ORCID Profile
0000-0001-5202-9428
Current Organisation
Sahlgrenska University Hospital
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Publisher: MDPI AG
Date: 05-11-2021
Abstract: Cerebral complications in preecl sia 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 preecl sia and ecl sia. We included women recruited to the South African Preecl sia 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 ecl sia (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 preecl sia (n = 4). Women with preecl sia 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 ecl sia but also women with preecl sia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. In conclusion, women with preecl sia and ecl sia show evidence of neuroinflammation and an injured blood–brain barrier. These findings are seen in particular among women with ecl sia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-03-2022
DOI: 10.1097/AOG.0000000000004696
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 10 th 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 preecl sia and SGA, we performed subgroup analyses based on preecl sia status. Among women who had an SGA neonate and co-existing preecl sia 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 preecl sia 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-08-2022
Abstract: The angiogenic factors soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) are postulated to be pathogenic disease drivers of preecl sia. If true, then circulating levels should become more deranged with increasing disease severity. We investigated the association between circulating sFlt‐1 and PlGF levels and severe adverse maternal outcomes among 348 women with preecl sia. Compared with 125 women with preecl sia without severe features, 25 women with preecl sia 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 preecl sia without severe features, 37 with ecl sia 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, preecl sia 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. Further angiogenic imbalance among women with preecl sia is likely a pathogenic disease driver responsible for the life‐threatening maternal complications.
Publisher: MDPI AG
Date: 20-04-2021
Abstract: Pre-ecl sia 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-ecl sia biobank in South Africa to facilitate research in the field of pre-ecl sia 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-ecl sia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological s les 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-ecl sia in a low-middle income country where the incidence of pre-ecl sia with organ complications is high. The study integrates different methods to investigate pre-ecl sia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
DOI: 10.1161/HYPERTENSIONAHA.118.12547
Abstract: Preecl sia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preecl sia. The aim of this study was to determine the association between PPI use during pregnancy and preecl sia risk in a population-based register cohort. Using the Swedish Pregnancy Register, we conducted a cohort study of nulliparous pregnant women delivering from January 2013 to July 2017. Associations between PPI use and preecl sia were investigated using logistic regression analyses with risk estimates presented as crude and adjusted odds ratios (aOR) with 95% CI. Of 157 720 nulliparous pregnant women, 6051 (3.8%) reported PPI use during pregnancy. PPI use during any point of pregnancy was associated with an increased risk of overall preecl sia (aOR of 1.17 95% CI, 1.04–1.32) and preecl sia at term (aOR of 1.20 95% CI, 1.04–1.39). However, PPI use recorded after 28 gestational weeks was associated with a reduced risk of preterm (delivery weeks) preecl sia (aOR of 0.63 95% CI, 0.41–0.96) and early (delivery weeks) preecl sia (aOR of 0.41 95% CI, 0.20–0.82). These findings highlight the heterogeneity of this disease, with a potential role PPIs for preventing preterm preecl sia when used in close proximity to disease onset. Targeting PPI use to women at greatest risk of preterm preecl sia may help prevent this severe form of disease.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-04-2022
Abstract: Preecl sia 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 preecl sia. At 36 weeks gestation preceding term preecl sia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preecl sia (PSG7, P =0.013 PSG9, P =0.0011). In s les collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preecl sia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preecl sia onset (PSG7, P .0001 PSG9, P =0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preecl sia who delivered at weeks gestation (PSG7, P =0.0008 PSG9, P .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 (Preecl sia Obstetric Adverse Events) cohort (n=72). PSG7 ( P =0.0027) and PSG9 ( P =0.0028) were elevated among patients who were preecl tic with severe features (PROVE cohort), but not significantly changed in those without severe features or with ecl sia. 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. Circulating PSG7 and PSG9 are increased before preecl sia onset and among those with established disease with their production and release potentially driven by placental inflammation.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.AJOG.2022.02.036
Abstract: There is no tool to accurately predict who is at risk of developing neurologic complications of preecl sia, and there is no objective method to determine disease severity. 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 preecl sia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. In this observational study, we included women from the South African Preecl sia Obstetric Adverse Events biobank. Plasma s les taken at diagnosis (preecl sia 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 s ling, maternal age, and parity. Compared with 28 women with normotensive pregnancies, 146 women with preecl sia 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 (ecl sia, 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 preecl sia 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 preecl sia 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 preecl sia complicated by pulmonary edema and women with preecl sia 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 ecl sia only. Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preecl sia.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 17-08-2120
Abstract: We investigated the biomarker potential of growth differentiation factor 15 (GDF‐15), a stress response protein highly expressed in placenta, to predict preecl sia. In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preecl sia cohort 2: 950 controls, 41 developed preecl sia), plasma concentrations of GDF‐15 at 36 weeks' gestation were significantly increased among those who developed preecl sia ( P .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 preecl sia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preecl sia (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 weeks' gestation due to preterm preecl sia 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 preecl sia ( P =0.0002), compared with 176 controls. In the Preecl sia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF‐15 was significantly increased in women with preecl sia with severe features ( P =0.02 n=14) compared to controls (n=14). We conclude circulating GDF‐15 is elevated among women more likely to develop preecl sia 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
DOI: 10.1097/AOG.0000000000003476
Abstract: To estimate the predictive value of signs and symptoms that occur before onset of ecl sia among pregnant women. Electronic databases, including MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched from inception to 2018. Search terms included ecl sia, predict, likelihood ratio, predictive value, and risk. Abstracts and later full texts were selected for review if a diagnosis of ecl sia was made, a comparator arm included (women without a diagnosis of ecl sia), and predictors of imminent ecl sia reported. Of 2,791 retrieved records, 11 were selected. Significant heterogeneity existed between studies, with differing designs, settings, participants, and signs or symptoms. In total, 28 signs or symptoms were reported, with visual disturbances and epigastric pain most common (six studies), followed by headache (five studies), and any edema (four studies). Data on study characteristics and predictive value of signs or symptoms were extracted, and, where appropriate, bivariate mixed-effect meta-analysis was applied to raw data. None of the pooled estimates were able to accurately predict ecl sia nor rule out ecl sia in their absence, with moderate specificity (83–94%) and poor sensitivity (29–56%). There is a dearth of high-quality studies investigating the predictive value of imminent signs and symptoms of ecl sia. Owing to the small number of studies, heterogeneity, and inconsistent reporting, it is difficult to provide accurate estimates of the predictive value of prodromal symptoms of ecl sia. Of the most commonly reported symptoms—visual disturbances, epigastric pain, and headache—none were able to accurately predict, nor rule out, imminent ecl sia. PROSPERO, CRD42018095076.
No related grants have been discovered for Lina Bergman.