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Abstract Background Metformin is a hypoglycaemic medication that has been proposed to treat or prevent preeclampsia. Combining national birth data from Scotland and Sweden, we investigated whether metformin used during pregnancy was associated with an altered risk of developing a hypertensive disorder of pregnancy. Methods We utilised data from two population-based cohorts: Scotland (2012–2018) and Sweden (2007–2019). Nulliparous women with gestational diabetes or type 2 diabetes who had birth outcome data linked with medications prescribed during pregnancy were included. The association between metformin prescription and hypertensive disorders of pregnancy was characterised using inverse probability weighted regression analysis, adjusting for variables that predict metformin use and potential confounders. Adverse neonatal outcomes were included as secondary outcomes. Results from both countries were then combined in a meta-analysis using a random effects model. Results The Scottish cohort included 3859 women with gestational diabetes or type 2 diabetes. Of these women, 30.8% (n = 1187) received at least one metformin prescription during pregnancy. For Sweden, 7771 women with gestational diabetes were included where 19.3% (1498) used metformin during pregnancy. Metformin prescription was not associated with an altered risk of any hypertensive disorder of pregnancy (Scotland adjusted relative risk (aRR) 0.88 [95% confidence interval (CI) 0.66–1.19]; Sweden aRR 1.08 [95% CI 0.86–1.37]) or preeclampsia (Scotland aRR 1.02 [95% CI 0.66–1.60]; Sweden aRR 1.00 [95% CI 0.72–1.39]). Combining adjusted results in a meta-analysis produced similar findings, with a pooled RR of 0.98 (95% CI 0.79–1.18) for any hypertensive disorder and RR 1.01 ([95% CI 0.73–1.28]) for preeclampsia. For neonatal outcomes, metformin was associated with a reduced risk of birthweight > 4500 g in Scotland (aRR 0.39 [95% CI 0.21–0.71]) but not in Sweden. There was no association between metformin and preterm birth or birthweight

Introduction Preterm pre-eclampsia is a leading cause of maternal morbidity and mortality. The Pre-eclampsia Intervention 2 (PI 2) trial suggested that metformin sustained release (XR) may prolong gestation by a week in pregnant women undergoing expectant management (7.6 days, geometric mean ratio 1.39, 95% CI 0.99 to 1.95; p=0.057). These findings should be confirmed with a larger sample size, and we need to know if such a prolongation improves neonatal outcome. Here, we describe the protocol for such a follow-up trial.Methods The PI 3 trial is a phase III, intention-to-treat, double-blind, placebo-controlled randomised clinical trial to assess if metformin XR can prolong gestation and improve neonatal outcomes in women undergoing expectant management for preterm pre-eclampsia. We will recruit women who are between 26+0 and 31+6 weeks pregnant. Women will be randomised to receive either 3 g metformin XR or an identical placebo in divided daily doses. The primary outcome is prolongation of pregnancy. Secondary outcomes are neonatal birth weight and length of neonatal care admission (an indicator of neonatal health at birth). All other outcomes will be exploratory. We will record tolerability and adverse events. We plan a sample size of 500 participants to be powered for the primary and secondary outcomes.Ethics and dissemination PI 3 has ethical approval (Health Research Ethics Committee 2, Stellenbosch University, Protocol number M21/03/007, Project ID 21639, Federal Wide Assurance Number 00001372, Institutional Review Board Number IRB0005239), and is registered with the Pan African Clinical Trial Registry (PACTR202104532026017) and the South African Medicine Control Council (20211211). Data will be presented at international conferences and published in peer-reviewed journals.Trial registration number PACTR202104532026017)

Abstract Background Delayed neurocognitive recovery and neurocognitive disorder are common postoperative complications among older adults. The assessment of these complications traditionally relies on analog neurocognitive tests, predominantly using the test battery from the ISPOCD-study as the standard approach. However, analog tests are time-consuming and necessitate trained staff which poses limitations. The potential availability of a digital neurocognitive test as an alternative to the ISPOCD remains unknown. We conducted a comparative study between the analog test battery from ISPOCD and the self-administrated digital test battery developed by Mindmore. Methods We conducted a crossover study with 50 cognitively healthy older adults ≥ 60 years of age recruited in Stockholm Sweden, between February and April 2022. The primary outcome focused on measuring comparability between the two test batteries. Our secondary outcomes included assessing participants’ perceptions and attitudes about the tests with qualitative interviews and their usability experiences. Results Fifty older adults, mean age 76, female 56%, with a university or college degree 48% participated in the study. The sub tests in two test batteries demonstrated a medium–large correlation (r = 0.3–0.5), except for one measure. For four out of six measures, significant differences were found with medium to large effect sizes, ranging from 0.57–1.43. Two categories were recognized in the qualitative analysis: self-competing in a safe environment, and experience with technology. Participants expressed feeling safe and at ease during the assessment, with some preferring the digital test over the analog. Participants reported a high level of usability with the digital test and a majority participants (n = 47) reported they would undergo the digital test for a potential future surgery. Conclusions The digital test battery developed by Mindmore offers several advantages, including rapid access to test results, easy comprehension, and use for participants, thereby increased accessibility of cognitive screening. Trial registration number NCT05253612; ClinicalTrials.gov, 24/02/2022.

Preeclampsia is a syndrome that continues to be a major contributor to maternal and neonatal mortality, especially in low-income countries. Low-dose aspirin reduces the risk of preeclampsia, but the mechanism is still unknown. Risk factors to identify women at risk of preeclampsia are based on clinical characteristics. Women identified as high-risk would benefit from aspirin treatment initiated, preferably at the end of the first trimester. Current efforts have largely focused on developing screening algorithms that incorporate clinical risk factors, maternal biomarkers, and uterine artery Doppler evaluated in the first trimester. However, most studies on preeclampsia are conducted in high-income settings, raising uncertainties about whether the information gained can be totally applied in low-resource settings. In low- and middle-income countries, lack of adequate antenatal care and late commencement of antenatal care visits pose significant challenges for both screening for preeclampsia and initiating aspirin treatment. Furthermore, the preventive effect of first-trimester screening based on algorithms and subsequent aspirin treatment is primarily seen for preterm preeclampsia, and reviews indicate minimal or no impact on reducing the risk of term preeclampsia. The lack of evidence regarding the effectiveness of aspirin in preventing term preeclampsia is a crucial concern, as 75% of women will develop this subtype of the syndrome. Regarding adverse outcomes, low-dose aspirin has been linked to a possible higher risk of postpartum hemorrhage, a condition as deadly as preeclampsia in many low- and middle-income countries. The increased risk of postpartum hemorrhage among women in low-income settings should be taken into consideration when discussing which pregnant women would benefit from the use of aspirin and the ideal aspirin dosage for preventing preeclampsia. In addition, women's adherence to aspirin during pregnancy is crucial for determining its effectiveness and complications, an aspect often overlooked in trials. In this review, we analyze the knowledge gaps that must be addressed to safely increase low-dose aspirin use in low- and middle-income countries, and we propose directions for future research.

Abstract Background Health Literacy is a crucial factor for health. In Europe, many people have limited health literacy (i.e. difficulties with accessing, understanding, appraising and using health information). This study aimed to evaluate the psychometrics of the Swedish versions of the HLS-EU-Q16 and HLS-EU-Q6, instruments that aims to assess health literacy. Methods In this prospective psychometric study convenience sampling was used, which gave a study population of 347 Swedish-speaking adults. The psychometric evaluation included item distributional statistics, construct validity testing, and principal component analysis to assess structural validity. Internal consistency and test-retest reliability was also investigated. Results For the Swedish version of HLS-EU-Q16, no floor effects were detected but a ceiling effect was noted among 28% of the respondents. Construct validity was supported as four out of five expected correlations was confirmed (educational level, self-perceived health, electronic health literacy and HLS-EU-Q6). In terms of structural validity, the principal component analysis yielded a four-factor structure with most items loading significantly only to one factor. The Swedish version of HLS-EU-Q16 had acceptable internal consistency (Cronbach’s α = 0.89, split-half reliability = 0.93) and test-retest reliability showed stability over time (Cohen’s κ = 0.822). For the Swedish version of HLS-EU-Q6, neither floor nor ceiling effects were observed. Construct validity was supported as HLS-EU-Q6 correlated as our a priori stated hypothesis. The principal component analysis did not support the unidimensionality of the scale as a two-factor structure was identified. The Swedish version of HLS-EU-Q6 had acceptable internal consistency (Cronbach’s α = 0.77, split-half reliability = 0.80) and test-retest reliability showed stability over time (Cohen’s κ = 0.812). According to the Swedish version of the HLS-EU-Q16, 71% of the participants were classified as having sufficient comprehensive health knowledge (CHL), while only 33% were classified as having this when the HLS-EU-Q6 was used. Conclusions The Swedish versions of the HLS-EU-Q16 and HLS-EU-Q6 have acceptable psychometric properties, and based on the results we recommend its use to measure CHL. However, we are hesitant to use Sw-HLS-EU-Q6 in estimating different CHL levels and further studies need to be conducted to establish validity and accuracy of the thresholds of HLS-EU-Q6.

Abstract Background Health literacy is an important social determinant of health and affects the ability to make decisions and take action to manage one’s health. The purpose of this study was to psychometrically examine the Arabic versions of HLS-EU-Q16 and HLS-EU-Q6 and their response patterns among Arabic-speaking persons in Sweden. Methods By convenience sampling from a variety of settings, a total of 335 participants were invited to participate. The participants completed a self-assessment of comprehensive health literacy by answering the Ar-HLS-EU-Q16 questionnaire, also including the six items for Ar-HLS-EU-Q6. Statistical analysis was guided by The COnsensus-based Standards for the selection of health Measurement Instruments. Floor/ceiling effects, construct, structural and criterion validity, test-retest reliability and internal consistency reliability were analysed. Results In total, 320 participants were included in the psychometric evaluation. Mean age was 42.1 (SD 12.5), 63% (n = 199) were females and 53% (n = 169) had at least 10 years of education. No floor or ceiling effect were found for the Ar-HLS-EU-Q16 or Ar-HLS-EU-Q6. For both instruments, construct validity was confirmed in four out of five expected correlations (weak positive correlation to educational level, self-perceived health, and years in Sweden; moderate positive correlation with higher sum score on the Arabic electronic health literacy scale, and strong positive correlation to higher Ar-HLS-EU-Q16/Ar-HLS-EU-Q6). For Ar-HLS-EU-Q16, the principal component analysis resulted in a three-factor model with all items significantly correlating to only one factor. For Ar-HLS-EU-Q6, the principal component analysis supported a one-factor solution. Criterion validity showed poor agreement between the two questionnaires with a Cohen κ 0.58 (p

Introduction Delayed neurocognitive recovery, also identified as early postoperative cognitive decline (POCD), is a common complication after surgery, with advanced age being the most important risk factor. As the geriatric population is increasing worldwide, and number of older adults undergoing surgery continues to rise, so will the incidence of POCD. Only a small proportion use digital cognitive tests for measuring postoperative neurocognitive performance compared with analogue tests. This study aims to evaluate a digital cognitive screening tool, Mindmore Postoperative version (Mindmore-P), in a perioperative setting to determine its feasibility and usability, and to compare preoperative cognition with early postoperative neurocognitive performance. Further, to determine associations between neurocognitive performance and perioperative factors as well as to explore patients’ experiences of early neurocognitive recovery.Methods and analysis We will include 50 patients (aged ≥60 years) undergoing elective abdominal surgery under general anaesthesia. Cognitive functions will be measured with Mindmore-P preoperatively and on postoperative day (POD) 1 or 2 as well as 2–3 weeks after surgery. Preoperatively, frailty, (Clinical Frailty Scale), depression (Geriatric Depression Scale-15), functional status (12-item WHO Disability Assessment Schedule 2.0) and pre-recovery status (Swedish web version Quality of Recovery Scale, SwQoR) will be measured. Delirium will be assessed by Nu-DESC (Nursing Delirium Screening Scale) twice a day, with start on POD 1 and until the patient is discharged from the hospital. Outcomes at 2–3 weeks postoperatively are postoperative recovery (SwQoR), depression, functional status and usability (System Usability Scale) of Mindmore-P. Postoperative recovery will also be measured POD 1 or 2. We will also explore feasibility and experience of early postoperative neurocognitive recovery with interviews approximately 1 month after surgery.Ethics and dissemination This study is approved by the Swedish Ethical Review Authority (REC Reference: 2022-03593-01) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, scientific conferences and in social media.Trial registration number NCT05564195.

Abstract Preeclampsia and cardiovascular disease (CVD) share multiple features and risk factors. Circulating angiotensin-converting enzyme 2 (ACE2) is increased in CVD and mediates SARS-CoV-2 entry into host cells, causing COVID-19 infection. The role of ACE2 in preeclampsia pathophysiology is unknown. We hypothesized that circulating ACE2 is increased in mid-pregnancy in women later developing preeclampsia. We included 296 women later developing preeclampsia (cases) and 333 women with a continuous healthy pregnancy (controls). Circulating ACE2 was measured with an immunoassay based on proximity extension assay technology, with levels being expressed as relative quantification on a log2 scale. Median (interquartile range) ACE2 levels were higher in cases than in controls; 3.84 (3.50–4.24) vs. 3.72 (3.45–4.04), p = 0.002. Adjusted logistic regression models showed a 60% increased risk for later development of preeclampsia with one unit elevation of ACE2 (adjusted odds ratio (aOR) 1.60, 95% confidence intervals (CI) 1.17–2.18). Preterm preeclampsia (diagnosis before 37 gestational weeks, n = 97) seemed to have a stronger ACE2 association than term preeclampsia, n = 199 (aORs, 95% Cis 2.14, 1.15–3.96 and 1.52, 1.04–2.23, respectively). Circulating ACE2 is increased at mid-pregnancy in women later developing preeclampsia, particularly preterm preeclampsia. Thus, our finding indicates a partly shared pathophysiological pathway between preeclampsia and CVD.

BackgroundPreterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies.MethodsSix databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline.ResultsThe search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth

Abstract Background Health inequities arise when the public cannot access and understand health information in an easy, accessible, and understandable way. Evidence supports that health literacy (HL) is a determinant for health outcomes, and when HL is limited this may have a major impact on morbidity as well as mortality. Migrants are known to have limited HL. Therefore, this study aimed to explore comprehensive health literacy (CHL) and electronic health literacy (eHL) among Arabic-speaking migrants in Sweden. Methods This was a cross-sectional observational study conducted in Sweden. A total of 703 persons were invited to participate between February and September 2019. Two questionnaires – the Health Literacy Survey European Questionnaire (HLS-EU-Q16) and the eHealth Literacy Scale (eHEALS) – and questions about self-perceived health and Internet use were distributed in Swedish and Arabic. Various statistical analyses were performed to determine the associations for limited CHL and eHL. Results A total of 681 respondents were included in the analysis. Of these, 334 (49%) were native Arabic-speaking migrants and 347 (51%) were native Swedish-speaking residents. CHL and eHL differed between the groups. The Arabic speakers had significantly lower mean sum scores in eHL 28.1 (SD 6.1) vs 29.3 (6.2), p = 0.012 and lower proportion of sufficient CHL 125 (38.9%) vs 239 (71.3%), p

Background and Objectives: Preeclampsia is a multisystem disorder that affects maternal endothelium. The glycocalyx lines and protects the endothelial surface. In severe systemic diseases, like sepsis, it is shed and glycocalyx degradation products can be detected in increased concentrations in plasma. The aim of this study was to compare circulating concentrations of glycocalyx degradation products in degrees of preeclampsia severity.Study design: In this observational study, we included women from the South African PROVE biobank. Women were divided into normotensive controls, women with preeclampsia without end-organ complications, women with a single end-organ complication and women with multiple end-organ complications. Plasma samples taken at inclusion after diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed with ELISA for syndecan-1, hyaluronic acid and thrombomodulin and compared between groups.Results: Women with preeclampsia (n = 47) had increased plasma concentrations of hyaluronic acid (100.3 ng/ml IQR 54.2–204 vs. 27.0 ng/ml IQR (13.5–66.6), p < 0,001) and thrombomodulin (4.22 ng/ml IQR 3.55–5.17 vs. 3.49 ng/ml IQR 3.01–3.68, p = 0.007) but not syndecan-1 compared with normotensive women (n = 10). There were no differences in plasma concentration in any of these biomarkers in women with preeclampsia with no end-organ complications (n = 10) compared with women with preeclampsia and one end-organ complication (n = 24). Women with preeclampsia with two or more end-organ complications (n = 13) had increased plasma concentrations of thrombomodulin (5.46 ng/ml, IQR 4.85–7.83 vs. 4.66 ng/ml, IQR 3.45–4.88, p = 0.042) compared with women with preeclampsia and no end-organ complications.Conclusion: Thrombomodulin was associated with disease severity and may be valuable for risk-stratifying women with preeclampsia.

Introduction Postoperative cognitive decline affects cognitive domains such as executive functions, memory, concentration and information processing. The analogue neuropsychological test developed by the International Study Group of Postoperative Cognitive Dysfunction (ISPOCD) is a well-established test for assessing cognitive performance. However, analogue tests are time-consuming, rarely cost-effective and can be at risk of administration bias. Digital solutions are comparable to analogue ones, have higher degrees of compliance and enable more standardised execution than analogue tests. Currently, there is a lack of recommendations for clinical evaluation of the patient’s cognition in the perioperative setting, standard care usually means no cognitive assessments prior or after the surgery. There is a need to find an equivalent neuropsychological test to the ISPOCD to make it accessible and easier to implement in a clinical context for perioperative patients. This study aims to examine how healthy seniors perform on two neuropsychological tests, analogue versus digital and measure equivalency between tests with correlation analysis.Methods and analysis This study will use a randomised cross-over design, including qualitative interviews regarding test experiences. Healthy participants ≥60 years of age will be eligible to participate in the study. Cognitive function will be measured by using the ISPOCD test and the Mindmore digital test. The participants will self-report depressive symptoms with the Geriatric Depression Scale-15, user experience of the digital test using a modified version of the System Usability Scale and answer questionnaires targeting their experiences after the tests. Furthermore, according to the Swedish Quality of Recovery Scale, self-reported concentration difficulties will also be measured.Ethics and dissemination The study has been approved by the Swedish Ethical Review Authority (Dnr 2021-05486-01) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, at scientific conferences, and in social media.Trial registration number 2021-01095; ClinicalTrials.gov.

Background The angiogenic factors soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are postulated to be pathogenic disease drivers of preeclampsia. If true, then circulating levels should become more deranged with increasing disease severity. Methods and Results We investigated the association between circulating sFlt‐1 and PlGF levels and severe adverse maternal outcomes among 348 women with preeclampsia. Compared with 125 women with preeclampsia without severe features, 25 women with preeclampsia and any of hemolysis, elevated liver enzymes, low platelet count syndrome, disseminated intravascular coagulation, or severe renal involvement had sFlt‐1 levels that were 2.63‐fold higher (95% CI, 1.81–3.82), sFlt‐1/PlGF levels that were 10.07‐fold higher (95% CI, 5.36–18.91) and PlGF levels that were 74% lower (adjusted fold change, 0.26 [95% CI, 0.18–0.39]). Compared with 125 women with preeclampsia without severe features, 37 with eclampsia had sFlt‐1 levels that were 2‐fold higher (2.02 [95% CI, 1.32–3.09]), sFlt‐1/PIGF levels that were 4.71‐fold higher (95% CI, 2.30–9.66) and PIGF levels that were 63% lower (0.43‐fold change [95% CI, 0.27–0.68]). Compared with those without severe features, preeclampsia with severe hypertension (n=146) was also associated with altered angiogenic levels (sFlt‐1, 1.71‐fold change [95% CI, 1.39–2.11]; sFlt/PlGF, 2.91 [95% CI, 2.04–4.15]; PlGF, 0.59 [95%CI 0.47–0.74]). We also found that sFlt‐1 and PlGF levels were altered by the number of maternal complications experienced. Conclusions Further angiogenic imbalance among women with preeclampsia is likely a pathogenic disease driver responsible for the life‐threatening maternal complications.

Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy‐specific β‐1 glycoprotein 7) and PSG9 (pregnancy‐specific β‐1 glycoprotein 9) in preeclampsia. Methods and Results At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P

Introduction Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care.Methods and analysis This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up.Ethics and dissemination By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals.Trial registration number ISRCTN13060768

Introduction There is limited knowledge on how the SARS-CoV-2 affects pregnancy outcomes. Studies investigating the impact of COVID-19 in early pregnancy are scarce and information on long-term follow-up is lacking.The purpose of this project is to study the impact of COVID-19 on pregnancy outcomes and long-term maternal and child health by: (1) establishing a database and biobank from pregnant women with COVID-19 and presumably non-infected women and their infants and (2) examining how women and their partners experience pregnancy, childbirth and early parenthood in the COVID-19 pandemic.Methods and analysis This is a national, multicentre, prospective cohort study involving 27 Swedish maternity units accounting for over 86 000 deliveries/year. Pregnant women are included when they: (1) test positive for SARS-CoV-2 (COVID-19 group) or (2) are non-infected and seek healthcare at one of their routine antenatal visits (screening group). Blood, as well as other biological samples, are collected at different time points during and after pregnancy. Child health up to 4 years of age and parent experience of pregnancy, delivery, early parenthood, healthcare and society in general will be examined using web-based questionnaires based on validated instruments. Short- and long-term health outcomes will be collected from Swedish health registers and the parents’ experiences will be studied by performing qualitative interviews.Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (dnr 2020-02189 and amendments 2020-02848, 2020-05016, 2020-06696 and 2021-00870) and national biobank approval by the Biobank Väst (dnr B2000526:970). Results from the project will be published in peer-reviewed journals.Trial registration number NCT04433364.

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF‐15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P

Introduction: Inflammation is central to initiation of labor and coagulation is closely interlinked with inflammation. Low-molecular-weight-heparin (LMWH) promotes inflammatory cervical remodeling, myometrium contractility and has been associated with shorter duration of labor. Material and methods: This was a cohort study of 136,661 deliveries 2013–2017, identified in the Swedish Pregnancy Register with prospectively collected pregnancy and labor characteristics. Information of duration of labor was retrieved from the electronic birth records and analyzed with Cox proportional hazard regressions according to previous or current thromboembolic disease (overall) with or without LMWH treatment with non-exposed as reference. Results: The crude hazard ratio for vaginal delivery was not different between women with thromboembolic disease and women without thromboembolic disease (HR 0.99, 95 % CI 0.91–1.09). A lower hazard ratio for vaginal delivery was observed among women with venous thromboembolism (VTE) with concomitant LMWH use/treatment (adjusted HR 0.86, 95 % CI 0.76−0.98) compared to non-exposed, implying a longer duration of labor in these cases. Conclusion: Thromboembolic disease was not associated with shorter duration of labor and in presence of LMWH these women experienced longer duration of labor.

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

Objective To develop and evaluate the psychometric properties of a scale measuring patient safety during the intrahospital transport process for intensive care.Design The scale was developed based on a theoretical model of the work system and patient safety, and items generated from participant observations. A Delphi study with international experts was used to establish content validity. Next, a cross-sectional study was undertaken to inform item reduction and evaluate construct validity and internal consistency.Setting The questionnaire was distributed to healthcare practitioners at 12 intensive care units in Sweden.Participants A total of 315 questionnaires were completed. Eligible participants were healthcare practitioners in the included units that performed an intrahospital transport during the study period. Inclusion criteria were (1) transports of patients within the hospital to undergo an examination or intervention, and (2) transports performed by staff from the intensive care unit. We excluded transports to a step-down unit or hospital ward.Outcome measures Psychometric evaluation, including item analysis, validity and reliability testing.Results Items were reduced from 55 to 24, informed by distributional statistics, initial reliabilities, factor loadings and communalities. The final factor model consisted of five factors, accounting for 59% of variance. All items loaded significantly on only one factor (>0.35). The original conceptual model of teamwork, transport-related tasks, tools and technologies, environment, and organisation was maintained with regrouping of items. Cronbach’s alpha ranged from 0.72 to 0.82 for each subscale (ie, factor).Conclusions The present study provides a self-report questionnaire to assess patient safety during intrahospital transport of patients in intensive care. The results indicate acceptable validity and reliability of the scale among a sample of Swedish healthcare practitioners. If further confirmatory testing supports the present results, this scale could be a useful tool to better understand safety prerequisites and improve clinical practice.

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood–brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

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

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

To evaluate if concentrations of the neuronal proteins neurofilament light chain and tau are changed in women developing preeclampsia and to evaluate the ability of a combination of neurofilament light chain, tau, S100B and neuron specific enolase in identifying neurologic impairment before diagnosis of preeclampsia.A nested case-control study within a longitudinal study cohort was performed. 469 healthy pregnant women were enrolled between 2004-2007 and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Plasma concentrations of tau and neurofilament light chain were analyzed in 16 women who eventually developed preeclampsia and 36 controls throughout pregnancy with single molecule array (Simoa) method and compared within and between groups. S100B and NSE had been analyzed previously in the same study population. A statistical model with receiving characteristic operation curve was constructed with the four biomarkers combined.Plasma concentrations of neurofilament light chain were significantly increased in women who developed preeclampsia in gestational week 33 (11.85 ng/L, IQR 7.48-39.93 vs 6.80 ng/L, IQR 5.65-11.40) and 37 (22.15 ng/L, IQR 10.93-35.30 vs 8.40 ng/L, IQR 6.40-14.30) and for tau in gestational week 37 (4.33 ng/L, IQR 3.97-12.83 vs 3.77 ng/L, IQR 1.91-5.25) in contrast to healthy controls. A combined model for preeclampsia with tau, neurofilament light chain, S100B and neuron specific enolase in gestational week 25 displayed an area under the curve of 0.77, in week 28 it was 0.75, in week 33 it was 0.89 and in week 37 it was 0.83. Median week for diagnosis of preeclampsia was at 38 weeks of gestation.Concentrations of both tau and neurofilament light chain are increased in the end of pregnancy in women developing preeclampsia in contrast to healthy pregnancies. Cerebral biomarkers might reflect cerebral involvement before onset of disease.

Abstract While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.