusion history as new characteristics associated with postpartum hemorrhage after vaginal delivery. The association of postpartum hemorrhage with a family history of postpartum hemorrhage suggests a hereditary hemorrhagic phenotype and calls for genetic studies. Identifying women at risk for postpartum hemorrhage is a key element of being prepared for this complication.

Predictors of Recurrent Venous Thromboembolism or Arterial Thrombotic Events during and after Anticoagulation for a First Venous Thromboembolism.

After first episodes of venous thromboembolism (VTE), patients are at increased risk of recurrent VTE and arterial thrombotic events (ATE) compared with the general population, two disorders that are influenced by anticoagulation. However, risk factors of these conditions occurring during and after anticoagulation are little described. Using cause-specific hazard regression models, we aimed to determine risk factors of the composite outcome recurrent VTE/ATE, and separately recurrent VTE or ATE, during and after anticoagulation in patients with first episodes of VTE from a prospective cohort. Hazard ratios (HRs) are given with 95% confidence intervals (CIs). A total of 2,011 patients treated for at least 3 months were included. A total of 647 patients had recurrent VTE/ATE (incidence: 4.69% per patient-years) during overall follow-up (median: 92 months). Of these events, 173 occurred during anticoagulation (incidence: 3.67% per patient-years). Among patients free of events at the end of anticoagulation, 801 had a post-anticoagulation follow-up ≥3 months; and 95 had recurrent VTE/ATE (incidence: 1.27% per patient-years). After adjustment for confounders, cancer-associated VTE (HR: 2.64, 95% CI: 1.70-4.11) and unprovoked VTE (HR: 1.95, 95% CI: 1.35-2.81) were the identified risk factors of recurrent VTE/ATE during anticoagulation (vs. transient risk factor-related VTE). Risk factors of recurrent VTE/ATE after anticoagulation included 50 to 65 years of age (vs. < 50, HR: 1.99, 95% CI: 1.04-3.81), older than 65 years (vs. < 50, HR: 5.28, 95% CI: 3.03-9.21), and unprovoked VTE (vs. transient risk factor-related VTE, HR: 2.06, 95% CI: 1.27-3.34). Cancer-associated VTE and unprovoked VTE are the main risk factors of recurrent VTE/ATE during anticoagulation, while older age and unprovoked VTE mainly predict the risk of these events after anticoagulation.

Clinical risk factors for vasculo-placental disorders: results from a prospective case-control study nested in HEMOTHEPP French cohort study.

OBJECTIVE: Determine clinical risk factors for vasculo-placental disorders in singleton pregnancies. DESIGN: Prospective case-control study nested in HEMOTHEPP French cohort. SETTING: Women delivered between June, 2015 and January, 2019 in any maternity ward of Finistère. POPULATION: Cases were women with vasculo-placental disorders (pre-eclampsia, intrauterine growth restriction (IUGR), placental abruption or stillbirth). Controls were women matched for age at delivery and parity. METHODS: Clinical data were collected by obstetricians or midwives during antenatal care visits and delivery, and recorded by trained research assistants. MAIN OUTCOME MEASURES: Occurrence of a vasculo-placental disorder. RESULTS: 505 women with vasculo-placental disorder (299 pre-eclampsia, 253 IUGR, 44 placental abruptions, 11 stillbirths) and 1515 matched controls were selected out of 20,075 participants. In multivariable analysis, four clinical parameters were associated with pre-eclampsia: obesity (Odd ratio (OR) = 3.11, 95%CI 2.11-4.58), French overseas origin (OR = 4.41, 95%CI 1.87-10.42), previous vasculo-placental disorder (OR = 5.14, 95%CI 2.72-9.70), aspirin during pregnancy (OR = 10.10, 95%CI 1.99-51.08). Three clinical parameters were associated with IUGR: auto-immune/inflammatory disorder (OR = 3.75, 95%CI 1.83-7.68), previous vasculo-placental disorder (OR = 3.63, 95%CI 2.06-6.41), smoking during pregnancy (OR = 2.66, 95%CI 1.91- 3.71). A previous venous thromboembolism (VTE) was associated with IUGR in univariable but not in multivariable analysis (OR = 3.72, 95%CI 0.82-17.00, p = 0.09). CONCLUSIONS: Clinical risk factors differ between IUGR and pre-eclampsia, the later, but not the former, being associated with cardiovascular risk factors.

Risk Factors for Major Adverse Cardiovascular Events and Major Adverse Limb Events after Venous Thromboembolism: A Large Prospective Cohort Study.

BACKGROUND: There is an increased risk of arterial events including major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after venous thromboembolism (VTE). However, their risk factors remain little explored. METHODS: We aimed to determine the risk factors for MACE (acute coronary syndrome/stroke/cardiovascular death) and MALE (limb ischemia/critical limb ischemia/non-traumatic amputation/any limb revascularization) after VTE. Competing risk models (Fine-Gray) were used in a multicenter prospective cohort of 4,940 patients (mean age: 64.6 years and median follow-up: 64 months). RESULTS: MACE occurred in 17.3% of participants (2.35% per patient-years) and MALE in 1.7% (0.27% per patient-years). In multivariable analysis, the identified risk factors for MACE were the age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 2.00, 95% confidence interval [CI]: 1.38-2.91), age >65 years (vs. <50 years, HR 4.85, 95% CI: 3.35-7.02), pulmonary embolism + deep vein thrombosis (DVT) (vs. isolated-DVT, HR: 1.25, 95% CI: 1.02-1.55), unprovoked-VTE (vs. transient risk factor associated-VTE, HR: 1.29, 95% CI: 1.04-1.59), current tobacco use (vs. never, HR: 1.45, 95% CI: 1.07-1.98), hypertension (HR: 1.61, 95% CI: 1.30-1.98), past history of symptomatic atherosclerosis (HR: 1.52, 95% CI: 1.17-1.98), heart failure (HR: 1.71, 95% CI: 1.21-2.42), atrial fibrillation (HR: 1.55, 95% CI: 1.15-2.08), and vena cava filter insertion (HR: 1.46, 95% CI: 1.03-2.08). The identified risk factors for MALE were the age of 50-65 years (vs. <50 years, HR: 3.49, 95% CI: 1.26-9.65) and atrial fibrillation (HR: 2.37, 95% CI: 1.15-4.89). CONCLUSIONS: Risk factors for MACE and MALE after VTE included some traditional cardiovascular risk factors, patient's comorbidities, and some characteristics of VTE.

Risk Factors of Cardiovascular Death after Venous Thromboembolism: Results from a Prospective Cohort Study.

BACKGROUND: Cardiovascular deaths (CVDTs) are more frequent in patients with venous thromboembolism (VTE) than in the general population; however, risk factors associated with this increased risk of CVDT in patients with VTE are not described. METHODS: To determine the risk factors of CVDT in patients with VTE from a multicenter prospective cohort study, Fine and Gray subdistribution hazard models were conducted. RESULTS: Of the 3,988 included patients, 426 (10.7%) died of CVDT during a median follow-up of 5 years. The risk factors of CVDT after multivariate analyses were: age of 50 to 65 years (vs. <50 years, hazard ratio [HR]: 3.22, 95% confidence interval [CI]: 1.67-6.62), age >65 years (vs. <50 years, HR: 7.60, 95% CI: 3.73-15.52), cancer-associated VTE (vs. transient risk factor-related VTE, HR: 1.73, 95% CI: 1.15-2.61), unprovoked VTE (vs. transient risk factor-related VTE, HR: 1.42, 95% CI: 1.02-2.00), past tobacco use (vs. never, HR: 1.43, 95% CI: 1.06-1.94), current tobacco use (vs. never, HR: 1.87, 95% CI: 1.15-3.01), hypertension (HR: 2.11, 95% CI: 1.51-2.96), chronic heart failure (HR: 2.28, 95% CI: 1.37-3.79), chronic respiratory failure (HR: 1.72, 95% CI: 1.02-2.89), and atrial fibrillation (HR: 1.67, 95% CI: 1.06-2.60). The risk of CVDT was significantly reduced with direct oral anticoagulants (vs. vitamin-K antagonists) and with longer duration of treatment (>3 months). CONCLUSION: Risk factors of CVDT after VTE include some traditional cardiovascular risk factors and other risk factors that are related to characteristics of VTE, and patients' comorbidities.

Correlation of biological parameters with placental parameters and pregnancy outcomes in pre-eclamptic women.

INTRODUCTION: Pre-eclampsia is characterized by maternal vascular malperfusion and chronic inflammation in placenta. Our purpose was to investigate the potential correlation of biological parameters with placental parameters and pregnancy outcomes in pre-eclamptic women. METHODS: Pre-eclamptic women were identified by interrogation of the Medical Registry Department in six French maternities between April 2013 and June 2018. Histological parameters in placentas (weight, macroscopic and microscopic lesions), baseline maternal characteristics and pregnancy outcomes (course of pregnancy, newborns' characteristics) were collected. Biological parameters were blood cell ratios (Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR)) collected at delivery and Placental growth factor (PlGF) measured in women with an available first trimester serum sample. Correlations of blood cell ratios and PlGF levels with placental parameters and pregnancy outcomes were assessed by Pearson's correlation test for quantitative parameters and by logistic regression analysis for qualitative parameters. RESULTS: 202 pregnancies were included, among which 68 had a first trimester PlGF quantification. No correlation was found between biological parameters and placental lesions. Low PLR was correlated with low placental weight (r = 0.156, p = 0.036) and with low birth weight (r = 0.179, p = 0.015). Low PlGF was correlated with long time from pre-eclampsia diagnosis to delivery (r = -0.250, p = 0.048). CONCLUSIONS: There is no correlation between biological parameters and placental lesions in pre-eclamptic women. Yet, low PLR at delivery is correlated with low placental and birth weights. Moreover, low first trimester PlGF is correlated with long time from pre-eclampsia diagnosis to delivery.