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  • 1.
    Alfonzo, Emilia
    et al.
    Sahlgrens Univ Hosp, Dept Obstet & Gynaecol, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynaecol, Med Gatan 3, S-41390 Gothenburg, Sweden.
    Wallin, Emelie
    Karolinska Univ Hosp, Div Obstet & Gynaecol, Dept Womens & Childrens Hlth, K 57, S-14186 Stockholm, Sweden;Karolinska Inst, K 57, S-14186 Stockholm, Sweden.
    Ekdahl, Linnea
    Skane Univ Hosp, Div Gynaecol Oncol, Dept Obstet & Gynaecol, S-22185 Lund, Sweden;Lund Univ, Fac Med, Dept Clin Sci Obstet & Gynaecol, S-22185 Lund, Sweden.
    Staf, Christian
    Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, S-41345 Gothenburg, Sweden.
    Radestad, Angelique Floter
    Karolinska Univ Hosp, Div Obstet & Gynaecol, Dept Womens & Childrens Hlth, K 57, S-14186 Stockholm, Sweden;Karolinska Inst, K 57, S-14186 Stockholm, Sweden.
    Reynisson, Petur
    Skane Univ Hosp, Div Gynaecol Oncol, Dept Obstet & Gynaecol, S-22185 Lund, Sweden;Lund Univ, Fac Med, Dept Clin Sci Obstet & Gynaecol, S-22185 Lund, Sweden.
    Stålberg, 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), Reproductive Health.
    Falconer, Henrik
    Karolinska Univ Hosp, Div Obstet & Gynaecol, Dept Womens & Childrens Hlth, K 57, S-14186 Stockholm, Sweden;Karolinska Inst, K 57, S-14186 Stockholm, Sweden.
    Persson, Jan
    Skane Univ Hosp, Div Gynaecol Oncol, Dept Obstet & Gynaecol, S-22185 Lund, Sweden;Lund Univ, Fac Med, Dept Clin Sci Obstet & Gynaecol, S-22185 Lund, Sweden.
    Dahm-Kahler, Pernilla
    Sahlgrens Univ Hosp, Dept Obstet & Gynaecol, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynaecol, Med Gatan 3, S-41390 Gothenburg, Sweden;Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, S-41345 Gothenburg, Sweden.
    No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study2019In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 116, p. 169-177Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the study was to compare overall survival (OS) and diseasefree survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. Patients and methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. Results: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50-2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66-1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. Conclusion: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery. (C) 2019 The Authors. Published by Elsevier Ltd.

  • 2.
    Altman, Daniel
    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), Reproductive Health. Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden;Stockholm Urogynecol Clin, Stockholm, Sweden.
    Geale, Kirk
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Falconer, Christian
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, S-18288 Stockholm, Sweden.
    Morcos, Edward
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Div Obstet & Gynecol, S-18288 Stockholm, Sweden.
    A generic health-related quality of life instrument for assessing pelvic organ prolapse surgery: correlation with condition-specific outcome measures2018In: International Urogynecology Journal, ISSN 0937-3462, E-ISSN 1433-3023, Vol. 29, no 8, p. 1093-1099Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the use of a generic and globally accessible instrument for assessing health-related quality of life (HR-QoL) in pelvic organ prolapse (POP) surgery. In a prospective multicenter setting, 207 women underwent surgery for apical prolapse [stage ae<yen>2, Pelvic Organ Prolapse Quantificcation (POP-Q) system] with or without anterior wall defect. Demographic and surgical characteristics were collected before surgery. Results of the 15-dimensional (15D) instrument and condition-specific pelvic floor symptoms as assessed using the Pelvic Floor Distress Inventory questionnaire (PFDI-20), including its subscales Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), Colorectal-Anal Distress Inventory-8 (CRADI-8), and Urinary Distress Inventory-6 (UDI-6), were assessed preoperatively and 2 months and 1 year after surgery. HR-QoL as estimated by 15D was improved 1 year after surgery (p < 0.001). Prolapse-related 15D profile-index measures (excretion, discomfort, sexual activity, distress, and mobility) were significantly improved after surgery (p < 0.05-0.001). Significant inverse associations were detected between increased 15D scores and a decrease in PFDI-20 and subscale scores (p < 0.001), indicating improvements on both instruments. Generic HR-QoL as estimated by 15D improved significantly after apical POP surgery and correlated with improvements of condition-specific outcome measures. These results suggest that a comprehensive evaluation of global HR-QoL is valid in assessing pelvic reconstructive surgery and may provide novel and important insights into previously understudied areas, such as cost-utility and cost-effectiveness analysis after urogynecological surgery.

  • 3.
    Anandavadivelan, P.
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Wikman, Anna
    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.
    Johar, A.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Lagergren, P.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, 2nd Floor,Norra Stationsgatan 67, S-17176 Stockholm, Sweden..
    Impact of weight loss and eating difficulties on health-related quality of life up to 10 years after oesophagectomy for cancer2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 4, p. 410-418Article in journal (Refereed)
    Abstract [en]

    Background: Severe weight loss is experienced by patients with eating difficulties after surgery for oesophageal cancer. The aim of this prospective cohort study was to asssess the influence of eating difficulties and severe weight loss on health-related quality of life (HRQoL) up to 10years after oesophagectomy.

    Methods: Data on bodyweight and HRQoL were collected at 6months, 3, 5 and 10years in patients who underwent surgery for oesophageal cancer in Sweden between 2001 and 2005. Exposures were percentage weight loss, and eating difficulties defined by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 questionnaire. Outcomes were HRQoL scores from the EORTC QLQ-C30 questionnaire. Repeated-measures ANOVA, adjusting for potential confounders, was used to assess the association between eating difficulties and weight loss (4 exposure groups) and HRQoL scores at each time point. Mean score differences (MDs) between time points or exposure groups were defined as clinically relevant in accordance with evidence-based interpretation guidelines.

    Results: In total, 92 of 104 10-year survivors (885 per cent) responded to the questionnaires. Weight loss was greatest within 6months of surgery. Patients with eating difficulties with or without weight loss reported clinically and statistically significantly worsened HRQoL in almost all aspects. The largest MD was seen between 5 and 10years after surgery for global quality of life, physical, role and social function (MD -22 to -30), as well for fatigue, nausea, dyspnoea, insomnia, appetite loss and diarrhoea (MD 24-36).

    Conclusion: Eating difficulties are associated with deterioration in several aspects of HRQoL up to 10years after surgery for oesophageal cancer.

  • 4.
    Anandavadivelan, Poorna
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Wikman, Anna
    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.
    Johar, Asif
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Lagergren, Pernilla
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Profiles of patient and tumour characteristics in relation to health-related quality of life after oesophageal cancer surgery2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0196187Article in journal (Refereed)
    Abstract [en]

    Strong deterioration in health-related quality of life (HRQOL) is a major concern in a sub-group of long-term oesophageal cancer survivors. This study aimed to identify potential clustering of patients and tumour variables that predicts such deterioration. Patient and tumour variables were collected in a prospective cohort of patients who underwent surgery for oesophageal cancer in Sweden 2001–2005. Latent cluster analysis identified statistically significant clustering of these variables. Multivariable logistic regression adjusted for age, BMI, tumour stage and marital status was used to determine odds ratios (ORs) with 95% confidence intervals (CIs) between patient profiles and HRQOL at 3 and 5 years from surgery. Among 155 included patients at 3 years, three patient profiles were identified: 1) ‘reference profile’ (males, younger age, employed, upper secondary education, co-habitating, urban dwellers, adenocarcinoma and advanced tumour stage) (n = 47;30%), 2) ‘adenocarcinoma profile’ (middle age, unemployed/retired, males, low education, co-habitating, adenocarcinoma, advanced tumour stage, tumour in lower oesophagus/cardia, and co-morbidities (n = 79;51%), and 3) ‘squamous-cell carcinoma profile’ (unemployed/retired, middle-age, males, low BMI, urban dwellers, squamous-cell carcinoma, tumour in upper/middle oesophagus (n = 29;19%). These profiles did not differ regarding most HRQOL measures. Exceptions were the squamous-cell carcinoma profile, reporting more constipation (OR = 5.69; 95%CI: 1.34–24.28) and trouble swallowing saliva (OR = 4.87; 95%CI: 1.04–22.78) and the adenocarcinoma profile reporting more dyspnoea (OR = 2.60; 95%CI: 1.00–6.77) and constipation (OR = 3.31; 95%CI: 1.00–10.97) compared to the reference profile. Three distinct patient profiles were identified but these could not explain the substantial deterioration in HRQOL observed in the sub-sample of survivors.

  • 5.
    Anandavadivelan, Poorna
    et al.
    Karolinska Inst, Stockholm, Sweden.
    Wikman, Anna
    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.
    Martin, Lena
    Dept Biosci & Nutr, Stockholm, Sweden.
    Rueb, Claudia
    Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England.
    Johar, Asif
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Malberg, Kalle
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Lagergren, Pernilla
    Karolinska Inst, Dept Mol Med & Surg, Surg Care Sci, Stockholm, Sweden.
    Extent of dumping symptoms and its association with malnutrition following surgery for oesophageal cancer2018In: Quality of Life Research, ISSN 0962-9343, E-ISSN 1573-2649, Vol. 27, no Supplement 1, p. S76-S76Article in journal (Other academic)
  • 6.
    Armuand, G.
    et al.
    Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden..
    Lampic, C.
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden..
    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.
    Wånggren, K.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Sydsjö, G.
    Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, SE-58183 Linkoping, Sweden.;Cty Council Ostergotland, Dept Gynecol & Obstet Linkoping, Linkoping, Sweden..
    Survey shows that Swedish healthcare professionals have a positive attitude towards surrogacy but the health of the child is a concern2018In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 107, no 1, p. 101-109Article in journal (Refereed)
    Abstract [en]

    Aim: In February 2016, Sweden upheld its ban on surrogacy following a Government enquiry. This survey investigated attitudes towards surrogacy among primary health professionals working with children and their experiences of working with families following surrogacy abroad.

    Methods: From April to November 2016, nurses, physicians and psychologist working in primary child health care in four counties in Sweden were invited to participate in a cross-sectional online survey about surrogacy.

    Results: The mean age of the 208 participants was 49.2years (range 27-68) and nearly 91% were women. Approximately 60% supported legalised surrogacy. Wanting a conscience clause to be introduced in Sweden was associated with not supporting surrogacy for any groups, while personal experiences of infertility and clinical experiences with families following surrogacy were associated with positive attitudes towards surrogacy for heterosexual couples. The majority (64%) disagreed that surrogate children were as healthy as other children, and many believed that they risked worse mental health (21%) and social stigmatisation (21%).

    Conclusion: We found that 60% supported legalised surrogacy, but many expressed concerns about the children's health and greater knowledge about the medical and psychosocial consequences of surrogacy is needed.

  • 7.
    Armuand, Gabriela
    et al.
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, SE-58183 Linkoping, Sweden.
    Sydsjo, Gunilla
    Linkoping Univ, Dept Clin & Expt Med, Fac Hlth Sci, SE-58183 Linkoping, Sweden;Cty Council Ostergotland, Dept Gynaecol & Obstet Linkoping, Linkoping, Sweden.
    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.
    Lampic, Claudia
    Karolinska Inst, Dept Womens & Childrens Hlth, Tomtebodavagen 18A, SE-17177 Stockholm, Sweden.
    Attitudes towards embryo donation among healthcare professionals working in child healthcare: a survey study2019In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 19, article id 209Article in journal (Refereed)
    Abstract [en]

    BackgroundThe aim of this study was to investigate attitudes towards embryo donation and embryo donation families among professionals working in primary child healthcare, and their experiences of these families.MethodsA cross-sectional online survey was conducted in Sweden between April and November 2016. A total of 712 primary healthcare physicians, registered nurses and psychologists were approached to participate in this study. The study-specific questionnaire measured attitudes and experiences in the following four domains: legalisation and financing, the family and the child's health, clinical experience of meeting families following embryo donation, and knowledge of embryo donation.ResultsOf the 189 women and 18 men who completed the questionnaire (response rate 29%), relatively few (13%) had clinical experience of caring for families following embryo donation. Overall, 69% supported legalisation of embryo donation for infertile couples, and 54% agreed it should be publicly funded. The majority (88%) agreed the child should have the right to know the donors' identity. Respondents did not believe that children conceived through embryo donation are as healthy as other children (50%), citing the risks of poor mental health (17%) and social stigmatization (18%). Approximately half reported low confidence in their own knowledge of embryo donation (47%) and wanted to know more (58%).ConclusionsThese results indicate relatively large support among healthcare professionals in Sweden for the legalisation of embryo donation. In order to provide adequate healthcare to families following embryo donation, there is a need to develop educational resources to increase knowledge about the medical and psychosocial consequences of embryo donation among healthcare professionals working in primary healthcare.

  • 8.
    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)
  • 9.
    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.

  • 10.
    Bandstein, Nadia
    et al.
    Karolinska Institutet.
    Wikman, Anna
    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.
    Ljung, Rickard
    Karolinska Institutet.
    Holzmann, Martin
    Karolinska Institutet.
    Survival and resource utilization in patients with chest pain evaluated with cardiac troponin T compared with high sensitivity cardiac troponin T2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 245, p. 43-48Article in journal (Refereed)
  • 11.
    Bandstein, Nadia
    et al.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med, Solna, Sweden..
    Wikman, Anna
    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.
    Ljung, Rickard
    Karolinska Inst, Inst Environm Med, Epidemiol Unit, Solna, Sweden..
    Holzmann, Martin J.
    Karolinska Univ Hosp, Dept Emergency Med, Huddinge, Sweden.;Karolinska Inst, Dept Internal Med, Solna, Sweden..
    Survival and resource utilization in patients with chest pain evaluated with cardiac troponin T compared with high-sensitivity cardiac troponin T2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 245, p. 43-48Article in journal (Refereed)
    Abstract [en]

    Background:

    It is uncertain how the implementation of high-sensitivity cardiac troponin T (hs-cTnT) has affected the survival of patients with chest pain in the emergency department (ED). We studied prognosis and resource utilization in terms of coronary angiographies and revascularizations (percutaneous coronary intervention or coronary artery bypass grafting) in patients evaluated with hs-cTnT compared with conventional troponin T (cTnT).

    Methods:

    All patients >25 years presenting with chest pain and at least one troponin level analyzed in the ED at the Karolinska University Hospital, Sweden, were included. Hazard ratios (HR) for all-cause mortality, coronary angiographies and revascularizations were adjusted for age, sex and comorbidities during 1 year of follow-up comparing patients tested with hs-cTnT (December 10, 2010 to December 31, 2013) with patients tested with cTnT (January 1, 2009 to December 9, 2010).

    Results:

    In total, 31,904 patients were included (n=12,485 tested with cTnT and n=24,729 using hs-cTnT). Patient characteristics, comorbidities, and medications were similar during the study period. The absolute risk of all-cause mortality was 3.7% for those tested with cTnT compared with 3.4% for hs-cTnT. After adjustment for confounders, an increased all-cause mortality was observed for patients tested with hs-cTnT (HR 1.15; 95% confidence interval (CI) 1.02-1.29). Coronary angiographies increased by 13% (HR 1.13; 95% CI 1.00-1.28) and revascularizations by 18% (HR 1.18; 95% CI 1.01-1.37) when using hs-cTnT.

    Conclusions:

    In an observational cohort study including patients with chest pain in the ED we found a small increase in mortality, coronary angiographies and revascularizations after the introduction of hs-cTnT.

  • 12.
    Bengtsdotter, Hanna
    et al.
    Örebro Univ, Dept Obstet & Gynaecol, Örebro, Sweden..
    Lundin, Cecilia
    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.
    Danielsson, Kristina Gemzell
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Bixo, Marie
    Umea Univ, Dept Clin Sci, Umea, Sweden..
    Baumgart, Juliane
    Örebro Univ, Dept Obstet & Gynaecol, Örebro, Sweden..
    Marions, Lena
    Karolinska Inst Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden..
    Brynhildsen, Jan
    Linkoping Univ, Dept Obstet & Gynaecol, Linkoping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Malmborg, Agota
    Linköping Univ, Dept Obstet & Gynaecol, Linköping, Sweden.;Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden..
    Lindh, Ingela
    Gothenburg Univ, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Obstet & Gynaecol, Gothenburg, Sweden..
    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.
    Ongoing or previous mental disorders predispose to adverse mood reporting during combined oral contraceptive use2018In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 23, no 1, p. 45-51Article in journal (Refereed)
    Abstract [en]

    Purpose: Previous studies have emphasised that women with pre-existing mood disorders are more inclined to discontinue hormonal contraceptive use. However, few studies have examined the effects of combined oral contraceptives (COC) on mood in women with previous or ongoing mental disorders. Materials and methods: This is a supplementary analysis of an investigator-initiated, double-blinded, randomised clinical trial during which 202 women were treated with either a COC (1.5mg estradiol and 2.5mg nomegestrolacetate) or placebo during three treatment cycles. The Mini International Neuropsychiatric Interview was used to collect information on previous or ongoing mental disorders. The primary outcome measure was the total change score in five mood symptoms on the Daily Record of Severity of Problems (DRSP) scale in the intermenstrual phase of the treatment cycle. Results: Women with ongoing or previous mood, anxiety or eating disorders allocated to COC had higher total DRSP -scores during the intermenstrual phase of the treatment cycle in comparison with corresponding women randomised to placebo, mean difference 1.3 (95% CI 0.3-2.3). In contrast, among women without mental health problems, no difference in total DRSP -scores between COC- and placebo users was noted. Women with a risk use of alcohol who were randomised to the COC had higher total DRSP -scores than women randomised to placebo, mean difference 2.1 (CI 95% 1.0-3.2). Conclusions: Women with ongoing or previous mental disorders or risk use of alcohol have greater risk of COC-induced mood symptoms. This may be worth noting during family planning and contraceptive counselling.

  • 13.
    Berggrund, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Enroth, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Lundberg, Martin
    OLINK Prote, Uppsala Sci Pk, SE-75183 Uppsala, Sweden.
    Assarsson, Erika
    OLINK Prote, Uppsala Sci Pk, SE-75183 Uppsala, Sweden.
    Stålberg, 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), Reproductive Health.
    Lindquist, David
    Umeå Univ, Dept Radiat Sci, SE-90187 Umeå, Sweden.
    Hallmans, Göran
    Umeå Univ, Dept Publ Hlth & Clin Med, Nutr Res, SE-90187 Umeå, Sweden.
    Grankvist, Kjell
    Umeå Univ, Dept Med Biosci, Clin Chem, SE-90187 Umeå, Sweden.
    Olovsson, Matts
    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.
    Gyllensten, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Identification of Candidate Plasma Protein Biomarkers for Cervical Cancer Using the Multiplex Proximity Extension Assay2019In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 4, p. 735-743Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.

  • 14.
    Bhandage, Amol
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Korol, Sergiy V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Tafreshiha, Atieh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Gohel, Priya
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden.
    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.
    Espes, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Carlsson, Per-Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    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.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Expression of calcium release-activated and voltage-gated calcium channels genes in peripheral blood mononuclear cells is altered in pregnancy and in type 1 diabetes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0208981Article in journal (Refereed)
    Abstract [en]

    Calcium (Ca2+) is an important ion in physiology and is found both outside and inside cells. The intracellular concentration of Ca2+ is tightly regulated as it is an intracellular signal molecule and can affect a variety of cellular processes. In immune cells Ca2+ has been shown to regulate e.g. gene transcription, cytokine secretion, proliferation and migration. Ca2+ can enter the cytoplasm either from intracellular stores or from outside the cells when Ca2+ permeable ion channels in the plasma membrane open. The Ca2+ release-activated (CRAC) channel is the most prominent Ca2+ ion channel in the plasma membrane. It is formed by ORAI1-3 and the channel is opened by the endoplasmic reticulum Ca2+ sensor proteins stromal interaction molecules (STIM) 1 and 2. Another group of Ca-2(+) channels in the plasma membrane are the voltage-gated Ca2+ (Ca-V) channels. We examined if a change in immunological tolerance is accompanied by altered ORAI, STIM and Ca-V gene expression in peripheral blood mononuclear cells (PBMCs) in pregnant women and in type 1 diabetic individuals. Our results show that in pregnancy and type 1 diabetes ORAI1-3 are up-regulated whereas STIM1 and 2 are down-regulated in pregnancy but only STIM2 in type 1 diabetes. Expression of L-, P/Q-, R- and T-type voltage-gated Ca2+ channels was detected in the PBMCs where the Ca(V)2.3 gene was up-regulated in pregnancy and type 1 diabetes whereas the Ca(V)2.1 and Ca(V)3.2 genes were up-regulated only in pregnancy and the Ca(V)1.3 gene in type 1 diabetes. The results are consistent with that expression of ORAI, STIM and Ca-V genes correlate with a shift in immunological status of the individual in health, as during pregnancy, and in the autoimmune disease type 1 diabetes. Whether the changes are in general protective or in type 1 diabetes include some pathogenic components remains to be clarified.

  • 15.
    Bondeson, Marie-Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ericson, Katharina
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Univ Uppsala Hosp, Dept Pathol & Cytol, Uppsala, Sweden.
    Gudmundsson, Sanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ameur, Adam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ponten, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wesström, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, 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), Reproductive Health.
    Frykholm, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wilbe, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    A nonsense mutation in CEP55 defines a new locus for a Meckel-like syndrome, an autosomal recessive lethal fetal ciliopathy.2017In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 92, no 5, p. 510-516Article in journal (Refereed)
    Abstract [en]

    Mutations in genes involved in the cilium-centrosome complex are called ciliopathies. Meckel-Gruber syndrome (MKS) is a ciliopathic lethal autosomal recessive syndrome characterized by genetically and clinically heterogeneous manifestations, including renal cystic dysplasia, occipital encephalocele and polydactyly. Several genes have previously been associated with MKS and MKS-like phenotypes, but there are still genes remaining to be discovered. We have used whole exome sequencing (WES) to uncover the genetics of a suspected autosomal recessive Meckel syndrome phenotype in a family with two affected fetuses. RNA studies and histopathological analysis was performed for further delineation. WES lead to identification of a homozygous nonsense mutation c.256C>T (p.Arg86*) in CEP55 (centrosomal protein of 55 kDa) in the affected fetus. The variant has previously been identified in carriers in low frequencies, and segregated in the family. CEP55 is an important centrosomal protein required for the mid-body formation at cytokinesis. Our results expand the list of centrosomal proteins implicated in human ciliopathies and provide evidence for an essential role of CEP55 during embryogenesis and development of disease.

  • 16.
    Bourlev, Vladimir
    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), Reproductive biology. Minist Healthcare Russian Federat, Natl Med Res Ctr Obstet Gynecol & Perinatol, Moscow, Russia.
    Moberg, Christian
    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.
    Ilyasova, Natalia
    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. Minist Healthcare Russian Federat, Natl Med Res Ctr Obstet Gynecol & Perinatol, Moscow, Russia.
    Davey, Eva
    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.
    Kallak, Theodora Kunovac
    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.
    Olovsson, Matts
    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.
    Vasoactive intestinal peptide is upregulated in women with endometriosis and chronic pelvic pain2018In: American Journal of Reproductive Immunology, ISSN 1046-7408, E-ISSN 1600-0897, Vol. 80, no 3, article id e12857Article in journal (Refereed)
    Abstract [en]

    Problem: Chronic pelvic pain (CPP) causes compromised the quality of life in women with endometriosis and is often attributed to local inflammation and ingrowth of nerve fibers. In this pilot study, we aimed to investigate whether the inflammation‐related vasoactive intestinal peptide (VIP) and interleukin (IL)‐6 were increased in affected patients.

    Method of study: Endometrial and endometriotic tissue biopsy specimens, and serum and peritoneal fluid (PF) samples, were obtained from 85 endometriosis patients and 53 controls. VIP and IL‐6 analysis and measurement of microvessel density in tissue were performed using immunohistochemistry, Western blotting, RT‐qPCR, and ELISA.

    Results: Compared with controls, VIP transcript and protein levels were increased in endometrium from endometriosis patients and further elevated in patients with CPP. In addition, microvessel density, a measurement of angiogenic activity, was increased in the endometrium and in endometriosis lesions in the same subset of patients. Serum and PF levels of VIP and IL‐6 were higher in women with endometriosis and CPP compared with endometriosis patients who reported no chronic pain.

    Conclusion: Vasoactive intestinal peptide is upregulated in endometriosis patients reporting chronic pain. Increased microvessel density in tissue and peritoneal fluid concentrations of IL‐6 indicate an elevated inflammation in the pelvic microenvironment of these patients.

  • 17.
    Breedh, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Comasco, Erika
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    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.
    Papadopoulos, Fotios C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ekselius: Psychiatry.
    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.
    Hypothalamic-pituitary-adrenal axis responsiveness, startle response, and sensorimotor gating in late pregnancy2019In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 106, p. 1-8Article in journal (Refereed)
    Abstract [en]

    During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual's response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen's d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen's d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen's d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen's d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.

  • 18.
    Bränn, Emma
    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), Reproductive Health. 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.
    Edvinsson, Åsa
    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.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    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.
    Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartumIn: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Article in journal (Refereed)
  • 19.
    Bränn, Emma
    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), Obstetrics and Reproductive Health Research.
    Edvinsson, Åsa
    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.
    Rostedt Punga, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    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.
    Inflammatory and anti-inflammatory markers in plasma: from late pregnancy to early postpartum2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 1863Article in journal (Refereed)
    Abstract [en]

    During pregnancy, the woman's body undergoes tremendous changes in immune system adaptation. The immunological shifts that occur in pregnancy can partially be explained by alterations in hormonal levels. Furthermore, during pregnancy, many autoimmune diseases go into remission, only to flare again in the early postpartum period. Given these important changes in the clinical course of a number of autoimmune disorders, surprisingly little has been done to investigate the inflammatory profile changes across pregnancy and the postpartum period. Thus, the aim of this study was to describe how inflammatory and anti-inflammatory markers change from late pregnancy to the early postpartum period, using a multiplexed assay consisting of both well-known as well as exploratory proteins. Two-hundred-and-ninety women were included in this study and donated a total of 312 blood samples; 198 in late pregnancy (similar to gw38) and 114 in the postpartum period (similar to w8). The plasma blood samples were analyzed for 92 immune system related protein markers using Proseek Multiplex Inflammation I panel, a high-sensitivity assay based on proximity extension assay technology. Fifty-six inflammatory and anti-inflammatory markers were significantly different between pregnancy and the postpartum, of which 50 survived corrections for multiple comparisons. Out of these 50 markers, 41 decreased from pregnancy to postpartum, while the remaining 9 increased in the postpartum period. The top five markers with the greatest decrease in the postpartum period were Leukemia inhibitory factor receptor (LIF-R), Latency-associated peptide Transforming growth factor beta-1 (LAP TGF-beta-1), C-C motif chemokine 28 (CCL28), Oncostatin M (OSM) and Fibroblast growth factor 21 (FGF21). Top three markers that increased in the postpartum period were Tumor necrosis factor ligand superfamily member 11 (TRANCE), Tumor necrosis factor ligand superfamily member 12 (TWEAK), and C-C motif chemokine/Eotaxin (CCL11). This study revealed that the majority of the markers decreased from pregnancy to postpartum, and only a few increased. Several of the top proteins that were higher in pregnancy than postpartum have anti-inflammatory and immune modulatory properties promoting pregnancy progress. These results clearly reflect the tremendous change in the immune system in the pregnancy to postpartum transition.

  • 20.
    Bränn, Emma
    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), Obstetrics and Reproductive Health Research.
    Fransson, Emma
    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. Karolinska Institutet, Stockholm, Sweden..
    White, Richard A
    Norwegian Institute of Public Health, Oslo, Norway.
    Papadopoulos, Fotios C
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Edvinsson, Åsa
    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.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Cunningham, Janet L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    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.
    Inflammatory markers in women with postpartum depressive symptoms2018In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547Article in journal (Refereed)
    Abstract [en]

    Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

  • 21.
    Comasco, Erika
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    de Maeyer, Hanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Vrettou, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    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.
    Olivier, Jocelien D. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Department Neurobiology, Unit Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9712 CP, The Netherlands.
    Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression2019In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 7, p. 3132-3142Article in journal (Refereed)
    Abstract [en]

    Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.

  • 22.
    Eckerdal, Patricia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kollia, Natasa
    Department of Biostatistics, Harokopio University, Athens, Greece.
    Karlsson, Linnea
    Department of Child Psychiatry, Turku University Hospital, Turku, Finland .
    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.
    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.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). 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.
    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.
    Epidural analgesia during Childbirth and Postpartum depressive symptoms: A cohort studyIn: Article in journal (Refereed)
  • 23.
    Edvinsson, Åsa
    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.
    Biological Aspects of Peripartum Depression2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Peripartum depression affects around 12% of women in pregnancy and postpartum, and about 2–3% of European pregnant women use antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). An increased risk of poor pregnancy outcomes has been described in women with antenatal depression and SSRI treatment during pregnancy. The biological mechanisms behind these complications are not fully understood and here we investigated several biological correlates of peripartum depression, and discriminated between the effects of antidepressant treatment and depression itself.

    In Paper I, attentional biases in pregnant and postpartum women were studied by using the Emotional Stroop Task, measuring reaction times to different stimuli. The major finding was shorter reaction times in postpartum depressed women, for emotionally valenced stimuli, which can be interpreted as emotional numbing.

    In Paper II, peripheral inflammatory markers were assessed by proximity extension assay technology in depressed, SSRI-treated and healthy pregnant women. Lower levels of 23 markers were found in women with antenatal depression, independent of treatment, compared with healthy controls. These findings suggest a dysregulated switch to the anti-inflammatory M2 milieu characterizing a normal third trimester.

    In Paper III, normal changes in inflammatory markers across pregnancy and postpartum were assessed in healthy pregnant and postpartum women. The majority (41) of the 50 markers that differed between groups were lower postpartum. These results clearly reflect the change in the immune system in pregnancy to postpartum transition.

    In Paper IV, placental gene and protein expression were investigated and nominally significant findings were noted for serotonin receptor 1A (HTR1A) and neuropeptide Y2 receptor (NPY2R), where women with untreated depression displayed higher gene expression than healthy controls. Protein expression analyses revealed higher levels of HTR1A in placentas from SSRI-treated women, compared with healthy controls and women with untreated depression. This suggests possible involvement of HTR1A in the effect of antenatal depression on the placenta.

    Overall, peripartum depression is associated with altered cognitive-emotional processing, lower levels of several mostly anti-inflammatory markers, and altered placental gene and protein expression. However, we found no major differences between untreated and treated depression.

  • 24.
    Edvinsson, Åsa
    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), Reproductive Health.
    Bränn, Emma
    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. 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.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Freyhult, Eva
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    White, Richard
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Olivier, Jocelien
    Univ Groningen, Groningen Inst Evolutionary Life Sci, Unit Behav Neurosci, Dept Neurobiol, Groningen, Netherlands..
    Bergquist, Jonas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Boström, Adrian E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Cunningham, Janet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lower inflammatory markers in women with antenatal depression brings the M1/M2 balance into focus from a new direction2017In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 80, p. 15-25Article in journal (Refereed)
    Abstract [en]

    Background: Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.

    Methods: 160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.

    Results: Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p = 0.000001, macrophage colony-stimulating factor 1 (CSF-1), p = 0.000004, and fractalkine (CX3CL1), p =0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p = 0.000011, vascular endothelial growth factor A (VEGF-A), p =0.000016, and IL-15 receptor subunit alpha (IL-15RA), p = 0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.

    Conclusion: Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.

  • 25.
    Edvinsson, Åsa
    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), Reproductive Health.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kallak, Theodora Kunovac
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Reproductive Biology in Uppsala (CRU).
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    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.
    Stener-Victorin, Elisabet
    Department of Physiology and Pharmacology, Karolinska Institute.
    Fornes, Romina
    Department of Physiology and Pharmacology, Karolinska Institute.
    Spigset, Olav
    Department of Clinical Pharmacology, St. Olav University Hospital.
    Lager, 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), Obstetrics and Reproductive Health Research.
    Olivier, Jocelien
    Neurobiology, unit Behavioral Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, the Netherlands.
    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.
    The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression studyManuscript (preprint) (Other academic)
  • 26.
    Edvinsson, Åsa
    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), 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.
    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.
    Gingnell, Malin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Ekselius, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Willebrand, Mimmie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala Univ, Dept Neurosci, Psychiat, Uppsala, Sweden..
    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.
    Different patterns of attentional bias in antenatal and postpartum depression2017In: Brain and Behavior, ISSN 2162-3279, E-ISSN 2162-3279, Vol. 7, no 11, article id e00844Article in journal (Refereed)
    Abstract [en]

    BackgroundBiased information processing in attention, memory, and interpretation is proposed to be central cognitive alterations in patients with major depressive disorder, but studies in women with peripartum depression are scarce. Because of the many similarities with depression in nonperipartum states as regards symptom profile and risk factors, we hypothesized that women with antenatal and postpartum depression would display attentional bias to negatively and positively valenced words. MethodsOne hundred and seventy-seven pregnant and 157 postpartum women were included. Among these, 40 suffered from antenatal depressive disorder and 33 from postpartum depressive disorder. An emotional Stroop task with neutral, positive, negative, and negatively valenced obstetric words was used. ResultsNo significant difference in emotional interference scores was noted between women with antenatal depression and nondepressed pregnant women. In contrast, women with postpartum depression displayed shorter reaction times to both positive (p=.028) and negative (p=.022) stimuli, compared with neutral words. Pregnant women on antidepressant treatment displayed longer reaction times to negatively valenced obstetric words in comparison with untreated depressed women (p=.012), and a trend toward greater interference in comparison with controls (p=.061). ConclusionsIn contrast with the hypothesis, we found no evidence of attentional bias to emotionally valenced stimuli in women with untreated peripartum depression. However, the shorter reaction times to emotional stimuli in women with postpartum depression may indicate emotional numbing, which in turn, is a functional impairment that may have repercussions for child development and well-being. Our findings emphasize the need to identify and treat women with postpartum depression at the earliest possible time point to ensure swift recovery and support for the family.

  • 27.
    Elenis, Evangelia
    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), 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.
    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.
    Sydsjö, Gunilla
    Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Obstet & Gynaecol, Linkoping, Sweden..
    Stavreus-Evers, Anneli
    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.
    Åkerud, 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), Reproductive Health.
    HRG C633T polymorphism and risk of gestational hypertensive disorders: a pilot study2018In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 19, article id 44Article in journal (Refereed)
    Abstract [en]

    Background: Preeclampsia and gestational hypertensive disorders are thought to occur due to endothelial cell dysfunction and abnormal placentation, triggered by angiogenesis-related factors yet undetermined. The aim of this study was to investigate whether a genetic polymorphism (SNP) of Histidine-rich glycoprotein (HRG), HRG C633T SNP, is associated with gestational hypertensive disorders.

    Methods: It was performed a nested case-control study from the BASIC Cohort of Uppsala University Hospital comprising 92 women diagnosed with gestational hypertensive disorders without other comorbidities and 200 women with full term uncomplicated pregnancies, all genotyped regarding HRG C633T SNP.

    Results: The genetic analysis of the study sample showed that C/C genotype was more prevalent among controls. The presence of the T-allele showed a tendency towards an increased risk of gestational hypertensive disorders. After clustering the study participants based on their genotype, it was observed that the odds for gestational hypertensive disorders among heterozygous C/T or homozygous T/T carriers were higher compared to homozygous C/C carriers [OR 1.72, 95% CI (1.04-2.84)]. The association remained significant even after adjustment for maternal age, BMI and parity.

    Conclusions: The HRG C633T genotype seems to be associated with gestational hypertensive disorders, and as part of a greater algorithm, might contribute in the future to the prediction of the individual susceptibility to the condition.

  • 28.
    Enroth, Stefan
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Berggrund, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lycke, Maria
    Broberg, John
    Lundberg, Martin
    Assarsson, Erika
    Olovsson, Matts
    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.
    Stålberg, 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), Reproductive Health.
    Sundfeldt, Karin
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    High throughput proteomics identifies a high-accuracy 11 plasma protein biomarker signature for ovarian cancer2019In: Communications biology, ISSN 2399-3642, Vol. 2, article id 221Article in journal (Refereed)
    Abstract [en]

    Ovarian cancer is usually detected at a late stage and the overall 5-year survival is only 30-40%. Additional means for early detection and improved diagnosis are acutely needed. To search for novel biomarkers, we compared circulating plasma levels of 593 proteins in three cohorts of patients with ovarian cancer and benign tumors, using the proximity extension assay (PEA). A combinatorial strategy was developed for identification of different multivariate biomarker signatures. A final model consisting of 11 biomarkers plus age was developed into a multiplex PEA test reporting in absolute concentrations. The final model was evaluated in a fourth independent cohort and has an AUC = 0.94, PPV = 0.92, sensitivity = 0.85 and specificity = 0.93 for detection of ovarian cancer stages I-IV. The novel plasma protein signature could be used to improve the diagnosis of women with adnexal ovarian mass or in screening to identify women that should be referred to specialized examination.

  • 29.
    Enroth, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Berggrund, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lycke, Maria
    Gothenburg Univ, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Lundberg, Martin
    OLINK Prote, Uppsala Sci Pk, S-75183 Uppsala, Sweden.
    Assarsson, Erika
    OLINK Prote, Uppsala Sci Pk, S-75183 Uppsala, Sweden.
    Olovsson, Matts
    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.
    Stålberg, 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), Reproductive Health.
    Sundfeldt, Karin
    Gothenburg Univ, Inst Clin Sci, Sahlgrenska Acad, Dept Obstet & Gynecol, Gothenburg, Sweden.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    A two-step strategy for identification of plasma protein biomarkers for endometrial and ovarian cancer2018In: Clinical Proteomics, ISSN 1542-6416, E-ISSN 1559-0275, Vol. 15, article id 38Article in journal (Refereed)
    Abstract [en]

    Background: Over 500,000 women worldwide are diagnosed with ovarian or endometrial cancer each year. We have used a two-step strategy to identify plasma proteins that could be used to improve the diagnosis of women with an indication of gynecologic tumor and in population screening.

    Methods: In the discovery step we screened 441 proteins in plasma using the proximity extension assay (PEA) and five Olink Multiplex assays (CVD II, CVD III, INF I, ONC II, NEU I) in women with ovarian cancer (n=106), endometrial cancer (n=74), benign ovarian tumors (n=150) and healthy population controls (n=399). Based on the discovery analyses a set of 27 proteins were selected and two focused multiplex PEA assays were developed. In a replication step the focused assays were used to study an independent set of cases with ovarian cancer (n=280), endometrial cancer (n=228), women with benign ovarian tumors (n=76) and healthy controls (n=57).

    Results: In the discovery step, 27 proteins that showed an association to cancer status were identified. In the replication analyses, the focused assays distinguished benign tumors from ovarian cancer stage III-IV with a sensitivity of 0.88 and specificity of 0.92 (AUC=0.92). The assays had a significantly higher AUC for distinguishing benign tumors from late stage ovarian cancer than using CA125 and HE4 (p=9.56e-22). Also, population controls could be distinguished from ovarian cancer stage III-IV with a sensitivity of 0.85 and a specificity of 0.92 (AUC=0.89).

    Conclusion: The PEA assays represent useful tools for identification of new biomarkers for gynecologic cancers. The selected protein assays could be used to distinguish benign tumors from ovarian and endometrial cancer in women diagnosed with an unknown suspicious pelvic mass. The panels could also be used in population screening, for identification of women in need of specialized gynecologic transvaginal ultrasound examination.

  • 30.
    Falconer, Henrik
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Palsdottir, Kolbrun
    Karolinska Inst, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Stålberg, 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), Reproductive Health.
    Dahm-Kähler, Pernilla
    Sahlgrens Acad, Inst Clin Sci, Gothenburg, Sweden.
    Ottander, Ulrika
    Umea Univ, Dept Clin Sci, Med Fak, Umea, Sweden.
    Lundin, Evelyn Serreyn
    Linkopings Univ, Obstet & Gynecol, Linkoping, Sweden;Linkopings Univ, Inst Klin & Expt Med, Linkoping, Sweden.
    Wijk, Lena
    Orebro Univ, Fac Med & Hlth, Orebro, Sweden.
    Kimmig, Rainer
    Univ Hosp Duisburg Essen, Gynecol & Obstet, Essen, Germany.
    Jensen, Pernille Tine
    Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark.
    Eriksson, Ane Gerda Zahl
    Univ Oslo, Gynecol Oncol, Oslo, Norway.
    Mäenpää, Johanna
    Tampere Univ, Fac Med & Med Technol, Tampere, Finland.
    Persson, Jan
    Lund Univ Hosptial, Dept Obstet & Gynecol, Lund, Sweden.
    Salehi, Sahar
    Karolinska Inst, Dept Womens & Childrens Hlth, S-17177 Stockholm, Sweden.
    Robot-assisted approach to cervical cancer (RACC): an international multi-center, open-label randomized controlled trial2019In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 29, no 6, p. 1072-1076Article in journal (Refereed)
    Abstract [en]

    Background: Radical hysterectomy with pelvic lymphadenectomy represents the standard treatment for early-stage cervical cancer. Results from a recent randomized controlled trial demonstrate that minimally invasive surgery is inferior to laparotomy with regards to disease-free and overall survival.

    Primary Objective: To investigate the oncologic safety of robot-assisted surgery for early-stage cervical cancer as compared with standard laparotomy.

    Study Hypothesis: Robot-assisted laparoscopic radical hysterectomy is non-inferior to laparotomy in regards to recurrence-free survival with the advantage of fewer post-operative complications and superior patient-reported outcomes.

    Trial Design: Prospective, multi-institutional, international, open-label randomized clinical trial. Consecutive women with early-stage cervical cancer will be assessed for eligibility and subsequently randomized 1:1 to either robot-assisted laparoscopic surgery or laparotomy. Institutional review board approval will be required from all participating institutions. The trial is coordinated from Karolinska University Hospital, Sweden.

    Major Inclusion/Exclusion Criteria: Women over 18 with cervical cancer FIGO (2018) stages IB1, IB2, and IIA1 squamous, adenocarcinoma, or adenosquamous will be included. Women are not eligible if they have evidence of metastatic disease, serious co-morbidity, or a secondary invasive neoplasm in the past 5 years.

    Primary Endpoint: Recurrence-free survival at 5 years between women who underwent robot-assisted laparoscopic surgery versus laparotomy for early-stage cervical cancer.

    Sample Size: The clinical non-inferiority margin in this study is defined as a 5-year recurrence-free survival not worsened by >7.5%. With an expected recurrence-free survival of 85%, the study needs to observe 127 events with a one-sided level of significance (alpha) of 5% and a power (1-beta) of 80%. With 5 years of recruitment and 3 years of follow-up, the necessary number of events will be reached if the study can recruit a total of 768 patients.

    Estimated Dates for Completing Accrual and Presenting Results: Trial launch is estimated to be May 2019 and the trial is estimated to close in May 2027 with presentation of data shortly thereafter.

  • 31.
    Frida, Viirman
    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.
    Att mäta negativ förlossningsupplevelse: En litteraturstudie2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Giving birth is a momentous event in a woman's life and the experience of childbirth is unique for every woman. A negative birth experience may impair breastfeeding and attachment to the newborn child. It can contribute to postpartum depression and correlation to post-traumatic stress disorder has also been found. Validated instruments for measuring childbirth experience are needed to identify women with negative birth experience in order to be able to offer them adequate help in recovery.

    Aim: To describe quantitative methods for measuring birth experience.

    Method: A literature review based on twelve original scientific articles with a quantitative approach was conducted to fulfill the aim.

    Result: Ten instruments for measuring birth experience quantitatively were found in this literature review. The instruments ranged in size from one to 32 questions and included rating scales where women were asked to rate to what degree they agreed with various statements, alternatively evaluate their overall childbirth experience in one global question. Dimensions of childbirth experience included in the instruments were, among others, professional support, participation, personal control, perceived safety and pain.

    Conclusion: Among the ten instruments, the Swedish Childbirth Experience Questionnaire (CEQ) was deemed to be the most reliable for identifying women in need of follow-up after a negative birth experience.

  • 32.
    Frida, Viirman
    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.
    Negativ förlossningsupplevelse över tid och postpartumdepression: En studie inom Juno-projektet2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Every year, 15,000 women in Sweden are estimated to suffer from postpartum depression. Since this condition affects the relationship with both children and partners, many individuals are affected. There is a relationship with negative birth experience.

    Aim: To investigate whether birth experience estimated during follow-up at the maternity clinic 6 – 8 weeks postpartum differs from birth experience estimated at delivery in women with negative birth experience, and to study what kind of support is offered to women who have symptoms of postpartum depression and negative birth experience.

    Method: The study was a descriptive, longitudinal study (two measurements) using a quantitative methodology. Two hundred and twenty-three women with negative birth experience were included. Birth experience was measured with a Likert scale and symptoms of postpartum depression were measured using the EPDS self-assessment form. Data on documented counseling was retrieved from patient records.

    Result: The main result was that negative birth experience at delivery was significantly less negative in estimation 8-12 weeks postpartum. However, all groups still scored negatively also in the retrospective estimation. There was no correlation between negative birth experience and symptoms of postpartum depression, but the prevalence of such symptoms was significantly higher in this study than in previous cross-sectional studies. Almost all women who had symptoms of postpartum depression during screening at Child Health Care Centrals had received documented counseling.

    Conclusion: It is clinically valuable to follow up all women with negative birth experience as they also have a negative birth experience in postnatal checkup 8-12 weeks postpartum. Several women with symptoms of postpartum depression were not detected at screening by Child Health Care Centers in this study. To address this problem, an extended postpartum follow-up with EPDS screening at the maternity clinic is proposed.

  • 33.
    Gingnell, Malin
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. 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.
    Toffoletto, Simone
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Wikström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Engman, Jonas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Bannbers, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. 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.
    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.
    Emotional anticipation after delivery - a longitudinal neuroimaging study of the postpartum period2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 114Article in journal (Refereed)
    Abstract [en]

    Neuroimaging research has begun to unveil the mechanisms behind emotion processing during the postpartum period, which, in turn, may be of relevance for the development of postpartum depression. The present study sought to longitudinally investigate the neural correlates of emotion anticipation during the postpartum period in healthy women. Functional magnetic resonance imaging was employed to measure the blood oxygen level-dependent signal in the brain in response to anticipation of negative emotional stimuli and during processing of images with positive or negative valence. The participating women were scanned twice: the first scan occurred during the first 48 hours after delivery, and the second was performed 4-6 weeks after delivery. The early postpartum period was characterized by higher anterior cingulate cortex reactivity during anticipation of negative emotional stimuli than the late postpartum period. This was accompanied by a negative relationship with insular reactivity during the early postpartum period and a trend towards an increase in insular reactivity in the late postpartum period. Thus, during the first four weeks of the postpartum period, a diminished top-down regulatory feedback on emotion-related areas of the brain was noted. This finding suggests a physiologically important adaptation during the healthy postpartum period.

  • 34.
    Halldorsdottir, Sandra
    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), Reproductive Health.
    Dahlstrand, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Stålberg, 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), Reproductive Health.
    Gynecologists are afraid of prescribing hormone replacement to endometrial/ovarian cancer survivors despite national guidelines-a survey in Sweden2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 4, p. 225-229Article in journal (Refereed)
    Abstract [en]

    Background: Prolonged survival in ovarian and endometrial cancer patients increases the importance of paying attention to quality of life. Hormone replacement therapy (HRT) after gynecologic cancer has been controversial. With this survey, we sought to describe Swedish gynecologists’ and gynecologic oncologists’ attitudes towards prescribing HRT to these cancer survivors and see if prescribing practice is consistent with the available evidence and national guidelines.

    Material and methods: A web-based survey containing three hypothetical cases with a total of 15 questions was distributed to gynecologists and gynecologic oncologists in Sweden. Respondents were asked about their HRT prescription practices in endometrial/ovarian cancer patients with moderate to severe menopausal symptoms.

    Results: In total 262 gynecologists and 24 gynecologic oncologists answered the survey. In the low-risk endometrial cancer case a majority of the gynecologists (55%) and gynecologic oncologists (66.7%) would prescribe local estrogen. A total of 30% of the gynecologists would prescribe estrogen replacement therapy (ERT) in the high-risk endometrial cancer case compared to 58.3% of the gynecologic oncologists. The gynecologic oncologists felt more comfortable treating patients with endometrial cancer than did gynecologists, and the gynecologists were more likely to read the national guidelines. In the ovarian cancer case, 63.7% of the gynecologists would prescribe HRT compared to 92% of the gynecologic oncologists.

    Conclusion: Swedish gynecologic oncologists have a more favorable attitude towards HRT for endometrial/ovarian cancer patients and feel more comfortable treating their patients than do gynecologists. This study illustrates a need for education in these matters in order not to withhold HRT from women due to doctors’ sometimes unjustified anxiety.

  • 35.
    Hastie, Roxanne
    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. Mercy Hosp Women, Mercy Perinatal, Melbourne, Vic, Australia;Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic, Australia.
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, 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 & Gynaecol, Cape Town, South Africa.
    Cluver, Catherin A.
    Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic, Australia;Stellenbosch Univ, Dept Obstet & Gynaecol, Cape Town, South Africa.
    Wikman, Anna
    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.
    Hannan, Natalie J.
    Mercy Hosp Women, Mercy Perinatal, Melbourne, Vic, Australia;Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic, Australia.
    Walker, Susan P.
    Mercy Hosp Women, Mercy Perinatal, Melbourne, Vic, Australia.
    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.
    Tong, Stephen
    Mercy Hosp Women, Mercy Perinatal, Melbourne, Vic, Australia;Univ Melbourne, Dept Obstet & Gynaecol, Translat Obstet Grp, Heidelberg, Vic, Australia.
    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.
    Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women A Swedish Population Register-Based Cohort Study2019In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 73, no 5, p. 1097-1103Article in journal (Refereed)
    Abstract [en]

    Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia. The aim of this study was to determine the association between PPI use during pregnancy and preeclampsia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preeclampsia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preeclampsia (aOR of 1.17; 95% CI, 1.04-1.32) and preeclampsia at term (aOR of 1.20; 95% CI, 1.04-1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery <37 weeks) preeclampsia (aOR of 0.63; 95% CI, 0.41-0.96) and early (delivery <34 weeks) preeclampsia (aOR of 0.41; 95% CI, 0.20-0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preeclampsia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preeclampsia may help prevent this severe form of disease.

  • 36.
    Hellstadius, Ylva
    et al.
    Department of Molecular Medicine and Surgery, Surgical Care Science, Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Lagergren, Jesper
    Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cancer Studies, King’s College London, London, UK; Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    Zylstra, Janine
    Division of Cancer Studies, King’s College London, London, UK; Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    Gossage, James
    Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cancer Studies, King’s College London, London, UK; Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    Davis, Andrew
    Department of Molecular Medicine and Surgery, Upper Gastrointestinal Surgery, Karolinska Institutet, Stockholm, Sweden; Division of Cancer Studies, King’s College London, London, UK; Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    M Hultman, Christina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lagergren, Pernilla
    Department of Molecular Medicine and Surgery, Surgical Care Science, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Division of Cancer Studies, King’s College London, London, UK.
    Wikman, Anna
    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.
    A longitudinal assessment of psychological distress after oesophageal cancer surgery2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 5, p. 746-752Article in journal (Refereed)
    Abstract [en]

    Background: Psychological distress is common among patients with oesophageal cancer. However, little is known about the course and predictors of psychological distress among patients treated with curative intent. Therefore, the aim of this study was to explore the prevalence, course and predictors of anxiety and depression in patients operated for oesophageal cancer, from prior to surgery to 12 months post-operatively. Methods: A prospective cohort of patients with oesophageal cancer (n ¼ 218) were recruited from one high-volume specialist oesophago-gastric treatment centre (St Thomas’ Hospital, London, UK). Anxiety and depression were assessed prior to surgery, 6 and 12 months post-operatively. Mixed-effects modelling was performed to investigate changes over time and to estimate the association between clinical and socio-demographic predictor variables and anxiety and depression symptoms. Results: The proportion of patients with anxiety was 33% prior to surgery, 28% at 6 months, and 37% at 12 months. Prior to surgery, 20% reported depression, 27% at 6 months, and 32% at 12-month follow-up. Anxiety symptoms remained stable over time whereas depression symptoms appeared to increase from pre-surgery to 6 months, levelling off between 6 and 12 months. Younger age, female sex, living alone and more severe self-reported dysphagia (i.e., difficulty swallowing) predicted higher anxiety symptoms. In-hospital complications, greater limitations in activity status and more severe selfreported dysphagia were predictive of higher depression. Conclusions: Many patients report psychological distress during the first year following oesophageal cancer surgery. Whether improving the experience of swallowing difficulties may also reduce distress among these patients warrants further study.

  • 37.
    Henriksson, Hanna E.
    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), Obstetrics and Reproductive Health Research.
    Malavaki, Christina
    Metabolic Engineering & Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece.
    Bränn, Emma
    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.
    Drainas, Vasilis
    Metabolic Engineering & Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece; Department of Chemical Engineering, University of Patras, Patras, Greece .
    Lager, 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), Obstetrics and Reproductive Health Research.
    Iliadis, Stavros I
    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.
    Papadopoulos, Fotios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    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.
    Chrousos, George P.
    First Department of Pediatrics, Athens University Medical School, Athens, Greece.
    Klapa, Maria I.
    Metabolic Engineering & Systems Biology Laboratory, Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece.
    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.
    Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms2019In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 9, article id 204Article in journal (Refereed)
    Abstract [en]

    Antenatal depression affects similar to 9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.

  • 38.
    Henriksson, Hanna E.
    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), Obstetric research.
    Sylvén, Sara M
    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), Obstetric research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Kallak, Theodora Kunovac
    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.
    Papadopoulos, Fotios
    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), Obstetric research.
    Seasonal patterns in self-reported peripartum depressive symptoms2017In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 43, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background: In the peripartum period, the literature on seasonality in depression is still scarce and studies present varying findings. The aims of this study were to investigate whether seasonal patterns in postpartum depressive symptoms previously identified in a Swedish study could be replicated in a larger study, as well as to assess seasonal patterns in depressive symptoms during pregnancy.

    Methods: This was a nested case-control study comprised of 4129 women who participated in the BASIC project and gave birth at Uppsala University Hospital, Uppsala, Sweden, between February 2010 and December 2015.

    Results: Women who gave birth in October-December 2011 had an increased odds of depressive symptoms at 6 weeks postpartum, when compared with women giving birth in April-June 2011 (aOR = 2.42; 95% CI: 1.12-5.26). The same pattern was found among women with a history of depression. No other seasonal patterns for depressive symptoms during pregnancy or at 6 weeks postpartum were identified.

    Conclusions: In general, no consistent seasonal patterns were found in peripartum depressive symptoms. Whether the seasonal patterns found in some studies during certain years may be due to other factors relating to specific years and seasons, such as extreme climatic conditions or other particular events, warrants further investigation.

  • 39.
    Henriksson, Hanna E.
    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), Obstetrics and Reproductive Health Research.
    White, Richard A.
    Norwegian Institute of Public Health, Oslo, Norway.
    Iliadis, Stavros I.
    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.
    Fransson, Emma
    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. Karolinska Institutet, Stockholm, Sweden.
    Papadopoulos, Fotios
    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 Medical Sciences.
    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.
    Spring peaks and autumn troughs identified in peripheral inflammatory markers during the peripartum periodIn: Article in journal (Refereed)
  • 40.
    Hesselman, Susanne
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    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.
    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.
    Wikman, Anna
    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.
    Neighborhood deprivation and adverse perinatal outcomes in Sweden: A population-based register study2019In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 8, p. 1004-1013Article in journal (Refereed)
    Abstract [en]

    Introduction: Neighborhood deprivation has been associated with adverse perinatal outcomes but it is unclear to what extent maternal and social risk factors explain the association and how a stressful environment per se contributes.

    Material and methods: A population-based register study including 218 030 deliveries in Sweden between January 2013 and July 2017 was conducted. Exposure was living in a deprived or severely deprived area defined by the National Operations Department of the Swedish Police Authority. Adverse perinatal outcomes included preterm births, small-for-gestational-age births and stillbirths. A propensity score-based method was used to control for individual baseline characteristics. Associations were investigated with logistic regression analyses and risk estimates are presented as crude (OR) and adjusted odds ratio (aOR) with 95% confidence interval (CI).

    Results: Living in a deprived neighborhood in Sweden was associated with extremely preterm births (deprived area OR 1.50, 95% CI 1.07-2.11, severely deprived OR 1.90, 95% CI 1.40-2.58), small-for-gestational-age birth (deprived OR 1.45, 95% CI 1.31-1.60, severely deprived OR 1.85, 95% CI 1.69-2.03) and stillbirth (deprived OR 1.62, 95% CI 1.17-2.26, severely deprived OR 1.56, 95% CI 1.11-2.19). After accounting for individual maternal and social risk factors, the risk of small for gestational age in severely deprived areas remained (aOR 1.45, 95% CI, 1.19-1.75).

    Conclusions: The contextual effect of living in a deprived neighborhood on the risk of extremely preterm births, small-for-gestational-age births and stillbirths was to a high extent explained by individual factors of women residing in exposed areas, yet remained for small-for-gestational-age births in severely deprived areas after adjustment for maternal and social risk factors.

  • 41.
    Hjerpe, Elisabet
    et al.
    Karolinska Univ Hosp, Dept Pathol & Oncol, Stockholm.; Karolinska Inst, Dept Oncol & Pathol, Stockholm.
    Staf, Christian
    Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, Gothenburg.
    Dahm-Kähler, Pernilla
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg.
    Stålberg, 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), Reproductive Health.
    Bjurberg, Maria
    Skåne Univ Hosp, Dept Hematol Oncol & Radiat Phys, Lund.; Lund Univ, Dept Clin Sci, Lund.
    Holmberg, Erik
    Sahlgrens Univ Hosp, Reg Canc Ctr Western Sweden, Gothenburg.; Sahlgrens Acad, Inst Clin Sci, Gothenburg.
    Borgfeldt, Christer
    Skåne Univ Hosp, Dept Obstet & Gynecol, Lund.; Lund Univ, Lund.
    Tholander, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Hellman, Kristina
    Karolinska Univ Hosp, Dept Pathol & Oncol, Stockholm.; Karolinska Inst, Dept Oncol & Pathol, Stockholm.
    Kjølhede, Preben
    Linköping Univ Hosp, Dept Obstet & Gynecol, Linköping.; Linköping Univ, Dept Clin & Expt Med, Linköping.
    Högberg, Thomas
    Lund Univ, Dept Canc Epidemiol, Lund.
    Rosenberg, Per
    Linköping Univ, Dept Clin & Expt Med, Linköping.; Linköping Univ, Dept Clin Oncol, Linköping.
    Åvall-Lundqvist, Elisabeth
    Karolinska Inst, Dept Oncol & Pathol, Stockholm; Linköping Univ, Dept Clin & Expt Med, Linköping.; Linköping Univ, Dept Clin Oncol, Linköping.
    Lymph node metastases as only qualifier for stage IV serous ovarian cancer confers longer survival than other sites of distant disease - a Swedish Gynecologic Cancer Group (SweGCG) study2018In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 3, p. 331-337Article in journal (Refereed)
    Abstract [en]

    Background: The International Federation of Gynecology and Obstetrics (FIGO) ovarian cancer staging system includes no sub-stage for lymph nodes (LN) as only distant disease manifestation. We explore the prognostic implication of LN as only stage IV classifier in serous ovarian cancer.

    Method: This is a nation-wide, population-based study on 551 women with serous stage IV cancers diagnosed between 2009–2014. We compare overall survival (OS) in women with LN as only distant metastatic site to those with pleural metastases only and to patients with other/multiple stage IV manifestations. Cox regression models were used for uni- and multivariable estimations.

    Results: Of 551stage IV cases, distant metastatic site was registered in 433. Median OS for women with LN (n = 51) was 41.4 months, compared to 25.2 and 26.8 months for patients with pleural (n = 195) or other/multiple (n = 187) distant metastases (p = .0007). The corresponding five-year survival rates were 32, 11 and 22%, respectively. Multivariable analyzes confirmed shorter survival for women with pleural (HR 2.99, p = .001) or other/multiple distant sites (HR 2.67, p = .007), as compared to LN cases. LN only patients lived 9.1 months longer after primary than after interval surgery, but this difference was not significant (p = .245).

    Conclusion: Women with stage IV serous ovarian cancer having lymph nodes as only distant metastatic site live longer than other stage IV patients.

  • 42.
    Husseini-Akram, Frida
    et al.
    Karolinska Inst, Danderyds Hosp, Div Obstet & Gynaecol, Dept Clin Sci, Stockholm, Sweden.
    Haroun, Sally
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Altmae, Signe
    Competence Ctr Hlth Technol, Tartu, Estonia;Univ Granada, Dept Biochem & Mol Biol, Fac Sci, Granada, Spain.
    Skjoldebrand-Sparre, Lottie
    Karolinska Inst, Danderyds Hosp, Div Obstet & Gynaecol, Dept Clin Sci, Stockholm, Sweden.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    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.
    Landgren, Britt-Marie
    Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
    Stavreus-Evers, Anneli
    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.
    Hyaluronan-binding protein 2 (HABP2) gene variation in women with recurrent miscarriage2018In: BMC Women's Health, ISSN 1472-6874, E-ISSN 1472-6874, Vol. 18, article id 143Article in journal (Refereed)
    Abstract [en]

    Background:

    Idiopathic recurrent miscarriage, defined as three or more consecutive miscarriages, is a distressing early pregnancy complication. Although, the etiology of recurrent miscarriage is still unknown, an aberrant regulation of the endometrial receptivity marker hyaluronan-binding protein 2 (HABP2) has been suggested. The objective of the present study was to investigate the effect of genetic variations of HABP2 in women with idiopathic recurrent miscarriage compared to fertile women.

    Methods:

    This study was designed as a case-control study. In total, 165 women who had three or more consecutive miscarriages and 289 fertile women were included in the study. Polymorphisms in the HABP2 gene were analyzed using TaqMan SNP Genotyping Assays. Three polymorphisms in the HABP2 gene, rs1157916, rs2240879 and rs7080536 (Marburg I) were studied.

    Results:

    Polymorphism in HABP2 showed no significant difference in women with recurrent miscarriage compared to fertile women, except for rs1157916 minor A allele that was more prevalent among RM patients (p = 0.058). Significantly higher live birth rate was observed among women with three to four miscarriages compared to those with more miscarriages (p = 0.001).

    Conclusions:

    Variations in the HABP2 gene did not seem to be involved in the etiology of recurrent miscarriage, while, the number of previous miscarriages had an impact on the live birth rate.

  • 43.
    Jansson, Caroline
    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), Reproductive biology.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Huffman, Carolyn
    College of Health Sciences, Appalachian State University, USA.
    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.
    Swanson, Kristen M
    School of Nursing, Seattle University, Seattle, WA, USA.
    Stavreus-Evers, Anneli
    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.
    Validation of the Revised Impact of Miscarriage Scale for Swedish conditions and comparison between Swedish and American couples' experiences after miscarriage2017In: European journal of contraception & reproductive health care, ISSN 1362-5187, E-ISSN 1473-0782, Vol. 22, no 6, p. 412-417Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is a lack of knowledge in women's and men's experience of miscarriage. The Revised Impact of Miscarriage Scale (RIMS) has been used in United States to measure the experiences after miscarriage. The first objective was to test the consistency of RIMS for Swedish conditions. The second purpose of this study was to compare Swedish and American couples' experience of miscarriage by use of the RIMS.

    METHODS: Forward and back translation was used for translating RIMS into Swedish. This is a hospital-based comparative study including Swedish couples (n = 70) and American couples (n = 70). The couples were matched by the women's age, week of miscarriage and number of children. All participants answered socio-demographic, fertility and depression-scale questions in addition to RIMS.

    RESULTS: Cronbach's alpha analysis was above 0.650, the mean value was 0.824. There was no significant difference between the Swedish and American participants on the factors 'Isolation/Guilt' and 'Devastating event', but the Swedish women and men scored significantly lower on the factor 'Loss of baby' than the American women and men. The men, Swedish and American combined, scored lower than the women in all factors but the correlation within the couples was similar for both Swedish and American couples.

    CONCLUSIONS: The high consistency between the countries suggests that the RIMS questionnaire is reliable for both women and men to be used in both countries and two of three factors were similar between the two countries.

  • 44.
    Jha, Paridhi
    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), Reproductive Health. Fdn Res Hlth Syst, Bengaluru, Karnataka, India.
    Larsson, Margareta
    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.
    Christensson, Kyllike
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.
    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.
    Evaluation of the psychometric properties of Hindi-translated Scale for Measuring Maternal Satisfaction among postnatal women in Chhattisgarh, India2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211364Article in journal (Refereed)
    Abstract [en]

    Satisfaction with childbirth services is a multi-dimensional phenomenon, providing relevant insights into women's opinion on quality of services received. Research studies report a dearth of standardised scales that quantify this phenomenon; and none have been tested in India to the best of authors' knowledge. The current study was undertaken to evaluate psychometric properties of Hindi version of the Turkish Scale for Measuring Maternal Satisfaction: Normal and Caesarean Births versions in order to fill this gap. A cross-sectional survey was conducted in selected public health facilities in Chhattisgarh, India. Healthy women (n = 1004) who gave birth to a single, live neonate, vaginally or via Caesarean section participated. Psychometric assessment was carried out in four steps: 1) scales translated from Turkish to Hindi; 2) Content Validity Index scores calculated for Hindi scales; 3) data collection; 4) statistical analyses for Hindi scales (Normal and Caesarean Birth).

    A 10-factor model with 36 items emerged for both scales. The Hindi- translated Normal Birth and Caesarean Birth scales had good internal reliability (Cronbach’s α coefficients of 0.85 and 0.80, respectively).

    The Hindi Scales for Measuring Maternal Satisfaction (Normal and Caesarean Birth) are valid and reliable tools for utilization in Indian health facilities. Their multi-dimensional nature presents an opportunity for the care providers and health administrators to incorporate women's opinions in intervention to improve quality of childbirth services. Having an international tool validated within India also provides a platform for comparing cross-country findings.

  • 45.
    Jonsdottir, Björg
    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), Reproductive Health.
    Ripoll, Montserrat Alemany
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Bergman, Antonina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Silins, Ilvars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    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.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Stålberg, 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), Reproductive Health.
    Comparison Of Pet-Mri And Mri Alone Predicting Carcinomatosis In Ovarian Cancer Using Peritoneal Cancer Index (Pci)2017In: International Journal of Gynecological Cancer, ISSN 1048-891X, E-ISSN 1525-1438, Vol. 27, no Supplement: 4, p. 300-301Article in journal (Other academic)
  • 46.
    Kallak, Theodora Kunovac
    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), Reproductive Health.
    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.
    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.
    Sandelin-Francke, Lotta
    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.
    Ubhayasekera, Kumari
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). 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.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Campbell, Rebecca E
    Centre for Neuroendocrinology, Department of Physiology, University of Otago School of Medical Sciences, Dunedin, New Zealand.
    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.
    Maternal and female fetal testosterone levels are associated with maternal age and gestational weight gain2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, no 4, p. 379-388Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Prenatal androgen exposure has been suggested to play a role in polycystic ovary syndrome. Given the limited information on what maternal characteristics influence maternal testosterone levels, and the even less explored routes by which female fetus androgen exposure would occur, the aim of this study was to investigate the impact of maternal age, BMI, weight gain, depressed mood and aromatase SNPs on testosterone levels in maternal serum and amniotic fluid of female fetuses.

    METHODS: Blood samples from pregnant women (n = 216) obtained in gestational weeks 35-39, and pre-labor amniotic fluid samples from female fetuses (n = 56), taken at planned Caesarean section or in conjunction with amniotomy for induction of labor, were analyzed. Maternal serum testosterone and amniotic fluid testosterone and cortisol were measured by tandem mass spectrometry.

    RESULTS: Multiparity (β = -0.28, P < 0.001), self-rated depression (β = 0.26, P < 0.001) and weight gain (β = 0.18, P < 0.05) were independent explanatory factors for the maternal total testosterone levels. Maternal age (β = -0.34, P < 0.001), weight gain (β = 0.19, P < 0.05) and amniotic fluid cortisol levels (β = 0.44, P < 0.001) were independent explanatory factors of amniotic fluid testosterone in female fetuses, explaining 64.3% of the variability in amniotic fluid testosterone.

    WIDER IMPLICATIONS OF THE FINDINGS: Young maternal age and excessive maternal weight gain may increase the prenatal androgen exposure of female fetuses. Further studies are needed to explore this finding.

  • 47.
    Larsson, Birgitta
    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), Obstetrics and Reproductive Health Research. Sundsvall Hosp, Res & Dev Ctr, S-84653 Sundsvall, Sweden.
    Karlström, Annika
    Mid Sweden Univ, Dept Nursing Sci, S-85170 Sundsvall, Sweden.
    Rubertsson, Christine
    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.
    Ternström, Elin
    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.
    Ekdahl, Johanna
    Mid Sweden Univ, Dept Psychol, S-83125 Ostersund, Sweden.
    Segebladh, Birgitta
    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.
    Hildingsson, Ingegerd
    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. Mid Sweden Univ, Dept Nursing Sci, S-85170 Sundsvall, Sweden.
    Birth preference in women undergoing treatment for childbirth fear: A randomised controlled trial2017In: Women and Birth, ISSN 1871-5192, E-ISSN 1878-1799, Vol. 30, no 6, p. 460-467Article in journal (Refereed)
    Abstract [en]

    Background: Childbirth fear is the most common underlying reason for requesting a caesarean section without medical reason.  The aim of this randomised controlled study was to investigate birth preferences in women undergoing treatment for childbirth fear, and to investigate birth experience and satisfaction with the allocated treatment.

    Methods: Pregnant women classified with childbirth fear (≥60 on the Fear Of Birth Scale) (n=258) were recruited at one university hospital and two regional hospitals over one year.  The participants were randomised (1:1) to intervention (Internet-based Cognitive Behaviour Therapy (ICBT)) (n=127) or standard care (face-to-face counselling) (n=131). Data were collected by questionnaires in pregnancy week 20-25 (baseline), week 36 and two months after birth.

    Results: Caesarean section preference decreased from 34% to 12% in the ICBT group and from 24% to 20% in the counselling group. Two months after birth, the preference for caesarean increased to 20% in the ICBT group and to 29% in the counselling group, and there was no statistically significant change over time. Women in the ICBT group were less satisfied with the treatment (OR 4.5). The treatment had no impact on or worsened their childbirth fear (OR 5.5). There were no differences between the groups regarding birth experience.

    Conclusion: Women’s birth preferences fluctuated over the course of pregnancy and after birth regardless of treatment method. Women felt their fear was reduced and were more satisfied with face-to-face counselling compared to ICBT. A higher percentage were lost to follow-up in ICBT group suggesting a need for further research.  

  • 48.
    Lindgren, Karin Elvine
    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), Reproductive Health.
    Yaldir, Fatma Gulen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hreinsson, Julius
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Univ Hosp, Karolinska Inst, Dept Clin Sci Intervent & Technol, SE-14186 Stockholm, Sweden;Karolinska Univ Hosp, Unit Reprod Med, SE-14186 Stockholm, Sweden.
    Holte, Jan
    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. Carl von Linne Clin, SE-75183 Uppsala, Sweden.
    Kårehed, 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), 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.
    Kaihola, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Differences in secretome in culture media when comparing blastocysts and arrested embryos using multiplex proximity assay2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 3, p. 143-152Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this study was to assess different patterns of the human embryo secretome analysed as protein levels in culture media. Furthermore, analyses to correlate protein levels with quality and timing to development of human embryos were performed.

    Material and methods: Human day-2 cryopreserved embryos were cultured for four days in an EmbryoScope((R)) with a time-lapse camera, and embryo quality was evaluated retrospectively. After culture, the media were collected and relative levels of secreted proteins were analysed using Proseek Multiplex Assays. Protein levels were evaluated in relation to timing to development and the ability to form a blastocyst.

    Results: Specific patterns of timing of development of blastocysts were found, where a difference in time to start of cavitation was found between high- and low-quality blastocysts. There appeared to be a correlation between specific protein patterns and successful formation of morulae and blastocysts. Embryos developing into blastocysts had higher levels of EMMPRIN than arrested embryos, and levels of caspase-3 were lower in high- versus low-quality blastocysts. Also, higher levels of VEGF-A, IL-6, and EMMPRIN correlated with shorter times to morula formation.

    Conclusions: The secretome and timing to development differ in embryos forming blastocysts and those that become arrested, and in high- versus low-quality blastocysts. The levels of certain proteins also correlate to specific times to development.

  • 49.
    Lingaiah, Shilpa
    et al.
    Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Morin-Papunen, Laure
    Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Piltonen, Terhi
    Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Puurunen, Johanna
    Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    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.
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Bloigu, Risto
    Univ Oulu, Med Informat & Stat Res Grp, Oulu, Finland..
    Risteli, Juha
    Oulu Univ Hosp, Dept Clin Chem, Oulu, Finland..
    Tapanainen, Juha S.
    Oulu Univ Hosp, Dept Obstet & Gynaecol, PEDEGO Res Unit, Med Res Ctr, Oulu, Finland.;Univ Oulu, Oulu, Finland.;Univ Helsinki, Dept Obstet & Gynaecol, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland..
    Bone markers in polycystic ovary syndrome: A multicentre study2017In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 87, no 6, p. 673-679Article in journal (Refereed)
    Abstract [en]

    Objective: Hyperandrogenism, hyperinsulinaemia and obesity, known characteristics of polycystic ovary syndrome (PCOS), may influence bone mineral density and biochemical markers of bone turnover (BTMs) can provide a noninvasive assessment of bone turnover. To this end, the serum concentrations of BTMs and 25-hydroxyvitamin D (25OHD) were analysed in women with PCOS, and their possible associations with metabolic parameters of PCOS were determined.

    Subjects and methods: Bone formation markers procollagen type I amino-terminal propeptide (PINP) and osteocalcin (OC), and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX), along with 25OHD, were measured in 298 women with PCOS and 194 healthy controls.

    Results: Serum levels of PINP (47.020.2 vs 58.1 +/- 28.6g/L, P<.001) and OC (18.2 +/- 7.5 vs 20.6 +/- 9.8g/L, P<.001) were decreased in women with PCOS compared with controls, whereas no significant differences were found in CTX and 25OHD levels. Age-stratified analyses suggested that PINP (50.5 +/- 21.7 vs 68.2 +/- 26.6g/L, P<.001) and OC levels (20.4 +/- 7.6 vs 25.5 +/- 9.6g/L, P<.001) were decreased only in the younger age group (30years) women with PCOS compared with controls. The formation markers and resorption marker decreased with age in both study groups.

    Conclusions: Bone formation markers were decreased in younger women with PCOS when compared with healthy women, which may affect bone mass in these women.

  • 50.
    Lingaiah, Shilpa
    et al.
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Morin-Papunen, Laure
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Piltonen, Terhi
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    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.
    Stener-Victorin, Elisabet
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Tapanainen, Juha S.
    Univ Oulu, Med Res Ctr, PEDEGO Res Unit, Dept Obstet & Gynaecol, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland;Univ Helsinki, Dept Obstet & Gynaecol, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Serum retinol-binding protein 4 levels in polycystic ovary syndrome2019In: Endocrine Connections, ISSN 2049-3614, E-ISSN 2049-3614, Vol. 8, no 6, p. 709-717Article in journal (Refereed)
    Abstract [en]

    Objective: Serum levels of retinol-binding protein 4 (RBP4), an adipokine thought to affect systemic insulin sensitivity, were compared between women with polycystic ovary syndrome (PCOS) and non-PCOS controls to evaluate the association of RBP4 with clinical, hormonal and metabolic parameters of PCOS. Subjects and methods: Serum RBP4 levels were analysed in 278 women with PCOS (age range 18-57 years) and 191 non-PCOS controls (age 20-53 years) by enzyme-linked immunosorbent assay. Results: Serum levels of RBP4 were increased in women with PCOS compared with control women in the whole population (45.1 +/- 24.0 (S.D.) vs 33.5 +/- 18.3 mg/L, P < 0.001). Age-stratified analysis showed that serum RBP4 levels were increased in women with PCOS aged <= 30 years compared with controls (47.7 +/- 23.5 vs 27.1 +/- 10.4 mg/L, P < 0.001), whereas no significant differences were seen in the other age groups. No significant correlations of RBP4 were seen with either steroids or indices of insulin resistance. Conclusions: Although serum RBP4 levels were increased in younger women with PCOS compared with age-matched non-PCOS controls, RBP4 does not seem to be a good marker of insulin resistance or other metabolic derangements in women with PCOS.

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