Anne Flem Jacobsen

• Kvenshagen, Line Norman; Kvenshagen, Hanna Norman; Holte, Kari; Jacobsen, Anne Flem; Størdal, Ketil & Hubin, Aliaksandr [Show all 7 contributors for this article] (2026). Association between Regional Labour Analgesia and Neonatal Heart Rate Immediately after Birth. Neonatology. ISSN 1661-7800. p. 1–8. doi: 10.1159/000550615.
• Leeves, Lisa Tangnes; Michelsen, Trond Melbye; Jacobsen, Anne Flem; Solhoff, Aslak Vimme; Gunnes, Nina & Sørbye, Ingvil Krarup (2025). Is indication for induction of labor associated with mode of delivery in term first births? A Norwegian registry-based study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 104(11), p. 2165–2177. doi: 10.1111/aogs.70060. Full text in Research Archive Show summary

  Introduction Few previous studies have examined the association between the indication for induction of labor (IOL) and the mode of delivery. To improve information for clinicians and women undergoing IOL, our study aimed to assess the association between the indication for IOL and the risk of cesarean and operative vaginal birth among nulliparous women with single cephalic term pregnancies. Furthermore, we examined whether associations varied by gestational length. Lastly, we evaluated reasons for cesarean and operative vaginal birth across indications for IOL. Material and Methods Data were extracted from the Medical Birth Registry of Norway from 2020 to 2021. We used the registered main indication for IOL. Multinomial logistic regression was applied to estimate relative risk ratios (RRRs) with associated 95% confidence intervals (CIs) of cesarean and operative vaginal birth versus spontaneous vaginal birth for the different IOL indications, using prelabor rupture of membranes (PROM) as the reference indication. Results Risk of cesarean versus spontaneous vaginal birth was four times higher for women induced due to large fetus compared to women induced due to PROM (adjusted RRR: 4.39; 95% CI: 3.21 to 5.99). Indications such as maternal request, post-term pregnancy, oligo−/polyhydramnios, preeclampsia/hypertension, and diabetes were associated with a 40%–91% increased relative risk of cesarean versus spontaneous vaginal birth compared to PROM. Relative risk of operative vaginal versus spontaneous vaginal birth was increased by 23%–29% for oligo−/polyhydramnios, diabetes, and post-term pregnancy compared to PROM. Indication large fetus had similar relative risk ratios at all gestational lengths. Rate of operative delivery for fetal distress was highest for IOL due to intrauterine growth restriction (IUGR). For secondary outcomes, IOL due to IUGR had the highest proportions of cesarean and operative vaginal birth for fetal distress. Indication post-term pregnancy had the highest proportion of cesarean birth for prolonged labor, while large fetus had the highest proportion of operative vaginal birth for prolonged labor. Conclusions Nulliparous women undergoing IOL for indications such as large fetus, post-term pregnancy, oligo-/polyhydramnios, preeclampsia/hypertension, and diabetes are at an elevated relative risk of cesarean versus spontaneous vaginal birth compared to IOL for PROM. In contrast, the relative risk of operative vaginal birth showed less variation by indication for IOL.

• Dybedal, Ingunn; Iversen, Nina; Jacobsen, Anne Flem; Bjørge, Line; Chaireti, Roza & Henriksson, Carola Elisabeth [Show all 12 contributors for this article] (2025). Hereditary antithrombin deficiency and venous thrombosis in pregnancy–results of a retrospective multicenter study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 23(9), p. 2807–2818. doi: 10.1016/j.jtha.2025.03.001. Full text in Research Archive Show summary

  Background The optimal anticoagulant regimen to prevent pregnancy-related venous thrombosis (VT) in women with antithrombin (AT) deficiency is unknown. Objectives This study aims to identify optimal doses of low-molecular-weight heparin (LMWH) to prevent pregnancy-related VT and to investigate if AT concentrate peripartum could reduce postpartum VT in women with AT deficiency. Methods This retrospective study includes 115 pregnancies in 57 women with subclassified AT deficiency treated with LMWH in Denmark, Norway, and Sweden (1991-2017). Results In pregnancies with high-risk AT deficiency, LMWH doses of <5000 IU/24 h, 5000 to 12 500 IU/24 h, and >12 500 IU/24 h revealed different VT risks (P = .02). The hazard ratios for VT were 1.0 (reference), 0.5 (95% CI [0.1, 2.3]), and 0 (95% CI [0, ∞]), correspondingly. Of the additional risk factors, only previous VT reached statistical significance. In 100 pregnancies with high-risk AT deficiency, 15 VTs occurred in contrast to none in the 15 pregnancies with low-/intermediate-risk AT deficiency. Six of the 12 antepartum VTs occurred before week 9. All had a prior VT, and 5 were hormone-associated. Of these 5, 1 had received a LMWH dose of 7500 IU/24 h and 3 had received a LMWH dose of 10 000 IU/24 h, respectively. AT concentrate, given peripartum in 66 of the 74 term pregnancies, resulted in 1 VT (1.5%). Without AT concentrate (8 pregnancies), 2 VTs occurred (25%; 95% CI [2, 61]). Peripartum hemorrhage (>1000 mL) occurred in 8 (11%) term pregnancies. Six had received therapeutic LMWH doses. Conclusion In high-risk AT deficiency pregnancies with previous VT, our results support prophylaxis with high prophylactic doses of LMWH from confirmed pregnancy. Hence, AT concentrate should be given peri-/postpartum

• Collange, Fanny; Bistervels, Ingrid M.; Buchmuller, Andrea; Wiegers, Hanke M.G.; Áinle, Fionnuala Ní & Verhamme, Peter [Show all 16 contributors for this article] (2025). Assessment of clinical probability scores for pulmonary embolism diagnosis during pregnancy and postpartum in women with a history of venous thromboembolism: a Highlow ancillary study. Research and Practice in Thrombosis and Haemostasis (RPTH). 10(1). doi: 10.1016/j.rpth.2025.103281. Full text in Research Archive
• Bekkenes, Maria Egeland; Jørgensen, Marte Morin; Jacobsen, Anne Flem; Fagerland, Morten Wang; Rakstad-Larsen, Helene & Aaberge, Lars [Show all 10 contributors for this article] (2025). Effects of Prophylactic Oxytocin or Carbetocin on Troponin Release and Postpartum Haemorrhage at Planned Caesarean Delivery: A Double-Blind Randomised Controlled Trial. BJOG: An International Journal of Obstetrics and Gynaecology. ISSN 1470-0328. 132(12), p. 1742–1752. doi: 10.1111/1471-0528.18312. Full text in Research Archive
• Berge, Magnus Bollum; Jacobsen, Anne Flem; Yli, Branka Markovic; Staff, Annetine; Gunnes, Nina & Falk, Ragnhild Sørum [Show all 8 contributors for this article] (2025). A direct comparison of the diagnostic accuracy of ST segment analysis (STAN) and fetal scalp blood sample lactate: A population-based observational study. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 308, p. 147–152. doi: 10.1016/j.ejogrb.2025.03.002. Full text in Research Archive Show summary

  Introduction: Fetal scalp blood sample (FBS) lactate and ST analysis (STAN) are adjuncts to cardiotocography (CTG) in high-risk deliveries, aiming to increase the specificity of the fetal monitoring. These methods have never been compared directly, through simultaneous evaluation in the same deliveries. Material and methods: We conducted a prospective, population-based study on deliveries with singleton, cephalic fetuses in gestational week ≥ 36 + 0 monitored with internal CTG. Cases were defined as deliveries with umbilical cord artery pH ≤ 7.10. For each case, the following three deliveries with umbilical cord artery pH > 7.10 were included as controls. The sensitivity and specificity of FBS lactate and STAN for the predefined adverse neonatal outcomes were compared using McNemar’s test. Results: Of 10,000 women included by passive consent, 178 deliveries were included as cases, and 516 as controls. STAN had a significantly higher sensitivity for the main outcome (pH ≤ 7.10) compared to FBS lactate (49 % vs. 40 %, p = 0.03). Although STAN showed a tendency toward a higher sensitivity for the secondary outcomes, differences were not statistically significant (p = 0.14–0.50). FBS lactate had significantly higher specificity for all outcomes (main outcome 88 % vs. 69 %, p < 0.01). Conclusions: STAN demonstrated a higher sensitivity for moderate acidemia compared to FBS lactate, but with lower specificity for all outcomes. These results do not not provide evidence to support the choice of one fetal surveillance system over the other. Further research should focus on how potential advantages of either method could be combined.

• Marsdal, Kjersti Engen; Sørbye, Ingvil Krarup; Bernitz, Stine; Adan, Nasreen; Grødal, Elin Baustad & Jacobsen, Anne Flem [Show all 7 contributors for this article] (2025). Clinical outcomes and feasibility of implementing outpatient labor induction with misoprostol: A prospective cohort study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. p. 647–657. doi: 10.1111/aogs.15029. Full text in Research Archive
• Berge, Magnus; Kessler, Jørg; Staff, Annetine & Jacobsen, Anne Flem (2025). The diagnostic accuracy of different fetal blood sample lactate cutoffs in labor, utilizing the StatStrip Xpress® lactate-meter: A population-based observational study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 104(8), p. 1496–1504. doi: 10.1111/aogs.15140. Full text in Research Archive Show summary

  Introduction: A recent study recommended 5.2 mmol/L as a cutoff for fetal blood sample (FBS) lactate in labor for the StatStrip Lactate®/Lactate Xpress® lactate meter. In the present study, we validated FBS lactate cutoffs in a larger population-based setting, with different CTG guidelines, testing external validity. Material and Methods: We conducted a prospective population-based study at Oslo University Hospital, Ullevål, Norway, a tertiary referral obstetric department with 7000 annual deliveries. Women with a singleton fetus in cephalic presentation in gestational week ≥36 + 0 were included in the analyses. We used ROC curves to calculate the area under the curve (AUC) and estimate the optimal cutoff for the following adverse neonatal outcomes: Umbilical cord pH ≤7.10, umbilical cord pH ≤7.05, metabolic acidosis (pH <7.0 and Base deficitextracellular fluid > 12 mmol/L), 1-minute Apgar score <4, 5-min Apgar score <7, hypoxic ischemic encephalopathy, and transfer to the neonatal intensive care unit. Analyses were restricted to women with a FBS lactate within 25 min prior to delivery. The study is registered in clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04779294). Results: Of 7816 included women, 1466 (19%) had a FBS lactate measurement within 25 min prior to delivery. The calculated optimal cutoff for FBS lactate varied by outcomes: 5-min Apgar score <7: AUC 0.69 (0.57–0.80), cutoff 4.0 mmol/L; metabolic acidosis: AUC 0.92 (0.78–1.00), cutoff 7.0 mmol/L; hypoxic ischemic encephalopathy: AUC 0.95 (0.86–1.00), cutoff 4.7 mmol/L. Sensitivity increased for some of the outcomes with a decreasing cutoff. Specificity increased for all outcomes with an increasing cutoff. Conclusions: We consider an FBS lactate cutoff of ≥5.2 mmol/L a good balance between high sensitivity for adverse neonatal outcomes and an acceptable number of needed interventions.

• Lahmami, Gulim; Räisänen, Sari; Jacobsen, Anne Flem; Yli, Branka Markovic; Tingleff, Tiril & Laine, Katariina (2024). Clinical examination for identifying low-risk pregnancies suitable for expectant management beyond 40–41 gestational weeks: maternal and fetal outcomes. Archives of Gynecology and Obstetrics. ISSN 0932-0067. doi: 10.1007/s00404-024-07869-5. Full text in Research Archive Show summary

  Purpose There is an ongoing discussion on whether the benefits of term elective labor induction outweigh its potential risks. This study evaluated the utility of a comprehensive clinical examination in identifying low-risk pregnancies suitable for expectant management beyond gestational age 40‒41 weeks and compared their outcomes with earlier labor induction by indication. Methods Pregnant women (n = 722) with ≥ 40 + 0 gestational weeks referred to a tertiary hospital were included in this prospective cohort. The study population was divided into the primary induction group (induction before 42 + 0 gestational weeks) and the expectant management group (spontaneous labor onset or induction at 42 + 0 gestational weeks), by decision based on a primary consultation. The Chi-square test and logistic regression were applied. The outcome measures were composite adverse fetal outcome (admission to a neonatal intensive care unit, metabolic acidosis, or Apgar score < 7 at 5 min), treatment with intrapartum antibiotics, intrapartum maternal fever ≥ 38 °C, intrapartum cesarean section, and postpartum hemorrhage ≥ 1500 ml. Results The main outcome measures did not differ significantly between the primary induction group (n = 258) and the expectant management group (n = 464): composite adverse fetal outcome (OR = 2.29, 95% CI = 0.92–5.68; p = 0.07), intrapartum cesarean section (OR = 1.00, 95% CI = 0.64–1.56; p = 1.00), postpartum hemorrhage ≥ 1500 ml (OR = 1.89, 95% CI = 0.92–3.90; p = 0.09), intrapartum maternal fever ≥ 38 °C (OR = 1.26, 95% CI = 0.83–1.93; p = 0.28), or treatment with intrapartum antibiotics (OR = 1.25, 95% CI = 0.77–2.02; p = 0.37). Conclusion A comprehensive clinical examination at 40‒41 gestational weeks can identify pregnancies that might be managed expectantly until 42 gestational weeks obtaining similar outcomes to those induced earlier.

• Lahmami, Gulim; Räisänen, Sari; Jacobsen, Anne Flem; Yli, Branislava Markovic; Tingleff, Tiril & Laine, Katariina (2023). Trends in Term Intrapartum Stillbirth in Norway. JAMA Network Open. 6(9), p. E2334830–E2334830. doi: 10.1001/jamanetworkopen.2023.34830. Full text in Research Archive Show summary

  Importance Fetal death during labor at term is a complication that is rarely studied in high-income countries. There is a need for large population-based studies to examine the rate of term intrapartum stillbirth in high-income countries and the factors associated with its occurrence. Objective To evaluate trends in term intrapartum stillbirth over time and to investigate the association between the trends and term intrapartum stillbirth risk factors from 1999 to 2018 in Norway. Design, Setting, and Participants This cohort study used data from the Medical Birth Registry of Norway from 1999 to 2018 to examine rates of term intrapartum stillbirth and risk factors associated with this event. A population of 1 021 268 term singleton pregnancies without congenital anomalies or antepartum stillbirths was included in analyses, which were performed from September 2022 to February 2023. Exposure The main exposure variable was time, which was divided into four 5-year periods: 1999 to 2003, 2004 to 2008, 2009 to 2013, and 2014 to 2018. Main Outcomes and Measures The primary study outcome was term intrapartum stillbirth. Risk ratios were calculated, and multivariable logistic regression analyses were conducted to identify factors associated with secular trends of term intrapartum stillbirth. Results The study population consisted of 1 021 268 term singleton births (maternal mean [SD] age, 29.72 [5.01] years; mean [SD] gestational age, 39.69 [1.27] weeks). During the study period, there were 95 term intrapartum stillbirths (0.09 per 1000 births). Maternal age, the proportion of individuals born in a country other than Norway, and the prevalence of gestational diabetes, labor induction, operative vaginal delivery, and previous cesarean delivery increased over the course of the study period. Conversely, the prevalence of infants large for gestational age, hypertensive disorder in pregnancy, and spontaneous vaginal delivery and the proportion of individuals who smoked decreased. The term intrapartum stillbirth rate decreased by 87% (95% CI, 68%-95%) from 0.15 per 1000 births in 1999 to 2008 to 0.02 per 1000 births in 2014 to 2018. Three in 4 term intrapartum stillbirths (70 of 95) occurred during intrapartum operative deliveries. The increased prevalence of older maternal age and obstetric risk factors were not associated with the variation in intrapartum stillbirth rates among the time periods. The prevalence of term intrapartum stillbirth was higher for individuals who gave birth in maternity units with fewer than 3000 annual births (adjusted odds ratio, 1.67; 95% CI, 1.07-2.61) than for those who gave birth in units with 3000 or more annual births. Conclusions and Relevance Findings of this study suggest that, despite increases in maternal and obstetric risk factors, term intrapartum stillbirth rates substantially decreased during the study period. Reasons for this decrease may be due to improvements in intrapartum care.

• Berge, Magnus Bollum; Kessler, Jørg; Yli, Branislava Markovic; Staff, Anne Cathrine; Gunnes, Nina & Jacobsen, Anne Flem (2023). Neonatal outcomes associated with time from a high fetal blood lactate concentration to operative delivery. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 102(8), p. 1106–1114. doi: 10.1111/aogs.14597. Full text in Research Archive Show summary

  Introduction: Adjunctive technologies to cardiotocography intend to increase the specificity of the diagnosis of fetal hypoxia. If correctly diagnosed, time to delivery could affect neonatal outcome. In the present study, we aimed to investigate the effect of time from when fetal distress is indicated by a high fetal blood sample (FBS) lactate concentration to operative delivery on the risk of adverse neonatal outcomes. Material and methods: We conducted a prospective observational study. Deliveries with a singleton fetus in cephalic presentation at 36+0weeks of gestation or later were included. Adverse neonatal outcomes, related to decision-to-delivery interval (DDI), were investigated in operative deliveries indicated by an FBS lactate concentration of at least 4.8 mmol/L. We applied logistic regression to estimate crude and adjusted odds ratios (aOR) of various adverse neonatal outcomes, with associated 95% confidence intervals (CI), for a DDI exceeding 20 minutes, compared with a DDI of 20 minutes or less. ClinicalTrials.gov Identifier: NCT04779294. Results: The main analysis included 228 women with an operative delivery indicated by an FBS lactate concentration of 4.8 mmol/L or greater. The risk of all adverse neonatal outcomes was significantly increased for both DDI groups compared with the reference group (deliveries with an FBS lactate below 4.2 mmol/L within 60 minutes before delivery). In operative deliveries indicated by an FBS lactate concentration of 4.8 mmol/L or more, there was a significantly increased risk of a 5-minute Apgar score less than 7 if the DDI exceeded 20 minutes, compared with a DDI of 20 minutes or less (aOR 8.1, 95% CI 1.1–60.9). We found no statistically significant effect on other short-term outcomes for deliveries with DDI longer than 20 minutes, compared with those with DDI of 20 minutes or less (pH ≤7.10: aOR 2.0, 95% CI 0.5–8.4; transfer to the neonatal intensive care unit: aOR 1.1, 95% CI 0.4–3.5). Conclusions: After a high FBS lactate measurement, the increased risk of adverse neonatal outcome is further augmented if the DDI exceeds 20 minutes. These findings give support to current Norwegian guidelines for intervention in cases of fetal distress.

• Bistervels, Ingrid M; Buchmüller, Andrea; Wiegers, Hanke M G; Áinle, Fionnuala Ní; Tardy, Bernard & Donnelly, Jennifer [Show all 16 contributors for this article] (2022). Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. The Lancet. ISSN 0140-6736. 400(10365), p. 1777–1787. doi: 10.1016/S0140-6736(22)02128-6. Full text in Research Archive Show summary

  Background Pregnancy-related venous thromboembolism is a leading cause of maternal morbidity and mortality, and thromboprophylaxis is indicated in pregnant and post-partum women with a history of venous thromboembolism. The optimal dose of low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy and the post-partum period is uncertain. Methods In this open-label, randomised, controlled trial (Highlow), pregnant women with a history of venous thromboembolism were recruited from 70 hospitals in nine countries (the Netherlands, France, Ireland, Belgium, Norway, Denmark, Canada, the USA, and Russia). Women were eligible if they were aged 18 years or older with a history of objectively confirmed venous thromboembolism, and with a gestational age of 14 weeks or less. Eligible women were randomly assigned (1:1), before 14 weeks of gestational age, using a web-based system and permuted block randomisation (block size of six), stratified by centre, to either weight-adjusted intermediate-dose or fixed low-dose low-molecular-weight heparin subcutaneously once daily until 6 weeks post partum. The primary efficacy outcome was objectively confirmed venous thromboembolism (ie, deep-vein thrombosis, pulmonary embolism, or unusual site venous thrombosis), as determined by an independent central adjudication committee, in the intention-to-treat (ITT) population (ie, all women randomly assigned to treatment). The primary safety outcome was major bleeding which included antepartum, early post-partum (within 24 h after delivery), and late post-partum major bleeding (24 h or longer after delivery until 6 weeks post partum), assessed in all women who received at least one dose of assigned treatment and had a known end of treatment date. This study is registered with ClinicalTrials.gov, NCT01828697, and is now complete. Findings Between April 24, 2013, and Oct 31, 2020, 1339 pregnant women were screened for eligibility, of whom 1110 were randomly assigned to weight-adjusted intermediate-dose (n=555) or fixed low-dose (n=555) low-molecular-weight heparin (ITT population). Venous thromboembolism occurred in 11 (2%) of 555 women in the weight-adjusted intermediate-dose group and in 16 (3%) of 555 in the fixed low-dose group (relative risk [RR] 0·69 [95% CI 0·32–1·47]; p=0·33). Venous thromboembolism occurred antepartum in five (1%) women in the intermediate-dose group and in five (1%) women in the low-dose group, and post partum in six (1%) women and 11 (2%) women. On-treatment major bleeding in the safety population (N=1045) occurred in 23 (4%) of 520 women in the intermediate-dose group and in 20 (4%) of 525 in the low-dose group (RR 1·16 [95% CI 0·65–2·09]). Interpretation In women with a history of venous thromboembolism, weight-adjusted intermediate-dose low-molecular-weight heparin during the combined antepartum and post-partum periods was not associated with a lower risk of recurrence than fixed low-dose low-molecular-weight heparin. These results indicate that low-dose low-molecular-weight heparin for thromboprophylaxis during pregnancy is the appropriate dose for the prevention of pregnancy-related recurrent venous thromboembolism.

• Brigtsen, Anne Karin; Jacobsen, Anne Flem; Dedi, Lumnije; Melby, Kjetil K.; Nygaard, Cathrine Skorpen & Fugelseth, Drude [Show all 7 contributors for this article] (2022). Group B Streptococcus colonization at delivery is associated with maternal peripartum infection. PLOS ONE. 17(4). doi: 10.1371/journal.pone.0264309. Full text in Research Archive Show summary

  Background Group B Streptococcus (GBS) is a major cause of serious neonatal infection but its role in maternal morbidity has received little investigation. The aim of this study was to determine whether GBS colonization at delivery is associated with increased risk of maternal peripartum infection. Methods In this prospective cohort study, 1746 unselected women had a vaginal-rectal culture taken at the onset of labor. Diagnosis of maternal peripartum infection was based on a combination of two or more signs or symptoms including fever, breast pain, severe wound or pelvic pain, purulent discharge and abnormal laboratory tests including C-reactive protein and white blood cell count occurring from labor until 2 weeks postpartum. The main outcome measure was the proportion of women with maternal peripartum infection according to GBS colonization status. Results A total of 25.9% (452/1746) women were colonized with GBS. The rate of peripartum infection was almost twice as high in colonized women (49/452 [10.8%]) vs. non-colonized women (81/1294 [6.3%]); OR 1.82 [1.26–2.64], p = 0.002). This association was confirmed in a multivariable model (OR 1.99 [1.35–2.95], p = 0.001). Women diagnosed with peripartum infection had a significantly longer hospital stay compared to women without peripartum infection (4 days (median) vs. 3 days, p < 0.001). Length of hospital stay did not differ between colonized and non-colonized women. Serotype IV GBS was more frequent in colonized women with peripartum infection than in women without peripartum infection (29.3% vs. 12.5%, p = 0.003). Conclusions GBS colonization at delivery is associated with increased risk of peripartum infection. Whether this increase is due directly to invasion by GBS or whether GBS colonization is associated with a more general vulnerability to infection remains to be determined.

• Waldum, Åsa; Lukasse, Mirjam; Staff, Anne Cathrine; Falk, Ragnhild Sørum; Sørbye, Ingvil & Jacobsen, Anne Flem (2022). Intrapartum pudendal nerve block analgesia and childbirth experience in primiparous women with vaginal birth: A cohort study. Birth. ISSN 0730-7659. 50(1), p. 1–10. doi: 10.1111/birt.12697. Full text in Research Archive Show summary

  Background A negative childbirth experience has short- and long-term consequences for both mother and child. This study aimed to investigate the association between intrapartum pudendal nerve block (PNB) analgesia and childbirth experience. Methods Primiparous women with a singleton cephalic vaginal live births at term at Oslo University Hospital from January 1, 2017, to June 1, 2019, were eligible for inclusion. The main outcome was total score on a childbirth experience questionnaire (range 1.0–4.0, higher score indicates better childbirth experience). An absolute risk difference of 0.10 was considered clinically relevant. Propensity score matching was used to adjust for differences in baseline characteristics between women with and without PNB. The analyses were stratified by spontaneous vs instrumental birth. Subanalyses of the questionnaire's domains (own capacity, professional support, perceived safety, and participation) were performed. Results Of 979 participating women, mean age was 32 years. Childbirth experience did not differ between women with and without PNB, either in spontaneous (absolute risk difference of the mean: −0.05, P value 0.36) or in instrumental birth (absolute risk difference of the mean: 0.03, P value 0.61). There were no statistically significant differences between PNB group scores for the separate domains. Conclusions Women's childbirth experiences did not differ between birthing people with or without PNB, either in spontaneous or in instrumental births. The clinical implications of our study should be interpreted in light of the pain-relieving effects of PNB.PNB should be provided on clinical indication, including for individuals with severe labor pain.

• Bistervels, Ingrid M.; Wiegers, Hanke M.G.; Áinle, Fionnuala Ní; Bleker, Suzanne M.; Chauleur, Céline & Donnelly, Jennifer [Show all 15 contributors for this article] (2022). Onset of labor and use of analgesia in women using thromboprophylaxis with 2 doses of low-molecular-weight heparin: insights from the Highlow study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(1), p. 57–67. doi: 10.1016/j.jtha.2022.11.004. Full text in Research Archive
• Fiskvik, Hilde; Jacobsen, Anne F.; Iversen, Nina; Henriksson, Carola Elisabeth & Jacobsen, Eva-Marie (2021). Treatment of Homozygous Type II Antithrombin Heparin-Binding Site Deficiency in Pregnancy. Case Reports in Obstetrics and Gynecology. ISSN 2090-6692. 2021, p. 1–3. doi: 10.1155/2021/4393821. Full text in Research Archive
• Sugulle, Meryam; Halldórsdóttir, Erna; Kvile, Janne; Berntzen, Line Dahlgaard & Jacobsen, Anne Flem (2021). Prospective assessment of vacuum deliveries from midpelvic station in a tertiary care university hospital: Frequency, failure rates, labor characteristics and maternal and neonatal complications. PLOS ONE. 16(11), p. 1–12. doi: 10.1371/journal.pone.0259926. Full text in Research Archive Show summary

  Background Midpelvic vacuum extractions are controversial due to reports of increased risk of maternal and perinatal morbidity and high failure rates. Prospective studies of attempted midpelvic vacuum outcomes are scarce. Our main aims were to assess frequency, failure rates, labor characteristics, maternal and neonatal complications of attempted midpelvic vacuum deliveries, and to compare labor characteristics and complications between successful and failed midpelvic vacuum deliveries. Study design Clinical data were obtained prospectively from all attempted vacuum deliveries (n = 891) over a one-year period with a total of 6903 births (overall cesarean section rate 18.2% (n = 1258). Student’s t-test, Mann-Whitney U-test or Chi-square test for group differences were used as appropriate. Odds ratios and 95% confidence intervals are given as indicated. The uni- and multivariable analysis were conducted both as a complete case analysis and with a multiple imputation approach. A p-value of <0.05 was considered statistically significant. Results Attempted vacuum extractions from midpelvic station constituted 36.7% (n = 319) of all attempted vacuum extractions (12.9% (n = 891) of all births). Of these 319 midpelvic vacuum extractions, 11.3% (n = 36) failed and final delivery mode was cesarean section in 86.1% (n = 31) and forceps in the remaining 13.9% (n = 5). Successful completion of midpelvic vacuum by 3 pulls or fewer was achieved in 67.1%. There were 3.9% third-degree and no fourth-degree perineal tears. Cup detachments were associated with a significantly increased failure rate (adjusted OR 6.13, 95% CI 2.41–15.56, p< 0.001). Conclusion In our study, attempted midpelvic vacuum deliveries had relatively low failure rate, the majority was successfully completed within three pulls and they proved safe to perform as reflected by a low rate of third-degree perineal tears. We provide data for nuanced counseling of women on vacuum extraction as a second stage delivery option in comparable obstetric management settings with relatively high vacuum delivery rates and low cesarean section rates.

• Waldum, Åsa; Staff, Anne Cathrine; Lukasse, Mirjam; Falk, Ragnhild Sørum; Sørbye, Ingvil & Jacobsen, Anne Flem (2021). Intrapartum pudendal nerve block analgesia and risk of postpartum urinary retention: a cohort study. International Urogynecology Journal. ISSN 0937-3462. 32(32), p. 2383–2391. doi: 10.1007/s00192-021-04768-0. Full text in Research Archive Show summary

  Introduction and hypothesis: Pudendal nerve block analgesia (PNB) is used as pain relief in the final stage of childbirth. We hypothesized that PNB is associated with higher rates of postpartum urinary retention. Methods: We performed a cohort study among primiparous women with a singleton, cephalic vaginal birth at Oslo University Hospital, Norway. Women receiving PNB were included in the exposed group, while the subsequent woman giving birth without PNB was included in the unexposed group. We compared the likelihood of postpartum urinary retention, defined as catheterization within 3 h after birth. Logistic regression analysis stratified by mode of delivery was performed adjusting for epidural analgesia, episiotomy and birth unit. Results: Of the 1007 included women, 499 were exposed to PNB and 508 were unexposed. In adjusted analyses, women exposed to PNB did not differ in likelihood of postpartum urinary retention compared to women unexposed to PNB in either spontaneous (odds ratio[OR]: 0.82, 95% confidence interval [CI] 0.55–1.22) or instrumental (OR 1.45, 95% CI 0.89–2.39) births. Furthermore, no differences between the groups were observed with excessive residual urine volume or catheterization after > 3 h. Conclusions: PNB was associated with neither risk of postpartum urinary retention nor excessive residual urine volume and is therefore unlikely to hamper future bladder function.

• Jacobsen, Anne Flem & Sandset, Per Morten (2021). Prior Thromboembolic Disease and Assisted Reproductive Therapy. Seminars in Reproductive Medicine. ISSN 1526-8004. doi: 10.1055/s-0041-1732375. Full text in Research Archive Show summary

  Abstract Assisted reproductive therapy (ART) increases the risk of venous thrombosis (VT) by 2- to 4-fold, whereas pregnancy increases the risk by 5- to 10-fold. Women with a history of VT undergoing ART are often suggested thromboprophylaxis. The literature is scarce and international guidelines are lacking. We made a review of the literature and base our suggestions primarily on expert opinions. We suggest women with a prior VT to use low-molecular-weight heparin as thromboprophylaxis starting from ovarian stimulation, throughout pregnancy, and 6 weeks postpartum. Assessment of VT risk should be done prior to ART. Adjustment of treatment to minimize the thrombotic risk, such as preventing ovarian hyperstimulation syndrome, single-embryo transfer, cryopreservation, and transfer of frozen embryos instead of fresh embryo in high-risk women, is suggested. Women with previous arterial thrombosis should continue aspirin during ART treatment, pregnancy, and postpartum.

• Berdzuli, Nino; Lomia, Nino; Staff, Anne Cathrine; Lazdane, Gunta; Pestvenidze, Ekaterine & Jacobsen, Anne Flem (2021). Audit of early and late maternal deaths in georgia: Potential for improving substandard obstetric care. International Journal of Women's Health. 13, p. 205–219. doi: 10.2147/IJWH.S288763. Full text in Research Archive Show summary

  Introduction: Quality of care is an important factor in reducing preventable maternal deaths, yet it is a significant challenge in many countries. Substandard and poor quality of care is the leading factor in two-thirds of maternal deaths in European countries. Our study investigated the deaths of all women of reproductive age in 2012 in Georgia. The aim was to define the underlying causes of maternal deaths and to identify the factors in women’s care which contributed to the fatal outcomes. Methods: A national Reproductive Age Mortality Survey was conducted in Georgia in 2014– 15. Data from multiple sources was triangulated to identify all deaths of women of reproductive age. This was followed by verbal autopsy diagnoses. Each case of early and late maternal death was investigated through interviews and medical record reviews at the last medical facility providing care for the deceased woman. A specialist panel reviewed and assigned underlying causes of death, assessed the management of each woman’s condition, and identified elements of suboptimal care. Results: We identified a total of 23 maternal deaths, including 15 (65%) early and eight (35%) late deaths. The maternal mortality ratio was 26.3 per 100 000 live births. The four leading causes of early maternal deaths were: sepsis, hemorrhage, embolism, and pregnancy-induced hypertension. Embolism and sepsis were the direct causes of the eight late maternal deaths. Cancer, tuberculosis, and postpartum suicide constituted the indirect causes of death. Improvements in care which would have made a difference to the outcomes were identified in 87% of early maternal deaths and 67% of late maternal deaths due to direct obstetric causes. Discussion: Delayed recognition and inappropriate management of maternal complications were common across almost all cases studied. The findings from Georgia highlight the conclusion that most maternal deaths were preventable and that improvement in obstetric care is urgently required.

• Waldum, Åsa; Jacobsen, Anne Flem; Lukasse, Mirjam; Staff, Anne Cathrine; Falk, Ragnhild Sørum & Vangen, Siri [Show all 7 contributors for this article] (2020). The provision of epidural analgesia during labor according to maternal birthplace: a Norwegian register study. BMC Pregnancy and Childbirth. 20(321). doi: 10.1186/s12884-020-03021-8. Full text in Research Archive Show summary

  Background: The provision of epidural analgesia during labor is ideally a shared decision between the woman and her health care provider. However, immigrant characteristics such as maternal birthplace could affect decision-making and thus access to pain relief. We aimed to assess disparities in the provision of epidural analgesia in planned vaginal birth according to maternal region of birth. Methods: We performed a nation-wide register study of 842,496 live-born singleton deliveries in Norway between 2000 and 2015. Maternal birthplace was categorized according to the Global Burden of Disease framework. The provision of epidural analgesia was compared in regression models stratified by parity and mode of delivery. Results: Compared to native-born women, primiparous women from Latin America/Caribbean countries with an instrumental vaginal delivery were most likely to be provided epidural analgesia (OR 2.12, 95%CI 1.69–2.66), whilst multiparous women from Sub-Saharan Africa with a spontaneous vaginal delivery were least likely to be provided epidural analgesia (OR 0.42, 95% C 0.39–0.44). Longer residence time was associated with a higher likelihood of being provided analgesia, whereas effects of maternal education varied by Global Burden of Disease group. Conclusions: Disparities in the likelihood of being provided epidural analgesia were observed by maternal birthplace. Further studies are needed to consider whether the identified disparities represent women’s own preferences or if they are the result of heterogeneous access to analgesia during labor.

• Sørbye, Ingvil; Oppegaard, Kevin Sunde; Weeks, Andrew; Marsdal, Kjersti Engen & Jacobsen, Anne Flem (2020). Induction of labor and nulliparity: A nationwide clinical practice pilot evaluation. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 99(12), p. 1700–1709. doi: 10.1111/aogs.13948. Full text in Research Archive Show summary

  Introduction Induction of labor has become an increasingly common obstetric procedure, but in nulliparous women or women with a previous cesarean section, it can pose a clinical challenge. Despite an overall expansion of medical indications for labor induction, there is little international consensus regarding the criteria for induction, or for the recommended methods among nulliparous women. In this light, we assessed variations in the practice of induction of labor among 21 birth units in a nationwide cohort of women with no prior vaginal birth. Material and methods We carried out a prospective observational pilot study of women with induced labor and no prior vaginal birth, across 21 Norwegian birth units. We registered induction indications, methods and outcomes from 1 September to 31 December 2018 using a web‐based case record form. Women were grouped into “Nulliparous term cephalic”, “Previous cesarean section” and “Other Robson” (Robson groups 6, 7, 8 or 10). Results More than 98% of eligible women (n=1818) were included and a wide variety of methods was used for induction of labor. In nulliparous term cephalic pregnancies, cesarean section rates ranged from 11.1% to 40.6% between birth units, whereas in the previous cesarean section group, rates ranged from 22.7% to 67.5%. The indications “large fetus” and “other fetal” indications were associated with the highest cesarean rates. Failed inductions and failure to progress in labor contributed most to the cesarean rates. Uterine rupture occurred in two women (0.11%), both in the previous cesarean section group. In neonates, 1.6% had Apgar <7 at 5 minutes, and 0.4% had an umbilical artery pH <7.00. Conclusions Cesarean rates and applied methods for induction of labor varied widely in this nationwide cohort of women without a prior vaginal birth. Neonatal outcomes were similar to those of normal birth populations. Results could indicate the need to move towards more standardized induction protocols associated with optimal outcomes for mother and baby.

• Lahmami, Gulim; Räisänen, Sari; Jacobsen, Anne Flem; Sole, Kristina Baker; BJARKØ, LISA & Laine, Katariina (2020). Adverse perinatal outcomes in 665,244 term and post-term deliveries—a Norwegian population-based study. European Journal of Obstetrics, Gynecology, and Reproductive Biology. ISSN 0301-2115. 247, p. 212–218. doi: 10.1016/j.ejogrb.2020.02.028. Full text in Research Archive
• Berdzuli, Nino; Lomia, Nino; Staff, Anne Cathrine; Kereselidze, Maia; Lazdane, Gunta & Jacobsen, Anne Flem (2020). Maternal mortality in Georgia: Incidence, causes and level of underreporting: A national reproductive age mortality study 2014. International Journal of Women's Health. 12, p. 277–286. doi: 10.2147/IJWH.S227349. Full text in Research Archive Show summary

  Introduction: Accurate data on maternal mortality are essential for assessing progress towards Sustainable Development Goals (SDG).The aim of the study was to determine the incidence and causes of maternal deaths in Georgia, then explore the potential for improvement of quality of maternal health care. The study’s secondary aims were to identify the level of underreporting of maternal deaths in Georgian vital statistics over 1 year (2012) and to compare these results with previous data from 2006. The study findings allow to support the country in developing evidence-based policies and tracking progress towards meeting SDG targets. Methods: A national Reproductive Age Mortality Survey (RAMOS) was conducted in Georgia in 2014– 15. Multiple data sources were used to identify deaths of women aged 15– 49 years between January and December 2012. All deaths in women of reproductive age were investigated through verbal autopsy (VA) diagnoses. Deaths in women during pregnancy or one-year postpartum were further investigated by conducting interviews and medical record reviews at the last medical facility which provided health care for the woman during her fatal condition. A specialist panel reviewed these cases and assigned underlining causes of deaths. Results: We found that 98% of deaths among women of reproductive age were registered by Georgia’s civil registration and vital statistics system (CRVS). A total of 918 deaths met the study inclusion criteria. Thirty-six (4.1%) women died during pregnancy or within one-year postpartum. Among these 36 deaths, 23 (63.8%) were maternal deaths, 15 early (either during pregnancy or 42 days postpartum) and eight late (43– 365 days postpartum) deaths (65.2% vs 34.8%). The remaining 13 of 36 deaths were coincidental deaths. Fourteen maternal deaths were reported by official statistics and nine deaths were not included in these statistics. Thus, the underreporting rate was 39%. Direct obstetric causes accounted for 73.9% (n=17) of maternal deaths, whereas 26.1% (n=6) were indirect. The leading causes of direct maternal deaths were infection (21.7%), hemorrhage (17.4%), pulmonary embolism (13.0%), and pregnancy-induced hypertension (8.7%). The RAMOS study calculated a maternal mortality ratio (early maternal deaths) of 26.3 per 100,000 live births compared with the official figure of 22.8 per 100,000 live births. Discussions: Registration of early maternal deaths significantly improved since last survey in 2008, while indirect and late maternal deaths continue to be unrecognized, as reflected in official Georgian statistics. The difference between RAMOS study findings and officially reported maternal mortality rates is minimal, showing improvements in detection of maternal deaths by the national maternal mortality surveillance system. The greatest number of direct obstetric deaths occur in the first week postpartum, which likely reflects deficiencies in quality of care.

• Borgen, Iren; Småstuen, Milada Cvancarova; Jacobsen, Anne Flem; Garnweidner-Holme, Lisa; Fayyad, Seraj & Noll, Josef [Show all 7 contributors for this article] (2019). Effect of the Pregnant+ smartphone application in women with gestational diabetes mellitus: A randomised controlled trial in Norway. BMJ Open. 9(11). doi: 10.1136/bmjopen-2019-030884. Full text in Research Archive Show summary

  Objective To assess the effect of the Pregnant+ app on the 2-hour glucose level of the routine postpartum oral glucose tolerance test (OGTT) among women with gestational diabetes mellitus (GDM). The Pregnant+ app was designed to provide information about GDM, and promote physical activity and a healthy diet. Design A multicentre, non-blinded randomised controlled trial. Setting Five diabetes outpatient clinics in the Oslo region. Participants Women ≥18 years old with a 2-hour OGTT blood glucose level ≥9 mmol/L who owned a smartphone; understood Norwegian, Urdu or Somali; and were <33 weeks pregnant. A total of 238 women were randomised; 158 women completed the OGTT post partum. Intervention The Pregnant+ app and usual care, the control group received usual care. Primary and secondary outcomes The primary outcome was the 2-hour blood glucose level of the routine postpartum OGTT. Secondary outcomes reported were mode of delivery, induction of labour, Apgar score, birth weight, transfer to the neonatal intensive care unit and breast feeding practice. Blood glucose levels during pregnancy, knowledge of diabetes, diet and physical activity are not reported. Results No difference was found for the 2-hour blood glucose level of the postpartum OGTT, with 6.7 mmol/L (95% CI 6.2 to 7.1) in the intervention group and 6.0 mmol/L (95% CI 5.6 to 6.3) in the control group. The significant difference in the proportion of emergency caesarean sections between the intervention group, 10 (8.8%) and the usual care group, 27 (22.1%), disappeared when adjusted for parity. There were no differences in birth weight, breast feeding practice, obstetric complications or transfer to the intensive neonatal care unit. No adverse events were registered. Conclusion The Pregnant+ app had no effect on 2-hour glucose level at routine postpartum OGTT. After controlling for parity, the difference in emergency caesarean section was not statistically significant.

• Borgen, Iren; Garnweidner-Holme, Lisa; Jacobsen, Anne Flem; Fayyad, Seraj; Småstuen, Milada Cvancarova & Lukasse, Mirjam (2019). Knowledge of gestational diabetes mellitus at first consultation in a multi-ethnic pregnant population in the Oslo region, Norway - a cross-sectional study. Ethnicity and Health. ISSN 1355-7858. doi: 10.1080/13557858.2019.1655530. Full text in Research Archive
• Iversen, Johanne Kolvik; Jacobsen, Anne Flem; Mikkelsen, Thea Falkenberg & Eggebø, Torbjørn Moe (2019). Structured clinical examinations in labor: rekindling the craft of obstetrics. Journal of Maternal-Fetal & Neonatal Medicine. ISSN 1476-7058. p. 1–8. doi: 10.1080/14767058.2019.1651283. Full text in Research Archive Show summary

  Objectives: Exact knowledge of fetal station and position is of paramount importance for reliable surveillance of labor progress and a prerequisite for safe operative vaginal procedures. Detailed clinical assessments are thoroughly described in old textbooks, but almost forgotten in contemporary obstetrics. Ultrasound is suggested as an objective diagnostic tool in active labor. Several publications have demonstrated a low correlation between ultrasound and clinical assessment of fetal head station and position, but the methods of clinical assessment in these studies are poorly described. We wanted to explore if a quality clinical assessment could perform better than clinical assessment in previous publications, by analyzing the correlation between a structured method of clinical assessment and intrapartum ultrasound. Methods: In all, 100 laboring women with cervical dilatation ≥7 cm were included in a prospective cohort study at Oslo University Hospital-Ullevål from October to December 2016. The study design was cross-sectional. Clinical examinations were performed by one special educated consultant (JKI), and transabdominal and transperineal ultrasound clips were recorded and examined by a blinded expert in intrapartum ultrasound (TME). Fetal position was classified as a clock face with 12 units (hourly divisions) and thereafter categorized as occiput anterior (OA), left occiput transverse (LOT), occiput posterior (OP), and right occiput transverse (ROT) positions. Fetal station was categorized clinically from −5 to +5 and measured with ultrasound as angle of progression (AoP) and head-perineum distance (HPD). AoP is the angle between a longitudinal line through the symphysis and a tangent to the head contour. HPD is the shortest distance between the fetal skull and the perineum. Results: Eight women were excluded due to strong contractions between clinical assessments and ultrasound measurements, fetal distress, or incomplete examinations. Fetal position assessed with ultrasound and clinical examination agreed exactly in 48/92 (52%) of cases, within one unit (hour) in 87/92 (95%) of cases and within two units in 90/92 (98%) of cases. It differed by three units in one case and by five units in one case. The agreement categorized into OA, LOT, OP, and ROT was good (Cohen’s kappa 0.72; 95% CI 0.61–0.84). For station, the agreement was very good for both HPD (Pearson correlation coefficient r = 0.86; 95% CI 0.80–0.91) and AoP (r = 0.77; 95% CI to 0.67–0.84). The correlation between HPD and AoP was good (r = 0.76; 95% CI 0.65–0.84). Conclusion: We found very good correlations between structured clinical assessments and ultrasound examinations, suggesting that an objective quality in clinical examinations is possible to achieve. More focus on clinical skills training may improve accuracy for clinicians.

• Dahm, Anders Erik A; Jacobsen, Eva-Marie; Wik, Hilde Skuterud; Jacobsen, Anne Flem; Mollnes, Tom Eirik & Kanse, Sandip [Show all 7 contributors for this article] (2019). Elevated complement C3 and C4 levels are associated with postnatal pregnancy-related venous thrombosis. Thrombosis and Haemostasis. ISSN 0340-6245. 119(9), p. 1481–1488. doi: 10.1055/s-0039-1692426. Full text in Research Archive Show summary

  High levels of complement C3 are associated with venous thrombosis (VT) in the general population. We investigated if high C3 and C4 levels were associated with pregnancy-related VT. We undertook the Norwegian VIP study, a case–control study of VT in pregnancy or within 3 months postpartum (cases, n = 313) and women without pregnancy-related VT (controls, n = 353). Determinants of C3 and C4 in the control women were investigated with linear regression and the odds ratio (OR) for pregnancy-related VT was calculated with logistic regression. We found that levels of C3 and C4 were associated with body mass index (BMI), C-reactive protein (CRP); with the coagulation factors (F) fibrinogen, FVIII, and FIX; and with the coagulation inhibitors antithrombin, protein C, protein S, and tissue factor pathway inhibitor. These associations were influenced by CRP levels. The crude OR for pregnancy-related VT was 1.8 (95% confidence interval [CI], 1.1–3.0) for C3 above the 90th percentile and 2.0 (95% CI, 1.2–3.2) for C4 above the 90th percentile. Stratification in antenatal and postnatal VT showed that C3 and C4 were only associated with postnatal VT with an OR for high C3 of 3.0 (95% CI, 1.8–5.0), and for high C4 of 2.6 (95% CI, 1.5–4.6). Adjustment for high FIX and BMI reduced the ORs. We conclude that the association between postnatal VT and C3 and C4 suggests that there is clinically relevant crosstalk between the complement and the coagulation system.

• Turowski, Gitta Erika; Parks, W. Tony; Arbuckle, Susan; Jacobsen, Anne Flem & Heazell, Alexsander (2018). The structure and utility of the placental pathology report. APMIS - Journal of Pathologiy, Microbiology and Immunology. ISSN 0903-4641. 126(7), p. 638–646. doi: 10.1111/apm.12842. Full text in Research Archive
• Olsson, Maja; Stanne, Tara M.; Pedersén, Annie; Lorentzen, Erik; Kara, Emrah & Martinez-Palaciàn, Adoraciòn [Show all 14 contributors for this article] (2018). Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 16(10), p. 2024–2034. doi: 10.1111/jth.14258. Full text in Research Archive Show summary

  Background Factor VII‐activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low‐frequency missense variant Marburg‐I (rs7080536) in the FSAP‐encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome‐wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene‐based tests. Using GWAS, we confirmed the strong association between the Marburg‐I variant and FSAP activity. HABP2 was also significant in the gene‐based analysis, and remained significant after exclusion of Marburg‐I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg‐I carriers, and this finding was replicated. A secondary genome‐wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg‐I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity.

• Nyfløt, Lill Trine; Sandven, Irene; Stray-Pedersen, Babill; Pettersen, Silje; Al-Zirqi, Iqbal Ahmad Abdelwahab & Rosenberg, Margit [Show all 8 contributors for this article] (2017). Risk factors for severe postpartum hemorrhage: A case-control study. BMC Pregnancy and Childbirth. 17:17, p. 1–9. doi: 10.1186/s12884-016-1217-0. Full text in Research Archive Show summary

  Background In high-income countries, the incidence of severe postpartum hemorrhage (PPH) has increased. This has important public health relevance because severe PPH is a leading cause of major maternal morbidity. However, few studies have identified risk factors for severe PPH within a contemporary obstetric cohort. Methods We performed a case-control study to identify risk factors for severe PPH among a cohort of women who delivered at one of three hospitals in Norway between 2008 and 2011. A case (severe PPH) was classified by an estimated blood loss ≥1500 mL or the need for blood transfusion for excessive postpartum bleeding. Using logistic regression, we applied a pragmatic strategy to identify independent risk factors for severe PPH. Results Among a total of 43,105 deliveries occurring between 2008 and 2011, we identified 1064 cases and 2059 random controls. The frequency of severe PPH was 2.5% (95% confidence interval (CI): 2.32–2.62). The most common etiologies for severe PPH were uterine atony (60%) and placental complications (36%). The strongest risk factors were a history of severe PPH (adjusted OR (aOR) = 8.97, 95% CI: 5.25–15.33), anticoagulant medication (aOR = 4.79, 95% CI: 2.72–8.41), anemia at booking (aOR = 4.27, 95% CI: 2.79–6.54), severe pre-eclampsia or HELLP syndrome (aOR = 3.03, 95% CI: 1.74–5.27), uterine fibromas (aOR = 2.71, 95% CI: 1.69–4.35), multiple pregnancy (aOR = 2.11, 95% CI: 1.39–3.22) and assisted reproductive technologies (aOR = 1.88, 95% CI: 1.33–2.65). Conclusions Based on our findings, women with a history of severe PPH are at highest risk of severe PPH. As well as other established clinical risk factors for PPH, a history of severe PPH should be included as a risk factor in the development and validation of prediction models for PPH.

• Borgen, Iren; Garnweidner-Holme, Lisa; Jacobsen, Anne Flem; Bjerkan, Kirsti; Fayyad, Seraj & Joranger, Pål [Show all 13 contributors for this article] (2017). Smartphone application for women with gestational diabetes mellitus: a study protocol for a multicentre randomised controlled trial. BMJ Open. 7(3). doi: 10.1136/bmjopen-2016-013117. Full text in Research Archive Show summary

  Introduction The promotion of a healthy diet, physical activity and measurement of blood glucose levels are essential components in the care for women with gestational diabetes mellitus (GDM). Smartphones offer a new way to promote health behaviour. The main aim is to investigate if the use of the Pregnant+ app, in addition to standard care, results in better blood glucose levels compared with current standard care only, for women with GDM. Methods and analysis This randomised controlled trial will include 230 pregnant women with GDM followed up at 5 outpatient departments (OPD) in the greater Oslo Region. Women with a 2-hour oral glucose tolerance test (OGTT) ≥9 mmol/L, who own a smartphone, understand Norwegian, Urdu or Somali and are <33 weeks pregnant, are invited. The intervention group receives the Pregnant+ app and standard care. The control group receives standard care only. Block randomisation is performed electronically. Data are collected using self-reported questionnaires and hospital records. Data will be analysed according to the intention-to-treat principle. Groups will be compared using linear regression for the main outcome and χ2 test for categorical data and Student's t-test or Mann-Whitney-Wilcoxon test for skewed distribution. The main outcome is the glucose level measured at the 2-hour OGTT 3 months postpartum. Secondary outcomes are a change in health behaviour and knowledge about GDM, quality of life, birth weight, mode of delivery and complications for mother and child.

• Bleker, Suzanne M.; Büchmuller, Andrea; Chauleur, Céline; Áinle, Fionnuala Ni; Donnelly, Jennifer & Verhamme, Peter [Show all 16 contributors for this article] (2016). Low-molecular-weight heparin to prevent recurrent venous thromboembolism in pregnancy: Rationale and design of the Highlow study, a randomised trial of two doses. Thrombosis Research. ISSN 0049-3848. 144, p. 62–68. doi: 10.1016/j.thromres.2016.06.001. Full text in Research Archive
• Bates, Shannon M.; Alonso-Coello, Pablo; Tikkinen, Kari A.O.; Ebrahim, Shanil; Lopes, Luciane Cruz & McDonald, Sarah D. [Show all 17 contributors for this article] (2016). Women's values and preferences and health state valuations for thromboprophylaxis during pregnancy: A cross-sectional interview study. Thrombosis Research. ISSN 0049-3848. 140, p. 22–29. doi: 10.1016/j.thromres.2015.12.015. Full text in Research Archive
• Tinholt, Mari; Sandset, Per Morten; Mowinckel, Marie-Christine; Garred, Øystein; Sahlberg, Kristine Kleivi & Kristensen, Vessela N. [Show all 10 contributors for this article] (2016). Determinants of acquired activated protein C resistance and D-dimer in breast cancer. Thrombosis Research. ISSN 0049-3848. 145, p. 78–83. doi: 10.1016/j.thromres.2016.08.003. Full text in Research Archive
• Garabet, Lamya Samir Noori; Gilboe, Inge-Margrethe; Mowinckel, Marie-Christine; Jacobsen, Anne Flem; Mollnes, Tom Eirik & Sandset, Per Morten [Show all 7 contributors for this article] (2016). Antiphospholipid antibodies are associated with low levels of complement C3 and C4 in patients with systemic Lupus Erythematosus. Scandinavian Journal of Immunology. ISSN 0300-9475. 84(2), p. 95–99. doi: 10.1111/sji.12445. Full text in Research Archive
• Smedberg, Janne; Bråthen, Marie; Waka, Marthe Sætre; Jacobsen, Anne Flem; Gjerdalen, Guri & Nordeng, Hedvig Marie Egeland (2016). Medication use and drug-related problems among women at maternity wards—a cross-sectional study from two Norwegian hospitals. European Journal of Clinical Pharmacology. ISSN 0031-6970. 72(7), p. 849–857. doi: 10.1007/s00228-016-2042-0. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Mowinckel, Marie-Christine & Sandset, Per Morten (2016). The role of inflammation in post-thrombotic syndrome after pregnancy-related deep vein thrombosis: A population-based, cross-sectional study. Thrombosis Research. ISSN 0049-3848. 138, p. 16–21. doi: 10.1016/j.thromres.2015.12.014. Full text in Research Archive
• Brigtsen, Anne Karin; Dedi, Lumnije; Melby, Kjetil K.; Holberg-Petersen, Mona; Radtke, Andreas & Lyng, Randi Valsø [Show all 10 contributors for this article] (2015). Comparison of PCR and serotyping of Group B Streptococcus in pregnant women: The Oslo GBS-study. Journal of Microbiological Methods. ISSN 0167-7012. 108, p. 31–35. doi: 10.1016/j.mimet.2014.11.001. Full text in Research Archive
• Eckman, Mark H.; Alonso-Coello, Pablo; Guyatt, Gordon H.; Ebrahim, Shanil; Tikkinen, Kari A.O. & Lopes, Luciane Cruz [Show all 17 contributors for this article] (2015). Women's values and preferences for thromboprophylaxis during pregnancy: A comparison of direct-choice and decision analysis using patient specific utilities. Thrombosis Research. ISSN 0049-3848. 136(2), p. 341–347. doi: 10.1016/j.thromres.2015.05.020. Full text in Research Archive
• Brigtsen, Anne Karin; Jacobsen, Anne Flem; Dedi, Lumnije; Melby, Kjetil K.; Fugelseth, Drude & Whitelaw, Andrew (2015). Maternal colonization with Group B streptococcus is associated with an increased rate of infants transferred to the neonatal intensive care unit. Neonatology. ISSN 1661-7800. 108, p. 157–163. doi: 10.1159/000434716. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem & Sandset, Per Morten (2015). Long-term outcome after pregnancy-related venous thrombosis. Thrombosis Research. ISSN 0049-3848. 135(1), p. S1–S4. doi: 10.1016/S0049-3848(15)50430-1. Full text in Research Archive
• Dahm, Anders Erik A; Tiscia, Gianluca; Holmgren, Asbjørn; Jacobsen, Anne Flem; Skretting, Grethe & Grandone, E. [Show all 7 contributors for this article] (2015). Genetic variations in the annexin A5 gene and the risk of pregnancy-related venous thrombosis. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 13(3), p. 409–413. doi: 10.1111/jth.12817. Full text in Research Archive
• Vangen, Siri; Ellingsen, Liv; Andersgaard, Alice Beathe; Jacobsen, Anne Flem; Lorentzen, Bjørg & Nyfløt, Lill Trine [Show all 10 contributors for this article] (2014). Mødredødsfall i Norge 2005-09. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 134(8), p. 836–839. doi: 10.4045/tidsskr.13.0203. Full text in Research Archive
• Kristiansen, Annette; Brandt, Linn; Agoritsas, Thomas; Akl, Elie A.; Berge, Eivind & Bondi, Johan Fridtjof [Show all 19 contributors for this article] (2014). Adaptation of trustworthy guidelines developed using the GRADE methodology: a novel five-step process. Chest. ISSN 0012-3692. 146(3), p. 727–734. doi: 10.1378/chest.13-2828. Full text in Research Archive Show summary

  BACKGROUND: Adaptation of guidelines for use at the national or local level can facilitate their implementation. We developed and evaluated an adaptation process in adherence with standards for trustworthy guidelines and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, aiming for efficiency and transparency. This article is the first in a series describing our adaptation of Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines for a Norwegian setting. METHODS: Informed by the ADAPTE framework, we developed a five-step adaptation process customized to guidelines developed using GRADE: (1) planning, (2) initial assessment of the recommendations, (3) modification, (4) publication, and (5) evaluation. We developed a taxonomy for describing how and why recommendations from the parent guideline were modified and applied a mixed-methods case study design for evaluation of the process. RESULTS: We published the adapted guideline in November 2013 in a novel multilayered format. The taxonomy for adaptation facilitated transparency of the modification process for both the guideline developers and the end users. We excluded 30 and modified 131 of the 333 original recommendations according to the taxonomy and developed eight new recommendations. Unforeseen obstacles related to acquiring a licensing agreement and procuring a publisher resulted in a 9-month delay. We propose modifications of the adaptation process to overcome these obstacles in the future. CONCLUSIONS: This case study demonstrates the feasibility of a novel guideline adaptation process. Replication is needed to further validate the usefulness of the process in increasing the organizational and methodologic efficiency of guideline adaptation.

• Mala, Tom; Harsem, Nina Kittelsen; Røstad, Signe; Mathisen, Lene Cecilie & Jacobsen, Anne Flem (2014). Perforation of the Pregnant Uterus during Laparoscopy for Suspected Internal Herniation after Gastric Bypass. Case Reports in Obstetrics and Gynecology. ISSN 2090-6692. 2014. doi: 10.1155/2014/720181. Full text in Research Archive
• Tinholt, Mari; Viken, Marte K; Dahm, Anders Erik A; Vollan, Hans Kristian Moen; Sahlberg, Kristine Kleivi & Garred, Øystein [Show all 16 contributors for this article] (2014). Increased coagulation activity and genetic polymorphisms in the F5, F10 and EPCR genes are associated with breast cancer: a case-control study. BMC Cancer. 14. doi: 10.1186/1471-2407-14-845. Full text in Research Archive Show summary

  Background The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. Methods 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. Results Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95% CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95% CI 4.4-11.3), and high thrombin peak (OR 6.1, 95% CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95% CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95% CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. Conclusions A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer.

• Kristiansen, Annette; Brandt, Linn; Agoritsas, Thomas; Akl, Elie A; Berge, Eivind & Jacobsen, Anne Flem [Show all 10 contributors for this article] (2014). Applying new strategies for the national adaptation, updating and dissemination of trustworthy guidelines: Results from the Norwegian adaptation of the American College of chest physicans evidence-based guidelines on antithrombotic therapy and the prevention of thrombosis, 9th edidion. Chest. ISSN 0012-3692. 146(3), p. 735–761. doi: 10.1378/chest.13-2993. Full text in Research Archive Show summary

  BACKGROUND: The Antithrombotic Therapy and the Prevention of Thrombosis, 9th Edition: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (AT9) represent trustworthy international guidelines for antithrombotic treatment and thromboprophylaxis. We describe major changes to the format and content resulting from applying new strategies for guideline adaptation and dissemination. METHODS: A Norwegian guideline panel of 46 experts completed a structured and systematic adaptation process, updated the recommendations based on new evidence, and rewrote the recommendations in an electronic multilayered presentation format. We published the adapted guideline using the web-based Making GRADE the Irresistible Choice Guideline Authoring and Publication Platform. RESULTS: We applied a novel presentation format to 333 recommendations from 11 of the 15 management chapters in AT9 and condensed and restructured them into 249 recommendations in a multilayered format. We added additional relevant information, such as 29 best-practice statements about new oral anticoagulants and practical information sections for 121 recommendations. Common reasons for modifications included feasibility of the recommendations in a national context, disagreement with applied baseline risk estimates, and reevaluation of the balance between the benefits and harms of interventions in relation to assumed typical patient preferences and values. The adapted guideline was published and disseminated online in November 2013. CONCLUSIONS: New strategies for adapting, updating, and disseminating trustworthy guidelines proved feasible and will provide Norwegian health-care professionals and patients with up-to-date guidance tailored to national circumstances.

• HELGADOTTIR, LINDA BJØRK; Turowski, Gitta Erika; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Roald, Borghild [Show all 7 contributors for this article] (2013). Classification of stillbirths and risk factors by cause of death a case-control study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 92(3), p. 325–333. doi: 10.1111/aogs.12044. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Fagerland, Morten; Sandvik, Leiv & Sandset, Per Morten (2013). Long-term mortality and incidence of cancer after pregnancy-related venous thrombosis: Results of a population-based cohort study. Thrombosis Research. ISSN 0049-3848. 131(6), p. 497–501. doi: 10.1016/j.thromres.2013.04.035. Full text in Research Archive
• Jacobsen, Anne Flem & Sandset, Per Morten (2012). Venous thromboembolism associated with pregnancy and hormonal therapy. Baillière's Best Practice & Research Clinical Haematology. ISSN 1521-6926. 25(3), p. 319–332. doi: 10.1016/j.beha.2012.07.006. Full text in Research Archive
• Dahm, Anders Erik A; Bezemer, Irene D; Bergrem, Astrid; Jacobsen, Anne Flem; Jacobsen, Eva-Marie & Skretting, Grethe [Show all 8 contributors for this article] (2012). Candidate gene polymorphisms and the risk for pregnancy-related venous thrombosis. British Journal of Haematology. ISSN 0007-1048. 157(6), p. 753–761. doi: 10.1111/j.1365-2141.2012.09121.x. Full text in Research Archive
• Bergrem, Astrid; Dahm, Anders Erik A; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Differential haemostatic risk factors for pregnancy-related deep-vein thrombosis and pulmonary embolism A population-based case-control study. Thrombosis and Haemostasis. ISSN 0340-6245. 108(6), p. 1165–1171. doi: 10.1160/TH12-05-0350. Full text in Research Archive
• HELGADOTTIR, LINDA BJØRK; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Jacobsen, Eva-Marie (2012). The association of antiphospholipid antibodies with intrauterine fetal death: A case-control study. Thrombosis Research. ISSN 0049-3848. 130(1), p. 32–37. doi: 10.1016/j.thromres.2011.11.029. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Long-term impact of pregnancy-related venous thrombosis on quality-of-life, general health and functioning: results of a cross-sectional, case–control study. BMJ Open. 2. doi: 10.1136/bmjopen-2012-002048. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Prevalence and predictors for post-thrombotic syndrome 3 to 16 years after pregnancy-related venous thrombosis: a population-based, cross-sectional, case-control study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 10(5), p. 840–847. doi: 10.1111/j.1538-7836.2012.04690.x. Full text in Research Archive
• HELGADOTTIR, LINDA BJØRK; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Jacobsen, Eva-Marie (2011). The association of inherited thrombophilia and intrauterine fetal death: a case-control study. Blood Coagulation and Fibrinolysis. ISSN 0957-5235. 22(8), p. 651–656. doi: 10.1097/MBC.0b013e32834a614c. Full text in Research Archive
• Bergrem, Astrid; Dahm, Anders Erik A; Jacobsen, Anne Flem; Mowinckel, Marie-Christine; Sandvik, Leiv & Sandset, Per Morten (2011). Resistance to activated protein C is a risk factor for pregnancy-related venous thrombosis in the absence of the F5 rs6025 (factor V Leiden) polymorphism. British Journal of Haematology. ISSN 0007-1048. 154(2), p. 241–247. doi: 10.1111/j.1365-2141.2011.08712.x. Full text in Research Archive Show summary

  Resistance to activated protein C (aPC) is most commonly due to the F5 rs6025 (factor V Leiden) polymorphism, which increases the risk of venous thrombosis. In the present population-based study of 313 cases and 353 controls, we investigated whether reduced sensitivity to aPC was associated with a history of pregnancy-related venous thrombosis. Calibrated automated thrombography was used to determine the sensitivity to aPC, and normalized aPC sensitivity ratio (n-aPC-sr) was calculated. Pregnant women and women using oral contraceptives and/or anticoagulants were excluded due to the effect on the n-aPC-sr. In women without the F5 rs6025 polymorphism, free tissue factor pathway inhibitor (TFPI), free protein S and protein C activity were associated with n-aPC-sr. Unadjusted odds ratio for venous thrombosis for women with n-aPC-sr in the 4th quartile as compared with n-aPC-sr below the 4th quartile was 2·4 (95% confidence interval 1·7-3·6). Adjusting for free protein S, free TFPI and age did not influence the odds ratios. Also in carriers of the F5 rs6025 polymorphism the risk for venous thrombosis was increased for women with higher n-aPC-sr. Our findings substantiate the importance of the aPC resistant phenotype as a risk factor for pregnancy-related venous thrombosis.

• HELGADOTTIR, LINDA BJØRK; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Jacobsen, Eva-Marie (2011). Incidence and risk factors of fetal death in Norway: a case-control study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 90(4), p. 390–397. doi: 10.1111/j.1600-0412.2011.01079.x. Full text in Research Archive Show summary

  Objective. To estimate incidence and risk factors for intrauterine fetal death (IUFD) in a Norwegian study-population applying two different control groups. Design. Case-control study. Setting. Two university hospitals in Oslo, Norway, January 1990 through December 2003. Sample. The cases: 377 women with IUFD. Controls: 1) all women delivering at the study-hospitals in the period (facility-based), and 2) 1 215 women with live births at one study-hospital in the period (selected). Methods. Information from cases and selected controls was collected from medical records. Data on facility-based controls were provided by the Medical Birth Registry of Norway. Data were analyzed using chi-squared test and logistic regression. Main outcome measures. Incidence of IUFD and adjusted odds ratios of risk factors. Results. The incidence was 4.1/1 000 deliveries. Small-for-gestational age (SGA) and placental abruption were the strongest risk factors for IUFD. Hypertensive disorders were of low risk if not associated with SGA. Low to moderate risk factors were pre-pregnancy diabetes mellitus, thyroid disease, placenta previa, gestational diabetes, smoking and twin pregnancy. Advanced maternal age was significant when compared with facility-based controls. Risk estimates pointed in the same direction independent of control-group. Hypertension appeared overestimated when using facility-based controls, whereas advanced age was underestimated in the analysis among selected controls. Conclusion. SGA has a strong association with IUFD, and the risk of hypertensive disorders is mediated through SGA. The other risk factors, except placental abruption, are of low prevalence and of limited importance in the prevention of a relatively low incidence, although dramatic, event like IUFD.

• Wik, Hilde Skuterud; Enden, Tone Rønnaug; Jacobsen, Anne Flem & Sandset, Per Morten (2011). Long-term quality of life after pregnancy-related deep vein thrombosis and the influence of socioeconomic factors and comorbidity. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 9(10), p. 1931–1936. doi: 10.1111/j.1538-7836.2011.04468.x. Full text in Research Archive
• Jacobsen, Anne Flem; Dahm, Anders Erik A; Bergrem, Astrid; Jacobsen, Eva-Marie & Sandset, Per Morten (2010). Risk of venous thrombosis in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A polymorphisms. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 8(11), p. 2443–2449. doi: 10.1111/j.1538-7836.2010.04038.x. Full text in Research Archive Show summary

  Background Pregnancy is associated with a ten-fold increased risk of venous thrombosis (VT) with different risk profiles for the ante- and postnatal periods. The purpose of this study was to assess the risk of pregnancy-related VT associated with the factor V Leiden and the prothrombin gene G20210A polymorphisms. Materials and Methods The study comprised 377155 women with 613232 pregnancies at 18 Norwegian hospitals from 1 January 1990 to 31 December 2003. Of total 559 cases with a validated first lifetime diagnosis of VT in pregnancy or within 14 weeks post-partum, and 1229 controls naive for VT, 313 cases and 353 controls donated biological material. Results The odds ratios for venous thrombosis during pregnancy or puerperium were 5.0 (95% CI 3.1 to 8.3) and 9.4 (2.1-42.4) for heterozygous carriers of the factor V Leiden and the prothrombin gene polymorphisms, respectively. All homozygous carriers of the factor V Leiden (n=8) and the prothrombin polymorphism (n=1) developed VT indicating a very high risk of VT. We estimated that pregnancy-related VT occurred in 1.1/1000 non-carriers, in 5.4/1000 heterozygous carriers of factor V Leiden, and in 9.4/1000 heterozygous carriers of the prothrombin polymorphism. To avoid one VT, the number of pregnant women needed to screen for these two polymorphisms and the number needed to be given thromboprophylaxis were 2015 and 157, respectively. Conclusions Although the relative risk for VT during pregnancy and after delivery was increased among carriers of the factor V Leiden and the prothrombin polymorphisms, the overall probability for pregnancy-related VT was low. Trial registration www.clinicaltrials.gov identifier number NCT00856076.

• Bergrem, Astrid; Jacobsen, Eva-Marie; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Skogstad, Marie Jeanette & Sandset, Per Morten (2010). The association of antiphospholipid antibodies with pregnancy-related first time venous thrombosis - a population-based case-control study. Thrombosis Research. ISSN 0049-3848. 125(5), p. E222–E227. doi: 10.1016/j.thromres.2009.12.006. Full text in Research Archive Show summary

  In this population-based case-control study we explored the association of antiphospholipid antibodies with pregnancy-related venous thrombosis. From 1990 through 2003 615 pregnant women were identified at 18 hospitals in Norway with a diagnosis of first time VT. In 2006, 531 of 559 eligible cases and 1092 of 1229 eligible controls were invited for further investigations. The final study population comprised 313 cases and 353 controls, who completed a comprehensive questionnaire and donated a single blood sample, 3-16years after index pregnancy. We report the results on lupus anticoagulant, anticardiolipin antibodies, and anti-ss(2) glycoprotein-1 antibodies alone, in combination, and with the contribution of the factor V Leiden and the prothrombin gene G20210A polymorphisms. Cut-off values for APAs were chosen according to current international consensus. 29 (9.3%) of the cases and 24 (6.8%) of the controls had at least one positive test for APAs (OR 1.4; 95% CI 0.8-2.5). Nine cases (2.8%) and no controls had more than one positive test (multi-positivity) for APAs. After excluding women with factor V Leiden or prothrombin polymorphisms, still 6 cases were multi-positive for APAs. We conclude that multi-positivity, but not single-positivity, for APAs was weakly associated with a history of ante- and postnatal VT.

• Jacobsen, Anne Flem; Skjeldestad, Finn Egil & Sandset, Per Morten (2008). Incidence and Risk Patterns of Venous Thromboembolism In Pregnancy and Puerperium – A Register-Based Case-Control Study. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. 198(2), p. 233.e1–233.e7. doi: 10.1016/j.ajog.2007.08.041. Full text in Research Archive Show summary

  Objective: To estimate the incidence of venous thromboembolism (VTE) in pregnancy and puerperium and to identify risk factors for pregnancy-related VTE. Study Design: A register-based case-control study with 613232 pregnancies from 1990 to 2003 in eleven Norwegian counties. Medical records for eligible cases were revisited and relevant medical data were transferred to a specific case-report-form. The diagnosis of VTE was based on strict criteria. Data were analyzed by chi-square test and forward stepwise logistic regression. Results: In total 615 cases were detected. The incidence of VTE was 1/1000 pregnancies. The ante- and postnatal incidences were quite similar. Antenatal risk factors were assisted reproduction, gestational diabetes, age over 35 years, multiple pregnancies, and primi-parity. Postnatal risk factors were Cesarean section, preeclampsia, assisted reproduction, abruptio placenta, and placenta previa. Conclusion: We found different ante- and postnatal risk patterns. Assisted reproduction and gestational diabetes were significant antenatal risk factors while Cesarean section and preeclampsia were strong postnatal risk factors.

• Jacobsen, Anne Flem; Skjeldestad, Finn Egil & Sandset, Per Morten (2008). Ante-and postnatal risk factors of venous thrombosis – a hospital-based case-control study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 6, p. 905–912. doi: 10.1111/j.1538-7836.2008.02961.x. Full text in Research Archive Show summary

  Objective: To study ante- and postnatal risk factors of venous thrombosis (VT) in pregnancy. Methods: A hospital-based case-control study. Cases were women with objectively verified VT during pregnancy or postpartum. Two controls were selected for each case. Validated risk factors were analyzed by chi-square test and logistic regression. Results: In total 559 cases with no prior VT, 268 ante- and 291 postnatal cases, were identified together with 1229 controls. Risk factor for antenatal VT were assisted reproduction technique (ART), antepartum immobilization, cigarette smoking, and slight weight gain (<7 kg). Conception after ART and multiple pregnancy showed additive effect, whereas antepartum immobilization and high body mass index (BMI) showed multiplicative effect on the risk for antepartum VT. No other interaction was found between risk factors for antepartum VT. Risk factors for postnatal VT were antepartum immobilization, cigarette smoking, IUGR, preeclampsia, emergency caesarean section, postpartum hemorrhage, infection, and surgery, and age and parity. Antepartum immobilization and high BMI and reoperation on the indication bleeding showed multiplicative effects on the risk of postnatal VT. Conclusions: Ante- and postpartum risk factors differed markedly. More attention should be paid to pregnant women of high BMI who are at risk for immobilization.

• Jacobsen, Anne Flem; Skjeldestad, Finn Egil & Sandset, Per Morten (2008). Ante- and postnatal risk factors of venous thrombosis: a hospital-based case-control study. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 6(6), p. 905–912. doi: 10.1111/j.1538-7836.2008.02961.x. Full text in Research Archive
• Jacobsen, Anne Flem & Sandset, Per Morten (2007). Management of venous thromboembolism (VTE) in pregnancy. Thrombosis Research. ISSN 0049-3848. 119, p. S12–S13. Full text in Research Archive
• Jacobsen, Anne Flem; Drolsum, Anders; Kløw, Nils-Einar; Dahl, Gunn Fallås; Qvigstad, Erik & Sandset, Per Morten (2004). Deep vein thrombosis after elective cesarean section. Thrombosis Research. ISSN 0049-3848. 113(5), p. 283–288. Full text in Research Archive Show summary

  INTRODUCTION: Pregnancy is associated with an overall 5-10 fold increased risk of venous thromboembolism (VTE). The absolute risk is highest during and shortly after delivery. Although operative delivery further increases the risk of VTE, there is no consensus on thromboprophylaxis after an elective cesarean. The aim of the present study was to investigate the frequency of symptomatic and asymptomatic deep venous thrombosis (DVT) in a low risk cesarean section population. MATERIALS AND METHODS: Fifty-nine women undergoing elective cesarean section were screened for DVT using triplex Doppler sonography 3-5 days after delivery. Markers of activated coagulation were also followed and all women were screened for thrombophilia. Postoperative thromboprophylaxis was not given. During the same period all cases of symptomatic VTE were also recorded. RESULTS: No DVT was detected by ultrasonography and no women developed symptomatic VTE during the six weeks follow-up period after delivery. Six women had thrombophilia. During the study period, a cesarean section was performed in 1067/5364 (20%) deliveries. Five of these women (0.47%) developed symptomatic pulmonary embolism, and all of these women had additional risk factors for VTE. CONCLUSION: The risk of DVT among healthy pregnant women undergoing elective cesarean section is low, and general medical thromboprophylaxis is probably not justified.

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• Carlsen, Karin C. Lødrup; Staff, Anne Cathrine; Arnesen, Harald; Bechensteen, Anne Grete; Jacobsen, Anne Flem & Omenaas, Ernst (2009). Forskningshåndboken. Fra ide til publikasjon. 4. utgave 2009. Oslo universitetssykehus HF. ISBN 9788247300220. 182 p. Full text in Research Archive
• Carlsen, Karin C. Lødrup; Staff, Anne Cathrine; Arnesen, Harald; Bechensteen, Anne Grete; Jacobsen, Anne Flem & Omenaas, Ernst (2009). The Research Handbook, From Idea to Publication. Oslo universitetssykehus HF. ISBN 9788247300220. 182 p. Full text in Research Archive Show summary

  Engelsk nettversjon av Forskningshåndboken 2009.

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• Sørbye, Ingvil Krarup; Gunnes, Nina; Solhoff, Aslak Vimme; Haavaldsen, Camilla; Kessler, Jørg & Kjøllesdal, Anne M [Show all 14 contributors for this article] (2025). Multicentre double-blind randomised placebo-controlled four-arm trial to assess the effect of oral sodium bicarbonate and intravenous hyoscine butylbromide on spontaneous delivery after induction of labour in nulliparous women: Protocol for the Safe Induction of Labour Trial (SAINT). doi: 10.1136/bmjopen-2024-093992. Full text in Research Archive
• Kessler, Jørg; Eggebø, Torbjørn Moe; Jacobsen, Anne Flem; Michelsen, Trond Melbye; Rasmussen, Svein & Yli, Branislava Markovic (2022). Can a population study assess the impact of fetal monitoring technology? Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. doi: 10.1111/aogs.14426. Full text in Research Archive
• Bekkenes, Maria Egeland; Jørgensen, Marte Morin; Jacobsen, Anne Flem; Fagerland, Morten; Rakstad-Larsen, Helene & Solberg, Ole Geir [Show all 10 contributors for this article] (2021). A study protocol for the cardiac effects of a single dose of either oxytocin 2.5 IU or carbetocin 100 µg after caesarean delivery: A prospective randomized controlled multi-centre trial in Norway. F1000 Research. 10:973, p. 1–17. doi: 10.12688/f1000research.73112.1. Full text in Research Archive Show summary

  Background: Both oxytocin and carbetocin are used to prevent uterine atony and post-partum haemorrhage after caesarean delivery in many countries, including Norway. Oxytocin causes dose-dependent ST-depression, troponin release, prolongation of QT-time and arrythmia, but little is known about myocardial effects of carbetocin. We have previously demonstrated comparable vasodilatory effects of oxytocin and carbetocin and are now undertaking a Phase 4 trial to investigate whether carbetocin causes similar changes to myocardial markers compared with oxytocin. Methods: Our randomized controlled trial will be conducted at three obstetrics units at Oslo University Hospital and Akershus University Hospital, Norway. Planned enrolment will be of 240 healthy, singleton pregnant women aged 18 to 50 years undergoing planned caesarean delivery. Based on pilot study data, each participant will receive a one-minute intravenous injection of either oxytocin 2.5 IU or carbetocin 100 µg during caesarean delivery. The prespecified primary outcome is the change from baseline in high-sensitive troponin I plasma concentrations at 6–10 hours after study drug administration. Secondary outcomes include uterine tone grade at 2.5 and five minutes after study drug administration, adverse events for up to 48 hours after study drug administration, estimated blood loss within eight hours of delivery, need for rescue treatment and direct/indirect costs. Enrolment and primary analysis are expected to be completed by the end of 2021. Discussion: Women undergoing caesarean delivery should be assessed for cardiovascular risk particularly as women with an obstetric history of pregnancy induced hypertension, gestational diabetes mellitus, preterm birth, placental abruption, and stillbirth are at increased risk of future cardiovascular disease. Any additional ischaemic myocardial risk from uterotonic agents will need to be balanced with the benefit of reducing the risk of postpartum haemorrhage. Any potential cardiotoxicity difference between oxytocin and carbetocin will help inform treatment decisions for pregnant women. Registration: Clinicaltrials.gov NCT03899961 (02/04/2019).

• Lukasse, Mirjam; Borgen, Iren; Garnweidner-Holme, Lisa; Småstuen, Milada Cvancarova & Jacobsen, Anne Flem (2019). Knowledge of gestational diabetes in a multi-ethnic population in the Oslo region - a cross-sectional study. Full text in Research Archive
• Brigtsen, Anne Karin; Jacobsen, Anne Flem; Dedi, Lumnije; Melby, Kjetil K.; Espeland, Cathrine Nygaard & Fugelseth, Drude [Show all 7 contributors for this article] (2019). Maternal peripartum infection in women colonized with group B Streptococcus at delivery: a prospective cohort study. Full text in Research Archive
• Borgen, Iren; Garnweidner-Holme, Lisa; Jacobsen, Anne Flem & Lukasse, Mirjam (2018). Gravid+ APP - et digitalt verktøy for gravide med svangerskapsdiabetes. Full text in Research Archive
• Borgen, Iren; Garnweidner-Holme, Lisa; Jacobsen, Anne Flem; Småstuen, Milada Cvancarova & Lukasse, Mirjam (2018). Kunnskap om svangerskapsdiabetes ved første konsultasjon i en flerkulturell populasjon i Oslo regionen - en tverrsnitt studie. Full text in Research Archive
• Dahm, Anders Erik A; Jacobsen, Eva-Marie; Jacobsen, Anne Flem; Wik, Hilde Skuterud & Sandset, Per Morten (2017). High complement C3 increases the risk for postnatal venous thrombosis. Full text in Research Archive
• Kessler, Jørg; Yli, Branislava Markovic; Stray-Pedersen, Babill; Jacobsen, Anne Flem; Saugstad, Ola Didrik & Henriksen, Tore (2016). Why did the authors perform a meta-analysis of studies with primary endpoints they consider clinically unimportant? Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 95(5), p. 606–607. doi: 10.1111/aogs.12876. Full text in Research Archive
• Nordeng, Hedvig Marie Egeland; Waka, Marthe Sætre; Jacobsen, Anne Flem; Bråthen, Marie; Gjerdalen, Guri & Rosenberg, M (2015). Drug-related problems among pregnant and lactating women – a multi-center study from maternity wards in Norway. Full text in Research Archive
• Jacobsen, Anne Flem; Kristiansen, Annette; Bjørge, Line; Henriksen, Tore; Eilertsen, Anette Løken & Sandset, Per Morten (2014). Antikoagulasjon ved venøs trombose i svangerskapet. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. p. 926–926. doi: 10.4045/tidsskr.13.1605. Full text in Research Archive
• Bergrem, Astrid; Dahm, Anders Erik A; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2013). Differential risk factors for pregnancy-related deep vein thrombosis and pulmonary embolism - Results from a population-based case-control study. Thrombosis Research. ISSN 0049-3848. 131, p. S75–S75. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Mortality after pregnancy-related venous thrombosis. Thrombosis Research. ISSN 0049-3848. 130(Supp. 1), p. S124–S124. doi: 10.1016/j.thromres.2012.08.062. Full text in Research Archive
• HELGADOTTIR, LINDA BJØRK; Turowski, Gitta Erika; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Roald, Borghild [Show all 7 contributors for this article] (2012). Classification of Stillbirths by Cause of Death and Risk Factor Analysis - a Case-control Study. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 91, p. 86–86. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Long-term impact of venous thrombosis on quality of life, general health and functioning: A cross-sectional, case-control study. Thrombosis Research. ISSN 0049-3848. 130, p. S123–S124. doi: 10.1016/j.thromres.2012.08.061. Full text in Research Archive
• Bergrem, Astrid; Dahm, Anders Erik A; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2012). Differential risk factors for pregnancy related deep vein thrombosis and pulmonary embolism' results from a population-based case-control study. Thrombosis Research. ISSN 0049-3848. 130, p. S122–S123. doi: 10.1016/j.thromres.2012.08.059. Full text in Research Archive
• HELGADOTTIR, LINDA BJØRK; Skjeldestad, Finn Egil; Jacobsen, Anne Flem; Sandset, Per Morten & Jacobsen, Eva-Marie (2011). Antiphospholipid antibodies and the risk of intrauterine fetal death - Results of a case-control study. Thrombosis Research. ISSN 0049-3848. 127(S3), p. S125–S125. Full text in Research Archive
• Wik, Hilde Skuterud; Jacobsen, Anne Flem; Sandvik, Leiv & Sandset, Per Morten (2011). Prevalence and predictors for post-thrombotic syndrome (PTS) three to 16 years after first-time pregnancy related venous thrombosis - a population-based case-control study. Thrombosis Research. ISSN 0049-3848. 127, p. S127–S127. Full text in Research Archive
• Bergrem, Astrid; Dahm, Anders Erik A; Jacobsen, Anne Flem; Mowinckel, Marie-Christine; Sandvik, Leiv & Sandset, Per Morten (2011). Reduced sensitivity to activated protein C in the absence of the factor V Leiden polymorphism is a risk factor for pregnancy related venous thrombosis. Thrombosis Research. ISSN 0049-3848. 127, p. S127–S127. Full text in Research Archive
• Sandset, Per Morten; Arnesen, Harald; Jacobsen, Anne Flem & Wergeland, Håkon (2010). Prophylaxis against Prosthetic Mitral Valve Thrombosis with Unfractionated Heparin Administered by an Elastometric Infusion Pump. Thrombosis Research. ISSN 0049-3848. 126(3), p. E232–E234. doi: 10.1016/j.thromres.2010.05.005. Full text in Research Archive
• Dahm, Anders Erik A; Bezemer, Irene D; Bergrem, Astrid; Jacobsen, Anne Flem; Jacobsen, Eva-Marie & Skretting, Grethe [Show all 8 contributors for this article] (2010). Candidate Gene Polymorphisms and the Risk for Pregnancy Related Venous Thrombosis. Blood. ISSN 0006-4971. 116(21), p. 1708–1709. Full text in Research Archive
• HELGADOTTIR, LINDA BJØRK; Helgadottir, LB; Skjeldestad, FE; Jacobsen, AF; Turowski, G & Roald, B [Show all 9 contributors for this article] (2009). Incidence and classification of intrauterine fetal death (IUFD) in the Oslo area 1990-2003. Thrombosis Research. ISSN 0049-3848. 123, p. S137–S137. Full text in Research Archive
• Jacobsen, Anne Flem; Skjeldestad, Finn Egil; Skogstad, Marie Jeanette & Sandset, Per Morten (2009). Epidemiology, risk factors and penetration of venous thrombosis (VT) in pregnancy among carriers of the factor V Leiden and the prothrombin gene G20210A mutations. Thrombosis Research. ISSN 0049-3848. 123, p. S134–S134. Full text in Research Archive
• Jacobsen, Anne Flem & Sandset, Per Morten (2007). Management of venous thromboembolism (VTE) in pregnancy. Full text in Research Archive
• Sandset, Per Morten; Arnesen, Harald; Jacobsen, Anne Flem & WERGELAND, HÅKON (2007). Anticoagulant treatment in a hypercoagulable woman with mechanical prosthetic mitral valve - failure of high-dose low molecular weight heparin (LMWH) treatment. Thrombosis Research 2007; 119, Suppl 1: S115, abstract 66. Full text in Research Archive
• Jacobsen, Anne Flem; Sandset, Per Morten & Skjeldestad, Finn Egil (2007). Incidence and risk factors of ante- and post-natal venous thromboembolism in pregnancy (VIP-study). Thromb Res 2007; 119, Suppl 1: S107, Abstract 39. Full text in Research Archive
• Jacobsen, Anne Flem; Drolsum, Anders; Kløw, Nils-Einar; Dahl, Gunn Fallås; Qvigstad, Erik & Sandset, Per Morten (2004). Venous thromboembolism after elective cesarean section. Full text in Research Archive Show summary

  Introduction: Pregnancy is associated with an overall 5-10 fold increased risk of venous thromboembolism (VTE). The absolute risk is highest during and shortly after delivery. Although operative delivery further increases the risk of VTE, there is no consensus on thromboprophylaxis after an elective cesarean. Aim: The aim of the study was to investigate the frequency of symptomatic and asymptomatic deep venous thrombosis (DVT), after low risk cesarean section. Materials and methods: Sixty-four women undergoing low risk elective cesarean section were screened for asymptomactic DVT using triplex Doppler sonography 3-5 days after delivery. Markers of activated coagulation were also followed and all women were screened for thrombophilia. Postoperative thromboprophylaxis was not given. Results: No DVT was detected by ultrasonography and no women developed symptomatic VTE during the six weeks follow-up period after delivery. Six women had thrombophilia. Five women were excluded because of infection, bleeding, or on patients own request, but none of these developed symptomatic VTE. During the same period, the department had 5364 deliveries. A cesarean section was performed in 1067 (20%) of the cases. In this cohort, we diagnosed objectively five (0.47%) cases of symptomatic postoperative pulmonary embolism (PE). No cases of symptomatic DVT were seen. All cases of PE had additional risk factors like obesity, severe preeclampsia, twin pregnancy, reoperation, immobilization, and placenta previa. Conclusion: The risk of DVT after low-risk, elective cesarean section is low, and general medical thromboprophylaxis is probably not justified.

• Øian, Pål; Jacobsen, Anne Flem & Kessler, Jørg (2014). Veileder i fødselshjelp 2014. Den norske legeforening. Full text in Research Archive

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