1. |
- Thorgeirsdottir, Lilja, et al.
(författare)
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Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study
- 2021
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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).
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2. |
- Bergman, Lina, 1982, et al.
(författare)
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PROVE-Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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3. |
- 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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4. |
- Junus, Katja, 1982-, et al.
(författare)
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Elevated mid-pregnancy plasma levels of angiotensin-converting enzyme 2 in women prior to the development of preeclampsia.
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)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.
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5. |
- Thorgeirsdottir, Lilja, et al.
(författare)
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Partners upplevelse av preeklampsi
- 2023
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Ingår i: Konferens Reproduktiv hälsa 2023.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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6. |
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7. |
- Van Heerden, P., et al.
(författare)
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Blood pressure as a risk factor for eclampsia and pulmonary oedema in pre-eclampsia
- 2021
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Ingår i: Pregnancy Hypertension-an International Journal of Womens Cardiovascular Health. - : Elsevier BV. - 2210-7789 .- 2210-7797. ; 26, s. 2-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We evaluated whether blood pressure and change in blood pressure measurements during pregnancy were associated with eclampsia or pulmonary oedema among women with pre-eclampsia. Study design: Observational study of women with eclampsia, pre-eclampsia complicated by pulmonary oedema and pre-eclampsia without end-organ complications (pre-eclampsia controls) at a large referral center in Cape Town, South Africa. Main outcome measures: Blood pressure measurements at presentation for antenatal care were compared to measurements after a diagnosis of pre-eclampsia. Mean blood pressures and changes in blood pressures were also calculated and compared between groups at different time points. A sub analysis including women who presented for antenatal care before 20 weeks of gestation was performed. Results: When diagnosed with pre-eclampsia, women with pulmonary oedema had increased systolic blood pressures and women with eclampsia had increased diastolic blood pressures compared to pre-eclampsia controls. There were no differences in blood pressure measurements in early pregnancy between women who later developed eclampsia or pulmonary oedema compared to pre-eclampsia controls. Conclusion: Blood pressure measurements in early pregnancy do not seem useful as a risk factor for the development of eclampsia or pulmonary oedema among women diagnosed with pre-eclampsia. Increased systolic or diastolic pressure at diagnosis of pre-eclampsia may be useful as a risk factor for the development of pulmonary oedema or eclampsia. Further research is needed to confirm these findings.
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8. |
- Wikström, Anna-Karin, et al.
(författare)
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Plasma levels of S100B during pregnancy in women developing pre-eclampsia.
- 2012
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Ingår i: Pregnancy hypertension. - : Elsevier BV. - 2210-7789 .- 2210-7797. ; 2:4, s. 398-402
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Tidskriftsartikel (refereegranskat)abstract
- S100B is suggested to be a peripheral biomarker of central nervous system injury with increased blood-brain barrier permeability. The aim of this study was to investigate if there is a difference in plasma levels of S100B throughout pregnancy between women developing pre-eclampsia and those who did not.A nested case-control study within a longitudinal study cohort was performed. Healthy pregnant women were enrolled and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Levels of S100B throughout pregnancy were analyzed with an ELISA assay.The levels of S100B did not change between gestational weeks 10 and 37 (0.047 vs. 0.052; p=0.71) in the healthy controls, but the S100B levels increased between corresponding weeks in women who developed pre-eclampsia (0.052 vs. 0.075; p<0.05). In gestational weeks 33 and 37 women who developed pre-eclampsia had higher levels of S100B than the controls (p=0.047 and p=0.010, respectively).S100B levels increase during pregnancy in women who develop pre-eclampsia and there is an increased S100B level in women who develop pre-eclampsia compared with healthy pregnancies several weeks before clinical symptoms of the disease. The increased amount of plasma S100B in women developing pre-eclampsia might be secondary to cerebral vascular damage and S100B is a potential peripheral biomarker reflecting cerebral involvement in pre-eclampsia.
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9. |
- Adam, Sumaiya, et al.
(författare)
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Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 56-67
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Forskningsöversikt (refereegranskat)abstract
- Gestational diabetes (GDM) impacts approximately 17million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.
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10. |
- Andersson, Malin E, 1978, et al.
(författare)
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Signs of neuroaxonal injury in preeclampsia-A case control study.
- 2021
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral 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.CSF 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.Women 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.NfL 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.
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11. |
- Asp, Joline, et al.
(författare)
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Alcohol exposure prior to pregnancy-does hazardous consumption affect placenta- and inflammatory-mediated pregnancy outcomes? A Swedish population-based cohort study.
- 2022
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 101:12, s. 1386-1394
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption during pregnancy is related to severe birth complications such as low birthweight, preterm birth and birth defects. During the last decade, the Alcohol Use Disorders Identification Test (AUDIT) has been used as a screening tool in Swedish maternal healthcare units to identify hazardous, pre-pregnancy alcohol use. However, evaluation of the screening with AUDIT, as well as adverse maternal or neonatal outcomes, has not been assessed at a national level.This was a population-based cohort study of 530458 births from 2013 to 2018 using demographic, reproductive and maternal health data from the Swedish Pregnancy Register. Self-reported alcohol consumption in the year before pregnancy, measured as AUDIT scores, was categorized into moderate (6-13 points) and high-risk (14-40 points) consumption, with low-risk (0-5 points) consumption as the reference group. Associations with pregnancy- and birth outcomes were explored with logistic regressions using generalized estimating equation models, adjusting for maternal and socioeconomic characteristics. Estimates are presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs).High-risk and moderate pre-pregnancy alcohol consumption was associated with preeclampsia, preterm birth and birth of an infant small for gestational age (SGA), but these associations were nonsignificant after adjustments. Prior moderate-risk (aOR 1.29, 95% CI 1.17-1.42) and high-risk consumption (aOR 1.62, 95% CI 1.17-2.25) increased the likelihood of intrapartum and neonatal infections.Apart from identifying hazardous alcohol consumption prior to pregnancy and the offer of counseling, screening with the AUDIT in early pregnancy indicates a high risk of inflammatory-/placenta-mediated pregnancy and birth outcomes. For most outcomes, AUDIT was not an independent contributor when adjusting for confounding factors. Hazardous alcohol use prior to pregnancy was independently linked to intrapartum and neonatal infections; conditions associated with morbidity and long-term sequalae. These associations may be explained by alcohol-induced changes in the maternal or fetal immune system in early pregnancy or persistent alcohol intake during pregnancy, or may depend on unidentified confounding factors.
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12. |
- Bartho, Lucy A, et al.
(författare)
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Circulating Chemerin Is Elevated in Women With Preeclampsia.
- 2023
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Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 164:5
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia.Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction.Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001). Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 × 10-6). RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells.Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.
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13. |
- Bergman, Lina, 1982, et al.
(författare)
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Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective 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.
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14. |
- Bergman, Lina, 1982, et al.
(författare)
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Cerebral biomarkers in neurologic complications of preeclampsia
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 227:2, s. 298.e1-298.e10
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. Objective: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. Study Design: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. Results: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64–2.88), 2.17-fold higher tau (95% confidence interval, 1.49–3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06–3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92–4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06–5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06–2.55), tau (4.44-fold higher; 95% confidence interval, 1.85–10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32–2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. Conclusion: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.
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15. |
- Bergman, Lina, 1982-
(författare)
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Cerebral biomarkers in women with preeclampsia
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
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16. |
- Bergman, Lina, 1982, et al.
(författare)
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Cognitive impairment in preeclampsia complicated by eclampsia and pulmonary edema after delivery
- 2021
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Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:7, s. 1280-1287
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Tidskriftsartikel (refereegranskat)abstract
- Introduction We aimed to assess cognitive function in women with preeclampsia stratified by severity, before and after onset of disease. Material and methods Prospective study performed at a referral hospital in Cape Town, South Africa. Pregnant women between 20 and 42 weeks of gestation with eclampsia, pulmonary edema and preeclampsia without severe features, and a normotensive pregnancy were approached. Women were included at diagnosis of preeclampsia or at admission for delivery (women with normotensive pregnancies). Two cognitive assessments, the Cognitive Failure Questionnaire to assess the cognitive function subjectively before inclusion in the study, and Montreal Cognitive Assessment to assess the current cognitive function objectively before discharge from the hospital after delivery, were performed. Results We included 61 women with eclampsia, 28 with preeclampsia complicated by pulmonary edema, 38 with preeclampsia without severe features, and 26 with normotensive pregnancies. There was no difference in cognitive function from early pregnancy between groups. Women with eclampsia and preeclampsia complicated by pulmonary edema scored lower on the Montreal Cognitive Assessment at time of discharge compared with women with normotensive pregnancies. The results were attenuated in pulmonary edema after adjustment for confounders. Conclusions Women with preeclampsia complicated by pulmonary edema and in particular eclampsia had impaired cognitive function after onset of disease compared with women with normotensive pregnancies. The impairment did not seem to be present before onset of disease. Women with preeclampsia without severe features did not have impaired cognitive function.
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17. |
- Bergman, Lina, 1982, et al.
(författare)
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Evidence of neuroinflammation and blood–brain barrier disruption in women with preeclampsia and eclampsia
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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18. |
- Bergman, Lina, 1982, et al.
(författare)
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Preeclampsia and increased permeability over the blood brain barrier - a role of vascular endothelial growth receptor 2.
- 2021
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Ingår i: American journal of hypertension. - : Oxford University Press (OUP). - 1941-7225 .- 0895-7061. ; 34:1, s. 73-81
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
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19. |
- 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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20. |
- Callbo, Paliz Nordlof, et al.
(författare)
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Novel Associations Between Mid-Pregnancy Cardiovascular Biomarkers and Preeclampsia: An Explorative Nested Case-Control Study
- 2024
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Ingår i: REPRODUCTIVE SCIENCES. - 1933-7191 .- 1933-7205. ; 31, s. 1391-1400
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of women at high risk of preeclampsia is important for prevention and increased surveillance of the disease. Current prediction models need improvement, particularly with regard to late-onset preeclampsia. Preeclampsia shares pathophysiological entities with cardiovascular disease; thus, cardiovascular biomarkers may contribute to improving prediction models. In this nested case-control study, we explored the predictive importance of mid-pregnancy cardiovascular biomarkers for subsequent preeclampsia. We included healthy women with singleton pregnancies who had donated blood in mid-pregnancy (similar to 18 weeks' gestation). Cases were women with subsequent preeclampsia (n = 296, 10% of whom had early-onset preeclampsia [< 34 weeks]). Controls were women who had healthy pregnancies (n = 333). We collected data on maternal, pregnancy, and infant characteristics from medical records. We used the Olink cardiovascular II panel immunoassay to measure 92 biomarkers in the mid-pregnancy plasma samples. The Boruta algorithm was used to determine the predictive importance of the investigated biomarkers and first-trimester pregnancy characteristics for the development of preeclampsia. The following biomarkers had confirmed associations with early-onset preeclampsia (in descending order of importance): placental growth factor (PlGF), matrix metalloproteinase (MMP-12), lectin-like oxidized LDL receptor 1, carcinoembryonic antigen-related cell adhesion molecule 8, serine protease 27, pro-interleukin-16, and poly (ADP-ribose) polymerase 1. The biomarkers that were associated with late-onset preeclampsia were BNP, MMP-12, alpha-L-iduronidase (IDUA), PlGF, low-affinity immunoglobulin gamma Fc region receptor II-b, and T cell surface glycoprotein. Our results suggest that MMP-12 is a promising novel preeclampsia biomarker. Moreover, BNP and IDUA may be of value in enhancing prediction of late-onset preeclampsia.
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21. |
- Carlberg, Niclas, et al.
(författare)
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Circulating concentrations of glycocalyx degradation products in preeclampsia
- 2022
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- 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 (100.3ng/ml IQR 54.2–204 vs. 27.0ng/ml IQR (13.5–66.6), p < 0,001) and thrombomodulin (4.22ng/ml IQR 3.55–5.17 vs. 3.49ng/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 (5.46ng/ml, IQR 4.85–7.83 vs. 4.66ng/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.
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22. |
- 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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23. |
- Cluver, Catherine Anne, et al.
(författare)
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Does metformin prolong pregnancy in preterm pre-eclampsia? A study protocol for a South African, hospital-based double-blind, randomised, placebo-controlled trial
- 2024
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Ingår i: BMJ OPEN. - 2044-6055. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- 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 (7.6days, 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+0and 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)
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24. |
- Cluver, C. A., et al.
(författare)
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The association of prenatal alcohol exposure on the cognitive abilities and behaviour profiles of 4-year-old children: a prospective cohort study
- 2019
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Ingår i: Bjog-an International Journal of Obstetrics and Gynaecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 126:13, s. 1588-1597
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DesignProspective cohort study. SettingCape Town, South Africa. PopulationA cohort of 500 children. MethodsChildren from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P <= 0.05 considered significant. Results were adjusted for confounding factors. Main outcome measuresThe Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. ResultsTwo hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. ConclusionsLow to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. Tweetable abstractLow to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds. Tweetable abstract Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.
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25. |
- Cluver, Catherine, et al.
(författare)
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Impact of fetal growth restriction on pregnancy outcome in women undergoing expectant management for preterm pre-eclampsia
- 2023
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Ingår i: Ultrasound in Obstetrics and Gynecology. - 1469-0705 .- 0960-7692. ; 62:5, s. 660-667
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess whether coexisting fetal growth restriction (FGR) influences pregnancy latency among women with preterm pre-eclampsia undergoing expectant management. Secondary outcomes assessed were indication for delivery, mode of delivery and rate of serious adverse maternal and perinatal outcomes. Methods: We conducted a secondary analysis of the Pre-eclampsia Intervention (PIE) and the Pre-eclampsia Intervention 2 (PI2) trial data. These randomized controlled trials evaluated whether esomeprazole and metformin could prolong gestation of women diagnosed with pre-eclampsia between 26 and 32 weeks of gestation undergoing expectant management. Delivery indications were deteriorating maternal or fetal status, or reaching 34 weeks' gestation. FGR (defined by Delphi consensus) at the time of pre-eclampsia diagnosis was examined as a predictor of outcome. Only placebo data from PI2 were included, as the trial showed that metformin use was associated with prolonged gestation. All outcome data were collected prospectively from diagnosis of pre-eclampsia to 6 weeks after the expected due date. Results: Of the 202 women included, 92 (45.5%) had FGR at the time of pre-eclampsia diagnosis. Median pregnancy latency was 6.8 days in the FGR group and 15.3 days in the control group (difference 8.5 days; adjusted 0.49-fold change (95% CI, 0.33–0.74); P < 0.001). FGR pregnancies were less likely to reach 34 weeks' gestation (12.0% vs 30.9%; adjusted relative risk (aRR), 0.44 (95% CI, 0.23–0.83)) and more likely to be delivered for suspected fetal compromise (64.1% vs 36.4%; aRR, 1.84 (95% CI, 1.36–2.47)). More women with FGR underwent a prelabor emergency Cesarean section (66.3% vs 43.6%; aRR, 1.56 (95% CI, 1.20–2.03)) and were less likely to have a successful induction of labor (4.3% vs 14.5%; aRR, 0.32 (95% CI, 0.10–1.00)), compared to those without FGR. The rate of maternal complications did not differ significantly between the two groups. FGR was associated with a higher rate of infant death (14.1% vs 4.5%; aRR, 3.26 (95% CI, 1.08–9.81)) and need for intubation and mechanical ventilation (15.2% vs 5.5%; aRR, 2.97 (95% CI, 1.11–7.90)). Conclusion: FGR is commonly present in women with early preterm pre-eclampsia and outcome is poorer. FGR is associated with shorter pregnancy latency, more emergency Cesarean deliveries, fewer successful inductions and increased rates of neonatal morbidity and mortality. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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26. |
- Cruickshank, Tess, et al.
(författare)
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Circulating growth differentiation factor 15 is increased preceding preeclampsia diagnosis: Implications as a disease biomarker
- 2021
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 10:16
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Tidskriftsartikel (refereegranskat)abstract
- 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<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks’ gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks’ gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preec-lampsia with severe features (P=0.02; n=14) compared to controls (n=14). CONCLUSIONS: We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio.
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27. |
- Dehaene, I., et al.
(författare)
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Accuracy of the combination of commercially available biomarkers and cervical length measurement to predict preterm birth in symptomatic women: A systematic review
- 2021
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Ingår i: European Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 258, s. 198-207
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Tidskriftsartikel (refereegranskat)abstract
- An accurate prognostic method for preterm birth (PTB) could avoid unnecessary treatment(s) with potentially negative effects. The objective was to explore the prognostic accuracy of commercially available bedside cervicovaginal biomarker tests in combination with cervical length (CL) compared to CL measurement alone and/or a biomarker test alone, for PTB within 7 days after testing symptomatic women at 22-34 weeks. The MEDLINE, Cochrane, Embase and Web of Science databases were searched from inception to August 28th, 2019. Seven hundred and eight articles were identified and screened using Rayyan. Studies reporting on the predictive accuracy of combined tests compared to CL or biomarker alone for the prediction of PTB within 7 days of testing in symptomatic women with intact membranes were included. A piloted data extraction form was used. Direct comparisons of the prognostic accuracy of the combination test with CL measurement or a biomarker alone were done, as well as comparisons of prognostic accuracy of the included combination tests (indirect comparisons). Twelve articles were included (seven on fetal fibronectin, four on phosphorylated insulin-like growth factor binding protein-1, one comparing both). A variety of CL cut-offs was reported. The results could not demonstrate superiority of a combination method compared to single methods. Due to data scarcity and quality, the superiority of either predictive test for PTB, either combination or single, cannot be demonstrated with this systematic review. We recommend further research to compare available biomarkers. (C) 2020 Elsevier B.V. All rights reserved.
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28. |
- Hartmann, S., et al.
(författare)
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Can single-cell and spatial omics unravel the pathophysiology of pre-eclampsia?
- 2023
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Ingår i: Journal of Reproductive Immunology. - : Elsevier. - 0165-0378 .- 1872-7603. ; 159
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Tidskriftsartikel (refereegranskat)abstract
- Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Characterised by the onset of hypertension and proteinuria in the second half of pregnancy, it can lead to maternal end-organ injury such as cerebral ischemia and oedema, pulmonary oedema and renal failure, and potentially fatal outcomes for both mother and fetus. The causes of the different maternal end-organ phenotypes of pre-eclampsia and why some women develop pre-eclampsia condition early in pregnancy have yet to be elucidated. Omics methods include proteomics, genomics, metabolomics, transcriptomics. These omics techniques, previously mostly used on bulk tissue and individually, are increasingly available at a single cellular level and can be combined with each other. Multi-omics techniques on a single-cell or spatial level provide us with a powerful tool to understand the pathophysiology of pre-eclampsia. This review will explore the status of omics methods and how they can and could contribute to understanding the pathophysiology of pre-eclampsia.
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29. |
- Hastie, R., et al.
(författare)
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Associations Between Soluble fms-Like Tyrosine Kinase-1 and Placental Growth Factor and Disease Severity Among Women With Preterm Eclampsia and Preeclampsia
- 2022
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Ingår i: Journal of the American Heart Association (JAHA). - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:16
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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30. |
- Hastie, R., et al.
(författare)
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Duration of labor among women with hypertensive disorders of pregnancy; A Swedish register cohort study
- 2020
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Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 251, s. 114-118
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Preeclampsia is a severe obstetric complication affecting 2–8% of pregnancies. There is a common belief that women with preeclampsia experience a shorter duration of labor, where it is thought that increased inflammation that occurs with the disease facilitates labor. However, little evidence exists to support or refute this. Thus, we undertook a register-based cohort study investigating the association between hypertensive disorders of pregnancy and labor duration. Study design: This was a Swedish register-based cohort study of nulliparous women with spontaneous or induced onset of labor at >34 weeks of gestation with a singleton fetus in cephalic presentation. Information of duration of labor was retrieved from electronic birth records and compared between women with hypertensive disorders and normotensives pregnancies. Data was represented as mean adjusted difference in hours (adjusted for pre-gestational disorders, maternal characteristics and mode of delivery) and adjusted hazard ratios (aHR), with an event defined as vaginal birth and women with intrapartum caesarean section censored. An aHR >1 indicated shorter duration of labor. Results: Among 101,531 women, 5548 (5.5%) developed a hypertensive disorder of pregnancy. The overall mean duration of labor was 9.43 (SD 5.32) hours. Women with hypertensive disorders experienced a shorter duration of labor compared to normotensive women, with an adjusted mean difference of -0.68 h (95% CI −0.90, −0.47) for gestational hypertension and -1.53 h (95% CI −1.72, −1.35) for preeclampsia. This corresponded to an aHR of 1.05 (95% CI 1.01, 1.10) and 1.12 (95% CI 1.08, 1.17), respectively. However, when we confined the analysis to those who labored spontaneously, the presence of hypertensive disorders did not alter duration of labor (aHR 0.98, 95% CI 0.95,1.01). Only women who were induced and also had hypertensive disorders experienced a shorter duration of labor (aHR 1.07, 95% CI 1.04,1.09). Conclusions: Hypertensive disorders did not alter labor duration among women with spontaneous onset of labor, however an association was observed among women who were induced. © 2020 Elsevier B.V.
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31. |
- Hastie, Roxanne, et al.
(författare)
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Low-Dose Aspirin for Preventing Birth of a Small-For-Gestational Age Neonate in a Subsequent Pregnancy.
- 2022
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Ingår i: Obstetrics and gynecology. - : Ovid Technologies (Wolters Kluwer Health). - 1873-233X .- 0029-7844. ; 139:4, s. 529-535
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Tidskriftsartikel (refereegranskat)abstract
- To estimate whether low-dose aspirin use is associated with an altered risk of delivering a small-for-gestational age (SGA) neonate among women with a history of having an SGA neonate in a prior pregnancy.We performed a Swedish register-based cohort study including women in their second pregnancy who had a history of having an SGA neonate (birth weight less than the 10th percentile). The association between use of low-dose aspirin in subsequent pregnancy and birth of an SGA neonate or a severely SGA neonate (birth weight less than the third percentile) were estimated using inverse propensity-weighted estimation, accounting for potential confounders.Among 8,416 women who gave birth to an SGA neonate in their first pregnancy, 801 (9.5%) used low-dose aspirin during their second pregnancy. The incidence of SGA neonates was similar among women using low-dose aspirin (21.7%) and those who did not use aspirin (20.7%). Low-dose aspirin use in pregnancy was not associated with an altered risk of having an SGA neonate (adjusted relative risk [aRR] 0.86, 95% CI 0.67-1.10) or a severely SGA neonate (aRR 0.98, 95% CI 0.71-1.34). Given the strong association between preeclampsia and SGA, we performed subgroup analyses based on preeclampsia status. Among women who had an SGA neonate and co-existing preeclampsia in their first pregnancy, low-dose aspirin was not associated with an altered risk of having an SGA (aRR 0.83, 95% CI 0.63-1.10) or severely SGA (aRR 1.02, 95% CI 0.73-1.44) neonate. Additionally, no association was seen among women who developed preeclampsia in their second pregnancy.Among women with a history of having an SGA neonate, low-dose aspirin was not associated with a decreased risk of having an SGA or severely SGA neonate in subsequent pregnancy. These findings suggest that low-dose aspirin should not be used to prevent recurrent SGA.
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32. |
- Hesselman, Susanne, 1973-, et al.
(författare)
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Duration of labor among women with thromboembolic events: A Swedish register study
- 2021
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Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology: X. - : Elsevier BV. - 2590-1613. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- 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. © 2021 The Authors
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33. |
- Jacobsson, Bo, 1960, et al.
(författare)
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Preterm delivery: an overview on epidemiology, pathophysiology and consequences for the individual and the society : Förtidsbörd största perinatala problemet - 5,7 procent av graviditeter i Sverige slutar för tidigt, inte klarlagt varför – kostar miljardbelopp varje år.
- 2019
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Ingår i: Läkartidningen. - 1652-7518. ; 116
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Tidskriftsartikel (refereegranskat)abstract
- Preterm delivery in Sweden constitutes 5.7 % of all deliveries, which is among the lowest rates in the world. There has not been any increase in the proportion of iatrogenic preterm deliveries during the last decades.The main hypothesis concerning the causality of preterm delivery is still that of the ascending infection from the vagina to the uterus and inflammation resulting in contractions, rupture of membranes and delivery. The mechanisms behind parturition at term are still elusive and this is also true for preterm delivery. The genetic contribution to preterm delivery is about 25-30 %. The first genes that are associated with preterm delivery and gestational duration have recently been published. Huge progress has been made in care of preterm born infants. Sweden has among the lowest rates of mortality and morbidity in the world, especially in the lowest gestational weeks. New modes of care, family-centered care and hospital-assisted home care, have empowered the parents and reduced the cost for care.
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34. |
- Kandel, Manju, et al.
(författare)
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PSG7 and 9 (Pregnancy-Specific β-1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia. : Pregnancy Specific beta-1 Glycoproteins (PSG) 7 and 9 - novel biomarkers for preeklampsia.
- 2022
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- 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 36weeks 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 32weeks 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<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL-6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt-1 (FMS-like tyrosine kinase-1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.
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35. |
- Killeen, Sarah Louise, et al.
(författare)
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Using FIGO Nutrition Checklist counselling in pregnancy: A review to support healthcare professionals.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 10-21
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Forskningsöversikt (refereegranskat)abstract
- The period before and during pregnancy is increasingly recognized as an important stage for addressing malnutrition. This can help to reduce the risk of noncommunicable diseases in mothers and passage of risk to their infants. The FIGO Nutrition Checklist is a tool designed to address these issues. The checklist contains questions on specific dietary requirements, body mass index, diet quality, and micronutrients. Through answering these questions, awareness is generated, potential risks are identified, and information is collected that can inform health-promoting conversations between women and their healthcare professionals. The tool can be used across a range of health settings, regions, and life stages. The aim of this review is to summarize nutritional recommendations related to the FIGO Nutrition Checklist to support healthcare providers using it in practice. Included is a selection of global dietary recommendations for each of the components of the checklist and practical insights from countries that have used it. Implementation of the FIGO Nutrition Checklist will help identify potential nutritional deficiencies in women so that they can be addressed by healthcare providers. This has potential longstanding benefits for mothers and their children, across generations.
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36. |
- Kupka, Ellen, et al.
(författare)
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Low-dose aspirin use in pregnancy and the risk of preterm birth: a Swedish register-based cohort study.
- 2023
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 228:3
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Tidskriftsartikel (refereegranskat)abstract
- Preterm birth is the leading cause of neonatal mortality and morbidity. Women who have had a previous preterm birth are at increased risk for preterm birth in their subsequent pregnancies. Low-dose aspirin use reduces the risk for preterm birth among women at risk of developing preeclampsia, however, it is unclear whether low-dose aspirin may reduce the risk of recurrent preterm birth.This study aimed to investigate the association between low-dose aspirin use and preterm birth among women with a previous preterm birth.We conducted a Swedish register-based cohort study and included women who had a first and second pregnancy between 2006 and 2019, with the first pregnancy ending in preterm birth (medically indicated or with spontaneous onset <37 weeks of gestation). The association between low-dose aspirin use and preterm birth in the second pregnancy was estimated via logistic regression via standardization and expressed as marginal relative risks with the 95% confidence interval.Among the study cohort (N=22,127), 3057 women (14%) were prescribed low-dose aspirin during their second pregnancy and 3703 women (17%) gave birth prematurely. Low-dose aspirin use was associated with a reduced risk for preterm birth, (marginal relative risk, 0.87; 95% confidence interval, 0.77-0.99). There were no statistically significant associations between low-dose aspirin use and an altered risk for moderate preterm birth, defined as birth between 32 and 36 weeks' gestation (marginal relative risk, 0.90; 95% confidence interval, 0.78-1.03), or very preterm birth, defined as birth <32 weeks' gestation (marginal relative risk, 0.75; 95% confidence interval, 0.54-1.04). Regarding the onset of preterm birth, low-dose aspirin use was associated with a reduced risk for spontaneous preterm birth (marginal relative risk, 0.70; 95% confidence interval, 0.57-0.86) but no reduction in the risk for medically indicated preterm birth (marginal relative risk, 1.09; 95% confidence interval, 0.91-1.30) was observed.Among women with a previous preterm birth, low-dose aspirin use was associated with a reduced risk for preterm birth. When investigating preterm birth by onset in the second pregnancy, low-dose aspirin use was associated with a reduced risk for spontaneous preterm birth. Our results suggest that low-dose aspirin may be an effective prophylaxis for recurrent preterm birth.
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37. |
- León, José, et al.
(författare)
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Disruption of the Blood-Brain Barrier by Extracellular Vesicles from Preeclampsia Plasma and Hypoxic Placentae: Attenuation by Magnesium Sulfate
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 78:5, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia, a pregnancy-related endothelial disorder, is associated with both cardiovascular and cerebrovascular complications. Preeclampsia requires the presence of a placenta as part of its pathophysiology, yet the role of this organ in the cerebrovascular complications remains unclear. Research has shown that circulating small extracellular vesicles (also known as exosomes) present in preeclampsia plasma can generate endothelial dysfunction, but it is unclear whether the impairment of function of brain endothelial cells at the blood-brain barrier is secondary to plasma-derived or placental-derived exosomes. In this study, we evaluated the effect of small extracellular vesicles isolated from plasma samples of women with preeclampsia (n=12) and women with normal pregnancy (n=11) as well as from human placental explants from normotensive pregnancies (n=6) subjected to hypoxia (1% oxygen) on the integrity of the blood-brain barrier, using both in vitro and animal models. Exposure of human-derived brain endothelial cell monolayers to plasma and plasma-derived small extracellular vesicles from preeclamptic pregnancies increased the permeability and reduced the transendothelial electrical resistance. A similar outcome was observed with hypoxic placental-derived small extracellular vesicles, which also increased the permeability to Evan's blue in the brain of C57BL6 nonpregnant mice. Cotreatment with magnesium sulfate reversed the effects elicited by plasma, plasma-derived, and hypoxic placental-derived small extracellular vesicles in the employed models. Thus, circulating small extracellular vesicles in plasma from women with preeclampsia or from hypoxic placentae disrupt the blood-brain barrier, which can be prevented using magnesium sulfate. These findings provide new insights into the pathophysiology of cerebral complications associated with preeclampsia.
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38. |
- Maxwell, Cynthia V, et al.
(författare)
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Management of obesity across women's life course: FIGO Best Practice Advice.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a chronic, progressive, relapsing, and treatable multifactorial, neurobehavioral disease. According to the World Health Organization, obesity affects 15% of women and has long-term effects on women's health. The focus of care in patients with obesity should be on optimizing health outcomes rather than on weight loss. Appropriate and common language, considering cultural sensitivity and trauma-informed care, is needed to discuss obesity. Pregnancy is a time of significant physiological change. Pre-, ante-, and postpartum clinical encounters provide opportunities for health optimization for parents with obesity in terms of, but not limited to, fertility and breastfeeding. Pre-existing conditions may also be identified and managed. Beyond pregnancy, women with obesity are at an increased risk for gastrointestinal and liver diseases, impaired kidney function, obstructive sleep apnea, and venous thromboembolism. Gynecological and reproductive health of women living with obesity cannot be dismissed, with accommodations needed for preventive health screenings and consideration of increased risk for gynecologic malignancies. Mental wellness, specifically depression, should be screened and managed appropriately. Obesity is a complex condition and is increasing in prevalence with failure of public health interventions to achieve significant decrease. Future research efforts should focus on interprofessional care and discovering effective interventions for health optimization.
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39. |
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40. |
- Poon, Liona C, et al.
(författare)
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Hypertensive disorders of pregnancy and long-term cardiovascular health: FIGO Best Practice Advice.
- 2023
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Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - : Wiley. - 1879-3479 .- 0020-7292. ; 160:Suppl 1, s. 22-34
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Tidskriftsartikel (refereegranskat)abstract
- Hypertensive disorders of pregnancy (HDP) are the most common causes of maternal and perinatal morbidity and mortality. They are responsible for 16% of maternal deaths in high-income countries and approximately 25% in low- and middle-income countries. The impact of HDP can be lifelong as they are a recognized risk factor for future cardiovascular disease. During pregnancy, the cardiovascular system undergoes significant adaptive changes that ensure adequate uteroplacental blood flow and exchange of oxygen and nutrients to nurture and accommodate the developing fetus. Failure to achieve normal cardiovascular adaptation is associated with the development of HDP. Hemodynamic alterations in women with a history of HDP can persist for years and predispose to long-term cardiovascular morbidity and mortality. Therefore, pregnancy and the postpartum period are an opportunity to identify women with underlying, often unrecognized, cardiovascular risk factors. It is important to develop strategies with lifestyle and therapeutic interventions to reduce the risk of future cardiovascular disease in those who have a history of HDP.
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41. |
- Roberts, J. M., et al.
(författare)
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Vision for Improving Pregnancy Health: Innovation and the Future of Pregnancy Research
- 2022
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Ingår i: Reproductive Sciences. - : Springer Science and Business Media LLC. - 1933-7191 .- 1933-7205. ; 29:10, s. 2908-2920
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Tidskriftsartikel (refereegranskat)abstract
- Understanding, predicting, and preventing pregnancy disorders have been a major research target. Nonetheless, the lack of progress is illustrated by research results related to preeclampsia and other hypertensive pregnancy disorders. These remain a major cause of maternal and infant mortality worldwide. There is a general consensus that the rate of progress toward understanding pregnancy disorders lags behind progress in other aspects of human health. In this presentation, we advance an explanation for this failure and suggest solutions. We propose that progress has been impeded by narrowly focused research training and limited imagination and innovation, resulting in the failure to think beyond conventional research approaches and analytical strategies. Investigations have been largely limited to hypothesis-generating approaches constrained by attempts to force poorly defined complex disorders into a single "unifying" hypothesis. Future progress could be accelerated by rethinking this approach. We advise taking advantage of innovative approaches that will generate new research strategies for investigating pregnancy abnormalities. Studies should begin before conception, assessing pregnancy longitudinally, before, during, and after pregnancy. Pregnancy disorders should be defined by pathophysiology rather than phenotype, and state of the art agnostic assessment of data should be adopted to generate new ideas. Taking advantage of new approaches mandates emphasizing innovation, inclusion of large datasets, and use of state of the art experimental and analytical techniques. A revolution in understanding pregnancy-associated disorders will depend on networks of scientists who are driven by an intense biological curiosity, a team spirit, and the tools to make new discoveries.
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42. |
- Thorgeirsdottir, Lilja, et al.
(författare)
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The experience of being a partner to a childbearing woman whose pregnancy is complicated by pre-eclampsia : A Swedish qualitative study
- 2023
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Ingår i: Sexual & Reproductive HealthCare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 36
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pre-eclampsia affects 3-5% of all pregnant women and is among the leading causes of maternal morbidity and mortality as well as iatrogenic preterm birth worldwide. Little is known about the experience of partners of women whose pregnancy is complicated by pre-eclampsia.Aim: To describe partners' experience of having a spouse whose pregnancy was complicated by pre-eclampsia.Methods: A qualitative study with in-depth interviews. Eight partners of women whose pregnancy was complicated by pre-eclampsia were interviewed and data were analysed using content analysis.Findings: Partners found themselves in an unfamiliar and unexpected situation. They experienced an information gap in which they tried to make sense of the situation by interpreting subtle signs. The situation left them feeling emotionally stretched, feeling like an outsider while trying to provide support for their extended family. The partners experienced a split focus after the baby was born, prioritising the baby while worrying about their spouse. Post-partum, they expressed needing time to process and heal after childbirth. A need for professional support was highlighted and concerns about a future pregnancy were voiced.Conclusion: Having a spouse who is diagnosed with pre-eclampsia is challenging and overwhelming. Our findings imply a need to develop a model of care for women with pre-eclampsia that includes their partner, i.e., the other parent.
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