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107. Reliability of recurrent pregnancy loss diagnosis coding in the Swedish National Patient Register: a validation study.

Author

Roepke, Emma Rasmark, Christiansen, Ole Bjarne, and Hansson, Stefan R

Subjects
RECURRENT miscarriage, PREGNANT women, MEDICAL registries, EPIDEMIOLOGICAL research, MEDICAL records, STATISTICAL reliability
Abstract

Background: The Swedish National Patient Registry (NPR) is a nationwide registry that is used extensively for epidemiological research. Using the NPR, we recently found a recurrent pregnancy loss (RPL) incidence of 650/100,000 (0.65%) pregnant women in Sweden. It is of great importance that the quality of the coding is good and reliable in order to use NPR data for research. To specifically study RPL in Sweden, a general validation of this diagnosis in the NPR is needed. Objective: To validate the diagnosis of RPL, defined as ≥3 consecutive miscarriages before 22 gestational weeks, recorded in the NPR and assess how registered miscarriages were verified clinically (ultrasound or urine/serum hCG) by reviewing the medical records. Materials and methods: In a cohort of 6,852 women diagnosed with RPL in Sweden, during 2003–2012, a total of 238 complete medical records from 38 hospitals were reviewed. A power calculation estimated that 228 medical records had to be reviewed for a positive predictive value (PPV) of 85% (95% CI) with a power of 90%. The ICD-10 diagnoses used for RPL were N96.9 and O26.2. Results: The diagnosis of RPL was confirmed in 202 out of 238 medical records resulting in a PPV of 85% (95% CI 78–89%) out of which 59% were verified with ultrasound whereas 35% were verified only by urine/serum hCG. Conclusion: The Swedish NPR is a valuable tool for epidemiological research. We found a high PPV of RPL in the NPR, supporting the use of these data for future research. [ABSTRACT FROM AUTHOR]

Published
2019
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108. Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue:a novel model of placental malaria

Author

Pehrson, Caroline, Mathiesen, Line, Heno, Kristine K, Salanti, Ali, dos Santos Marques Resende, Mafalda, Dzikowski, Ron, Damm, Peter, Hansson, Stefan R, King, Christopher L, Schneider, Henning, Wang, Christian W, Lavstsen, Thomas, Theander, Thor G, Knudsen, Lisbeth E, Nielsen, Morten A, Pehrson, Caroline, Mathiesen, Line, Heno, Kristine K, Salanti, Ali, dos Santos Marques Resende, Mafalda, Dzikowski, Ron, Damm, Peter, Hansson, Stefan R, King, Christopher L, Schneider, Henning, Wang, Christian W, Lavstsen, Thomas, Theander, Thor G, Knudsen, Lisbeth E, and Nielsen, Morten A

Abstract

BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design. The objective of this study was to adapt and describe a biologically relevant model of parasite adhesion in intact placental tissue. RESULTS: The ex vivo placental perfusion model was modified to study adhesion of infected erythrocytes binding to CSA, endothelial protein C receptor (EPCR) or a transgenic parasite where P. falciparum erythrocyte membrane protein 1 expression had been shut down. Infected erythrocytes expressing VAR2CSA accumulated in perfused placental tissue whereas the EPCR binding and the transgenic parasite did not. Soluble CSA and antibodies specific against VAR2CSA inhibited binding of infected erythrocytes. CONCLUSION: The ex vivo model provides a novel way of studying receptor-ligand interactions and antibody mediated inhibition of binding in placental malaria.

Published
2016

114. Adhesion of Plasmodium falciparum infected erythrocytes in ex vivo perfused placental tissue: a novel model of placental malaria

Author

Pehrson, Caroline, primary, Mathiesen, Line, additional, Heno, Kristine K., additional, Salanti, Ali, additional, Resende, Mafalda, additional, Dzikowski, Ron, additional, Damm, Peter, additional, Hansson, Stefan R., additional, King, Christopher L., additional, Schneider, Henning, additional, Wang, Christian W., additional, Lavstsen, Thomas, additional, Theander, Thor G., additional, Knudsen, Lisbeth E., additional, and Nielsen, Morten A., additional

Published
2016
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122. [97-POS]

Author

Anderson, Ulrik D., primary, Gram, Magnus, additional, Thilaganathan, Basky, additional, Åkerström, Bo, additional, and Hansson, Stefan R., additional

Published
2015
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123. [167-POS]

Author

Anderson, Ulrik D., primary, Gram, Magnus, additional, Jälmby, Maya, additional, Åkerström, Bo, additional, and Hansson, Stefan R., additional

Published
2015
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126. Syncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia

Author

Cronqvist, Tina, primary, Saljé, Karen, additional, Familari, Mary, additional, Guller, Seth, additional, Schneider, Henning, additional, Gardiner, Chris, additional, Sargent, Ian L., additional, Redman, Christopher W., additional, Mörgelin, Matthias, additional, Åkerström, Bo, additional, Gram, Magnus, additional, and Hansson, Stefan R., additional

Published
2014
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128. A1M/α1-Microglobulin Protects from Heme-Induced Placental and Renal Damage in a Pregnant Sheep Model of Preeclampsia

Author

Wester-Rosenlöf, Lena, primary, Casslén, Vera, additional, Axelsson, Josefin, additional, Edström-Hägerwall, Anneli, additional, Gram, Magnus, additional, Holmqvist, Madlene, additional, Johansson, Martin E., additional, Larsson, Iréne, additional, Ley, David, additional, Marsal, Karel, additional, Mörgelin, Matthias, additional, Rippe, Bengt, additional, Rutardottir, Sigurbjörg, additional, Shohani, Behnaz, additional, Åkerström, Bo, additional, and Hansson, Stefan R., additional

Published
2014
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129. Gene expression profiling of placentae from women with early- and late-onset pre-eclampsia : down-regulation of the angiogenesis related genes ACVRL1 and EGFL7 in early-onset disease

Author

Junus, Katja, Centlow, Magnus, Wikström, Anna-Karin, Larsson, Irene, Hansson, Stefan R, Olovsson, Matts, Junus, Katja, Centlow, Magnus, Wikström, Anna-Karin, Larsson, Irene, Hansson, Stefan R, and Olovsson, Matts

Abstract

The underlying mechanisms behind the obstetric condition pre-eclampsia (PE) are still unclear. Manifestation of PE is heterogeneous and it has therefore been proposed to be a syndrome with different causes rather than one disease with a specific aetiology. Recently, we showed differences in circulating angiogenic factors between two subgroups - early- and late-onset PE. To further elucidate the differences between the two, we investigated placental gene expression profiles. Whole genome microarray technology and bioinformatic analysis were used to evaluate gene expression profiles in placentae from early- (24-32 gestational weeks, n=8) and late-onset (36-41 gestational weeks, n=7) PE. The results were verified by using quantitative real-time PCR. We found significant differences in the expression of 196 genes in early- compared with late-onset PE, 45 of these genes showing a fold change above 2. Bioinformatic analysis revealed alterations in angiogenesis and regulation of cell motility. Two angiogenesis-associated transcripts (Egfl7 and Acvrl1) showed lower expression in early-onset PE vs. late-onset PE (p=0.037 and p=0.003) and vs. gestational age-matched controls (p=0.007 and p=0.011). We conclude that angiogenesis-associated genes are regulated in a different manner in the two subgroups, and that the gene expression profiles of early- and late-onset PE diverge, supporting the hypothesis of early- and late-onset PE being at least partly two separate entities.

Published
2012
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149. Extracellular fetal hemoglobin induces increases in glomerular permeability: inhibition with α1-microglobulin and tempol.

Author

Sverrisson, Kristinn, Axelsson, Josefin, Rippe, Anna, Gram, Magnus, Åkerström, Bo, Hansson, Stefan R., and Rippe, Bengt

Abstract

Extracellular fetal hemoglobin (HbF) and adult hemoglobin (HbA) are proinflammatory and generate ROS. Increased plasma levels of extracellular HbF have recently been reported to occur in early preeclampsia. α1-Microglobulin (A1M) is a physiological heme-binding protein and radical scavenger that has been shown to counteract vascular permeability increases induced by HbA in the perfused placenta. The present study was performed to investigate whether HbF and HbA will increase glomerular permeability in vivo and to test whether A1M and tempol, a ROS scavenger, can prevent their effects. Anesthetized Wistar rats were continuously infused intravenously with either HbA, HbF, or cyano-inactivated HbF together with FITC-Ficoll-70/400, inulin, and 51Cr-labeled EDTA for 2 h. Plasma samples and urine samples (left ureter) were taken repeatedly and analyzed by high-performance size exclusion chromatography to assess glomerular sieving coefficients for Ficoll of radius 10–80 Å. In separate experiments, A1M or tempol was given before and during Hb infusions. Extracellular HbF caused rapid, transient increases in glomerular permeability to large Ficoll molecules (50–80Å), contrary to the effects of HbA and cyano-inactivated HbF. For HbF, glomerular sieving coefficients for Ficoll of radius 60Å increased from 3.85 ± 0.85 × 10−5 to 2.60 ± 0.96 × 10−4 at 15 min, changes that were abrogated by tempol and reduced by A1M. In conclusion, our data demonstrate that extracellular HbF, infused systemically, can acutely increase glomerular permeability through inducing oxidative stress. [ABSTRACT FROM AUTHOR]

Published
2014
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150. Syncytiotrophoblast Vesicles Show Altered micro-RNA and Haemoglobin Content after Ex-vivo Perfusion of Placentas with Haemoglobin to Mimic Preeclampsia.

Author

Cronqvist, Tina, Saljé, Karen, Familari, Mary, Guller, Seth, Schneider, Henning, Gardiner, Chris, Sargent, Ian L., Redman, Christopher W., Mörgelin, Matthias, Åkerström, Bo, Gram, Magnus, and Hansson, Stefan R.

Subjects
TROPHOBLAST, MICRORNA, HEMOGLOBINS, PLACENTA, PREECLAMPSIA, COTYLEDONS
Abstract

Background: Cell-free foetal haemoglobin (HbF) has been shown to play a role in the pathology of preeclampsia (PE). In the present study, we aimed to further characterize the harmful effects of extracellular free haemoglobin (Hb) on the placenta. In particular, we investigated whether cell-free Hb affects the release of placental syncytiotrophoblast vesicles (STBMs) and their micro-RNA content. Methods: The dual ex-vivo perfusion system was used to perfuse isolated cotyledons from human placenta, with medium alone (control) or supplemented with cell-free Hb. Perfusion medium from the maternal side of the placenta was collected at the end of all perfusion phases. The STBMs were isolated using ultra-centrifugation, at 10,000×g and 150,000×g (referred to as 10K and 150K STBMs). The STBMs were characterized using the nanoparticle tracking analysis, identification of surface markers and transmission electron microscopy. RNA was extracted and nine different micro-RNAs, related to hypoxia, PE and Hb synthesis, were selected for analysis by quantitative PCR. Results: All micro-RNAs investigated were present in the STBMs. Mir-517a, mir-141 and mir-517b were down regulated after Hb perfusion in the 10K STBMs. Furthermore, Hb was shown to be carried by the STBMs. Conclusion: This study showed that Hb perfusion can alter the micro-RNA content of released STBMs. Of particular interest is the alteration of two placenta specific micro-RNAs; mir-517a and mir-517b. We have also seen that STBMs may function as carriers of Hb into the maternal circulation. [ABSTRACT FROM AUTHOR]

Published
2014
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