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  • 1.
    Akram, Frida Hosseini
    et al.
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Johansson, Bengt
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Mollerstrom, Gunnar
    Oxback Clin, Sodertalje, Sweden..
    Landgren, Britt-Marie
    Karolinska Inst, CLINTEC, 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.
    Skjoldebrand-Sparre, Lottie
    Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy2017In: Journal of Women's Health, ISSN 1540-9996, E-ISSN 1931-843X, Vol. 26, no 11, p. 1231-1235Article in journal (Refereed)
    Abstract [en]

    Background: Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy.

    Materials and Methods: In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n=611), one low-risk group comprising women without risk factors for thyroid disorder (n=511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n=88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed.

    Results: The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p=0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0mIU/L.

    Conclusions: High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since approximate to 10% of women with SCH or hypothyroidism could not be diagnosed in this way.

  • 2.
    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.

  • 3.
    Dommett, Emilie
    et al.
    Univ Cambridge, Cambridge, England..
    Colleoni, Francesca
    Univ Cambridge, Cambridge, England..
    Kingdom, John
    Univ Toronto, Toronto, ON, Canada..
    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.
    Murray, Andrew
    Univ Cambridge, Cambridge, England..
    Burton, Graham
    Univ Cambridge, Cambridge, England..
    Yung, Hong Wa
    Univ Cambridge, Cambridge, England..
    Reduced Mitochondrial Respiration In Placentas From Early Onset Pre-Eclampsia: Potential Roles Of The Mitochondrial Unfolded Protein Response2017In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 57, p. 274-275Article in journal (Other academic)
  • 4.
    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.

  • 5.
    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.

  • 6.
    Gustafsson, Felicia
    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.
    Correlations between anthropometricmeasurements, fasting-insulin andrespiratory quotent in obese children2015Independent thesis Basic level (professional degree), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The number of obese children has increased with almost 100 % in a few decades. Deceases like insulin-resistance and type-2 diabetes often comes with overweight and worldwide research to prevent and cure these complications is constantly approaching. This study provides with greater knowledge of what correlations there are between anthropometric measurements, insulin resistance and respiratory quotient.For this study, data from 83 children and teenagers was included. The medical records from their first visit to the pediatric science unit at Uppsala University Hospital was used. To measure basal metabolic rate (BMR), indirect respiratory calorimetrics was used to measure the respiratory ratio at rest and fasting (RQ-BMR), and blood samples were collected to analyze fs-(fasting) insulin. The anthropometric measurements that were taken were waist, waist-height-ratio (WtHR), waist-hip ratio (WHR), waist-hip-height ratio (WHtR), waist circumference (AC), waist circumference-height ratio (ACHR), sagittal abdominal diameter (SAD) and Sagittal abdominal diameter-height ratio (SADHR).Correlations between fs-insulin and WHtR, WCHR, SAD and SADHR was found for the whole group of participators in this study. The strongest correlation was to WHtR for boys and SAD for girls. The RQ-BMR correlated the best with SADHR and ACHR. No correlations between RQ-BMR were found specifically for boys or girls.

  • 7.
    Gustavsson, Inger M.
    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.
    Aarnio, Riina
    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.
    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.
    Lindberg, Julia Hedlund
    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.
    Sanner, 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 biology.
    Wikström, Ingrid
    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.
    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.
    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 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.
    Randomised study of HPV prevalence and detection of CIN2+ in vaginal self-sampling compared to cervical specimens collected by medical personnel.2019In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 1, p. 89-97Article in journal (Refereed)
    Abstract [en]

    We conducted a randomised study to compare vaginal self-sampling with assisted sampling by medical personnel on the cervix for HPV testing in primary screening. The first aim was to determine if the HPV prevalence is independent of sampling location (vagina versus cervix) and the person performing the sampling. The second aim was to evaluate if the two sampling strategies differed in the detection rate of CIN2+. In total, 19,523 women were randomised into two groups, with 9926 invited to perform self-sampling (SS arm) using the Rover VIBA-brush and 9597 offered assisted sampling using the cytobrush (AS arm). All samples were applied to the indicating FTA elute card and analysed for high-risk HPV using the hpVIR real-time PCR assay. The outcome for the first aim was HPV prevalence and for the second aim the number of CIN2+ based on histology. In the SS arm, 52.7% of invited women participated in the study, as compared to 34.2% in the AS arm. All samples contained sufficient amount of nuclear DNA for a valid HPV result, with vaginal samples having a higher DNA amount than cervical samples (p < 4.62 × 10-11 ). HPV prevalence was 4.6% in the SS arm and 4.1% in the AS arm (p = 5.5 × 10-2 ), and the distribution of HPV types similar between arms. There was no difference in the prevalence of CIN2+ per 1000 women screened between arms (p = 0.86). The results show that vaginal self-sampling is an equivalent alternative to sampling by medical personnel for HPV typing and identification of CIN2+.

  • 8.
    Hermansson, Ruth S.
    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. Orebro Univ, Fac Med & Hlth, Dept Oncol, Orebro, 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.
    Hoxell, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Lindström, Annika K
    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, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna. Orebro Univ, Fac Med & Hlth, Clin Res Ctr, Orebro, Sweden..
    HPV prevalence and HPV-related dysplasia in elderly women2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0189300Article in journal (Refereed)
    Abstract [en]

    Introduction: In Sweden, where screening ends at the age of 60, about 30% of the cervical cancer cases occur in women older than 60. The aim of the present study was to investigate the prevalence of HPV and cervical dysplasia in women of 60 years and above.

    Patients and methods: From September 2013 until June 2015, 1051 women aged 60-89 years (mean 68 years) were sampled for an HPV test when attending an outpatient gynecology clinic. Women with positive results had a second HPV test and liquid based cytology (LBC), after 3.5 months on average. Those with a positive second HPV test were examined by colposcopy, and biopsy and a sample for LBC was obtained.

    Results: The prevalence of HPV was 4.1%, (95% CI 3.0-5.5, n = 43) at the first test, and at the second test 2.6% remained positive (95% CI 1.7-3.8, n = 27). The majority of women positive in both HPV tests, had dysplasia in histology, 81.5% (22/27) (4 CIN 2-0.4%, 18 CIN 1-1.7%). HPV-related dysplasia was found in 2.1%, (95% CI 1.3-3.2,n = 22) of the 1051 women. Four of the 22 women with positive HPV tests also had abnormal cytology, one ASCUS and three CIN 1. No cancer or glandular dysplasia was detected.

    Conclusion: A significant proportion of elderly women were found to have a persistent cervical HPV infection. Among them there was a high prevalence of CIN diagnosed by histology. The HPV test showed high sensitivity and specificity in detecting CIN in elderly women, while cytology showed extremely low sensitivity.

  • 9.
    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.

  • 10.
    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.

  • 11.
    Junus, Katja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Majali-Martinez, Alejandro
    Department of Obstetrics and Gynecology, Medical University of Graz, Austria.
    Kallak, Theodora Kunovac
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    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.
    Primary Term Trophoblasts Release NT-proBNPManuscript (preprint) (Other academic)
  • 12.
    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.

  • 13.
    Lindström, Annika
    et al.
    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. Örebro Univ, Clin Res Ctr, Fac Med & Hlth, Örebro, Sweden.
    Sanchez Hermansson, Ruth
    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. Örebro Univ, Fac Med & Hlth, Dept Oncol, Örebro, Sweden.
    Gustavsson, Inger M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Lindberg, Julia Hedlund
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    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.
    Cervical dysplasia in elderly women performing repeated self-sampling for HPV testing2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0207714Article in journal (Refereed)
    Abstract [en]

    Background About 30% of the cervical cancer cases in Sweden occur in women older than 60. The primary aim was to evaluate the acceptability of repeated self-sampling at home for HPV-testing in elderly women. The prevalence of HPV and HPV related dysplasia as well as the sensitivity of cytology was evaluated. Methods Repeated self-sampling at home for HPV testing was offered 375 women in each of the four age groups 60, 65, 70 and 75 years. Women with two consecutive positive HPV tests were examined with sampling for histology and cytology. Findings A self-sample was provided by 59.5% (893/1500) of the invited women. The overall prevalence of HPV was 4.4% (95% CI 3.2-6.0, n = 39) in the first test, and 2.5% were persistent positive in the second test (95% C 1.6-3.8, n = 22) collected on average 5.5 months later. Dysplasia, was found in 1.8% (16/893) (95% CI 1.1-3.0) and CIN 2+ in 1.0% (9/893) (95% CI 0.5-2.0) of the women. Of the 16 women with dysplasia in histology, 13 (81.2%) had a normal cytology. Interpretation Repeated self-sampling at home combined with HPV testing was well accepted among elderly women. A high prevalence of CIN was diagnosed by histology. Cytology showed extremely low sensitivity and should not be recommended for this age group.

  • 14.
    Skírnisdottir, Ingiridur
    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.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Seidal, Tomas
    Department of Pathology, Halmstad Medical Center Hospital, Halmstad, Sweden.
    Clinical significance of growth factor receptor EGFR and angiogenesis regulator VEGF‑R2 in patients with ovarian cancer at FIGO stages I-II.2018In: International Journal of Oncology, ISSN 1019-6439, Vol. 53, no 4, p. 1633-1642Article in journal (Refereed)
    Abstract [en]

    The aim of the present retrospective cohort study was to investigate the prognostic effect of epidermal growth factor receptor (EGFR) and the angiogenesis regulator vascular endothelial growth factor receptor 2 (VEGF‑R2) on disease-free survival (DFS) rate and recurrent disease, and their association with clinicopathological characteristics in 131 patients with International Federation of Gynecology and Obstetrics (FIGO) stages I-II epithelial ovarian cancer. The techniques of tissue microar-rays and immunohistochemistry were used for the positive detection of the markers. The frequency of positive staining in tumors for EGFR was 24% and for VEGF‑R2 was 77%. Across the cohort, there was a total of 34/131 recurrences (26%) and the 5‑year DFS rate was 68%. In a multivariate logistic regression analysis with recurrent disease as the endpoint, FIGO stage (OR=9.7), type (I/II) of tumor (OR=3.0) and VEGF‑R2 status (OR=0.2) were all found to be independent predictive factors in the cohort of patients (n=131). For patients with non‑serous tumors (n=78), the FIGO stage (OR=76), type (I/II) of tumor (OR=44), EGFR status (OR=0.05) and VEGF‑R2 status (OR=0.008) were all significant and independent predictive factors. On comparing the four subgroups, in terms of concomitant EGFR and VEGF‑R2 status, in a survival analysis, the subgroup of patients (n=21) with concomitant positive expression of EGFR and VEGF‑R2 had a 5‑year DFS rate of 100%. Therefore, the prognostic effect of EGFR and VEGF‑R2 for recurrent disease and survival rates was confirmed by the above findings. Certain results in the present study were not in line with results from previous studies on the prognostic effect of EGFR and VEGF‑R2. An increasing number of preclinical and clinical observations have shown that the process of angiogenesis remains to be fully elucidated. Therefore, one of the challenges for future ovarian cancer investigations is to identify which biomarkers may be used as predictive and prognostic markers.

  • 15.
    Vaegter, Katarina Kebbon
    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. Carl von Linne Clin, Uppsala Sci Pk, Uppsala, Sweden; PCG Clin Serv, Uppsala, Sweden.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala Univ, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden;Uppsala Univ, Dept Publ Hlth & Caring Sci Geriatr, Uppsala, Sweden.
    Tilly, Johanna
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. PCG Clin Serv, Uppsala, Sweden.
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Brodin, Thomas
    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, Uppsala Sci Pk, Uppsala, Sweden; PCG Clin Serv, Uppsala, 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, Uppsala Sci Pk, Uppsala, Sweden; Univ Agr Sci Uppsala, Ctr Reprod Biol Uppsala, Uppsala, Sweden; PCG Clin Serv, Uppsala, Sweden.
    Construction and validation of a prediction model to minimize twin rates at preserved high live birth rates after IVF2019In: Reproductive Biomedicine Online, ISSN 1472-6483, E-ISSN 1472-6491, Vol. 38, no 1, p. 22-29Article in journal (Refereed)
    Abstract [en]

    Research question: Elective single-embryo transfer (eSET) at blastocyst stage is widely used to reduce the frequency of multiple pregnancies after IVF. There are, however, concerns about increased risks for the offspring with prolonged embryo culture. Is it possible to select embryos for transfer at the early cleavage stage and still achieve low twin rates at preserved high live birth rates? Design: A prediction model (PM) was developed to optimize eSET based on variables known 2 days after oocyte retrieval (fresh day 2 embryo transfers; double-embryo transfers 1999-2002 (n=2846) and SET 1999-2003 (n=945); n total=3791). Seventy-five variables were analysed for association with pregnancy chance and twin risk and combined for PM construction. This PM was validated in 2004-2016 including frozen-thawed transfers (FET), to compare cumulative live birth rate (CLBR) and twin rate before (1999-2002 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2007, n=3495) and after (2004-2011 fresh embryo transfers plus FET from the same oocyte retrievals until the end of 2016, n=11195) implementing the model. Results: The PM was constructed from four independent variables: female age, embryo score, ovarian sensitivity and treatment history. The calibration, i.e. the fit of observed versus predicted results, was excellent both at construction and at validation. Without compromising CLBR, twin rate was reduced from 25.2% to 3.8%, accompanied by profound improvements in perinatal outcome. Conclusion: The results provide the first successful construction, validation and impact analysis of a day 2 transfer PM to reduce multiple pregnancies.

  • 16.
    Volgsten, Helena
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jansson, Caroline
    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.
    Darj, Elisabeth
    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), International Maternal and Reproductive Health and Migration. Department of Public Health and Nursing, NTNU-Norwegian University of Science and Technology and Department of Obstetrics and Gynecology, St Olav's Hospital, Trondheim, Norway.
    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.
    Women's experiences of miscarriage related to diagnosis, duration, and type of treatment.2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Women with miscarriage experience several negative emotional feelings such as grief, isolation, coping, and despair. However, less is known about how the type of treatment and diagnosis of miscarriage influence the emotional experience.

    MATERIAL AND METHODS: The present study was a randomized prospective longitudinal cohort study, in which women with spontaneous miscarriage (n = 35), and women with missed miscarriage (n = 67), were included to answer 3 validated questionnaires: Revised Impact of Miscarriage Scale, Perinatal Grief Scale, and Montgomery and Åsberg Depression Rating Scale, concerning experience of miscarriage, psychological well-being, and mental health 1 week and 4 months after finalized treatment.

    RESULTS: There was no difference between the 2 diagnosis groups in feelings as measured by Revised Impact of Miscarriage Scale, Montgomery and Åsberg Depression Rating Scale, and Perinatal Grief Scale 1 week after the miscarriage. However, the psychological well-being improved significantly 4 months after the miscarriage. Separated by treatment, women treated with misoprostol alone had more depressive symptoms than women treated with misoprostol and subsequent vacuum aspiration.

    CONCLUSIONS: It can be concluded that diagnosis of miscarriage had limited influence on the experiences of miscarriage, but shorter duration of treatment with misoprostol and subsequent vacuum aspiration resulted in fewer depressive symptoms.

  • 17.
    Volgsten, Helena
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Jansson, Caroline
    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.
    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.
    Darj, Elisabeth
    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), International Maternal and Reproductive Health and Migration. Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Obstetrics and Gynecology, St Olav’s Hospital, Trondheim, Norway.
    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.
    Longitudinal study of emotional experiences, grief and depressive symptoms in women and men after miscarriage2018In: Midwifery, ISSN 0266-6138, E-ISSN 1532-3099, Vol. 64, p. 23-28Article in journal (Refereed)
    Abstract [en]

    Objective: Although miscarriage is common and affects up to 20 % of pregnant women, little is known about these couples’ short term and long term experiences after miscarriage.The aim of the present study was to study emotional experience, grief and depressive symptoms in women and men,one week and four months after miscarriage. Research design /setting:Women, (n=103), and their male partner (n=78), were recruited at the gynecological clinic after miscarriage. Control women were recruitedfrom the general population.Three validated questionnaires concerning psychological wellbeing and mental health, RIMS, PGS and MADRS-S were answered by the participants one week and four months after the miscarriage. Findings: It was shown that for women, the emotional experiences of miscarriage, grief and depressive symptoms were more pronounced than for their male partners. Grief and depressive symptoms were reduced with time, which was not the case for the emotional experiences of miscarriage. Previous children was favorable for emotional experience while previous miscarriage or infertility treatment made the emotional experience worse. Conclusion: Grief and depressive symptoms is reducedover time while emotional experiences such as isolation, loss of baby and a devastating event persist for longer time than four months. Lack of previous children, previous miscarriageand infertility diagnosis could increase negative emotional experiencesafter miscarriage, this was especially pronounced for grief reaction.The questionnaires could be used both clinically and in research to understand the emotional experiences after miscarriage.

  • 18.
    Zeisler, H.
    et al.
    Med Univ Vienna, Dept Obstet & Gynecol, Vienna, Austria.
    Llurba, E.
    Univ Autonoma Barcelona, Vall dHebron Univ Hosp, Barcelona, Spain.
    Chantraine, F. J.
    Univ Liege, CHR Citadelle, Liege, Belgium.
    Vatish, M.
    Univ Oxford, Oxford, England.
    Staff, A. C.
    Oslo Univ Hosp, Oslo, Norway;Univ Oslo, Oslo, Norway.
    Sennstrom, M.
    Karolinska Univ Hosp, Stockholm, 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.
    Brennecke, S. P.
    Univ Melbourne, Dept Obstet & Gynaecol, Melbourne, Vic, Australia;Royal Womens Hosp, Melbourne, Vic, Australia.
    Stepan, H.
    Univ Leipzig, Leipzig, Germany.
    Allegranza, D.
    Roche Diagnost Int Ltd, Rotkreuz, Switzerland.
    Schoedl, M.
    Roche Diagnost GmbH, Penzberg, Germany.
    Grill, S.
    Roche Diagnost GmbH, Penzberg, Germany.
    Hund, M.
    Roche Diagnost Int Ltd, Rotkreuz, Switzerland.
    Verlohren, S.
    Charite, Berlin, Germany.
    Soluble fms-like tyrosine kinase-1 to placental growth factor ratio: ruling out pre-eclampsia for up to 4weeks and value of retesting2019In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 53, no 3, p. 367-375Article in journal (Refereed)
    Abstract [en]

    Objectives

    The soluble fms-like tyrosine kinase-1 ( sFlt-1) to placental growth factor ( PlGF) ratio is generally elevated some time before and at the clinical onset of pre-eclampsia. The PROGNOSIS study validated a sFlt-1/PlGF ratio cut-off of = 38 to rule out the onset of pre-eclampsia within 1week of testing in women with suspected disease. The aim of this study was to assess the predictive value of the sFlt-1/PlGF ratio to rule out the onset of pre-eclampsia for up to 4 weeks, and to assess the value of repeat measurements.

    Methods

    This was an exploratory post-hoc analysis of data from the PROGNOSIS study performed in pregnant women aged = 18 years with suspected pre-eclampsia, who were at 24+ 0 to 36+ 6weeks' gestation at their first clinic visit. Serum samples were collected at the first visit and weekly thereafter. sFlt-1 and PlGF levels were measured using Elecsys (R) sFlt-1 and PlGF immunoassays. Whether the sFlt-1/PlGF ratio cut-off of = 38 used to rule out the onset of pre-eclampsia within 1week could predict the absence of pre-eclampsia 2, 3, and 4 weeks post-baseline was assessed. The value of repeat sFlt-1/PlGF testing was assessed by examining the difference in sFlt-1/PlGF ratio 2 and 3 weeks after the first measurement in women with, and those without, pre-eclampsia or adverse fetal outcome.

    Results

    On analysis of 550 women, sFlt-1/PlGF ratio = 38 ruled out the onset of pre-eclampsia 2 and 3weeks post-baseline with high negative predictive values (NPV) of 97.9% and 95.7%, respectively. The onset of pre-eclampsia within 4weeks was ruled out with a high NPV (94.3%) and high sensitivity and specificity (66.2% and 83.1%, respectively). Compared with women who did not develop pre-eclampsia, those who developed pre-eclampsia had significantly larger median increases in sFlt-1/PlGF ratio at 2 weeks (., 31.22 vs 1.45; P< 0.001) and at 3 weeks (., 48.97 vs 2.39; P< 0.001) after their initial visit. Women who developed pre-eclampsia and/or adverse fetal outcome compared with those who did not had a significantly greater median increase in sFlt-1/PlGF ratio over the same period (., 21.22 vs 1.40; P< 0.001 at 2weeks;., 34.95 vs 2.30; P< 0.001 at 3weeks).

    Conclusion

    The Elecsys (R) immunoassay sFlt-1/PlGF ratio can help to rule out the onset of pre-eclampsia for 4 weeks in women with suspected pre-eclampsia.

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