Margareta Hellgren

The incidence of pregnancy rhinitis

The purpose of this study was to define the cumulative incidence of pregnancy rhinitis, and to study whether smoking, asthma, hayfever or month of conception are risk factors. A questionnaire was delivered during 1 year in 10 antenatal care centers in one Swedish county. Questions were asked by midwives on the ordinary check-up visits throughout pregnancy. Five centers with response rates of 70% or more, including 599 women, were evaluated. The cumulative incidence of pregnancy rhinitis was 22%. Smokers had a significantly increased incidence with a relative risk enhancement of 69%, whereas hayfever, asthma, and month of conception had no statistically significant influence on incidence. Pregnancy rhinitis was shown to appear at any time during gestation.

Haemostatic changes during continuous oestradiolprogestogen treatment of postmenopausal women

Summary. To identify changes in haemostatic balance during continuous oestradiol‐progestogen treatment, 60 postmenopausal women with climacteric complaints, mean age 55.4 years (range 44–68) were randomly allocated to receive one of four hormone replacement regimens for one year. All four formulations were administered daily and continuously, each contained 2 mg of 17 β‐oestradiol in combination with either norethisterone acetate, 1 mg (group A) or 0.5 mg (group B) or megestrol acetate, 5 mg (group C) or 2.5 mg (group D). No significant changes occurred during treatment within or between the groups in platelet count, fibrinogen and 2‐antiplasmin. Activated partial thromboplastin time was shortened (P<0.05) in group D and a decline in factor VII activity and antigen (P<0.001) and in AT1II activity (P<0.05) was noted in group A. Protein C tended to decline in all treatment groups but statistically significant changes were noted only in groups A and C. Two women developed crural thrombosis during the observation period.

Comparison of four continuously administered progestogen plus oestradiol combinations for climacteric complaints

Summary. Sixty women with climacteric complaints who had not menstruated for at least 1 year were randomly allocated to receive one of four hormonal replacement regimens. All four formulations were administered daily and continuously and each contained 2 mg of micronized oestradiol‐17β in combination with either norethisterone acetate 1 mg (group A) or 0·5 mg (group B) or megestrol acetate 5 mg (group C) or 2·5 mg (group D). The clinical efficacy was the same although the alleviation of vasomotor symptoms was somewhat slower in those women receiving preparation A. The endometrium was atrophied in nearly all biopsies. Irregular uterine bleeding was almost entirely confined to the earlier phase of the study and was substantially less with the formulation containing 1 mg norethisterone acetate. It is concluded that a continuous oestradiol‐progestogen combination can be used for longterm treatment of climacteric complaints in postmenopausal women and that after 4 months the clinical efficacy is the same irrespective of the type and dose of progestogen administered.

Changes in Blood Coagulation and Fibrinolysis in the Normal Puerperium

Blood coagulation and fibrinolysis variables have been studied in the normal puerperium in order to facilitate the decision to discontinue thrombosis prophylaxis after delivery. 16 women were followed longitudinally from the 1st to the 6th week post partum. Factor VIII activity and related antigen, fibrinogen, fibrinopeptide A, antithrombin III, plasminogen, tissue plasminogen activator (t-PA), fast inhibitor of t-PA, alpha 2-antiplasmin, urokinase inhibitors, fragment B beta 15-42 and kallikrein inhibition were analyzed. Both blood coagulation and fibrinolysis were significantly increased during the first 2 weeks, although simultaneously increased inhibitor capacity of both systems was present. 3 weeks post partum, blood coagulation and fibrinolysis were generally normalized, although the inhibitors remained raised compared to nonpregnant controls throughout the observation period.

Prospective Longitudinal Study of Thromboelastography and Standard Hemostatic Laboratory Tests in Healthy Women During Normal Pregnancy

BACKGROUND:Hemostatic disorders are common in obstetric complications. Thromboelastography (TEG®) simultaneously measures coagulation and fibrinolysis within 10 to 20 minutes. Our primary aim in this prospective longitudinal study was to obtain knowledge about physiological changes in TEG® variables during normal pregnancy and 8 weeks postpartum. The secondary aims were to compare TEG® variables during pregnancy with TEG® variables 8 weeks postpartum and gestational weeks 10 to 15 and to correlate TEG® variables to standard laboratory analyses. METHODS:Blood samples were collected from 45 healthy pregnant women at gestational weeks 10 to 15, 20 to 22, 28 to 30, and 38 to 40, and at 8 weeks postpartum. The following TEG® analyses were performed: time until start of clotting (TEG®-R), time until 20-mm clot firmness (TEG®-K), angle of clotting (TEG®-Angle), maximum amplitude (TEG®-MA), and lysis after 30 minutes (TEG®-LY30). Activated partial thromboplastin time, prothrombin time, soluble fibrin, antithrombin, D-dimer, and platelet count were analyzed. RESULTS:Compared to 8 weeks postpartum TEG®-R was at least 0.9 minutes shorter (upper limit 99% confidence intervals) until gestational weeks 28 to 30 and the mean reduction varied between 23%–26%. TEG®-K was at least 0.1 minutes shorter throughout pregnancy and the mean reduction varied between 18%–35%. TEG®-Angle was at least 2.5 degrees greater during pregnancy and the mean increase varied between 12%–20%. TEG®-MA was also at least 0.4 mm greater during pregnancy and the mean increase varied between 6%–8%. TEG®-LY30 was at least 0.03% lower during gestational weeks 28 to 30 and 38 to 40 and the mean reduction varied between 67%–73%. The routine coagulation laboratory values were within normal pregnant limits. There were no or weak correlations between TEG® and the laboratory variables. CONCLUSIONS:TEG® demonstrates increased coagulability and decreased fibrinolysis during pregnancy. There was a faster initiation of hemostasis, with a minor increase in clot strength. Fibrinolysis decreased during late pregnancy. Alternative cutoff limits for TEG® variables may be required during pregnancy. Standard hemostatic laboratory tests were as expected during pregnancy. Future studies are needed to ascertain whether viscoelastic methods are preferable to standard hemostatic tests for the diagnosis of coagulopathy during obstetric hemorrhage.

Major obstetric haemorrhage: monitoring with thromboelastography, laboratory analyses or both?

BACKGROUND Haemorrhage is a common cause of morbidity and mortality in the obstetric population. The aim of this study was to compare the use of thromboelastography and laboratory analyses to evaluate haemostasis during major obstetric haemorrhage. A secondary aim was to evaluate correlations between the results of thromboelastography, laboratory analyses and estimated blood loss. METHODS Forty-five women with major obstetric haemorrhage and 49 women with blood loss <600 mL were included. The following thromboelastography analyses were performed: time to start of clotting (TEG-R), time to 20 mm of clot firmness (TEG-K), rate of clot growth (TEG-Angle), maximum amplitude of clot (TEG-MA) and lysis after 30 min (TEG-LY30). In addition, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, antithrombin and D-dimer were measured. RESULTS Thromboelastography variables reflecting clot stability and fibrinolysis were decreased in women with massive obstetric haemorrhage compared to women with normal bleeding, while clot initiation was accelerated. Laboratory analyses also showed impaired haemostasis with the most pronounced differences in platelet count, fibrinogen concentration and antithrombin activity. The strongest correlations existed between fibrinogen and TEG-MA and between estimated blood loss and TEG-MA, fibrinogen and antithrombin, respectively. CONCLUSIONS Impaired haemostasis, demonstrated by thromboelastography and laboratory analyses, was found after an estimated blood loss of 2000 mL. Thromboelastography provides faster results than standard laboratory testing which is advantageous in the setting of on-going obstetric haemorrhage. However, laboratory analyses found greater differences in coagulation variables, which correlated better with estimated blood loss.

Pregnancy-related deaths due to pulmonary embolism in Sweden

Background. The objective of this study was to report deaths from amniotic fluid embolism (AFE) and pregnancy‐related venous thromboembolism (VTE), to study contributing factors, and to analyse mortality trends. Methods. Using the Swedish Cause of Death Register (CDR), we identified all women aged 15–44, who died during 1990–1999, with VTE or AFE coded as the underlying or contributory cause of death. We scrutinised medical records, and women who had died during pregnancy or within 6 weeks of terminated pregnancy were included. We also used data from the Medical Birth Register (MBR) on incident and fatal cases. Mortality data from the 1970s and 1980s were based on previous studies, in which cases were identified through register linkage (CDR and MBR). Results. Five women died of AFE and 10 of VTE – 6 in early pregnancy – during the 1990s. Five of the cases were not registered as maternal deaths. Only 4 cases were reported as pregnancy‐related deaths from pulmonary embolism (PE). Cesarean section/surgery without thromboprophylaxis, overweight, severe intercurrent disease, delays in seeking health care, and verbal miscommunication were contributing factors in the VTE cases. VTE mortality rates (pregnancy >28 weeks and/or a registered birth) were 1.0 (0.5–1.8), 0.8 (0.3–1.6), and 0.4 (0.1–1.0) per 100,000 live births during the 1970s, 1980s and 1990s, respectively; the corresponding respective figures for AFE were 1.0 (0.5–1.8), 1.1 (0.6–2.1), and 0.5 (0.2–1.1) per 100,000 live births. The case fatality rate for VTE decreased from 4.5% in the 1970s, to 0.6% in the 1990s, paralleled with quadrupled incidence. The case fatality rate for AFE was unaltered and high, around 45%, during those 3 decades. Conclusions. Mortality from pregnancy‐related PE in Sweden is in the lowest range ever reported, and shows a downward trend during the 1990s, with a shift towards early pregnancy. In order to monitor mortality trends, death certificate quality must improve, and registers must be linked routinely.

Efficacy of obstetric thromboprophylaxis and long‐term risk of recurrence of venous thromboembolism

Objective. To study the efficacy of thromboprophylaxis with low molecular weight heparin (LMWH) in pregnant women with one previous venous thromboembolic event (VTE). Secondary aims were to study the long‐term risk of secondary recurrence, bleeding and obstetric complications. Design. A prospective national study of long‐term LMWH thromboprophylaxis in Sweden. Settings. All hospitals in Sweden during January 1998–December 2002, Participants. Pregnant women with one previous VTE and controls drawn from the Swedish Medical Birth Registry. The women were cross‐matched with the Swedish Hospital Discharge Register to identify all recurrences and to ascertain the annual risk of recurrence. Main Outcome Measures. Recurrence of VTE, bleeding complications at delivery and obstetric complications. Results. 326 of 393 registered women could be evaluated. The relative risk reduction in VTE was 88%. There was an absolute increased risk of VTE during the thromboprophylaxis period: 1.2% compared to 0.2% among controls (p<0.001). The risk during the immediate post‐treatment period (43–100 days post‐partum) was increased 28‐fold. The annual incidence of VTE after delivery was 1%. The risk of hematoma and major blood loss at delivery was increased during thromboprophylaxis (p<0.001). There were no differences in the incidences of preeclampsia, intrauterine growth restriction or placental abruption. Conclusions. The relative risk reduction in VTE during thromboprophylaxis was 88%. After pregnancy, the annual long‐term risk of recurrence was 1%. The risk was most pronounced in the post‐treatment period. There was an increased risk of bleeding complications among women given LMWH, but there was no effect on obstetric complications.

Magnetic resonance imaging and ultrasonography in diagnosis of pelvic vein thrombosis during pregnancy.

INTRODUCTION Pelvic deep vein thrombosis (DVT) is difficult to diagnose during pregnancy. In a two-center trial, we evaluated the agreement between ultrasonography and magnetic resonance imaging (MRI) in diagnosing the extent of DVT into the pelvic veins during pregnancy. MATERIALS AND METHODS Pregnant women with proximal DVT were examined both with ultrasound and MRI as part of a study designed for treatment of DVT during pregnancy. Ultrasound was performed using color flow by specialist in vascular ultrasound with Doppler and compression techniques. The MRI sequences consisted of a 2D Time of Flight angiography with arterial flow suppression and maximum intensity projection reconstructions; a 3D, T1-w-prepared gradient echo sequence with fat saturation for thrombus imaging; a steady-state free precession sequence; and a Turbo-Spin-Echo. No contrast agent was used. Proportion of agreement (kappa) for detection of DVT in individual veins was measured for different ipsilateral veins and inferior vena cava. RESULTS All 27 patients were imaged with both techniques at an average gestational age of 29 weeks (range 23-39). Three cases (11.5%) of DVT in the pelvic veins were missed on ultrasound but detected by MRI. The upper limit of the DVT was always depicted at a higher (20 cases, 65.4%) or the same level (seven cases, 34.6%) on MRI than on ultrasound. Agreement expressed as kappa was 0.33 (95% CI 0.27-0.40) demonstrating only fair agreement. In one woman the thrombus had propagated into the inferior vena cava, shown only on MRI. CONCLUSION Our study suggests that in pregnant women there is only fair agreement between ultrasound and MRI for determination of extent of DVT into pelvic veins, with MRI showing consistently more detailed depiction of extension. Our results indicate that MRI has an important role as a complementary technique in the diagnosis of DVT during pregnancy.

Factor V Leiden mutation and pregnancy-related complications

OBJECTIVE The objective of the study was to determine the prevalence of the factor V Leiden (FVL) mutation and its association with obstetric complications, blood loss during delivery, and venous thromboembolism (VTE). STUDY DESIGN This was a prospective, observational, case-cohort study of 491 FVL carriers and 1055 controls derived from 6003 screened women. Data were analyzed with a Student t test and cross-tabulation. RESULTS FVL carriership prevalence was 8.3%. Gestational age at delivery, birthweight deviation, gestational hypertension, and preeclampsia incidences did not differ between groups. The incidences of placental abruption, neonatal asphyxia, eclampsia, intrauterine fetal death, intrapartum death, and unexplained late miscarriage were low. The incidence of major blood loss at delivery was lower in carriers. There were 3 VTEs among carriers and none among controls. CONCLUSION FVL carriership did not influence pregnancy-induced hypertension, birthweight, or prematurity but raised the risk of venous thromboembolism and lowered the risk of major blood loss.