A total blood volume or more transfused during pregnancy or after childbirth: Individual patient data from six international population-based observational studies.

BACKGROUND: This study aimed to compare incidence, management and outcomes of women transfused their blood volume or more within 24 hours during pregnancy or following childbirth. METHODS: Combined analysis of individual patient data, prospectively collected in six international population-based studies (France, United Kingdom, Italy, Australia, the Netherlands and Denmark). Massive transfusion in major obstetric haemorrhage was defined as transfusion of eight or more units of red blood cells within 24 hours in a pregnant or postpartum woman. Causes, management and outcomes of women with massive transfusion were compared across countries using descriptive statistics. FINDINGS: The incidence of massive transfusion was approximately 21 women per 100,000 maternities for the United Kingdom, Australia and Italy; by contrast Denmark, the Netherlands and France had incidences of 82, 66 and 69 per 100,000 maternities, respectively. There was large variation in obstetric and haematological management across countries. Fibrinogen products were used in 86% of women in Australia, while the Netherlands and Italy reported lower use at 35-37% of women. Tranexamic acid was used in 75% of women in the Netherlands, but in less than half of women in the UK, Australia and Italy. In all countries, women received large quantities of colloid/crystalloid fluids during resuscitation (>3·5 litres). There was large variation in the use of compression sutures, embolisation and hysterectomy across countries. There was no difference in maternal mortality; however, variable proportions of women had cardiac arrests, renal failure and thrombotic events from 0-16%. INTERPRETATION: There was considerable variation in the incidence of massive transfusion associated with major obstetric haemorrhage across six high-income countries. There were also large disparities in both transfusion and obstetric management between these countries. There is a requirement for detailed evaluation of evidence underlying current guidance. Furthermore, cross-country comparison may empower countries to reference their clinical care against that of other countries.

The increasing role of a retained placenta in postpartum blood loss: a cohort study.

PURPOSE: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage. METHODS: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses. RESULTS: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases.

Aetiology and treatment of severe postpartum haemorrhage.

This thesis is comprised of three studies focusing on severe postpartum haemorrhage (PPH). PPH is a major cause of maternal morbidity and mortality worldwide. Risk factors include retained placenta, prolonged duration of the third stage of labour, previous caesarean section, and operative vaginal delivery. Occurrence and development of PPH are, however, unpredictable and can sometimes give rise to massive haemorrhage or even hysterectomy and maternal death. Severe haemorrhage can lead to coagulopathy causing further haemorrhage and requiring substitution with blood transfusions. The aim of this thesis was to investigate causes of severe PPH and investigate methods of early prevention. 
The first study was a randomised controlled double-blinded trial investigating the effect of treatment with pre-emptive fibrinogen on women with severe PPH. The primary outcome was the need for red blood cell transfusion at 6 weeks postpartum. A total of 249 women were randomised to either 2 grams of fibrinogen or placebo. The mean concentration of fibrinogen increased significantly in the intervention group compared to the placebo group (0.40 g/l, confidence interval: 0.15-0.65), but there was no difference in the need for postpartum blood transfusions (relative risk 0.95, confidence interval: 0.15-1.54). No thromboembolic complications were detected.
The second study was a population-based observational study including 245 women receiving ≥10 red blood cell transfusion due to PPH. The cohort was identified by combining data from The Danish Transfusion Database with The Danish Medical Birth Registry, with further data extraction and validation through review of patient charts. The main causes of massive postpartum transfusion were atony (38%) and abnormal invasive placenta (25%). Two of the women in the cohort died, an additional six had a cardiac arrest, and a total of 128 women (52%) required a hysterectomy. Hysterectomy was associated with increased blood loss, increased number of blood transfusions, a higher fresh frozen plasma to red blood cell ratio (p=0.010), and an increased number of red blood cells before first platelet transfusion (p=0.023). Hysterectomy led to haemostasis in only 70% of cases.
The third study was a register-based cohort study, includ-ing 43,357 vaginal deliveries from two large Danish maternity units. Different cut-offs were used to define PPH. There was a difference in distribution of causes depending on the cut-off used, with atony playing a decreasing role and a retained placenta an increasing role the higher the cut-off used. In a multivariate linear regression model retained placenta was identified as a strong predictor of quantity of blood loss. The duration of the third stage of labour was a very weak predictor after adjusting for the influence of a retained placenta. 
In conclusion, an improved diagnosis of the causes of PPH especially retained placenta, together with an early recognition and treatment of coagulopathy, seem to be important in reducing severe PPH in an aim to minimize associated maternal morbidity.

Survival of ovarian cancer patients in Denmark: Results from the Danish gynaecological cancer group (DGCG) database, 1995-2012.

BACKGROUND: Ovarian cancer has a high mortality rate, especially in Denmark where mortality rates have been reported higher than in adjacent countries with similar demographics. This study therefore examined recent survival and mortality among Danish ovarian cancer patients over an 18-year study period. METHODS: This nationwide registry-based observational study used data from the Danish Gynecology Cancer Database, Danish Pathology Registry, and Danish National Patient Registry. All patients with ovarian cancer diagnosed between 1995 and 2012 were included in the study. The data sources were linked via the patients' personal identification number and the analyses included data on cancer stage, age, survival, surgery status and comorbidity. The computed outcome measures were age-adjusted mortality rates and age-adjusted overall and relative survival rates for one and five years. RESULTS: We identified 9972 patients diagnosed with ovarian cancer in the period 1995-2012. The absolute one-year mortality rate decreased from 42.8 (CI 40.3-45.6) in 1995-1999 to 28.3 (CI 25.9-30.9) in 2010-2012, and the five-year mortality rate decreased from 28.2 (CI 27.0-29.5) in 1995-1999 to 23.9 (CI 22.9-25.0) in 2005-2009. After stratification by age, comorbidity and cancer stage, the decrease in one-year mortality was most substantial in the 65-74 year old age group 41.1 (CI 38.8-43.5) to 26.5 (CI 24.4-28.7) and for stage III 39.1 (CI 35.1-43.6) to 22.9 (CI 19.9-26.5) and stage IV 91.3 (CI 80.8-103.2) to 41.9 (CI 35.5-49.5). For overall survival, we showed an increase in one-year survival from 68% (CI 66-69%) in 1995-1999 to 76% (CI 74-78%) in 2010-2012 and an increase in five-year survival from 33% (CI 32-35%) in 1995-1999 to 36% (CI 34-38%) in 2005-2009. Relative survival showed similar increases through the period. CONCLUSIONS: Ovarian cancer survival in Denmark has improved substantially from 1995 to 2012, bringing Denmark closer to the standards set by adjacent countries.