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  • 1.
    Adam, Sumaiya
    et al.
    Univ Pretoria, Fac Hlth Sci, Sch Med, Dept Obstet & Gynecol, Pretoria, South Africa.;Univ Pretoria, Fac Hlth Sci, Diabet Res Ctr, Pretoria, South Africa..
    McIntyre, Harold David
    Univ Queensland, Mater Hlth, Mater Hlth Campus, South Brisbane, Qld, Australia..
    Tsoi, Kit Ying
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Kapur, Anil
    World Diabet Fdn, Copenhagen, Denmark..
    Ma, Ronald C.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Dias, Stephanie
    South African Med Res Council, Biomed Res & Innovat Platform BRIP, Cape Town, South Africa..
    Okong, Pius
    St Francis Hosp Nsambya, Dept Obstet & Gynecol, Kampala, Uganda..
    Hod, Moshe
    Helen Schneider Hosp Women, Rabin Med Ctr, Petah Tiqwa, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel..
    Poon, Liona C.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynecol, Hong Kong, Peoples R China..
    Smith, Graeme N.
    Queens Univ, Kingston Hlth Sci Ctr, Dept Obstet & Gynecol, Kingston, ON, Canada..
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.
    Algurjia, Esraa
    World Assoc Trainees Obstet & Gynecol WATOG, Paris, France.;Elwya Matern Hosp, Baghdad, Iraq..
    O'Brien, Patrick
    UCL, Inst Womens Hlth, London, England..
    Medina, Virna P.
    Univ Valle, Univ Libre, Fac Hlth, Dept Obstet & Gynecol,Clin Imbanaco Quiron Salud, Cali, Colombia..
    Maxwell, Cynthia, V
    Univ Toronto, Maternal Fetal Med, Sinai Hlth, Toronto, ON, Canada.;Univ Toronto, Womens Coll Hosp, Ontario, ON, Canada..
    Regan, Lesley
    Imperial Coll London, London, England..
    Rosser, Mary L.
    Columbia Univ, Dept Obstet & Gynecol, Irving Med Ctr, New York, NY USA..
    Jacobsson, Bo
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden.;Inst Publ Hlth, Dept Genet & Bioinformat, Domain Hlth Data & Digitalisat, Oslo, Norway..
    Hanson, Mark A.
    Univ Hosp Southampton, Inst Dev Sci, Southampton, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England..
    O'Reilly, Sharleen L.
    Univ Coll Dublin, Natl Matern Hosp, UCD Perinatal Res Ctr, Sch Med, Dublin, Ireland.;Univ Coll Dublin, Sch Agr & Food Sci, Dublin, Ireland..
    McAuliffe, Fionnuala M.
    Univ Coll Dublin, Natl Matern Hosp, UCD Perinatal Res Ctr, Sch Med, Dublin, Ireland..
    Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice2023In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 160, no S1, p. 56-67Article in journal (Refereed)
    Abstract [en]

    Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.

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  • 2.
    Akerstrom, Magnus
    et al.
    Inst Stress Med, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Sengpiel, Verena
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Ctr Perinatal Med & Hlth, Gothenburg, Sweden..
    Hadzibajramovic, Emina
    Inst Stress Med, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Carlsson, Ylva
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Ctr Perinatal Med & Hlth, Gothenburg, Sweden..
    Graner, Sofie
    Karolinska Inst, Ctr Pharmacoepidemiol, Dept Med, Stockholm, Sweden.;Danderyd Hosp, BB Stockholm, Stockholm, Sweden..
    Andersson, Ola
    Lund Univ, Dept Clin Sci Lund, Paediat, Lund, Sweden.;Skane Univ Hosp, Dept Neonatol, Malmö, Sweden..
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Naurin, Elin
    Univ Gothenburg, Dept Polit Sci, Gothenburg, Sweden..
    Veje, Malin
    Sahlgrens Univ Hosp, Dept Infect Dis, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Biomed, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden..
    Wessberg, Anna
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Reg Vastra Gotaland, Gothenburg, Sweden.;Univ Gothenburg, Inst Hlth & Care Sci, Sahlgrenska Acad, Gothenburg, Sweden..
    Linden, Karolina
    Univ Gothenburg, Inst Hlth & Care Sci, Sahlgrenska Acad, Gothenburg, Sweden.;Inst Hlth & Care Sci, POB 457, S-40530 Gothenburg, Sweden..
    The COPE Staff study: Study description and initial report regarding job satisfaction, work-life conflicts, stress, and burnout among Swedish maternal and neonatal healthcare workers during the COVID-19 pandemic2023In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 162, no 3, p. 989-997Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo describe the study design of the COPE Staff cohort study on working conditions for maternal and neonatal healthcare workers (MNHCWs), and present baseline data regarding job satisfaction, work-life conflicts, stress, and burnout. MethodsBetween January and April 2021, 957 MNHCWs (administrative and medical staff) completed a baseline survey. Average levels of job satisfaction, work-life conflicts, stress, and burnout, and associations to perceived workload were assessed. ResultsThe average levels of job satisfaction, work-life conflicts, stress, and burnout were 68.6 (95% confidence interval [CI] 64.3-72.8), 42.6 (95% CI 37.3-48.0), 42.0 (95% CI 37.7-46.3), and 1.9 (95% CI 1.6-2.2), respectively. The respondents scoring above critical values indicating clinical burnout ranged between 3% and 18%, respectively, for the four burnout sub-dimensions. Women reported significantly higher levels of stress and burnout. Younger participants had lower job satisfaction and higher levels of work-life conflicts, stress, and burnout. Higher perceived workload was significantly associated with lower job satisfaction levels and higher levels of work-life conflicts, stress, and burnout. ConclusionsOur results indicate associations between MNHCWs perceived workload and job satisfaction, work-life conflicts, stress, and burnout during the COVID-19 pandemic. Eighteen percent scored above critical values for exhaustion.

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  • 3.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Elevated plasma level of arginine and its metabolites at labor among women with preeclampsia: A prospective cohort study.2024In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, article id hpae131Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia complicates 3-5% of all pregnancies and is associated with higher levels of asymmetric (ADMA) and symmetric (SDMA) dimethylarginines. Dimethylarginines are inhibitors of nitric oxide, which is a uterine smooth muscles relaxant. Women with hypertensive disorders experience a shorter labor duration compared to normotensive women. However, very little is known about the possible biochemical mechanisms behind differences in labor duration. In this study we aimed to investigate if women with preeclampsia had higher levels of arginines (ADMA, SDMA and L-arginine) at labor than controls, and also investigate the association between arginines and labor duration.

    METHODS: The study was based on data from the Swedish, Uppsala County population-based, prospective cohort BASIC, between 2009 and 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at labor from women with preeclampsia (n=47) and normotensive pregnancy (n=90). We also analyzed inflammation markers CRP, TNF-R1, TNF-R2 and GDF-15.

    RESULTS: Women with preeclampsia had higher levels of ADMA (p<0.001), SDMA (p<0.001), L-arginine (p<0.001), TNF-R1 (p<0.001), TNF-R2 (p=0.03) and GDF-15 (p<0.01) compared to controls. Further, ADMA and SDMA, not inflammation markers, were negatively correlated to labor duration in preeclampsia. No correlations were observed when comparing arginines and inflammation markers.

    CONCLUSIONS: Among women with preeclampsia, our novel findings of higher level of arigines, negative correlation of arginines to duration of labor and absence of correlation of arginines to inflammation markers might support the theory that it is not inflammation but arginines which could be associated with shorter duration of labor in preeclampsia.

  • 4.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bystrom, Ludvig
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Kullinger, Merit
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research, County of Västmanland.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Elevated Plasma Levels of Arginines During Labor Among Women with Spontaneous Preterm Birth: A Prospective Cohort Study2024In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 91, no 6, article id e13889Article in journal (Refereed)
    Abstract [en]

    Problem: Preterm birth (PTB) is a leading cause of infant mortality and morbidity. The pathogenesis of PTB is complex and involves many factors, including socioeconomy, inflammation and infection. Asymmetric dimethylarginine, ADMA and symmetric dimethylarginine, SDMA are involved in labor as inhibitors of nitric oxide, a known relaxant of the uterine smooth muscles. Arginines are scarcely studied in relation to PTB and we aimed to investigate arginines (ADMA, SDMA and L-arginine) in women with spontaneous PTB and term birth.

    Methods of the Study: The study was based on data from the population-based, prospective cohort BASIC study conducted in Uppsala County, Sweden, between September 2009 and November 2018. Arginines were analyzed by Ultra-High Performance Liquid Chromatography using plasma samples taken at the onset of labor from women with spontaneous PTB (n = 34) and term birth (n = 45). We also analyzed the inflammation markers CRP, TNF-R1 and TNF-R2 and GDF-15.

    Results: Women with spontaneous PTB had higher plasma levels of ADMA (p < 0.001), and L-Arginine (p = 0.03). In addition, inflammation marker, TNF-R1 (p = 0.01) was higher in spontaneous PTB compared to term birth. Further, in spontaneous PTB, no significant correlations could be observed when comparing levels of arginines with inflammation markers, except ADMA versus CRP.

    Conclusions: These findings provide novel evidence for the potential involvement of arginines in the pathogenesis of spontaneous PTB and it seems that arginine levels at labor vary independently of several inflammatory markers. Further research is warranted to investigate the potential of arginines as therapeutic targets in the prevention and management of spontaneous PTB.

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  • 5.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Lindström, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Reproductive Health.
    Maternal and Perinatal Outcomes in Singleton Nulliparous Spontaneous Preterm Birth with and without Preterm Premature Rupture of Membranes—A National Population-Based Cohort Study2024In: American Journal of Perinatology, ISSN 0735-1631, E-ISSN 1098-8785, Vol. 41, no S 01, p. e958-e967Article in journal (Refereed)
    Abstract [en]

    Objective Preterm birth (PTB, birth before 37 gestational weeks) is the leading cause of neonatal death and a major challenge for obstetric and neonatal care. About two-thirds of PTBs are spontaneous PTB (sPTB), of which approximately 30% start with preterm premature rupture of membranes (PPROM). The aim of the study was to investigate risk factors and maternal and perinatal outcomes in sPTB with and without PPROM.

    Study Design This is a national population-based cohort study including all singleton pregnancies in nulliparous women with spontaneous onset of labor and vaginal births (n = 266,968) registered in the Swedish Medical Birth Register 2005 to 2014. sPTB with PPROM (sPTB-PPROM) and sPTB without PPROM were compared regarding risk factors and maternal and perinatal outcomes. Logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adjustments were made for maternal age, body mass index, country of birth, smoking, chronic hypertension, pregestational and gestational diabetes, and gestational length.

    Results sPTB-PPROM (n = 5,037), compared with sPTB without PPROM (n = 8,426), was more common in women with previous spontaneous abortions, prepregnancy urinary tract infections, chronic hypertension, and gestational diabetes and had a higher risk of postpartum endometritis (aOR: 2.78, 95% CI: 1.55–5.00). Infants born to women with sPTB-PPROM had a lower risk of birth asphyxia (aOR: 0.60, 95% CI: 0.43–0.83), respiratory distress syndrome (aOR: 0.86, 95% CI: 0.70–1.00), retinopathy of prematurity (aOR: 0.93, 95% CI: 0.92–0.94), necrotizing enterocolitis (aOR: 0.95, 95% CI: 0.94–0.96), and higher risk of hypoglycemia (aOR: 1.14, 95% CI: 1.01–1.28), and hyperbilirubinemia (aOR: 1.28, 95% CI: 1.19–1.38) compared with infants born to sPTB without PPROM.

    Conclusion Our findings of risk factors and distinct differences in adverse outcomes after sPTB-PPROM compared with sPTB without PPROM are of vital importance and might serve as a basis when elaborating programs for the prevention and management of PPROM.

  • 6.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Sub-clinical atherosclerosis in the common carotid artery in women with/without previous pre-eclampsia: A seven-year follow-up2019In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 290, p. 206-213Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Pre-eclampsia is associated with increased risk of cardiovascular disease and premature death. However, conventional common carotid artery intima-media thickness (CCA-IMT) measurement does not reflect this. In contrast, measurement of the individual CCA intima and media thicknesses clearly indicates increased vascular risk both at diagnosis and about one year after pre-eclampsia. This study examined whether individual CCA wall layers, risk factors for cardiovascular disease, and markers of endothelial dysfunction had normalized or remained unfavorable seven years after pre-eclampsia.

    METHODS: The individual CCA intima and media thicknesses were measured using 22 MHz ultrasound. Conventional cardiovascular risk factors were recorded. A thick intima, thin media and high intima/media thickness ratio (I/M) are signs of sub-clinical atherosclerosis.

    RESULTS: The median age of women with previous pre-eclampsia (cases = 23) or normal pregnancies (controls = 35) was 39/37 years. At follow-up (median about seven years), the intima remained thicker and the I/M was higher in cases than in controls [all p < 0.0001; p < 0.001 after adjustment for time to follow-up, body mass index (BMI), and mean arterial pressure (MAP)], whereas the CCA-IMT was illogically thinner. Further, BMI, MAP, hip circumference, abdominal height, serum endostatin and apolipoprotein B levels were higher in cases (all p < 0.05). Intima and I/M measurements were correlated with age, MAP, endostatin and apolipoprotein B, whereas no logical correlations were found for CCA-IMT.

    CONCLUSIONS: The arteries in cases but not controls were still adversely affected after seven years. Measuring intima thickness and I/M appears preferable to measuring CCA-IMT for demonstrating vascular risk after pre-eclampsia.

  • 7.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia2017In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 50, p. 93-99Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

    METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

    RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

    CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

  • 8.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.
    Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 241, p. 417-422Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

    METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

    RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

    CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

  • 9.
    Akhter, Tansim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Larsson, Marita
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Bondesson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Dept Med Chem, Analyt Pharmaceut Chem, Uppsala, Sweden..
    Hedeland, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden.;Uppsala Univ, Dept Med Chem, Analyt Pharmaceut Chem, Uppsala, Sweden..
    Naessén, Tord
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Dimethylarginines correlate to common carotid artery wall layer dimensions and cardiovascular risk factors in pregnant women with/without preeclampsia: A group comparative study2021In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 258, p. 288-293Article in journal (Refereed)
    Abstract [en]

    Objectives: Asymmetric- and symmetric dimethylarginines (ADMA, SDMA) are elevated in cardiovascular disease (CVD). Preeclampsia is a pregnancy-specific syndrome and is an independent risk factor for subsequent CVD. Aims were to investigate whether ADMA, SDMA levels and L-arginine/ADMA and I.arginine/SDMA ratios during pregnancy and their changes from pregnancy to postpartum are associated to arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia. Study design: Dimethylarginines were analyzed by LC-MS, and the common-carotid-artery (CCA) intima and media thicknesses were estimated using 22-MHz non-invasive ultrasonography in women with preeclampsia (cases = 48) and normal pregnancies (controls = 58) in similar gestational age, with reassessment one-year postpartum. A thick intima, thin media and high intima/media ratio (I/M) indicates a less healthy arterial wall. Results: The median age of cases and controls was 30 years. During pregnancy, women with preeclampsia had higher plasma ADMA, SDMA and lower t-arginine/ADMA and L-arginine/SDMA (all p <0.01) than women with normal pregnancies. Further, ADMA, SDMA, L-arginine/ADMA and L-arginine/SDMA correlated to intima thickness (r(s) = 0.33/0.33/-0.33/-0.35 and p <0.01), UM (r(s) = 0.26/0.28/-0.22/-0.26 and p <0.05) and mean arterial pressure (MAP) (rs = 0.43/0.42/-0.39/-0.40 and p <0.0001). Changes in ADMA, SDMA and t-arginine/SDMA from pregnancy to postpartum correlated to changes in intima thickness (r(s) = 0.22/0.32/-0.21 and p < 0.05/<0.01/<0.05), I/M (r(s) = 0.22/0.31/0.08 and p < 0.05/<0.01/=0.43) and MAP (r(s) = 0.31/0.53/-0.25 and p < 0.01/<0.001/<0.05). No correlations were found for conventional CCA intima-media-thickness. Conclusions: Dimethylarginines were associated to signs of adverse effects on arterial wall layer dimensions and cardiovascular risk factors in women with and without preeclampsia, during pregnancy and to their changes from pregnancy up to one-year postpartum. (C) 2021 The Authors. Published by Elsevier B.V.

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  • 10.
    Alkmark, M.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Wennerholm, U-B
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Saltvedt, S.
    Karolinska Univ Hosp, Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Bergh, C.
    Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Carlsson, Y.
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Elden, H.
    Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Hlth & Caring Sci, Gothenburg, Sweden..
    Fadl, H.
    Örebro Univ, Fac Med & Hlth, Dept Obstet & Gynaecol, Örebro, Sweden..
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Ladfors, L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Sengpiel, V
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Wesström, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hagberg, H.
    Univ Gothenburg, Sahlgrenska Acad, Dept Obstet & Gynaecol, Ctr Perinatal Med & Hlth,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    Svensson, M.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Sch Publ Hlth & Community Med, Gothenburg, Sweden..
    Induction of labour at 41 weeks of gestation versus expectant management and induction of labour at 42 weeks of gestation: a cost-effectiveness analysis2022In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 129, no 13, p. 2157-2165Article in journal (Refereed)
    Abstract [en]

    Objective To assess the cost-effectiveness of induction of labour (IOL) at 41 weeks of gestation compared with expectant management until 42 weeks of gestation. Design A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting Fourteen Swedish hospitals during 2016-2018. Population Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41 weeks of gestation to IOL or to expectant management and induction at 42 weeks of gestation. Methods Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures The cost per gained life year and per gained QALY. Results The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was euro4108 in the IOL group (n = 1373) and euro4037 in the expectant management group (n = 1373), with a mean difference of euro71 (95% CI -euro232 to euro379). The ICER for IOL compared with expectant management was euro545 per life year gained and euro623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions Induction of labour at 41 weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42 weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract Induction of labour at 41 weeks of gestation is cost-effective compared with expectant management until 42 weeks of gestation.

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  • 11.
    Alkmark, Marten
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Ctr Perinatal Med & Hlth, Dept Obstet & Gynecol,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Obstet, Reg Vastra Gotaland, Gothenburg, Sweden..
    Keulen, Judit K. J.
    Univ Amsterdam, Amsterdam UMC, Dept Obstet & Gynaecol, Amsterdam Reprod & Dev Res Inst, Amsterdam, Netherlands..
    Kortekaas, Joep C.
    Radboud Univ Nijmegen Med Ctr, Dept Obstet & Gynaecol, Nijmegen, Netherlands..
    Bergh, Christina
    Gothenburg Univ, Dept Obstet & Gynecol, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Reprod Med, Gothenburg, Sweden..
    van Dillen, Jeroen
    Radboud Univ Nijmegen Med Ctr, Dept Obstet & Gynaecol, Nijmegen, Netherlands..
    Duijnhoven, Ruben G.
    Univ Amsterdam, Amsterdam UMC, Dept Obstet & Gynaecol, Amsterdam Reprod & Dev Res Inst, Amsterdam, Netherlands..
    Hagberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Ctr Perinatal Med & Hlth, Dept Obstet & Gynecol,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Obstet, Reg Vastra Gotaland, Gothenburg, Sweden..
    Mol, Ben Willem
    Monash Univ, Dept Obstet & Gynaecol, Monash Med Ctr, Clayton, Vic, Australia.;Univ Aberdeen, Aberdeen Ctr Womens Hlth Res, Aberdeen, Scotland..
    Molin, Mattias
    Stat Consulting Grp, Gothenburg, Sweden..
    van der Post, Joris A. M.
    Univ Amsterdam, Amsterdam UMC, Dept Obstet & Gynaecol, Amsterdam Reprod & Dev Res Inst, Amsterdam, Netherlands..
    Saltvedt, Sissel
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wennerholm, Ulla-Britt
    Univ Gothenburg, Sahlgrenska Acad, Ctr Perinatal Med & Hlth, Dept Obstet & Gynecol,Inst Clin Sci, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Obstet, Reg Vastra Gotaland, Gothenburg, Sweden..
    de Miranda, Esteriek
    Univ Amsterdam, Amsterdam UMC, Dept Obstet & Gynaecol, Amsterdam Reprod & Dev Res Inst, Amsterdam, Netherlands..
    Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials2020In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 17, no 12, article id e1003436Article, review/survey (Refereed)
    Abstract [en]

    BackgroundThe risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.Methods and findingsWe searched PubMed, Excerpta Medica dataBASE (Embase), The Cochrane Library, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and PsycINFO on February 21, 2020 for RCTs comparing IOL at 41 weeks with expectant management until 42 weeks in women with uncomplicated pregnancies. Individual participant data (IPD) were sought from eligible RCTs. Primary outcome was a composite of severe adverse perinatal outcomes: mortality and severe neonatal morbidity. Additional outcomes included neonatal admission, mode of delivery, perineal lacerations, and postpartum haemorrhage. Prespecified subgroup analyses were conducted for parity (nulliparous/multiparous), maternal age (<35/≥35 years), and body mass index (BMI) (<30/≥30). Aggregate data meta-analysis (MA) was performed to include data from RCTs for which IPD was not available.

    From 89 full-text articles, we identified three eligible RCTs (n = 5,161), and two contributed with IPD (n = 4,561). Baseline characteristics were similar between the groups regarding age, parity, BMI, and higher level of education. IOL resulted overall in a decrease of severe adverse perinatal outcome (0.4% [10/2,281] versus 1.0% [23/2,280]; relative risk [RR] 0.43 [95% confidence interval [CI] 0.21 to 0.91], p-value 0.027, risk difference [RD] −57/10,000 [95% CI −106/10,000 to −8/10,000], I2 0%). The number needed to treat (NNT) was 175 (95% CI 94 to 1,267).

    Perinatal deaths occurred in one (<0.1%) versus eight (0.4%) pregnancies (Peto odds ratio [OR] 0.21 [95% CI 0.06 to 0.78], p-value 0.019, RD −31/10,000, [95% CI −56/10,000 to −5/10,000], I2 0%, NNT 326, [95% CI 177 to 2,014]) and admission to a neonatal care unit ≥4 days occurred in 1.1% (24/2,280) versus 1.9% (46/2,273), (RR 0.52 [95% CI 0.32 to 0.85], p-value 0.009, RD −97/10,000 [95% CI −169/10,000 to −26/10,000], I2 0%, NNT 103 [95% CI 59 to 385]). There was no difference in the rate of cesarean delivery (10.5% versus 10.7%; RR 0.98, [95% CI 0.83 to 1.16], p-value 0.81) nor in other important perinatal, delivery, and maternal outcomes. MA on aggregate data showed similar results.

    Prespecified subgroup analyses for the primary outcome showed a significant difference in the treatment effect (p = 0.01 for interaction) for parity, but not for maternal age or BMI. The risk of severe adverse perinatal outcome was decreased for nulliparous women in the IOL group (0.3% [4/1,219] versus 1.6% [20/1,264]; RR 0.20 [95% CI 0.07 to 0.60], p-value 0.004, RD −127/10,000, [95% CI −204/10,000 to −50/10,000], I2 0%, NNT 79 [95% CI 49 to 201]) but not for multiparous women (0.6% [6/1,219] versus 0.3% [3/1,264]; RR 1.59 [95% CI 0.15 to 17.30], p-value 0.35, RD 27/10,000, [95% CI −29/10,000 to 84/10,000], I2 55%).

    A limitation of this IPD-MA was the risk of overestimation of the effect on perinatal mortality due to early stopping of the largest included trial for safety reasons after the advice of the Data and Safety Monitoring Board. Furthermore, only two RCTs were eligible for the IPD-MA; thus, the possibility to assess severe adverse neonatal outcomes with few events was limited.ConclusionsIn this study, we found that, overall, IOL at 41 weeks improved perinatal outcome compared with expectant management until 42 weeks without increasing the cesarean delivery rate. This benefit is shown only in nulliparous women, whereas for multiparous women, the incidence of mortality and morbidity was too low to demonstrate any effect. The magnitude of risk reduction of perinatal mortality remains uncertain. Women with pregnancies approaching 41 weeks should be informed on the risk differences according to parity so that they are able to make an informed choice for IOL at 41 weeks or expectant management until 42 weeks.

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  • 12.
    Alkmark, Mårten
    et al.
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Carlsson, Ylva
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Brismar Wendel, Sophia
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.
    Elden, Helen
    Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Hlth & Care Sci, Gothenburg, Sweden.
    Fadl, Helena
    Örebro Univ, Fac Med & Hlth, Dept Obstet & Gynecol, Örebro, Sweden.
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Ladfors, Lars
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Saltvedt, Sissel
    Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Sengpiel, Verena
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Wessberg, Anna
    Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Hagberg, Henrik
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Wennerholm, Ulla-Britt
    Univ Gothenburg, Ctr Perinatal Med & Hlth, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Reg Västra Götaland, Dept Obstet & Gynecol, Sahlgrenska Univ Hosp, Gothenburg, Sweden.
    Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS)2021In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 100, no 8, p. 1463-1477Article in journal (Refereed)
    Abstract [en]

    Introduction

    Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41+0 to 42+0 to 1 weeks of gestation.

    Material and methods

    In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score.

    Results

    Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] vs 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31–1.89]; maternal composite 2.3% [17/744] vs 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58–4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3–6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups.

    Conclusions

    Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.

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  • 13.
    Andersson, Malin
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol & Intens Care, Gothenburg, Sweden..
    Oras, Jonatan
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol & Intens Care, Gothenburg, Sweden..
    Thorn, Sven Egron
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol & Intens Care, Gothenburg, Sweden..
    Karlsson, Ove
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol & Intens Care, Gothenburg, Sweden..
    Kalebo, Peter
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Radiol, Gothenburg, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London, England.;UK Dementia Res Inst, London, England..
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden..
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden.;Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.;Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa..
    Signs of neuroaxonal injury in preeclampsia-A case control study2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 2, article id e0246786Article in journal (Refereed)
    Abstract [en]

    Background Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma. Methods CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum. Results Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy. Conclusion NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.

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  • 14.
    Ankarcrona, Victoria
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Kallner, Helena Kopp
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Wendel, Sophia Brismar
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Attitudes and knowledge regarding episiotomy use and technique in vacuum extraction: A web-based survey among doctors in Sweden2022In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 269, p. 62-70Article in journal (Refereed)
    Abstract [en]

    Objectives: Correct episiotomy use and technique may prevent obstetric anal sphincter injuries. We aimed to explore the attitudes, use, and technique regarding episiotomy among doctors in Sweden, and their willingness to contribute to a randomized controlled trial of lateral episiotomy or no episiotomy in vacuum extraction in nulliparous women.

    Study design: A web-based survey was sent to members of the Swedish Society of Obstetrics and Gynecology (n = 2140). The survey included 31 questions addressing personal characteristics, use of episiotomy, a two-dimensional picture on which the respondents drew an episiotomy, and questions regarding attitudes towards episiotomy and participation in a randomized controlled trial. We calculated the proportion of supposedly protective episiotomies (fulfilling criteria of a lateral or mediolateral episiotomy and a length >= 30 mm). We compared the results between obstetricians, gynecologists, and residents using Chi-square and Kruskal-Wallis tests for differences between groups, and logistic regression to estimate the odds ratio (OR) of drawing a protective episiotomy.

    Results: We received 432 responses. Doctors without a vacuum delivery in the past year were excluded, leaving 384 respondents for further analyses. In all, 222 (57.8%) doctors reported use of episiotomy in<50% of vacuum extractions. We obtained 308 illustrated episiotomies with a median angle of 53 degrees, incision point distance from the midline of 21 mm, and length of 36 mm, corresponding to a lateral episiotomy. Few doctors combined these parameters correctly resulting in 167 (54.2%) incorrectly drawn episiotomies. Residents drew shorter episiotomies than obstetricians and gynecologists. Doctors ranked episiotomy the least important intervention to prevent obstetric anal sphincter injuries in vacuum extraction. Doctors contributing to an ongoing randomized controlled trial of lateral episiotomy or no episiotomy in vacuum extraction were more able to draw a protective episiotomy (OR 3.69, 95% confidence interval 1.94-7.02).

    Conclusions: Doctors in Sweden reported restrictive use of episiotomy in vacuum extraction and depicted lateral type episiotomies, although the majority were incorrectly drawn. Preventive episiotomy was ranked of low importance. Our results imply a need for education, training, and guidelines to increase uptake of correct episiotomy technique, which could result in improved prevention of obstetric anal sphincter injuries.

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  • 15.
    Ankarcrona, Victoria
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Karlstrom, Sofie
    Karolinska Univ Hosp, Dept Obstet & Gynecol, Huddinge, Sweden..
    Sylvan, Sissela
    Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Starck, Marianne
    Skane Univ Hosp, Dept Surg, Pelv Floor Ctr, Malmö, Sweden..
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Wendel, Sophia Brismar
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Stockholm, Sweden.;Danderyd Hosp, Dept Obstet & Gynecol, S-18288 Stockholm, Sweden..
    Episiotomy in vacuum extraction, do we cut the levator ani muscle?: A prospective cohort study2022In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 33, no 12, p. 3391-3399Article in journal (Refereed)
    Abstract [en]

    Introduction and hypothesis Vaginal delivery may lead to levator ani muscle (LAM) injury or avulsion. Episiotomy may reduce obstetric anal sphincter injury in operative vaginal delivery, but may increase the risk of LAM injury. Our aim was to assess whether lateral episiotomy in vacuum extraction (VE) in primiparous women causes LAM injury. Methods A prospective cohort study of 58 primiparous women with episiotomy nested within an ongoing multicenter randomized controlled trial of lateral episiotomy versus no episiotomy in VE (EVA trial) was carried out in Sweden. LAM injury was evaluated using 3D endovaginal ultrasound 6-12 months after delivery and Levator Ani Deficiency (LAD) score. Episiotomy scar properties were measured. Characteristics were described and compared using Chi-squared tests. We stipulated that if a lateral episiotomy cuts the LAM, >= 50% would have a LAM injury. Among those, >= 50% would be side specific. We compared the observed prevalence with a test of one proportion. Results Twelve (20.7%, 95% CI 10.9-32.9) of 58 women had a LAD (p < 0.001, compared with the stipulated 50%). Six (50.0%, 95% CI 21.1% to 78.9%) of 12 women had a LAD on the episiotomy side, including those with bilateral LAD (p = 1.00). Two (16.7%, 95% CI 2.1% to 48.4%) of 12 women had a LAD exclusively on the episiotomy side (p = 0.02). Conclusions There was no excessive risk of cutting the LAM while performing a lateral episiotomy. LAD was not seen in women with episiotomies shorter than 18 mm.

  • 16.
    Asp, Joline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Lager, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Clinical Research Sörmland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Alcohol exposure prior to pregnancy-does hazardous consumption affect placenta- and inflammatory-mediated pregnancy outcomes? A Swedish population-based cohort study2022In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 101, no 12, p. 1386-1394Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Alcohol consumption during pregnancy is related to severe birth complications such as low birthweight, preterm birth and birth defects. During the last decade, the Alcohol Use Disorders Identification Test (AUDIT) has been used as a screening tool in Swedish maternal healthcare units to identify hazardous, pre-pregnancy alcohol use. However, evaluation of the screening with AUDIT, as well as adverse maternal or neonatal outcomes, has not been assessed at a national level.

    MATERIAL AND METHODS: This was a population-based cohort study of 530 458 births from 2013 to 2018 using demographic, reproductive and maternal health data from the Swedish Pregnancy Register. Self-reported alcohol consumption in the year before pregnancy, measured as AUDIT scores, was categorized into moderate (6-13 points) and high-risk (14-40 points) consumption, with low-risk (0-5 points) consumption as the reference group. Associations with pregnancy- and birth outcomes were explored with logistic regressions using generalized estimating equation models, adjusting for maternal and socioeconomic characteristics. Estimates are presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs).

    RESULTS: High-risk and moderate pre-pregnancy alcohol consumption was associated with preeclampsia, preterm birth and birth of an infant small for gestational age (SGA), but these associations were nonsignificant after adjustments. Prior moderate-risk (aOR 1.29, 95% CI 1.17-1.42) and high-risk consumption (aOR 1.62, 95% CI 1.17-2.25) increased the likelihood of intrapartum and neonatal infections.

    CONCLUSIONS: Apart from identifying hazardous alcohol consumption prior to pregnancy and the offer of counseling, screening with the AUDIT in early pregnancy indicates a high risk of inflammatory-/placenta-mediated pregnancy and birth outcomes. For most outcomes, AUDIT was not an independent contributor when adjusting for confounding factors. Hazardous alcohol use prior to pregnancy was independently linked to intrapartum and neonatal infections; conditions associated with morbidity and long-term sequalae. These associations may be explained by alcohol-induced changes in the maternal or fetal immune system in early pregnancy or persistent alcohol intake during pregnancy, or may depend on unidentified confounding factors.

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  • 17.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Eckerdal, Patricia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Investigating the association between neuroticism and adverse obstetric and neonatal outcomes2019In: Scientific Reports, E-ISSN 2045-2322, Vol. 9, article id 15470Article in journal (Refereed)
    Abstract [en]

    Neuroticism is not only associated with affective disorders but also with certain somatic health problems. However, studies assessing whether neuroticism is associated with adverse obstetric or neonatal outcomes are scarce. This observational study comprises first-time mothers (n = 1969) with singleton pregnancies from several cohorts based in Uppsala, Sweden. To assess neuroticism-related personality, the Swedish universities Scales of Personality was used. Swedish national health registers were used to extract outcomes and confounders. In logistic regression models, odds ratios (ORs) with 95% confidence intervals (Cis) were calculated for the outcomes by an increase of 63 units of neuroticism (equalling the interquartile range). Analyses were adjusted for maternal age, educational level, height, body mass index, year of delivery, smoking during pregnancy, involuntary childlessness, and psychiatric morbidity. Main outcomes were mode of delivery, gestational diabetes mellitus, gestational hypertension, preeclampsia, induction of delivery, prolonged delivery, severe lacerations, placental retention, postpartum haemorrhage, premature birth, infant born small or large for gestational age, and Apgar score. Neuroticism was not independently associated with adverse obstetric or neonatal outcomes besides gestational diabetes. For future studies, models examining sub-components of neuroticism or pregnancy-specific anxiety are encouraged.

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  • 18.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Eckerdal, Patricia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Child and Adolescent Psychiatry.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Neuroticism is not independently associated with adverse obstetric or neonatal outcomes: An observational studyIn: Article in journal (Refereed)
  • 19.
    Axfors, Cathrine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Volgsten, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Skoog Svanberg, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Ramklint, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Obstetrics and Reproductive Health Research.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 4, p. 470-478Article in journal (Refereed)
    Abstract [en]

    Introduction

    Elevated neuroticism is associated with higher health care utilization in the general population. This study aimed to investigate the association between neuroticism and the use of publicly financed antenatal care in obstetric low‐risk women, taking predisposing and need factors for health care utilization into consideration.

    Material and methods

    Participants comprised 1052 obstetric low‐risk women (no chronic diseases or adverse pregnancy conditions) included in several obstetrics/gynecology studies in Uppsala, Sweden. Neuroticism was self‐rated on the Swedish universities Scales of Personality. Medical records of their first subsequent pregnancy were scanned for antenatal care use. Associations between antenatal care use and neuroticism were analyzed with logistic regression (binary outcomes) or negative binomial regression (count outcomes) comparing the 75th and 25th neuroticism percentiles. Depending on the Akaike information criterion the exposure was modeled as either linear or with restricted cubic splines. Analyses were adjusted for predisposing (sociodemographic and parity) and need factors (body mass index and psychiatric morbidity).

    Results

    After adjustment, women with higher neuroticism had more fetal ultrasounds (incidence rate ratio = 1.09, 95% confidence interval (CI) 1.02‐1.16), more emergency visits to an obstetrician/gynecologist (incidence rate ratio = 1.22, 95% CI 1.03‐1.45) and were more likely to visit a fear‐of‐childbirth clinic (odds ratio = 2.71, 95% CI 1.71‐4.29). Moreover, they more often consulted midwives in specialized antenatal care facilities (significant J‐shaped association).

    Conclusions

    Neuroticism was associated with higher utilization of publicly financed antenatal care in obstetric low‐risk women, even after adjusting for predisposing and need factors. Future studies should address the benefits of interventions as a complement to routine antenatal care programs to reduce subclinical anxiety.

  • 20.
    Ayres-de-Campos, Diogo
    et al.
    Univ Lisbon, Santa Maria Univ Hosp, Med Sch, Lisbon, Portugal..
    Louwen, Frank
    Goethe Univ Frankfurt Main, Dept Obstet & Gynecol, Frankfurt, Germany.;Univ Hosp, Frankfurt, Germany..
    Vivilaki, Victoria
    Univ West Attica, Dept Nursing, Athens, Greece..
    Benedetto, Chiara
    Univ Div St Anna Hosp, Dept Gynecol & Obstet, Div Pathol, Turin, Italy..
    Modi, Neena
    Imperial Coll London, Sch Publ Hlth, Sect Neonatal Med, London, England..
    Wielgos, Miroslaw
    Lazarski Univ, Natl Med Inst Minist Interior, Med Fac, Dept Obstet & Perinatol, Warsaw, Poland..
    Tudose, Melania-Elena Pop
    Carol Davila Univ Med, Emergency Hosp, Fac Midwifery & Nursing, Obstet Dept, Bucharest, Buzau, Romania..
    Timonen, Susanna
    Turku Univ Hosp, Turku, Finland..
    Reyns, Marlene
    Turku Univ Hosp, Turku, Finland..
    Yli, Branka
    Oslo Univ Hosp, Delivery Dept, Dept Delivery, Oslo, Norway..
    Stenback, Pernilla
    Arcada Univ Appl Sci, Helsinki, Finland..
    Nunes, Ines
    Univ Porto, Fac Med, Dept Obstet & Gynecol, Unidade Local Saude Gaia Espinho, Porto, Portugal..
    Yurtsal, Burcu
    Sivas Cumhuriyet Univ, Dept Midwifery, Sivas, Turkiye..
    Vayssiere, Christophe
    Toulouse III Univ, Paule Viguier Hosp, Dept Obstet Gynecol Reprod, CHU Toulouse, Toulouse, France..
    Roth, Georges -Emmanuel
    Hop Univ Strasbourg, Dept Obstet & Gynecol, Strasbourg, France..
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Bakker, Petra
    Amsterdam UMC, Dept Obstet & Gynecol, Locat VU Med Ctr, Amsterdam, Netherlands..
    Lopriore, Enrico
    Leiden Univ, Med Ctr, Dept Neonatol, Leiden, Netherlands..
    Verlohren, Stefan
    Charite Univ Med Berlin, Dept Obstet, Berlin, Germany..
    Jacobsson, Bo
    Gothenburg Univ, Sahlgrenska Acad, Sahlgrenska Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden..
    European Association of Perinatal Medicine (EAPM), European Board and College of Obstetricians and Gynaecologists (EBCOG), European Midwives Association (EMA). Joint position statement: Substandard and disrespectful care in labour - because words matter2024In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 296, p. 205-207Article in journal (Refereed)
    Abstract [en]

    Substandard or disrespectful care during labour should be of serious concern for healthcare professionals, as it can affect one of the most important events in a woman's life. Substandard care refers to the use of interventions that are not considered best -practice, to the inadequate execution of interventions, to situations where bestpractice interventions are withheld from patients, or there is lack of adequate informed consent. Disrespectful care refers to forms of verbal and non-verbal communication that affect patients' dignity, individuality, privacy, intimacy, or personal beliefs. There are many possible underlying causes for substandard and disrespectful care in labour, including difficulties in modifying behaviours, judgmental or paternalistic attitudes, personal interests and individualism, and a human tendency to make less arduous, less difficult, or less stressful clinical decisions. The term "obstetric violence" is used in some parts of the world to describe various forms of substandard and disrespectful care in labour, but suggests that it is mainly carried out by obstetricians and is a serious form of aggression, carried out with the intent to cause harm. We believe that this term should not be used, as it does not help to identify the underlying problem, its causes, or its correction. In addition, it is generally seen by obstetricians and other healthcare professionals as an unjust and offensive term, generating a defensive and less collaborative mindset. We reach out to all individuals and institutions sharing the common goal of improving women's experience during labour, to work together to address the underlying causes of substandard and disrespectful care, and to develop common strategies to deal with this problem, based on mutual comprehension, trust and respect

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  • 21.
    Bartho, Lucy A.
    et al.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia.;Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, 163 Studley Rd, Heidelberg, Vic 3084, Australia..
    Kandel, Manju
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Walker, Susan P.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Cluver, Catherine A.
    Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7505 Cape Town, South Africa..
    Hastie, Roxanne
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia.;Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7505 Cape Town, South Africa..
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7505 Cape Town, South Africa; Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, S-40530 Gothenburg, Sweden.
    Pritchard, Natasha
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Cannon, Ping
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Nguyen, Tuong-Vi
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Wong, Georgia P.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    MacDonald, Teresa M.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Keenan, Emerson
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Hannan, Natalie J.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Tong, Stephen
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Kaitu'u-Lino, Tu'uhevaha J.
    Univ Melbourne, Mercy Hosp Women, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Circulating Chemerin Is Elevated in Women With Preeclampsia2023In: Endocrinology, ISSN 0013-7227, E-ISSN 1945-7170, Vol. 164, no 5, article id bqad041Article in journal (Refereed)
    Abstract [en]

    Background: Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia.

    Methods: Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96 hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction.

    Results: Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001).

    Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 × 10−6).

    RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells.

    Conclusions: Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.

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  • 22.
    Bauer, Ilena
    et al.
    Univ Tubingen, German Ctr Diabet Res DZD eV, FMEG Ctr, Inst Diabet Res & Metab Dis,Helmholtz Ctr Munich, Otfried Muller Str 47, D-72076 Tubingen, Germany..
    Hartkopf, Julia
    Univ Tubingen, German Ctr Diabet Res DZD eV, FMEG Ctr, Inst Diabet Res & Metab Dis,Helmholtz Ctr Munich, Otfried Muller Str 47, D-72076 Tubingen, Germany..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Schaal, Nora K.
    Heinrich Heine Univ, Dept Expt Psychol, Dusseldorf, Germany..
    Preissl, Hubert
    Univ Tubingen, German Ctr Diabet Res DZD eV, FMEG Ctr, Inst Diabet Res & Metab Dis,Helmholtz Ctr Munich, Otfried Muller Str 47, D-72076 Tubingen, Germany.;Univ Hosp Tuebingen, Div Endocrinol Diabetol & Nephrol, Dept Internal Med 4, Tubingen, Germany..
    Derntl, Birgit
    Univ Tubingen, Tuebingen Ctr Mental Hlth TuCMH, Dept Psychiat & Psychotherapy, Tubingen, Germany.;Univ Tubingen, LEAD Grad Sch & Res Network, Tubingen, Germany..
    Schleger, Franziska
    Univ Tubingen, German Ctr Diabet Res DZD eV, FMEG Ctr, Inst Diabet Res & Metab Dis,Helmholtz Ctr Munich, Otfried Muller Str 47, D-72076 Tubingen, Germany..
    Acute relaxation during pregnancy leads to a reduction in maternal electrodermal activity and self-reported stress levels2021In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 21, no 1, article id 628Article in journal (Refereed)
    Abstract [en]

    Background Prenatal maternal stress can have adverse effects on birth outcomes and fetal development. Relaxation techniques have been examined as potential countermeasures. This study investigates different relaxation techniques and their effect on self-reported stress levels and physiological stress levels in pregnant women. Methods In this cross-sectional study, 38 pregnant women in their 30th to 40th gestational week were assigned to one of three, 20-min lasting relaxation groups: listening to music (N = 12), following a guided imagery (N = 12) or resting (N = 12). The intervention, i.e., acute relaxation (music, guided imagery or resting) took place once for each study participant. Study inclusion criteria were age over 18 years, German speaking, singleton and uncomplicated pregnancy during the 30th and 40th week of gestation. The stress levels were determined during the study. Current stress level during the study was assessed by a visual analogue scale. Chronic stress levels were assessed by the Trier Inventory of Chronic Stress and the Pregnancy Distress questionnaire. Multivariate analyses of covariance were performed and dependent measures included stress levels as well as physiological measures, i.e., cardiovascular activity (electrocardiogram) and skin conductance levels. Results All three forms of relaxation led to reduced maternal stress which manifested itself in significantly decreased skin conductance, F(3,94) = 18.011, p = .001, eta(2)(p) = .365, and subjective stress levels after the interventions with no significant group difference. Post-intervention stress ratings were further affected by gestational age, with less subjective relaxation in women later in gestation, F (1, 34)=4.971, p = .032, eta(2)(p) = .128. Conclusion Independent of relaxation technique, single, 20-min relaxation intervention (music, guided imagery or resting) can significantly reduce maternal stress. Notably, women at an earlier stage in their pregnancy reported higher relaxation after the intervention than women later in gestation. Hence, gestational age may influence perceived stress levels and should be considered when evaluating relaxation or stress management interventions during pregnancy.

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  • 23.
    Bengtsson, Frida
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ekéus, Cecilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hagelroth, Amelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ahlsson, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Neonatal outcomes of elective labor induction in low-risk term pregnancies2023In: Scientific Reports, E-ISSN 2045-2322, Vol. 13, article id 15830Article in journal (Refereed)
    Abstract [en]

    The rate of labor induction has increased in recent years. The results of previously conducted studies examining associations between elective induction of labor (IOL) and neonatal outcomes have been contradictory. The aim of this study was to examine the intrinsic neonatal risks following IOL. We conducted a population-based cohort study, including all women with recorded low-risk singleton pregnancies at a gestational age between 37+0 and 41+6 weeks in Sweden from 1999 to 2017. Data were collected from the Swedish Medical Birth register. Two study groups were compared-the elective induction group with the spontaneous labor onset group. The results showed that the rate of elective IOL increased from 7.2% in 1999 to 16.4% in 2017. Elective IOL was associated with a higher OR for chorioamnionitis, bacterial sepsis, intracranial hemorrhage, assisted ventilation, hyperbilirubinemia, APGAR<7 at 5 min, and neonatal seizures compared to deliveries with spontaneous labor onset. Regarding mortality outcomes, no significant differences were shown between the groups for either early term or full-term deliveries. We conclude that IOL is associated with neonatal complications, although causality could not be established in this observational study. It is important to be aware of the increased risk and perform IOL with caution.

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  • 24.
    Berbres, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Reproductive Health and Migration. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Centre for Research and Development, Gävleborg.
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Ternström, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Reproductive Health Research. Dalarna Univ, Sch Hlth & Welf, Falun, Sweden..
    Schytt, Erica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna. Western Norway Univ Appl Sci, Fac Hlth & Social Sci, Bergen, Norway..
    Women's use of Swedish health care during the postpartum period in relation to maternal country of birth-A population-based study2024In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 103, no 10, p. 2101-2111Article in journal (Refereed)
    Abstract [en]

    Introduction: Migrant women are a heterogenous group with both higher and lower risk for pregnancy complications and adverse birth outcomes compared with women in the receiving countries. This study aimed to investigate women's use of Swedish healthcare postpartum, in terms of hospital stay >48 h, readmission to hospital, and specialized out-patient clinic visits, in relation to maternal country of birth. Material and Methods: A population-based register study including 278 219 primiparous and 367 776 multiparous women in Sweden (2014-2019) using data from Swedish Pregnancy Register, National Patient Register and Statistics Sweden. Multivariable logistic regression analyses were used to estimate associations between maternal country of birth and outcomes, adjusting for year of birth, maternal age, education, pre-gestational hypertension and diabetes, and healthcare region, presented as crude and adjusted odds ratios (aOR) with 95% confidence interval (CI) with Swedish-born women as reference. Results: Subgroups of migrant women had higher odds of postpartum hospital stays > 48 h, particularly women from Eritrea (primiparous aOR 2.80, CI 2.49-3.15; multiparous aOR 2.78, CI 2.59-2.98), Somalia (primiparous aOR 2.61, CI 2.34-2.92; multiparous aOR 1.87, CI 1.79-1.97), and India (primiparous aOR 2.52, CI 2.14-2.97; multiparous aOR 2.61, CI 2.33-2.93), compared to Swedish-born women. Primiparous women from Afghanistan (aOR 1.32, CI 1.08-1.6), Iraq (aOR 1.30, CI 1.16-1.46), and Iran (aOR 1.23, CI 1.04-1.45) had slightly higher odds of hospital readmission, along with multiparous women from India (aOR 1.34, CI 1.02-1.76) and Somalia (aOR 1.24, CI 1.11-1.38). Specialized out-patient clinic visits were most common in primiparous women from Somalia (aOR 1.47, CI 1.35-1.59), Iran (aOR 1.31, CI 1.22-1.42) and Afghanistan (aOR 1.31, CI 1.18-1.46), and in multiparous women from Iran (aOR 1.30, CI 1.20-1.41) and Iraq (aOR 1.15, CI 1.11-1.20), however less common in women from some other countries. Conclusions: The use of Swedish health care during the postpartum period varied among women, depending on their country of birth. Women from certain countries had particularly high odds of postpartum hospital stays exceeding 48 h, compared to Swedish-born women, regardless of parity and pre-gestational medical disorders. Further studies are needed to determine whether the individual needs of migrant women are being met during the postpartum period or not.

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  • 25.
    Bergendahl, Sandra
    et al.
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Ankarcrona, Victoria
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Leijonhufvud, Asa
    Lund Univ, Clin Sci Helsingborg, Dept Clin Sci Lund, Lund, Sweden.
    Hesselman, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Karlstrom, Sofie
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Kallner, Helena Kopp
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    Wendel, Sophia Brismar
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden.
    Lateral episiotomy versus no episiotomy to reduce obstetric anal sphincter injury in vacuum-assisted delivery in nulliparous women: study protocol on a randomised controlled trial2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 3, article id e025050Article in journal (Refereed)
    Abstract [en]

    Obstetric anal sphincter injury (OASIS) occurs in 5%-7% of normal deliveries and increases with vacuum extraction (VE) to 12%-14% in nulliparous women in Sweden. Lateral/mediolateral episiotomy may reduce the prevalence of OASIS at VE in nulliparous women. The current use of episiotomy is restrictive. The protective effect and consequences are uncertain. This trial will investigate if lateral episiotomy can reduce the prevalence of OASIS and assess short-term and long-term effects. Methods and analysis This is a multicentre randomised controlled trial of lateral episiotomy versus no episiotomy in nulliparous women with a singleton, live fetus, after gestational week 34+0 with indication for VE. A lateral episiotomy of 4 cm is cut at crowning, 1-3 cm from the midline, at a 60 degrees angle. The primary outcome is OASIS by clinical diagnosis analysed according to intention to treat. To demonstrate a 50% reduction in OASIS prevalence (from 12.4% to 6.2%), 710 women will be randomised at a 1:1 ratio. Secondary outcomes are pain, blood loss, other perineal injuries, perineal complications, Apgar score, cord pH and neonatal complications. Web-based questionnaires at baseline, 2 months, 1 and 5 years will be used to assess pain, incontinence, prolapse, sexual function, quality of life and childbirth experience. A subset of women will receive follow-up by pelvic floor sonography and pelvic examination. Mode of delivery and recurrence of OASIS/episiotomy in subsequent pregnancies will be assessed at 5 and 10 years using register data. Ethics and dissemination The trial is open for enrolment. The trial has received ethical approval from the Regional Ethical Review Board of Stockholm and full funding from the Swedish Research Council. Women are interested in participation. The predominant restrictive view on episiotomy may limit recruitment. Results are of global interest and will be disseminated in peer-reviewed journals and at international congresses.

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  • 26.
    Bergendahl, Sandra
    et al.
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Jonsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Hesselman, Susanne
    Ctr Clin Res Dalarna, Dept Womens & Childrens Hlth, Falun, Sweden..
    Ankarcrona, Victoria
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Leijonhufvud, Åsa
    Lund Univ, Dept Clin Sci Helsingborg, Helsingborg, Sweden..
    Wihlbäck, Anna-Carin
    Umeå Univ, Dept Clin Sci Obstet & Gynecol, Umeå, Sweden..
    Wallström, Tove
    Karolinska Inst, South Gen Hosp, Dept Clin Sci & Educ, Stockholm, Sweden..
    Rydström, Emmie
    Växjö Cent Hosp, Dept Obstet & Gynecol, Växjö, Sweden..
    Friberg, Hanna
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Kallner, Helena Kopp
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Wendel, Sophia Brismar
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Lateral episiotomy or no episiotomy in vacuum assisted delivery in nulliparous women (EVA): multicentre, open label, randomised controlled trial2024In: BMJ. British Medical Journal, ISSN 0959-8146, E-ISSN 0959-535X, Vol. 385, article id e079014Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the effect of lateral episiotomy, compared with no episiotomy, on obstetric anal sphincter injury in nulliparous women requiring vacuum extraction.

    DESIGN: A multicentre, open label, randomised controlled trial.

    SETTING: Eight hospitals in Sweden, 2017-23.

    PARTICIPANTS: 717 nulliparous women with a single live fetus of 34 gestational weeks or more, requiring vacuum extraction were randomly assigned (1:1) to lateral episiotomy or no episiotomy using sealed opaque envelopes. Randomisation was stratified by study site.

    INTERVENTION: A standardised lateral episiotomy was performed during the vacuum extraction, at crowning of the fetal head, starting 1-3 cm from the posterior fourchette, at a 60° (45-80°) angle from the midline, and 4 cm (3-5 cm) long. The comparison was no episiotomy unless considered indispensable.

    MAIN OUTCOME MEASURES: The primary outcome of the episiotomy in vacuum assisted delivery (EVA) trial was obstetric anal sphincter injury, clinically diagnosed by combined visual inspection and digital rectal and vaginal examination. The primary analysis used a modified intention -to -treat population that included all consenting women with attempted or successful vacuum extraction. As a result of an interim analysis at significance level alpha=0.01, the primary endpoint was tested at 4% significance level with accompanying 96% confidence interval (CI).

    RESULTS: From 1 July 2017 to 15 February 2023, 717 women were randomly assigned: 354 (49%) to lateral episiotomy and 363 (51%) to no episiotomy. Before vacuum extraction attempt, one woman withdrew consent and 14 had a spontaneous birth, leaving 702 for the primary analysis. In the intervention group, 21 (6%) of 344 women sustained obstetric anal sphincter injury, compared with 47 (13%) of 358 women in the comparison group (P=0.002). The risk difference was -7.0% (96% CI -11.7% to -2.5%). The risk ratio adjusted for site was 0.47 (96% CI 0.23 to 0.97) and unadjusted risk ratio was 0.46 (0.28 to 0.78). No significant differences were noted between groups in postpartum pain, blood loss, neonatal outcomes, or total adverse events, but the intervention group had more wound infections and dehiscence.

    CONCLUSIONS: Lateral episiotomy can be recommended for nulliparous women requiring vacuum extraction to significantly reduce the risk of obstetric anal sphincter injury.

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  • 27.
    Bergman, Karl
    et al.
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden.;Stellenbosch Univ, Tygerberg Hosp, Fac Med & Hlth Sci, Div Cardiol, Cape Town, Western Cape, South Africa..
    Svanvik, Teresia
    Univ Gothenburg, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Basic, Carmen
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Rosengren, Annika
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Sandstrom, Tatiana Zverkova
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Celind, Jimmy
    Univ Gothenburg, Inst Clin Sci, Gothenburg, Sweden.;Univ Gothenburg, Inst Med, Sahlgrenska Osteoporosis Ctr, Gothenburg, Sweden..
    Sjöland, Helen
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics.
    Schaufelberger, Maria
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Thunström, Erik
    Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Mol & Clin Med, Gothenburg, Sweden..
    Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study2024In: Open heart, E-ISSN 2053-3624, Vol. 11, no 1, article id e002728Article in journal (Refereed)
    Abstract [en]

    Background and aims Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia.

    Methods In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases.

    Results Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls.

    Conclusion Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

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  • 28.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Department of Clinical Sciences, Sahlgrenska Academy, Gothenburg University , Gothenburg, Sweden;Department of Obstetrics and Gynecology, Stellenbosch University , Stellenbosch, South Africa;Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Sciences, University of Bío-Bío , Chillán, Chile.
    Acurio, Jesenia
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Leon, Jose
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Gatu, Emily
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Friis, Therese
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Nelander, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lara, Evelyn
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Aguayo, Claudio
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Torres-Vergara, Pablo
    Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillán, Chile..
    Wikström, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.
    Escudero, Carlos
    Vascular Physiology Laboratory, Department of Basic Sciences, Faculty of Basic Sciences, University of Bío-Bío Chillán, Chile..
    Preeclampsia and Increased Permeability Over the Blood–Brain Barrier: A Role of Vascular Endothelial Growth Receptor 2 2021In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 34, no 1, p. 73-81Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.

    METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.

    RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.

    CONCLUSION: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.

  • 29.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynaecol, S-41650 Gothenburg, Sweden.;Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Bergman, Karl
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, S-41650 Gothenburg, Sweden..
    Langenegger, Eduard
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Moodley, Ashley
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Griffith-Richards, Stephanie
    Stellenbosch Univ, Div Radiodiag, Dept Med Imaging & Clin Oncol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Hall, David
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Joubert, Lloyd
    Stellenbosch Univ, Div Cardiol, Dept Med Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    Herbst, Philip
    Univ Med Ctr Groningen, Dept Obstet & Gynaecol, NL-9713 Groningen, Netherlands..
    Schell, Sonja
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa..
    van Veen, Teelkien
    Univ Med Ctr Groningen, Dept Obstet & Gynaecol, NL-9713 Groningen, Netherlands..
    Belfort, Michael
    Baylor Coll Med, Dept Obstet & Gynaecol, Houston, TX 77004 USA..
    Tong, Stephen Y. C.
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Walker, Susan
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Hastie, Roxanne
    Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3010, Australia..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynaecol, Fac Med & Hlth Sci, ZA-7505 Cape Town, South Africa.;Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Parkville, Vic 3010, Australia..
    PROVE-Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia2021In: Cells, E-ISSN 2073-4409, Vol. 10, no 4, article id 959Article in journal (Refereed)
    Abstract [en]

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.

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  • 30.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.;Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.;Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Carlberg, Niclas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol, Gothenburg, Sweden..
    Belfort, Michael
    Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA..
    Tolcher, Mary C.
    Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA..
    Panerai, Ronney B.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
    van Veen, Teelkien
    Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands..
    Cerebral perfusion pressure and autoregulation in eclampsia-a case control study2021In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 225, no 2, article id 185.e1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. OBJECTIVE: This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. STUDY DESIGN: This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. RESULTS: We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). CONCLUSION: Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.

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  • 31.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Stellenbosch Univ, Fac Med & Hlth Sci, Dept Obstet & Gynecol, Cape Town, South Africa.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, PO Kvinnokliniken SU Ostra, SE-41685 Gothenburg, Sweden..
    Cluver, Catherine
    Stellenbosch Univ, Fac Med & Hlth Sci, Dept Obstet & Gynecol, Cape Town, South Africa.;Univ Melbourne, Translat Obstet Grp, Dept Obstet & Gynaecol, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Carlberg, Niclas
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Anesthesiol, Gothenburg, Sweden..
    Belfort, Michael
    Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA..
    Tolcher, Mary C.
    Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA..
    Panerai, Ronney B.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England..
    Van Veen, Teelkien
    Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands..
    Impaired cerebral autoregulation, cerebral perfusion pressure, and intracranial pressure in eclampsia2022In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 226, no 2, p. 287-288Article in journal (Other academic)
  • 32.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden; Stellenbosch Univ, Dept Obstet & Gynecol, Stellenbosch, South Africa.
    Escudero, Carlos Alonso
    Univ Bio Bio, Dept Basic Sci, Vasc Physiol Lab, Chillan, Chile.;Grp Res & Innovat Vasc Hlth, GRIVAS Hlth, Chillan, Chile..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynecol, Stellenbosch, South Africa.;Mercy Hosp Women, Dept Obstet & Gynaeol, Mercy Perinatal, Melbourne, Vic, Australia.;Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic, Australia..
    Hastie, Roxanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Stellenbosch Univ, Dept Obstet & Gynecol, Stellenbosch, South Africa; Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic, Australia.
    Torres-Vergara, Pablo
    Grp Res & Innovat Vasc Hlth, GRIVAS Hlth, Chillan, Chile.;Univ Concepcion, Fac Farm, Dept Farm, Concepcion, Chile..
    Editorial: Preeclampsia and the brain: Pre-clinical and clinical studies of cerebral involvement in preeclampsia2023In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 14, article id 1151091Article in journal (Other academic)
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  • 33.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Hastie, Roxanne
    Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Bokstrom-Rees, Emma
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden..
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden.;UCL, Dept Neurodegenerat Dis, Inst Neurol, Queen Sq, London, England.;United Kingdom Dementia Res Inst, London, England.;Hong Kong Ctr Neurodegenerat Dis, Hong Kong, Peoples R China..
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, Mölndal, Sweden..
    Schell, Sonja
    Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa..
    Imberg, Henrik
    Stat Konsultgruppen, Gothenburg, Sweden.;Chalmers Univ Technol, Dept Math Sci, Gothenburg, Sweden.;Univ Gothenburg, Gothenburg, Sweden..
    Langenegger, Eduard
    Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa..
    Moodley, Ashley
    Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa..
    Walker, Susan
    Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Tong, Stephen
    Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.;Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Melbourne, Vic, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic, Australia..
    Cerebral biomarkers in neurologic complications of preeclampsia2022In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 227, no 2, p. 298.e1-298.e10Article in journal (Refereed)
    Abstract [en]

    Background: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. Objective: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. Study Design: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. Results: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64-2.88), 2.17-fold higher tau (95% confidence interval, 1.49-3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06-3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92-4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06-5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06-2.55), tau (4.44-fold higher; 95% confidence interval, 1.85-10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32-2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. Conclusion: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.

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  • 34.
    Bergman, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7500 Cape Town, South Africa; Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, S-41685 Gothenburg, Sweden.
    Hastie, Roxanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics. Univ Melbourne, Dept Obstet & Gynecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia; Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia.
    Zetterberg, Henrik
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41345 Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-41385 Mölndal, Sweden.;UCL Inst Neurol, Dept Neurodegenerat Dis, Queen Sq, London WC1N3BG, England.;UK Dementia Res Inst, London WC1E6BT, England.;Hong Kong Ctr Neurodegenerat Dis, Kowloon, Clear Water Bay, Hong Kong 999077, Peoples R China..
    Blennow, Kaj
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, S-41345 Mölndal, Sweden.;Sahlgrens Univ Hosp, Clin Neurochem Lab, S-41385 Mölndal, Sweden..
    Schell, Sonja
    Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7500 Cape Town, South Africa..
    Langenegger, Eduard
    Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7500 Cape Town, South Africa..
    Moodley, Ashley
    Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7500 Cape Town, South Africa..
    Walker, Susan
    Univ Melbourne, Dept Obstet & Gynecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Tong, Stephen
    Univ Melbourne, Dept Obstet & Gynecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Cluver, Catherine
    Stellenbosch Univ, Dept Obstet & Gynecol, ZA-7500 Cape Town, South Africa.;Univ Melbourne, Dept Obstet & Gynecol, Translat Obstet Grp, Heidelberg, Vic 3084, Australia.;Mercy Hosp Women, Mercy Perinatal, Heidelberg, Vic 3084, Australia..
    Evidence of Neuroinflammation and Blood-Brain Barrier Disruption in Women with Preeclampsia and Eclampsia2021In: Cells, E-ISSN 2073-4409, Vol. 10, no 11, article id 3045Article in journal (Refereed)
    Abstract [en]

    Cerebral complications in preeclampsia are leading causes of maternal mortality. Animal models suggest that an injured blood-brain barrier and neuroinflammation may be important but there is paucity of data from human studies. Therefore, we aimed to evaluate this in women with preeclampsia and eclampsia. We included women recruited to the South African Preeclampsia Obstetric Adverse Events (PROVE) biobank. Blood and cerebrospinal fluid (CSF) were collected around delivery. CSF was analyzed for neuroinflammatory markers interleukin 1 beta, interleukin 6, interleukin-8 and tumor necrosis factor alpha (TNF-alpha). The CSF to plasma albumin ratio was measured to assess blood-brain barrier function. Women with eclampsia (n = 4) showed increased CSF concentrations of all pro-inflammatory cytokines and TNF-alpha compared to women with normotensive pregnancies (n = 7) and also for interleukin-6 and TNF-alpha compared to women with preeclampsia (n = 4). Women with preeclampsia also showed increases in pro-inflammatory cytokines IL-6 and IL-8 but not TNF-alpha in the CSF compared to women with normotensive pregnancies. In particular, women with eclampsia but also women with preeclampsia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. In conclusion, women with preeclampsia and eclampsia show evidence of neuroinflammation and an injured blood-brain barrier. These findings are seen in particular among women with eclampsia.

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  • 35.
    Bergman, Lina