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Åkerud, Helena
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Publications (10 of 84) Show all publications
Friis, T., Wikström, A.-K., Acurio, J., Leon, J., Zetterberg, H., Blennow, K., . . . Bergman, L. (2022). Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia. Cells, 11(5), Article ID 789.
Open this publication in new window or tab >>Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia
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2022 (English)In: Cells, E-ISSN 2073-4409, Vol. 11, no 5, article id 789Article in journal (Refereed) Published
Abstract [en]

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 mu g/L, p < 0.001 and 0.08 vs. 0.05 mu g/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.

Place, publisher, year, edition, pages
MDPI AG, 2022
Keywords
blood-brain barrier, preeclampsia, pregnancy, in vitro studies, cerebral biomarkers, NfL, tau, NSE, S100B
National Category
Obstetrics, Gynecology and Reproductive Medicine Neurosciences
Identifiers
urn:nbn:se:uu:diva-471012 (URN)10.3390/cells11050789 (DOI)000768983100001 ()35269411 (PubMedID)
Note

De två sista författarna delar sistaförfattarskapet.

Available from: 2022-04-01 Created: 2022-04-01 Last updated: 2022-04-01Bibliographically approved
Sterpu, I., Pilo, C., Lindqvist, P. G., Åkerud, H. & Wiberg Itzel, E. (2022). Predictive factors in pregnancies with reduced fetal movements: a pilot study. The Journal of Maternal-Fetal & Neonatal Medicine, 35(23), 4543-4551
Open this publication in new window or tab >>Predictive factors in pregnancies with reduced fetal movements: a pilot study
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2022 (English)In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 35, no 23, p. 4543-4551Article in journal (Refereed) Published
Abstract [en]

Background Pregnancies with reduced fetal movements (RFM) are at risk for poor neonatal outcomes and stillbirth. Aim To investigate whether Doppler measurements or angiogenic factors are good predictors of adverse neonatal outcomes in pregnancies with RFM. Methods This is a prospective pilot cohort study of 3243 women seeking care for RFM. Standard care was carried out in all cases. An extra Doppler examination was performed in 128 women to assess the flow in the middle cerebral artery, the umbilical artery, and the uterine artery. In 62/128 pregnancies, a maternal blood sample was obtained for angiogenic and antiangiogenic factors. The composite neonatal outcome of the study was one or more of the following factors: Apgar score <7 at 5 ', arterial aPh in the umbilical cord <= 7.1, transfer to Neonatal Intensive Care (NICU), stillbirth, and small for gestational age (SGA). Results In 14.1% (18/128) of the Doppler group and 11.7% (365/3115) of the standard care group, there was an adverse neonatal outcome (p = .51). A higher intervention rate was found in the Doppler group (28% vs. 5.4%, p < .01). The predictive model of adverse neonatal outcomes in women with RFM with angiogenic factors was 0.73 (95% CI 0.54-0.92). The area under the curve improved to 0.89 (CI 95% 0.81-0.97) when parity was added to the model. Conclusion Angiogenic factors may have a place in the prediction of the neonatal outcome of RFM pregnancies. The prediction model's capacity was driven by parity. The obstetrical intervention rate increased with additional Doppler examinations.

Place, publisher, year, edition, pages
Taylor & Francis, 2022
Keywords
Doppler, reduced fetal movement, ultrasound
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-494963 (URN)10.1080/14767058.2020.1855135 (DOI)000596643300001 ()36062520 (PubMedID)
Available from: 2023-01-23 Created: 2023-01-23 Last updated: 2023-01-23Bibliographically approved
Elbagir, S., Mohammed, N., Kaihola, H., Svenungsson, E., Gunnarsson, I., Manivel, V. A., . . . Rönnelid, J. (2020). Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies. Lupus, 29(5), 463-473
Open this publication in new window or tab >>Elevated IgA antiphospholipid antibodies in healthy pregnant women in Sudan but not Sweden, without corresponding increase in IgA anti-β2 glycoprotein I domain 1 antibodies
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2020 (English)In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 29, no 5, p. 463-473Article in journal (Refereed) Published
Abstract [en]

Objective: The role of antiphospholipid antibodies (aPL) during apparently normal pregnancy is still unclear. IgA aPL are prevalent in populations of African origin. Our aim was to measure all isotypes of anticardiolipin (anti-CL) and anti–β2 glycoprotein I (anti-β2GPI) in healthy pregnant and non-pregnant women of different ethnicities.

Methods: Healthy Sudanese pregnant women (n = 165; 53 sampled shortly after delivery), 96 age-matched Sudanese female controls and 42 healthy pregnant and 249 non-pregnant Swedish women were included. IgA/G/M anti-CL and anti-β2GPI were tested at one time point only with two independent assays in Sudanese and serially in pregnant Swedes. IgA anti-β2GPI domain 1 and as controls IgA/G/M rheumatoid factor (RF), IgG anti–cyclic citrullinated peptide 2 (anti-CCP2) and anti–thyroid peroxidase (anti-TPO) were investigated in Sudanese females.

Results: Pregnant Sudanese women had significantly higher median levels of IgA anti-CL, IgA anti-β2GPI (p < 0.0001 for both antibodies using two assays) and IgM anti-β2GPI (both assays; p < 0.0001 and 0.008) compared with non-pregnant Sudanese. IgA anti-CL and anti-β2GPI occurrence was increased among Sudanese pregnant women compared with national controls. No corresponding increase during pregnancy was found for IgA anti-β2GPI domain 1 antibodies. Both IgG anti-CL and IgG control autoantibodies decreased during and directly after pregnancy among Sudanese. Serially followed Swedish women showed no changes in IgA aPL, whereas IgG/M anti-CL decreased.

Conclusions: IgA aPL are increased in Sudanese but not in Swedish women, without corresponding increase in IgA domain 1. Whether due to ethnicity and/or environmental influences the occurrence of IgA aPL during Sudanese pregnancies, and its clinical significance, is yet to be determined.

Place, publisher, year, edition, pages
SAGE Publications, 2020
Keywords
Africa, Antiphospholipid antibodies, IgA, Sudan, healthy, pregnancy
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:uu:diva-411089 (URN)10.1177/0961203320908949 (DOI)000517082000001 ()32106789 (PubMedID)
Funder
Swedish Rheumatism Association
Available from: 2020-05-27 Created: 2020-05-27 Last updated: 2020-12-07Bibliographically approved
Skírnisdottir, I., Åkerud, H., Seidal, T. & Sundström-Poromaa, I. (2019). Cell Cycle Regulator p27 Mediates Body Mass IndexEffects in Ovarian Cancer in FIGO-stages I-II. Cancer Genomics & Proteomics, 16(6), 443-450
Open this publication in new window or tab >>Cell Cycle Regulator p27 Mediates Body Mass IndexEffects in Ovarian Cancer in FIGO-stages I-II
2019 (English)In: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 16, no 6, p. 443-450Article in journal (Refereed) Published
Abstract [en]

Background/Aim: The aim of the present study was to evaluate the association between body mass index (BMI), the biomarker p27, and the clinical factors in FIGO-stages I-II ovarian cancer. Patients and Methods: A total of 128 patients with ovarian cancer were included in the study. For testing differences in univariate analyzes we used the Pearson's Chi-square test and the log-rank test. For multivariate analyses the logistic regression and Cox regression models were used with recurrent disease and disease free survival as endpoints, respectively. Results: Patients with BMI <= 25 kg/m(2) had a significantly better 5-year disease free survival compared with patients with BMI >25 kg/m(2) in the total series of patients (p=0.008), and in the series of patients (n=77) with non-serous tumors (p=0.047). Patients with p27-positive non-serous tumors had higher survival compared to patients with p27-negative non-serous tumors (p=0.020). Conclusion: The cell cycle regulator p27 mediates BMI effects in ovarian cancer in FIGO-stages I-II.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2019
Keywords
BMI, p27, non-serous tumors, ovarian cancer, FIGOstages I-II.
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-396005 (URN)10.21873/cgp.20148 (DOI)000493397500004 ()31659099 (PubMedID)
Available from: 2019-10-28 Created: 2019-10-28 Last updated: 2019-11-18Bibliographically approved
Kaihola, H., Yaldir, F. G., Bohlin, T., Samir, R., Hreinsson, J. & Åkerud, H. (2019). Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts. PLOS ONE, 14(12), Article ID e0226419.
Open this publication in new window or tab >>Levels of caspase-3 and histidine-rich glycoprotein in the embryo secretome as biomarkers of good-quality day-2 embryos and high-quality blastocysts
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2019 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 12, article id e0226419Article in journal (Refereed) Published
Abstract [en]

Morphological assessment at defined developmental stages is the most important method to select viable embryos for transfer and cryopreservation. Timing of different developmental stages in embryo development has been shown to correlate with its potential to develop into a blastocyst. However, improvements in pregnancy rates by using time-lapse techniques have been difficult to validate scientifically. Therefore, there is a need for new methods, preferably non-invasive methods based on metabolomics, genomics and proteomics, to improve the evaluation of embryo quality even further. The aim of this study was to investigate if different levels of caspase-3 and histidine-rich glycoprotein (HRG), secreted by the embryo into the culture media, can be used as biomarkers of embryo quality. In this study, a total of 334 samples of culture media were collected from in vitro fertilization (IVF) treatments at three different clinics. Protein analysis of the culture media was performed using multiplex proximity extension protein analysis to detect levels of caspase-3 and HRG in the embryo secretome. Protein levels were compared in secretome samples from high- and low-quality blastocysts and embryos that became arrested during development. Correlation between protein levels and time to morula formation was also analyzed. Furthermore, protein levels in secretomes from day-2 cultured embryos were compared on the basis of whether or not pregnancy was achieved. The results showed that caspase-3 levels were lower in secretomes from high-quality vs. low-quality blastocysts and those that became arrested (p ≤ 0.05 for both). In addition, higher HRG levels correlated with a shorter time to morula formation (p ≤ 0.001). Caspase-3 levels were also lower in secretomes from day-2 cultured embryos resulting in a pregnancy vs. those that did not (p ≤ 0.05). Furthermore, it was shown that caspase-3 might be used as a marker for predicting potential success rate after transfer of day-2 cultured embryos, where a caspase-3 cutoff level of 0.02 gave a prediction probability of 68% (p = 0.038). In conclusion, in future prediction models, levels of caspase-3 and HRG might be used as potential markers of embryo quality, and secreted caspase-3 levels could to some extent predict the outcome after transfer of day-2 cultured embryos.

National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:uu:diva-411088 (URN)10.1371/journal.pone.0226419 (DOI)000534249400039 ()31856190 (PubMedID)
Funder
Swedish Research Council, FF-2017-477
Available from: 2020-05-27 Created: 2020-05-27 Last updated: 2021-06-14Bibliographically approved
Sterpu, I., Anfelter, P., Wray, S., Kaihola, H., Åkerud, H. & Wiberg-Itzel, E. (2019). The association of second trimester biomarkers in amniotic fluid and fetal outcome. The Journal of Maternal-Fetal & Neonatal Medicine, 32(21), 3627-3632
Open this publication in new window or tab >>The association of second trimester biomarkers in amniotic fluid and fetal outcome
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2019 (English)In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 32, no 21, p. 3627-3632Article in journal (Refereed) Published
Abstract [en]

Objective: To identify the level of amniotic fluid lactate (AFL), placental growth factor (PLGF), and vascular endothelial growth factor (VEGF) at second trimester amniocentesis, and to compare levels in normal pregnancies with pregnancies ending in a miscarriage, an intrauterine growth restricted fetus (IUGR) or decreased fetal movements.

Study design: A prospective cohort study. Amniotic fluid was consecutively collected at amniocentesis in 106 pregnancies. Fetal wellbeing at delivery was evaluated from medical files and compared with the levels of AFL, VEGF, and PLGF at the time of amniocentesis.

Results: The median level of AFL was 6.9 mmol/l, VEGF 0.088 pg/ml, and PLGF 0.208 pg/ml. The median levels of AFL in pregnancies ended in miscarriage were significantly higher (10.7 mmol/l) compared to those with a live new-born (6.9 mmol/L, p = .02). The levels of VEGF (p = .2) and PLGF (p = .7) were not affected. In pregnancies with an IUGR, the median level of AFL was higher compared to those with normal fetal growth (p = .003). No differences VEGF (p = .5), but significant lower PLGF were found in IUGR pregnancies (p = .03).

Conclusions: Pregnancies ending in a miscarriage or with IUGR had significantly higher median values of AFL but lower values of PLGF in the amniotic fluid at the time of second trimester amniocentesis compared to normal pregnancies.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Biomarkers, amniocentesis, AFL, PLGF, VEGF
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-392116 (URN)10.1080/14767058.2018.1469127 (DOI)000478069900020 ()29685073 (PubMedID)
Available from: 2019-09-06 Created: 2019-09-06 Last updated: 2019-09-06Bibliographically approved
Edvinsson, Å., Hellgren, C., Kallak, T. K., Åkerud, H., Skalkidou, A., Stener-Victorin, E., . . . Sundström Poromaa, I. (2019). The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression study.. BMC Pregnancy and Childbirth, 19, Article ID 479.
Open this publication in new window or tab >>The effect of antenatal depression and antidepressant treatment on placental tissue: a protein-validated gene expression study.
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2019 (English)In: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 19, article id 479Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Antenatal depression affects 10-20% of pregnant women. Around 2-4% of European pregnant women use antidepressant treatment, most commonly selective serotonin reuptake inhibitors (SSRIs). Poor pregnancy outcomes, such as preterm birth and low birth weight, have been described in women with antenatal depression and in pregnant women on SSRI treatment. However, the effects of antenatal depression and antidepressant treatment on the placenta are largely unknown. The aim of this work was to compare placental gene and protein expression in healthy women, women with untreated antenatal depression and women on antidepressant treatment during pregnancy.

METHODS: Placental samples from 47 controls, 25 depressed and 45 SSRI-treated women were analysed by means of qPCR using custom-designed TaqMan low-density arrays (TLDAs) for 44 genes previously known to be involved in the pathophysiology of depression, and expressed in the placenta. Moreover, placental protein expression was determined by means of immunohistochemistry in 37 healthy controls, 13 women with untreated depression and 21 women on antidepressant treatment. Statistical comparisons between groups were performed by one-way ANOVA or the Kruskal-Wallis test.

RESULTS: Nominally significant findings were noted for HTR1A and NPY2R, where women with untreated depression displayed higher gene expression than healthy controls (p < 0.05), whereas women on antidepressant treatment had similar expression as healthy controls. The protein expression analyses revealed higher expression of HTR1A in placentas from women on antidepressant treatment, than in placentas from healthy controls (p < 0.05).

CONCLUSION: The differentially expressed HTR1A, both at the gene and the protein level that was revealed in this study, suggests the involvement of HTR1A in the effect of antenatal depression on biological mechanisms in the placenta. More research is needed to elucidate the role of depression and antidepressant treatment on the placenta, and, further, the effect on the fetus.

Keywords
Antenatal depression, Antidepressant treatment, Immunohistochemistry, Placental gene expression, Placental protein expression, Selective serotonin reuptake inhibitors, TaqMan low-density array
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-404635 (URN)10.1186/s12884-019-2586-y (DOI)000511434300009 ()31805950 (PubMedID)
Funder
Swedish Research Council, VR:521-2013-2339
Available from: 2020-02-25 Created: 2020-02-25 Last updated: 2020-03-11Bibliographically approved
Wiberg-Itzel, E., Wray, S. & Åkerud, H. (2018). A randomized controlled trial of a new treatment for labor dystocia. The Journal of Maternal-Fetal & Neonatal Medicine, 31(17), 2237-2244
Open this publication in new window or tab >>A randomized controlled trial of a new treatment for labor dystocia
2018 (English)In: The Journal of Maternal-Fetal & Neonatal Medicine, ISSN 1476-7058, E-ISSN 1476-4954, Vol. 31, no 17, p. 2237-2244Article in journal (Refereed) Published
Abstract [en]

Objective: Labor dystocia is an intransigent, high-profile issue in obstetric care. Amniotic fluid lactate (AFL) reflects the uterine metabolic status. High levels associate with subsequent need for operative intervention due to dystocia. In sports medicine, it is known that lactic acid can affect muscular performance and can be decreased by bicarbonate given orally before physical activity.

Material and methods: Two hundred dystocic deliveries were included. At the confirmation of dystocia, the AFL-level was analyzed. Deliveries were randomized to an intake of bicarbonate or not. In the non-bicarbonate-group, stimulation with oxytocin was started immediately. In the bicarbonate-group, bicarbonate was given; and oxytocin was started 1hour after the intake. New sampling of AF was performed after 1hour in both groups. Outcome measured: if an oral intake of bicarbonate changes the AFL levels and enhances delivery outcome in dystocic deliveries.

Results: Bicarbonate decreases the AFL levels (p<.001). The spontaneous vaginal delivery rate after treatment with bicarbonate was increased (p=.007), without affecting the fetal outcome.

Conclusions: An increase of spontaneous vaginal deliveries resulted from bicarbonate ingestion by dystocic women. A decreased level of AFL-level was shown. This simple, low cost treatment has the potential to improve maternal morbidity and satisfaction worldwide.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
Keywords
AFL, bicarbonate, caesarean, dystocia, labor
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-356816 (URN)10.1080/14767058.2017.1339268 (DOI)000432700800002 ()28587493 (PubMedID)
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Sterpu, I. S., Åkerud, H., Kaihola, H. & Itzel, E. W. (2018). Angiogenic factors as biomarkers for fetal wellbeing during delivery. Paper presented at 38th Annual Meeting and Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine, JAN 29-FEB 03, 2018, Dallas, TX. American Journal of Obstetrics and Gynecology, 218(1: Supplement), S186-S186
Open this publication in new window or tab >>Angiogenic factors as biomarkers for fetal wellbeing during delivery
2018 (English)In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 218, no 1: Supplement, p. S186-S186Article in journal, Meeting abstract (Other academic) Published
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-350205 (URN)10.1016/j.ajog.2017.10.224 (DOI)000422946900296 ()
Conference
38th Annual Meeting and Pregnancy Meeting of the Society-for-Maternal-Fetal-Medicine, JAN 29-FEB 03, 2018, Dallas, TX
Note

Meeting Abstract: 295

Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Edvinsson, Å., Olivier, J., Hellgren, C., Kallak, T. K., Åkerud, H., Skalkidou, A., . . . Sundström Poromaa, I. (2018). Antenatal Depression and Placental Function: A Protein Validated Gene Expression Study. Paper presented at Meeting of the International-Federation-of-Placenta-Associations (IFPA), SEP 21-24, 2018, Tokyo, JAPAN. Placenta, 69, E62-E62
Open this publication in new window or tab >>Antenatal Depression and Placental Function: A Protein Validated Gene Expression Study
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2018 (English)In: Placenta, ISSN 0143-4004, E-ISSN 1532-3102, Vol. 69, p. E62-E62Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
W B SAUNDERS CO LTD, 2018
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-367143 (URN)000444236500217 ()
Conference
Meeting of the International-Federation-of-Placenta-Associations (IFPA), SEP 21-24, 2018, Tokyo, JAPAN
Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2018-11-29Bibliographically approved
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