Search

PURPOSE: Existing evidence estimates a twofold risk of venous thromboembolisms (VTEs) if tourniquet is applied during total knee arthroplasties (TKAs). However, this estimate relies on multiple trials with a low number of patients analyzing VTEs as a secondary outcome. We hypothesized that tourniquet-use increases the risk of symptomatic VTE within 90 days of contemporary primary TKA and aimed to use the extensive Danish healthcare registries to quantify this risk.METHODS: Prospectively collected registry data from Danish patients receiving primary TKAs between 2014 and 2018 were included in the study. Patients were divided by tourniquet-use during surgery. By merging information from four nationwide registries, the study included 44 baseline characteristics with the potential to confound the association between tourniquet-use and VTE. Incidence rate and odds ratios were used to compare the risk of VTE within 90 days of surgery.RESULTS: 19,804 patients of whom 10,111 (51%) were operated with tourniquet and 9693 (49%) without were included. The mean age (SD) was 70 (9) in both groups and 62% were females in the tourniquet group compared with 61% in the no tourniquet group. The groups were similarly comparable across all other baseline characteristics except type of post-operative thromboprophylaxis, type of anaesthesia, implant fixation, and year of surgery. The 90-days incidence of VTE was 0.77% (95% CI 0.60-0.94) in the tourniquet group compared with 1.10% (95% CI 0.90-1.31) in the no tourniquet group. Following adjustment for the unbalanced confounders, the odds ratio for VTE was 0.77 (95% CI 0.54-1.10) associated with tourniquet-use.CONCLUSION: In contemporary TKAs the rate of VTE within 90 days is low and not significant altered by tourniquet-use. Thus, tourniquet can safely be applied during primary TKA-surgery without jeopardizing the risk of postoperative VTE.LEVEL OF EVIDENCE: II-prospective cohort study.

Only a minority of patients with the biochemical features of NS receive hospital diagnoses specific to NS.Patients identified with hospital-recorded NS are considerably different from those with biochemical features of NS.Laboratory databases should complement hospital databases to fully elucidate the burden of NS and the prognosis of NS patients.Background: Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS. Methods: We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients or emergency room visitors) in the Danish National Patient Registry and compared them to adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining date of admission or laboratory findings as index date. We characterised these cohorts by demographics, comorbidity, medication use, and laboratory and histopathological findings. Results: We identified 1,139 patients with hospital-recorded NS and 5,268 patients with nephrotic proteinuria and hypoalbuminemia of which 760 patients were identified with both. Within one year of the first recorded nephrotic proteinuria and hypoalbuminemia, 18 while 87 most recent eGFR was substantially lower (median of 35 vs. 61 ml/min/1.73 m2), fewer underwent kidney biopsies around index date (341, and prevalence of thromboembolic disease (257 and diabetes (398 was higher when compared to patients with hospital-recorded NS. Conclusions: Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they reveal a lower eGFR and more comorbidity. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS. Background: Registry-based studies of nephrotic syndrome (NS) may only include a subset of patients with biochemical features of NS. To address this, we compared patients with laboratory-recorded nephrotic proteinuria and hypoalbuminemia to patients with hospital-recorded NS.Methods: We identified adult patients with first-time hospital-recorded NS (inpatients, outpatients, or emergency-room visitors) in the Danish National Patient Registry and compared them with adults with first-time recorded nephrotic proteinuria and hypoalbuminemia in Danish laboratory databases during 2004-2018, defining the date of admission or laboratory findings as the index date. We characterized these cohorts by demographics, comorbidity, medication use, and laboratory and histopathologic findings.Results: We identified 1139 patients with hospital-recorded NS and 5268 patients with nephrotic proteinuria and hypoalbuminemia; of these, 760 patients were identified in both cohorts. Within 1 year of the first record of nephrotic proteinuria and hypoalbuminemia, 18% had recorded hospital diagnoses indicating the presence of NS, and 87% had diagnoses reflecting any kind of nephropathy. Among patients identified with nephrotic proteinuria and hypoalbuminemia, their most recent eGFR was substantially lower (median of 35 versus 61 ml/min per 1.73 m 2), fewer underwent kidney biopsies around the index date (34% versus 61%), and the prevalence of thromboembolic disease (25% versus 17%) and diabetes (39% versus 18%) was higher when compared with patients with hospital-recorded NS. Conclusions: Patients with nephrotic proteinuria and hypoalbuminemia are five-fold more common than patients with hospital-recorded NS, and they have a lower eGFR and more comorbidities. Selective and incomplete recording of NS may be an important issue when designing and interpreting studies of risks and prognosis of NS.

Routine biomarker results from hospital laboratory information systems, covering hospitals and general practitioners, in Denmark are available to researchers through access to the regional Clinical Laboratory Information System Research Database at Aarhus University and the nationwide Register of Laboratory Results for Research. This review describes these two data sources. The laboratory databases have different geographical and temporal coverage. They both include individual-level biomarker results that are electronically transferred from laboratory information systems. The biomarker results can be linked to all other Danish registries at the individual level, using the unique identifier, the CPR number. The databases include variables such as the CPR number, date and time (hour and minute) of sampling, NPU code, and name of the biomarker, identification code for the laboratory and the requisitioner, the test result with the corresponding unit, and the lower and upper reference limits. Access to the two databases differs since they are hosted by two different institutions. Data cannot be transferred outside Denmark, and direct access is provided only to Danish institutions. It is concluded that access to data on routine biomarkers expands the detailed biological and clinical information available on patients in the Danish healthcare system. The full potential is enabled through linkage to other Danish healthcare registries.

Testing the antibody response to vaccination (diagnostic vaccination) is crucial in the clinical evaluation of primary immunodeficiency diseases. Guidelines from the American Academy of Allergy, Asthma & Immunology (AAAAI) provide detailed recommendations for diagnostic vaccination with pure pneumococcal polysaccharide vaccines (PPV). However, the degree of compliance with these guidelines and the utility of the guidelines in actual practice are undescribed. To address this, we systematically evaluated diagnostic vaccination in adult patients with suspected primary immunodeficiency diseases in a single tertiary center from 2011 to 2016 (n = 229). We found that full compliance with the AAAAI guidelines was achieved for only 39 patients (17%), suggesting that the guidelines are not easy to follow. Worse, interpretation according to the guidelines was heavily influenced by which serotype-specific antibodies that were used for the evaluation. We found that the arbitrary choices of serotype-specific antibodies could change the fraction of patients deemed to have ‘adequate immunity’ by a factor of four, exposing an inherent flaw in the guidelines. The flaw relates to dichotomous principles for data interpretation under the AAAAI guidelines. We therefore propose a revised protocol for diagnostic vaccination limited to PPV vaccination, subsequent antibody measurements, and data interpretation using Z-scores. The Z-score compiles multiple individual antibody levels, adjusted for different weighting, into one single continuous variable for each patient. In contrast to interpretation according to the AAAAI guidelines, the Z-scores were robust to variations in the choice of serotype-specific antibodies used for interpretation. Moreover, Z-scores revealed reduced immunity after vaccination in the patients with recurrent pneumonia (a typical symptom of antibody deficiency) compared with control patients. Assessment according to the AAAAI guidelines failed to detect this difference. We conclude that our simplified protocol and interpretation with Z-scores provides more robust clinical results and may enhance the value of diagnostic vaccination.

Functional antibody deficiency is clinically assessed from antibody responses to vaccination. However, diagnostic vaccination is complex and may fail in practice. We hypothesized that the levels of naturally occurring antibodies against galactose-α-1,3-galactose (αGal) may represent alternative markers of functional antibody capacity. We included data from 229 patients with suspected primary immunodeficiency in a retrospective study. Antibody levels against αGal and twelve pneumococcal serotypes were determined with solid-phase immunoassays. Pneumococcal vaccinations and treatment with normal human immunoglobulin were assessed from medical records. Anti-αGal antibody levels correlated positively with anti-pneumococcal antibody levels measured before and after pneumococcal vaccination. Contrary to the anti-pneumococcal antibody levels, the anti-αGal antibody level showed potential for predicting subsequent immunoglobulin treatment - a marker of disease severity. Naturally occurring antibodies may reflect the functional capacity tested by diagnostic vaccination but add more useful clinical data. The clinical utility of this easy test should be evaluated in prospective studies.

Essentials Risk of pregnancy-related venous thromboembolism may be increased in inflammatory bowel disease. We performed a study on inflammatory bowel disease and pregnancy-related venous thromboembolism. Inflammatory bowel disease is a risk factor for pregnancy-related venous thromboembolism. Proper disease control before conception is pivotal to avoid venous thromboembolism. SummaryBackground The incidence of inflammatory bowel disease (IBD) increases, and thus is more common, in pregnant women. IBD is a risk factor for venous thromboembolism (VTE) but it is not clear whether IBD predisposes women to an excess risk of VTE during pregnancy and the postpartum period. Methods This was a nationwide population-based cohort study of all deliveries during 1980–2013 in Denmark, using data from two nationwide health registries: the Danish National Patient Registry and the Medical Birth Registry. We computed incidence rates (IRs) per 1000 person-years, and crude and adjusted relative risks (RRs) with 95% confidence intervals (CIs) for VTE during pregnancy and the first 12 postpartum weeks in women with and without IBD. Results We included 1 046 754 women with 1 978 701 deliveries. We identified 3465 VTE events during pregnancy and 1302 VTE events postpartum. The IR for VTE during pregnancy was 4.20 (95% CI, 2.83–5.58) in IBD patients and 2.41 (95% CI, 2.33–2.50) in women without IBD, corresponding to an RR of 1.72 (95% CI, 1.22–2.43). Adjustment for maternal age and smoking (pregnancies during 1991–2013) yielded an adjusted RR of 1.67 (95% CI, 1.15–2.41). IBD flare was associated with an RR of 2.64 (95% CI, 1.69–4.14) for VTE during pregnancy. The IR for postpartum VTE was 7.03 (95% CI, 3.87–10.20) among IBD patients and 2.88 (95% CI, 2.72–3.04) in women without IBD, corresponding to an adjusted RR of 2.10 (95% CI, 1.33–3.30). Conclusions IBD is a risk factor for VTE during pregnancy and postpartum.

Routine biomarker results from hospital laboratory information systems, covering hospitals and general practitioners, in Denmark are available to researchers through access to the regional Clinical Laboratory Information System Research Database at Aarhus University and the nationwide Register of Laboratory Results for Research. This review describes these two data sources. The laboratory databases have different geographical and temporal coverage. They both include individual-level biomarker results that are electronically transferred from laboratory information systems. The biomarker results can be linked to all other Danish registries at the individual level, using the unique identifier, the CPR number. The databases include variables such as the CPR number, date and time (hour and minute) of sampling, NPU code, and name of the biomarker, identification code for the laboratory and the requisitioner, the test result with the corresponding unit, and the lower and upper reference limits. Access to the two databases differs since they are hosted by two different institutions. Data cannot be transferred outside Denmark, and direct access is provided only to Danish institutions. It is concluded that access to data on routine biomarkers expands the detailed biological and clinical information available on patients in the Danish healthcare system. The full potential is enabled through linkage to other Danish healthcare registries.

PROBLEM: The lectin pathway of the complement system may be involved in the pathogenesis of preeclampsia. We aimed to investigate changes in serum concentrations of a broad range of lectin pathway proteins during normal pregnancy and their association with preeclampsia, placental infarctions and intrauterine growth restriction (IUGR).METHOD OF STUDY: We included 51 women with normotensive pregnancies and 54 women with pregnancies complicated by preeclampsia. Blood samples were obtained at gestational weeks 16, 33, 37, and after delivery for the normotensive pregnant women and before and after delivery for women with preeclampsia. Mannose-binding lectin (MBL), H- and M-ficolin, collectin liver-1 (CL-L1), MBL-associated serine proteases (MASPs)-1, -2 and -3 and MBL-associated proteins of 19 (MAp19) and 44 (MAp44) kDa were analysed. Clinical information was obtained from medical records. The placentae were examined by two experienced perinatal pathologists.RESULTS: Lectin pathway protein concentrations generally increased during normal pregnancy and decreased after delivery in both normotensive pregnant women and women with preeclampsia. Exceptions were MASP-3 which increased after delivery in both groups (pCONCLUSIONS: In general, lectin pathway protein serum concentrations increased during normal pregnancy. H-ficolin and MASP-3 may be involved in the pathophysiology of preeclampsia and IUGR and could be potential future preeclampsia biomarkers. This article is protected by copyright. All rights reserved.

Background: High dose chemotherapy (HDT) burdens patients with a high risk of serious infections while neutropenic. The role of host antibodies as risk factors for infections is unclear. Our aim was to investigate if pre-HDT levels of IgG antibodies against terminal Galα3Gal (anti-αGal) predict infections. Anti-αGal is reported to be the most abundant antibody in human plasma and is able to recognize most sepsis-causing Gram-negative bacteria. The antibody exerts poor complement activation, which promotes pathogen survival by blocking access of more effective complement activators. This may be particularly problematic in neutropenic patients. Thus, we hypothesized that patients with high anti-αGal serum concentrations are particularly prone to suffer infections following HDT. Methods: We conducted a clinical cohort study on patients ≥16 years receiving HDT with autologous stem cell transplantation for myelomatosis (MM) or non-Hodgkin lymphoma (NHL) at Department of Hematology, Aarhus University Hospital, Denmark from 25 November 2009 through 26 June 2015. Of eligible patients (N=308), we excluded previous transplanted (N=14), those without a pre-HDT serum sample available for anti-αGal quantification (N=115), and recipients of plasma transfusion/IgG substitutions within 90 days before the pre-HDT serum sample and until end of follow-up (N=9). All included received prophylactic antimicrobial therapy (levofloxacin and fluconazol) and filgrastim. Serum anti-αGal was quantified using an in-house Time-resolved Immuno-Fluoremetric Assay. We ascertained infectious episodes within 30 days following the date of autologous stem cell re-infusion through review of all medical charts and data retrieval from the laboratory information systems, blinded for anti-αGal concentrations. Infectious episodes were defined as fever (≥38.5°C) or hypothermia ( 21 mg/L preceded by at least 24 hours without any of these. We used a Cox proportional hazards model to investigate the association between anti-αGal concentrations and risk of infection, with adjustment for total plasma IgG concentrations, ABO blood group, comorbidity, and underlying disease (MM or NHL) in the adjusted hazard ratios (HR). Optimum cutoff for dichotomizing was determined from ROC analysis applying Youden´s J statistic and groups were compared by Kaplan-Meier method. Results: We included 170 patients (MM, 55%; males, 58%; median age 62 years). Severe neutropenia was transient in all, with blood neutrophils increasing to above 500/µL on median day 11 (range 8-18). We identified one infectious episode in 103 patients (61%) and two episodes in six (3.5%) patients. The infectious episodes began during severe neutropenia in 92% of the patients. The infection types were fever of unknown origin (FUO) (72%), pneumonia (19%), catheter related (4.3%), typhlitis (1.7%), C. difficile colitis (1.7%), and hypothermia of unknown origin (0.87%). None died from infections. Pre-HDT serum was collected on median day -31 (range -142- -16). Anti-αGal was detectable in all but one sample, averaging 0.51 mg/dL (range: 0.016-12). Overall, anti-αGal concentrations predicted infectious episodes (all types), crude HR 1.2 (95% confidence interval (CI) 1.1-1.4), adjusted HR 1.1 (95% CI: 1.0-1.3). Using anti-αGal at 1.3 mg/dL as cut-off, we identified that patients with higher concentrations (N=41) experienced considerably increased risk of infectious episodes (crude estimates): all types, HR 1.7 (95% CI: 1.3-3.2); FUO, HR 2.0 (95%CI: 1.5-4.5); and pneumonia HR 2.1 (95%CI: 0.83-8.7). Discussion: We found that high anti-αGal serum concentrations predict an increased risk of infection after HDT. These findings support that anti-αGal may critically enhance pathogen-survival in the neutropenic host. Studies of other cohorts and mechanistic studies are required. Our findings may pave the way for future optimized risk stratification and therapeutic measures. Disclosures No relevant conflicts of interest to declare.

Objective: Foetal growth retardation (FGR) is a leading cause of perinatal death and long-term harms at survivors. Placental infarction plays a role in FGR, yet, no trials have evaluated whether low molecular weight heparins increase birth weight in ongoing FGR pregnancies. Methods: An open-labelled randomized trial in Denmark during 2011–2016, including singleton pregnant women with FGR (estimated foetal weight < 2.3 percentile) diagnosed before gestational weeks 32. Participants were randomly assigned using sealed, blinded envelopes 1:1 to tinzaparin (4500 IU daily until 37 gestational weeks) or no tinzaparin. The primary outcomes were the observed birthweight relative to the expected for gestational age and gender, and foetal growth rates in the two trial groups evaluated by an intention to treat analysis. Results: We enrolled 53 women. The mean gestational age was 261 days in the tinzaparin group and 246 days in the no treatment group. The mean birth weight was 2229 g in the tinzaparin group compared to 1968 g in the no treatment group. However, the birth weight relative to the expected from gestational age and gender was only 2.5 percentage points higher in the tinzaparin group [−5.1 to 10.0] (p = 0.51). The foetal growth rate during follow-up was 124 g/week in the tinzaparin group and 119 g/week in the no treatment group, a difference of 5 g/week [−19 to 29] (p = 0.67). Two perinatal deaths both occurred in the no treatment group. Conclusion: We found no evidence of a tinzaparin effect on the foetal growth rate or the birth weight after adjustment for gestational age.

STUDY QUESTION: What is the risk of venous thromboembolism (VTE) in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF?SUMMARY ANSWER: The VTE risk is low in the 12 weeks following early pregnancy loss in pregnancies conceived by IVF.WHAT IS KNOWN ALREADY: There is an excess VTE risk during first trimester in complete IVF pregnancies leading to delivery. It is unknown whether this excess VTE risk also is present in IVF pregnancies terminated by early pregnancy loss (implantation failure, missed abortion, or spontaneous or induced abortion before 10 completed gestational weeks).STUDY DESIGN, SIZE, DURATION: A nationwide registry-based cohort study including all Danish IVF pregnancies registered in the Danish IVF Register between 1995 and 2005. Women who underwent frozen embryo replacement or oocyte donation were not included.PARTICIPANTS/MATERIALS, SETTING, METHODS: We included all 24 931 IVF treatments leading to pregnancy among 19 260 women. We identified 16 701 complete IVF pregnancies, 7567 IVF pregnancies with early pregnancy loss, and 663 IVF pregnancies terminated by late abortion (≥gestational weeks 10). We followed women for 12 weeks after termination of pregnancy and calculated the absolute risk of VTE during follow-up with 95% CI. As a relative risk estimate, we calculated the risk ratio for VTE following IVF pregnancies with early loss compared to the VTE risk following complete IVF pregnancies.MAIN RESULTS AND THE ROLE OF CHANCE: During the 12 weeks of follow-up, only one case of VTE occurred in the group of early pregnancy loss, none in the late abortion group, and 13 VTE cases occurred in complete IVF pregnancies. The VTE risk per 10 000 pregnancies was 1.3 [0.03-7.4] for IVF pregnancies with early loss and 7.8 [4.1-13.3] for complete pregnancies; the corresponding risk ratio was 0.17 [0.02-1.3]. Thus, we found a low absolute VTE risk in the 12 weeks following early pregnancy loss in IVF pregnancies. The relative VTE risk was low in comparison to the VTE risk in early gestation reported for complete IVF pregnancies and for Danish background pregnancies.LIMITATIONS, REASONS FOR CAUTION: Despite the use of complete nationwide data, only a few VTE events were available for the statistical analyses thereby limiting the precision of our estimates. We included both inpatient and outpatient VTE hospital diagnoses, but we cannot rule out the occurrence of VTE cases not diagnosed at hospital and hence not registered in the National Patient Registry. No information was available on the use of prophylactic low molecular weight heparin: access to such might have helped to explain our findings, but would not have changed our conclusions.WIDER IMPLICATIONS OF THE FINDINGS: The results of the present study do not indicate a need for prophylactic anticoagulant therapy in women suffering early IVF pregnancy loss without other risk factors.STUDY FUNDING/COMPETING INTEREST(S): No external funding was obtained for this study. There are no conflicts of interest to declare.

In Denmark, biennial population screening for colorectal cancer was introduced in 2014 for all aged 50–74 years. Five laboratories representative for the regional division of Denmark perform the immunochemical testing of faecal occult blood in the screening samples (iFOBT, OC-Sensor (Eiken Chemical, cut-off 100 µg/L)). In July 2016, a new agreement on the public post-delivery entailed an increased lag time (five days) from the screening participant drops the screening sample into a mail-box until sample arrival at the laboratories. Previous work had reported that a lag time above five days led to more false negative iFOBT tests. We investigated if this was true also under Danish conditions. We performed two stability tests; one with sample storage at 30 °C for 14 days (N = 60), and another with sample storage at room temperature for 13 days (N = 10). We extracted data from our laboratory information system (LABKA) on all iFOBT tests performed in the entire Central Denmark Region (N = 104,328 patients) during the last six months for each calendar year 2014–16. For each year, we computed the distribution of iFOBT tests below and above cut-off. Our stability tests showed no positive samples switching to false negative after storage; however, some negative samples turned false positive, especially at 30 °C. The data showed no change in the distribution of iFOBT tests below and above cut-off after July 2016. We found no evidence that an enhanced lag time increased the number of false negative iFOBT tests in the Danish screening program for colorectal cancer.

Introduction The possible significance of thrombophilia in ischemic stroke remains controversial. We aimed to study inherited and acquired thrombophilias as risk factors for ischemic stroke, transient ischemic attack (TIA) and amaurosis fugax in young patients. Materials and methods We included patients aged 18 to 50 years with ischemic stroke, TIA or amaurosis fugax referred to thrombophilia investigation at Aarhus University Hospital, Denmark from 1 January 2004 to 31 December 2012 (N = 685). Clinical information was obtained from the Danish Stroke Registry and medical records. Thrombophilia investigation results were obtained from the laboratory information system. Absolute thrombophilia prevalences and associated odds ratios (OR) with 95% confidence intervals (95% CI) were reported for ischemic stroke (N = 377) and TIA or amaurosis fugax (N = 308). Thrombophilia prevalences for the general population were obtained from published data. Results No strong associations were found between thrombophilia and ischemic stroke, but patients with persistent presence of lupus anticoagulant (3%) had an OR at 2.66 (95% CI 0.84–9.15) for ischemic stroke. A significantly higher risk of TIA/amaurosis fugax was found for factor V Leiden heterozygote (12%) (OR: 1.99 (95% CI 1.14–3.28)). No other inherited or acquired thrombophilia was associated with ischemic stroke, TIA or amaurosis fugax. Conclusions In young patients, thrombophilia did not infer an increased risk of ischemic stroke. Only factor V Leiden heterozygote patients had an increased risk of TIA/amaurosis fugax, and persistent presence of lupus anticoagulant was likely associated with ischemic stroke. We suggest the testing restricted to investigation of persistent presence of lupus anticoagulant.

Summary Background Placenta-mediated complications are leading causes of maternal and fetal morbidity and mortality. We hypothesized that a preconception history of venous thromboembolism (VTE) is associated with increased risk of placenta-mediated pregnancy complications. Methods A nationwide population-based cohort study of all singleton pregnancies leading to delivery from 1997 to 2012 (n = 964 967). We obtained data on placenta-mediated pregnancy complications from the Danish Medical Birth Registry and data on VTE before pregnancy from the Danish National Patient Registry. We computed absolute risks, crude and adjusted risk differences (RDs) using a binomial regression model, and crude and adjusted risk ratios (RRs) from a modified Poisson regression model. Results Overall, 1419 women had a preconception history of VTE, while 578 112 did not. Preeclampsia occurred in 4.2% of pregnancies in the VTE group and in 2.7% of pregnancies in a comparison cohort (adjusted RD = 1.3%, 95% confidence interval (CI) 0.6–2.0%; adjusted RR = 1.5, 95% CI 1.3–1.8). Stillbirth occurred in 0.7% of pregnancies in the VTE group and in 0.4% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI 0.02–0.6%; adjusted RR = 1.8, 95% CI 1.1–3.0). Placental abruption occurred in 0.8% of pregnancies in the VTE group and in 0.5% of pregnancies in the comparison cohort (adjusted RD = 0.3%, 95% CI − 0.05–0.6%; adjusted RR = 1.6, 95% CI 1.1–2.4). Small-for-gestational-age infants accounted for 10.9% of live births in the VTE group and 9.8% of live births in the comparison cohort (adjusted RD = 0.6%, 95% CI − 0.5–1.7%; adjusted RR = 1.1, 95% CI 0.9–1.3). Conclusion Women with a history of VTE were at increased risk of placenta-mediated complications.

Objective. To investigate copeptin as a biomarker for small-for-gestational-age. Methods. We conducted a nested case-control study on maternal copeptin levels measured in gestational week 12 and 19 and risk of small-for-gestational age. Cases were defined as pregnant women who delivered a small-for-gestational-age infant. Small-for-gestational age was defined as a birth weight - 22% or less than expected according to gestational age (n = 39). Controls were pregnant women who delivered a normal-weight infant (n = 119). The copeptin ultrasensitive Kryptor kit (BRAHMS) was used to determine copeptin in maternal serum. We established reference ranges for copeptin by 95% prediction intervals with 90% confidence intervals. Paired and unpaired t-tests were performed to test the null-hypothesis of no difference in copeptin levels within and between the groups. Results. The reference intervals for copeptin in normal pregnancies were 1.24-5.51 pmol/L (90% confidence intervals on upper and lower limit were 1.13-1.37 and 5.00-6.08 pmol/L) at gestational week 12, and 1.30-5.09 pmol/L (90% confidence intervals were 1.19-1.42 and 4.65-5.57 pmol/L) at gestational week 19. Copeptin levels decreased from week 12-19 in cases (p = 0.02), whereas no change was observed in controls (p = 0.61). We found no difference in copeptin levels in cases compared to controls in gestational week 12 (p = 0.10) and week 19 (p = 0.81). Conclusion. The present study could not demonstrate copeptin as a novel biomarker for small-for-gestational-age.

The Present foraminiferal distribution (live + dead) in Freemansundet between Barentsøya and Edgeøya, Svalbard, has been compared with assemblages in raised marine Holocene deposits in Guldalen on Edgeeya. Four distinct foraminiferal assemblages were identified in Freemansundet, the Elphidium excavatum-Cassidulina reniforme assemblage, the Elphidium hallandense assemblage, the Cibicides lobatulus assemblage and the Elphidium incertum-Haynesina orbiculare assemblage. Four assemblage zones (Zones A-D) have been established in the glaciomarine to marine sediment sequence in Guldalen. Only two of the recent fauna! types were represented here. The Elphidium excavatum-Cassidulina reniforme assemblage, which reflects a proximal glacier environment, was found in the lowermost Zone A (the Elphidium excavatum Zone) and in Zone C (the Elphidium excavatum-Cassidulina reniforme Zone) in the Guldalen stratigraphy; the Elphidium incertum-Haynesina orbiculare assemblage, which reflects ameliorated shallow water conditions, was found in the uppermost Zone D in Guldalen. The marine sequence in Guldalen represents a relatively short period of time during the Early Holocene (ca 9700 to 8300 BP). The succession of the foraminiferal assemblages suggests that the deglaciation was interrupted by a cold period with glacial stagnation just after 9600 bp (Zone B. the Astrononion gallowayi-Nonionellina labradorica Zone).

Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p < 0.0001) and from second to third trimester (p < 0.0001). The level of fibrinogen rose significantly from second to third trimester (p < 0.0001). Protein S showed a statistically significant fall in the level from first to second trimester (p < 0.0001) and remained stable thereafter. Conclusion. Changes during pregnancy in plasma D-dimer, protein S and fibrinogen were confirmed. Further clinical studies are needed to clarify a clinical useful cut-off point for D-dimer in pregnancy. We suggest careful attention to a low peripartum fibrinogen, since it indicates an increased bleeding risk. We confirmed an earlier suggested lower cut-off point for protein S, during pregnancy. Abstract Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women in gestational week 11-17, with normal current pregnancy. Blood samples were collected in gestational weeks 11-17, 21-27 and 34-37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution(®). Results. A significant rise in D-dimer was found from first to second trimester (p