| 1. |
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| 2. |
- Wadell, M., et al.
(författare)
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Challenges imposed by the COVID-19 pandemic on the Obstetrics and Gynecology residency program: a mixed-methods Swedish survey in the COPE Staff cohort study
- 2022
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Ingår i: Bmc Medical Education. - : Springer Science and Business Media LLC. - 1472-6920. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background To outline how the training program and work situation of residents in Obstetrics and Gynecology (OB-GYN) was affected by the pandemic and to illuminate how residents experienced these changes. Methods As part of the COVID-19 in Pregnancy and Early Childhood Staff (COPE Staff) cohort study, between January and May 2021, all participating residents were invited to answer a 28-question online Resident Survey focusing on their specialist education, work situation and experiences during the COVID-19 pandemic. Descriptive statistics were given in percentages for categorical variables and means and standard deviations (SD) for continuous variables. Univariate comparative analyses were performed with the use of the Pearson's Chi-2-test for dichotomous data. The association between residents' worry about the quality and length of their specialist training, with extra clinical hours and transfer to other healthcare institutions were assessed by multivariate logistic regression. Free text responses were analyzed by content analysis. Results Of the 162 participating OB-GYN residents, 69% expressed concern that the pandemic would have a negative impact on their training. Ninety-five (95%) reported cancellation/postponement of educational activities, 70% performed fewer surgeries and 27% had been transferred to other healthcare institutions where about half reported having gained more general knowledge as a physician. Working extra clinical hours was reported by 69% (7.4 +/- 5.3 hours per week) and 14% had considered changing their profession due to the pandemic. Senior residents, compared to junior residents, more often experienced cancelled/postponed clinical rotations (30% vs 15%, P=0.02) and reported performing fewer surgeries (P=0.02). The qualitative analysis highlighted the lack of surgical procedural training as a major concern for residents. Conclusion The COVID-19 pandemic has strongly impacted the training program and work situation of OB-GYN residents in Sweden. Residents were concerned over the negative impact of the pandemic on their training program and senior residents reported more missed educational opportunities as compared to junior residents. Program directors, head of institutions and clinical supervisors can use the problem areas pinpointed by this study to support residents and compensate for missed educational opportunities. While hands-on-training and operating time cannot be compensated for, the authors hope that the findings of the study can help develop new strategies to minimize the negative impact of the current and future pandemics on resident education and work situation.
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| 3. |
- Åkerström, Magnus, 1981, et al.
(författare)
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The COPE Staff study : Study description and initial report regarding job satisfaction, work-life conflicts, stress, and burnout among Swedish maternal and neonatal healthcare workers during the COVID-19 pandemic
- 2023
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Ingår i: International Journal of Gynecology & Obstetrics. - : John Wiley & Sons. - 0020-7292 .- 1879-3479. ; 162:3, s. 989-997
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo describe the study design of the COPE Staff cohort study on working conditions for maternal and neonatal healthcare workers (MNHCWs), and present baseline data regarding job satisfaction, work-life conflicts, stress, and burnout. MethodsBetween January and April 2021, 957 MNHCWs (administrative and medical staff) completed a baseline survey. Average levels of job satisfaction, work-life conflicts, stress, and burnout, and associations to perceived workload were assessed. ResultsThe average levels of job satisfaction, work-life conflicts, stress, and burnout were 68.6 (95% confidence interval [CI] 64.3-72.8), 42.6 (95% CI 37.3-48.0), 42.0 (95% CI 37.7-46.3), and 1.9 (95% CI 1.6-2.2), respectively. The respondents scoring above critical values indicating clinical burnout ranged between 3% and 18%, respectively, for the four burnout sub-dimensions. Women reported significantly higher levels of stress and burnout. Younger participants had lower job satisfaction and higher levels of work-life conflicts, stress, and burnout. Higher perceived workload was significantly associated with lower job satisfaction levels and higher levels of work-life conflicts, stress, and burnout. ConclusionsOur results indicate associations between MNHCWs perceived workload and job satisfaction, work-life conflicts, stress, and burnout during the COVID-19 pandemic. Eighteen percent scored above critical values for exhaustion.
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| 4. |
- Alkmark, Mårten, 1973, et al.
(författare)
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Efficacy and safety of oral misoprostol versus transvaginal balloon catheter for labor induction: An observational study within the SWEdish Postterm Induction Study (SWEPIS)
- 2021
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:8, s. 1463-1477
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Induction of labor is increasing. A common indication for induction of labor is late term and postterm pregnancy at 41 weeks or more. We aimed to evaluate if there are any differences regarding efficacy, safety, and women's childbirth experience between oral misoprostol and transvaginal balloon catheter for cervical ripening in women with a low-risk singleton pregnancy and induction of labor at 41(+0) to 42(+0 to 1) weeks of gestation. Material and methods In this observational study, based on data from the Swedish Postterm Induction Study (SWEPIS), a multicenter randomized controlled trial, a total of 1213 women with a low-risk singleton pregnancy at 41 to 42 weeks of gestation were induced with oral misoprostol (n = 744) or transvaginal balloon catheter (n = 469) at 15 Swedish delivery hospitals. The primary efficacy outcome was vaginal delivery within 24 h and primary safety outcomes were neonatal and maternal composite adverse outcomes. Secondary outcomes included time to vaginal delivery and mode of delivery. Women's childbirth experience was assessed with the Childbirth Experience Questionnaire (CEQ 2.0) and visual analog scale. We present crude and adjusted mean differences and relative risks (RR) with 95% CI. Adjustment was performed for a propensity score based on delivery hospital and baseline characteristics including Bishop score. Results Vaginal delivery within 24 h was significantly lower in the misoprostol group compared with the balloon catheter group (46.5% [346/744] versus 62.7% [294/469]; adjusted RR 0.76 95% CI 0.640.89]). Primary neonatal and maternal safety outcomes did not differ between groups (neonatal composite 3.5% [36/744] vs 3.2% [15/469]; adjusted RR 0.77 [95% CI 0.31-1.89]; maternal composite 2.3% [17/744] versus 1.9% [9/469]; adjusted RR 1.70 [95% CI 0.58-4.97]). Adjusted mean time to vaginal delivery was increased by 3.8 h (95% CI 1.3-6.2 h) in the misoprostol group. Non-operative vaginal delivery and cesarean delivery rates did not differ. Women's childbirth experience was positive overall and similar in both groups. Conclusion Induction of labor with oral misoprostol compared with a transvaginal balloon catheter was associated with a lower probability of vaginal delivery within 24 h and a longer time to vaginal delivery. However, primary safety outcomes, non-operative vaginal delivery, and women's childbirth experience were similar in both groups. Therefore, both methods can be recommended in women with low-risk postdate pregnancies.
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| 5. |
- Alkmark, Mårten, 1973, et al.
(författare)
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Induction of labour at 41weeks of gestation versus expectant management and induction of labour at 42weeks of gestation: a cost-effectiveness analysis
- 2022
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:13, s. 2157-2165
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the cost-effectiveness of induction of labour (IOL) at 41weeks of gestation compared with expectant management until 42weeks of gestation. Design: A cost-effectiveness analysis alongside the Swedish Post-term Induction Study (SWEPIS), a multicentre, randomised controlled superiority trial. Setting: Fourteen Swedish hospitals during 2016–2018. Population: Women with an uncomplicated singleton pregnancy with a fetus in cephalic position were randomised at 41weeks of gestation to IOL or to expectant management and induction at 42weeks of gestation. Methods: Health benefits were measured in life years and quality-adjusted life years (QALYs) for mother and child. Total cost per birth was calculated, including healthcare costs from randomisation to discharge after delivery, for mother and child. Incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in mean cost between the trial arms by the difference in life years and QALYs, respectively. Sampling uncertainty was evaluated using non-parametric bootstrapping. Main outcome measures: The cost per gained life year and per gained QALY. Results: The differences in life years and QALYs gained were driven by the difference in perinatal mortality alone. The absolute risk reduction in mortality was 0.004 (from 6/1373 to 0/1373). Based on Swedish life tables, this gives a mean gain in discounted life years and QALYs of 0.14 and 0.12 per birth, respectively. The mean cost per birth was €4108 in the IOL group (n=1373) and €4037 in the expectant management group (n=1373), with a mean difference of €71 (95%CI −€232 to €379). The ICER for IOL compared with expectant management was €545 per life year gained and €623 per QALY gained. Confidence intervals were relatively wide and included the possibility that IOL had both lower costs and better health outcomes. Conclusions: Induction of labour at 41weeks of gestation results in a better health outcome and no significant difference in costs. IOL is cost-effective compared with expectant management until 42weeks of gestation using standard threshold values for acceptable cost per life year/QALY. Tweetable abstract: Induction of labour at 41weeks of gestation is cost-effective compared with expectant management until 42weeks of gestation.
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| 6. |
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| 7. |
- Bergman, Lina, 1982, et al.
(författare)
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Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
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Tidskriftsartikel (refereegranskat)abstract
- Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. 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 (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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| 8. |
- Carlsson, Ylva, 1975
(författare)
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Apoptotic mechanisms in the neonatal brain following hypoxia-ischemia
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neonatal encephalopathy is often perinatally acquired and caused by hypoxia-ischemia (HI). Brain injury develops with a delay, over 12-48 hours, after the insult. Hypothermia, an established neuroprotective treatment, saves 1 infant in 9 from neurological deficits suggesting that there is room for further improvement. HI leads to cell death through multiple pathways, including apoptosis. The aim of this thesis was to investigate different apoptotic pathways and to explore possible ... merapoptotic targets for future pharmacological treatment after perinatal brain injury. We investigated (I) the involvement of caspase-2 alone, (II) and in combination with hypothermia, (III) the role of c-Jun N-terminal kinase (JNK), and (IV) Cyclophilin D (CypD), a regulator of the mitochondrial membrane permeability transition pore. Materials and methods: Wild type (WT) C57BL/6 and transgenic mice with gene deletion of caspase-2 (I, II) and CypD (IV) were used in the ibotenate (excitotoxic)-model (I), and/or Rice-Vannucci´s HI-model (I-IV) at postnatal day 5 (I) or 9 (I-IV). The mixed lineage kinase inhibitor CEP-1347 was used to explore the role of JNK after neonatal HI (III). Results: Caspase-2-deficient mice demonstrated less gray and white matter injury after both neonatal HI and an excitotoxic insult (I). Hypothermia provided additional protection in caspase-2 deficient mice (II). CEP-1347 was neuroprotective in the immature brain, by reducing apoptosis and attenuating microgliosis (III). CypD gene deficiency enhanced HI injury and Bax inhibitory peptide (BIP) reduced injury in the immature brain, whereas CypD deletion protected and BIP had no effect on brain damage in the mature mouse brain. Apoptosis was more pronounced in the immature CypD deficient mice than in WT controls, while adults showed minimal apoptotic activation. Conclusion: Apoptosis has a more prominent role in the immature brain and different pathways leading to cell death after HI are at play in the immature as compared to the adult brain. This suggests that different pharmacological interventions are required in the immature and the mature brain. We suggest that caspase-2 as well as Bax dependent mitochondrial permeabilization are important neuroprotective targets in neonatal HI brain injury.
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| 9. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Combined effect of hypothermia and caspase-2 gene deficiency on neonatal hypoxic-ischemic brain injury.
- 2012
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Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 71:5, s. 566-72
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Tidskriftsartikel (refereegranskat)abstract
- Intoduction:Hypoxia-ischemia (HI) injury in term infants develops with a delay during the recovery phase, opening up a therapeutic window after the insult. Hypothermia is currently an established neuroprotective treatment in newborns with neonatal encephalopathy (NE), saving one in nine infants from developing neurological deficits. Caspase-2 is an initiator caspase, a key enzyme in the route to destruction and, therefore, theoretically a potential target for a pharmaceutical strategy to prevent HI brain damage.Methods:The aim of this study was to explore the neuroprotective efficacy of hypothermia in combination with caspase-2 gene deficiency using the neonatal Rice-Vannucci model of HI injury in mice.Results:HI brain injury was moderately reduced in caspase-2(-/-) mice as compared with wild-type (WT) mice. Five hours of hypothermia (33°C ) vs. normothermia (36°C) directly after HI provided additive protection overall (temperature P = 0.0004, caspase-2 genotype P = 0.0029), in the hippocampus and thalamus, but not in other gray matter regions or white matter. Delayed hypothermia initiated 2h after HI in combination with caspase-2 gene deficiency reduced injury in the hippocampus, but not in other brain areas.Discussion:In conclusion, caspase-2 gene deficiency combined with hypothermia provided enhanced neuroprotection as compared with hypothermia alone.
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| 10. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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| 11. |
- Carlsson, Ylva, 1975, et al.
(författare)
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COVID-19 in Pregnancy and Early Childhood (COPE): study protocol for a prospective, multicentre biobank, survey and database cohort study.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- 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.This is a national, multicentre, prospective cohort study involving 27 Swedish maternity units accounting for over 86000 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 4years 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.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.NCT04433364.
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| 12. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Genetic inhibition of caspase-2 reduces hypoxic-ischemic and excitotoxic neonatal brain injury.
- 2011
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Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 70:5, s. 781-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Perinatal brain injury is a major cause of neurodevelopmental handicaps. Multiple pathways of oxidant stress, inflammation, and excitotoxicity lead to cell damage and death, including caspase-dependent apoptosis. Caspase-2 (Casp2; Nedd-2, Ich-1) is a developmentally regulated initiator caspase, which poorly cleaves other caspases but can initiate mitochondrial outer membrane permeabilization. We have investigated if Casp2 could mediate perinatal ischemic brain damage. METHODS: Casp2 expression in human neonatal brains and developmental patterns in rats and mice were evaluated. Casp2-deficient (Casp2(-/-) ), wild-type (WT), and heterozygous (Casp2(+/-) ) newborn C57BL/6 mice were subjected to hypoxia-ischemia (unilateral carotid occlusion + exposure to 10% oxygen for 50 minutes) or intracerebral injection of the excitotoxic N-methyl-D-aspartate-receptor agonist ibotenate. In addition, Casp2 specific siRNAs were preinjected into the brain of WT newborn mice 24 hours before ibotenate treatment. Brain tissues were examined by immunohistochemical staining (cresyl violet, MAP2, NF68, Casp2, Casp3) and Western blotting. Lesion volumes and injury in the cortical plates and white matter were quantified together with activated Casp3. RESULTS: Casp2 is highly expressed in the neonatal brain. Casp2-deficient mice subjected to hypoxia-ischemia at postnatal day 9 present significantly lower cerebral infarction, reduced white matter injury, and reduced Casp3 activation in the thalamus and hippocampus. Both Casp2(-/-) mice and siRNA-administered WT mice conferred reduction of gray and white matter injury after excitotoxic insult at postnatal day 5. Casp3 activation was also found reduced in Casp2-deficient mice subjected to excitotoxicity. INTERPRETATION: These data suggest for the first time a role of Casp2 in neonatal brain damage. ANN NEUROL 2011;
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| 13. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Parents’ experiences of the information provided at the antenatal clinic regarding foetal diagnostics – A qualitative interview study
- 2021
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Ingår i: Sexual and Reproductive Healthcare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 29
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study aimed to examine the pregnant women's and their partner's experience of the information given at the antenatal clinic regarding screening methods. Methods: A qualitative interview study was conducted in the Gothenburg area in Sweden. Ten women and seven partners expecting their first child were interviewed adjacent to the second-trimester ultrasound examination. The data were analysed using qualitative content analysis. Results: The findings present an overall theme, three main categories, and ten subcategories. The overall theme showed a nonhomogeneous and individually based picture concerning the meaning and purpose of the methods, need for improvement of information, parents own information seeking, and the encounter with the midwife was also experienced as an influential encounter. The main categories show that diversity relates to the level of information given, voluntariness, the possibility of abnormal findings, and varying needs to thorough information and pre-existing knowledge. The midwifés impact was related to attitude, openness for questions, time for explanations, and the balance between providing enough information to support without worrying the parents. Conclusions: Although previous research has pointed out a decade ago that information regarding foetal diagnostics is lacking, this study shows that these shortcomings still exist and that improvement is needed. The given information should be explicit concerning the purpose, limitations, and voluntariness of prenatal testing. Sufficient time for questions and discussion is as important as considering the parents’ pre-existing knowledge, individual thoughts or questions, and a neutral attitude from the midwife is desirable.
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| 14. |
- Carlsson, Ylva, 1975, et al.
(författare)
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Role of mixed lineage kinase inhibition in neonatal hypoxia-ischemia.
- 2009
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 31:5, s. 420-6
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Tidskriftsartikel (refereegranskat)abstract
- Hypoxic-ischemic brain injury is often delayed and involves both apoptotic and immunoregulatory mechanisms. In this study, we used a neonatal model of hypoxia-ischemia to examine the effect of the mixed lineage kinase (MLK) inhibitor CEP-1347 on brain damage, apoptosis and inflammation. The tissue volume loss was reduced by 28% (p = 0.019) in CEP-1347-treated versus vehicle-treated rats and CEP-1347 significantly attenuated microgliosis at 7 days (p = 0.038). CEP-1347 decreased TUNEL-positive staining as well as cleaved caspase 3 immunoreactivity. CEP-1347 did not affect the expression of pro-inflammatory cytokines IL-1 beta, IL-6 and MCP-1, nor did it affect the expression of OX-42 (CR3) and OX-18 (MHC I) 24 h after the insult. In conclusion, the MLK inhibitor CEP-1347 has protective effects in a neonatal rat model of hypoxia-ischemia, which is mainly related to reduced apoptosis.
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| 15. |
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| 16. |
- Chauvier, D, et al.
(författare)
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Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible caspase inhibitor.
- 2011
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Brain protection of the newborn remains a challenging priority and represents a totally unmet medical need. Pharmacological inhibition of caspases appears as a promising strategy for neuroprotection. In a translational perspective, we have developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563, which reaches the brain, and inhibits caspases activation, mitochondrial release of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal arterial stroke with a 6-h therapeutic time window, and has no adverse effects on physiological parameters. Safety pharmacology investigations, and toxicology studies in rodent and canine neonates, suggest that TRP601 is a lead compound for further drug development to treat ischemic brain damage in human newborns.
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| 17. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome.
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:1
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Tidskriftsartikel (refereegranskat)abstract
- Prenatal screening has historically focused primarily on detection of fetal aneuploidies. Cell-free DNA (cfDNA) now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (22q11.2DS or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2DS, large cohort studies with postnatal confirmatory testing to assess test performance have not been reported.To assess the performance of SNP-based cfDNA prenatal screening for detection of 22q11.2DS.Patients who had SNP-based cfDNA prenatal screening for 22q11.2DS were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation with chromosomal microarray. The primary outcome was sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cfDNA for detection of all deletions, including the classical deletion and nested deletions that are ≥500kb, in the 22q11.2 low copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2DS and performance of an updated cfDNA algorithm that was evaluated blinded to pregnancy outcome.Of 20,887 women enrolled, genetic outcome was available in 18,289 (87.6%). Twelve 22q11.2DS cases were confirmed in the cohort, including five (41.7%) nested deletions, yielding a prevalence of 1:1524. In the total cohort, cfDNA reported 17,976 (98.3%) as low risk for 22q11.2DS and 38 (0.2%) as high-risk; 275 (1.5%) were non-reportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% CI: 42.8, 94.5); specificity of 99.84% (95% CI: 99.77, 99.89); PPV of 23.7% (95% CI: 11.44, 40.24) and NPV of 99.98% (95% CI: 99.95, 100). None of the cases with a non-reportable result was diagnosed with 22q11.2DS. The updated algorithm detected 10/12 cases (83.3%; 95% CI: 51.6-97.9) with a lower false positive rate (0.05% vs. 0.16%, p<0.001) and a PPV of 52.6% (10/19; 95% CI 28.9-75.6).Noninvasive cfDNA prenatal screening for 22q11.2DS can detect most affected cases, including smaller nested deletions, with a low false positive rate.
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| 18. |
- Dar, Pe'er, et al.
(författare)
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Cell-free DNA screening for trisomies 21, 18 and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation
- 2022
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 227:2
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Tidskriftsartikel (refereegranskat)abstract
- Cell-free DNA (cfDNA) non-invasive prenatal screening for trisomy (T) 21, 18, and 13 has been rapidly adopted into clinical practice. However, prior studies are limited by lack of follow up genetic testing to confirm outcomes and accurately assess test performance, particularly in women at low-risk for aneuploidy.To compare the performance of cfDNA screening for T21, T18 and T13 between women at low and high-risk for aneuploidy in a large, prospective cohort with genetic confirmation of results.A multicenter prospective observational study at 21 centers in 6 countries. Women who had SNP-based cfDNA screening for T21, T18 and T13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. Test performance and test failure (no-call) rates were assessed for the cohort and women with low and high prior risk for aneuploidy were compared. An updated cfDNA algorithm, blinded to pregnancy outcome, was also assessed.20,194 were enrolled at median gestational age of 12.6 weeks (IQR:11.6, 13.9). Genetic outcomes were confirmed in 17,851 (88.4%): 13,043 (73.1%) low-risk and 4,808 (26.9%) high-risk for aneuploidy. Overall, 133 trisomies were diagnosed (100 T21; 18 T18; 15 T13). cfDNA screen positive rate was lower in low- vs. high-risk (0.27% vs. 2.2%, p<0.0001). Sensitivity and specificity were similar between groups. The positive predictive value (PPV) for the low and high-risk groups was 85.7% vs. 97.5%, p=0.058 for T21; 50.0% vs. 81.3%, p=0.283 for T18; and 62.5% vs. 83.3, p=0.58 for T13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. Trisomy rate was higher in the 287 with no-call results than patients with a result on a first draw (2.8% vs. 0.7%, p=0.001). The updated algorithm showed similar sensitivity and specificity to the study algorhitm with a lower no-call rate.In women at low-risk for aneuploidy, SNP-based cfDNA has high sensitivity and specificity, PPV of 85.7% for T21 and 74.3% for the three common trisomies. Patients who receive a no-call result are at increased risk of aneuploidy and require additional investigation.
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| 19. |
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| 20. |
- Ginstman, Charlotte, 1975-, et al.
(författare)
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Pharmacokinetics of Oral Levonorgestrel in Women After Roux-en-Y Gastric Bypass Surgery and in BMI-Matched Controls
- 2020
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Ingår i: Obesity Surgery. - : Springer. - 0960-8923 .- 1708-0428. ; 30:6, s. 2217-2224
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Tidskriftsartikel (refereegranskat)abstract
- Background: Women are advised to primarily use non-oral contraceptive alternatives after Roux-en-Y gastric bypass since it is not known if the surgery affects the pharmacokinetics of oral contraceptives.Methods: This is a multi-center, open label, phase 2 pharmacokinetic study performed at the University Hospital of Linkoping and the Clinical Trials Center, Department of Obstetrics and Gynecology, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Fifteen women aged 18-40 years who had previously undergone Roux-en-Y gastric bypass surgery and reached a BMI < 30 were included. Fifteen BMI-matched women with no previous history of Roux-en-Y gastric bypass surgery served as a control group. After administration of a single dose of a combined oral contraceptive containing 0.03 mg ethinylestradiol/0.15 mg levonorgestrel, serum levonorgestrel concentrations were determined during a 24-h period using ultra performance liquid chromatography/tandem mass spectrometry. The area under the plasma concentration time curve of levonorgestrel (AUC(0-24h)) was the main outcome measure.Results: There were no significant differences in the studied pharmacokinetic parameters, AUC(0-24h), total AUC, peak serum concentration (C-max), time to peak serum concentrations (T-max), apparent oral clearances of levonorgestrel (CLoral), or terminal half-lives (t1/2) between the groups.Conclusion: This is to our knowledge the first study to evaluate the pharmacokinetics of oral levonorgestrel in women with a BMI < 30 at least 1 year after RYGB compared with a BMI-matched group of women. We could not find any significant pharmacokinetic differences between the groups, suggesting that oral levonorgestrel may be used in non-obese women after Roux-en-Y gastric bypass once a stable body weight has been reached.
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| 21. |
- Hallingström, Maria, et al.
(författare)
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The association between selected mid-trimester amniotic fluid candidate proteins and spontaneous preterm delivery
- 2020
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 33:4, s. 583-592
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore inflammatory response and identify early potential biomarkers in mid-trimester amniotic fluid associated with subsequent spontaneous preterm delivery (PTD). Methods: A cohort study was performed at Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, between 2008 and 2010. Amniotic fluid was collected from consecutive women undergoing mid-trimester transabdominal genetic amniocentesis at 14–19 gestational weeks. Clinical data and delivery outcome variables were obtained from medical records. The analysis included 19 women with spontaneous PTD and 118 women who delivered at term. A panel of 26 candidate proteins was analyzed using Luminex xMAP technology. Candidate protein concentrations were analyzed with ANCOVA and adjusted for plate effects. Results: The median gestational age at delivery was 35 + 3 weeks in women with spontaneous PTD and 40 + 0 weeks in women who delivered at term. Nominally significantly lower amniotic fluid levels of adiponectin (PTD: median 130,695 pg/mL (IQR 71,852–199,414) vs term: median 185,329 pg/mL (IQR (135,815–290,532)), granulocyte-macrophage colony stimulating factor (PTD: median 137 pg/mL (IQR 74–156) vs term: median 176 pg/mL (IQR 111–262)), and macrophage migration inhibitory factor (PTD: median 3025 pg/mL (IQR 1885–3891) vs term: median 3400 pg/mL (IQR 2181–5231)) were observed in the spontaneous PTD group, compared with the term delivery group, after adjusting for plate effects. No significant differences remained after Bonferroni correction for multiple comparisons. Conclusions: Our results are important in the process of determining the etiology behind spontaneous PTD but due to the non-significance after Bonferroni correction, the results should be interpreted with caution. Further analyses of larger sample size will be required to determine whether these results are cogent and to examine whether microbial invasion of the amniotic cavity or intra-amniotic inflammation occurs in asymptomatic women in the mid-trimester with subsequent spontaneous PTD.
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| 22. |
- Hellström, Sara, et al.
(författare)
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A follow up on the feasibility after national implementation of magnesium sulfate for neuroprotection prior to preterm birth.
- 2023
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : John Wiley & Sons. - 1600-0412 .- 0001-6349. ; 102:12, s. 1741-1748
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Tidskriftsartikel (refereegranskat)abstract
- The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4 ) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6g MgSO4 1-24h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation.Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0-31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre-eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded.A total of 388 women were eligible and 79% received treatment with MgSO4 . Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7h, median 3.4h).There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians.
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| 23. |
- Iorizzo, L., et al.
(författare)
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Proposed cutoff for fetal scalp blood lactate in intrapartum fetal surveillance based on neonatal outcomes: a large prospective observational study
- 2022
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Ingår i: BJOG: An International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 129:4, s. 636-646
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Determination of lactate in fetal scalp blood (FBS) during labour has been recognised since the 1970s. The internationally accepted cutoff of >4.8mmol/l indicating fetal acidosis is exclusive for the point-of-care device (POC) LactatePro™, which is no longer in production. The aim of this study was to establish a new cutoff for scalp lactate based on neonatal outcomes with the use of the StatstripLactate®/StatstripXpress® Lactate system, the only POC designed for hospital use. Design: Observational study. Setting: January 2016 to March 2020 labouring women with indication for FBS were prospectively included from seven Swedish and one Australian delivery unit. Population: Inclusion criteria: singleton pregnancy, vertex presentation, ≥35+0weeks of gestation. Method: Based on the optimal correlation between FBS lactate and cord pH/lactate, only cases with ≤25minutes from FBS to delivery were included in the final calculations. Main outcome measures: Metabolic acidosis in cord blood defined as pH <7.05 plus BDecf >10mmol/l and/or lactate >10mmol/l. Results: A total of 3334 women were enrolled of whom 799 were delivered within 25minutes. The areas under the receiver operating characteristics curves (AUC) and corresponding optimal cutoff values were as follows; metabolic acidosis AUC 0.87 (95% CI 0.77–0.97), cutoff 5.7mmol/l; pH <7.0 AUC 0.83 (95% CI 0.68–0.97), cutoff 4.6mmol/l; pH <7.05 plus BDecf ≥12mmol/l AUC 0.97 (95% CI 0.92–1), cutoff 5.8mmol/l; Apgar score <7 at 5minutes AUC 0.74 (95% CI 0.63–0.86), cutoff 5.2mmol/l; and pH <7.10 plus composite neonatal outcome AUC 0.76 (95% CI 0.67–0.85), cutoff 4.8mmol/l. Conclusion: A scalp lactate level <5.2mmol/l using the StatstripLactate®/StatstripXpress® system will safely rule out fetal metabolic acidosis. Tweetable abstract: Scalp blood lactate <5.2mmol/l using the StatstripLactate®/StatstripXpress system has an excellent ability to rule out fetal acidosis.
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| 24. |
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| 25. |
- Jonsdotter, Andrea, 1984, et al.
(författare)
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Maternal and fetal serum concentrations of magnesium after administration of a 6-g bolus dose of magnesium sulfate (MgSO4) to women with imminent preterm delivery
- 2022
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 101:8, s. 856-861
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Magnesium sulfate is used world-wide to treat pregnant women at imminent risk of preterm delivery in order to protect the brain of the premature infant. Previous research has shown that magnesium sulfate decreases the risk of cerebral palsy by similar to 30% in infants born preterm. Despite this, the dosage required for optimal neuroprotection remains unknown. We aimed to investigate whether 6 g magnesium sulfate given as a single bolus dose was tolerable for the women and infants and whether the desired target concentration in the mother's blood was reached and non-toxic level in the infant could be ensured. Material and methods: In total, 49 women who were at risk of delivery prior to 32 weeks of gestation were recruited. They received a bolus dose of 6 g magnesium sulfate intravenously between 1 and 24 h prior to giving birth and were closely monitored during and after infusion. Blood samples from the patients were analyzed at different time-points (20-30 min after start of infusion, 1, 2, 6 and 24 h) post-administration. Blood samples from the umbilical cord were also taken directly after birth to assess the concentration of magnesium in the infant. Results: None of the women who received magnesium sulfate reached serum magnesium concentrations >3.3 mmol/L. In all, 72% of the women showed serum magnesium levels within the therapeutic interval (2.0-3.5 mmol/L) and no adverse events were observed during the infusion. The serum magnesium levels in the mothers declined to pre-bolus-levels within 24 h after delivery. Serum magnesium levels in the umbilical cord samples ranged from 0.87 to 1.4 mmol/L, which means that all but two were within the normal expected range for a newborn premature infant. Conclusions: A bolus dose of 6 g magnesium sulfate was well tolerated and without any serious side effects in either mother or infant. Most of our women reached the targeted concentration range of serum magnesium levels after infusion was completed. Their infants had magnesium levels within acceptable levels, regardless of gestational week or mother's body mass index.
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