| 1. |
- 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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| 2. |
- 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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| 3. |
- Bergman, Lina, et al.
(författare)
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Cerebral perfusion pressure and autoregulation in eclampsia-a case control study
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 225:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. OBJECTIVE: This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. STUDY DESIGN: This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. RESULTS: We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). CONCLUSION: Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.
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| 4. |
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| 5. |
- 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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| 6. |
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| 7. |
- Bokström-Res, Emma, et al.
(författare)
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Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia
- 2023
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Ingår i: Pregnancy Hypertension. - : Elsevier. - 2210-7789 .- 2210-7797. ; 31, s. 38-45
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia.Study design: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure.Main outcome measures: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies.Results: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP.Conclusions: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Cluver, Catherine, et al.
(författare)
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Interventions for treating genital Chlamydia trachomatis infection in pregnancy
- 2017
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Ingår i: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2017:9
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Forskningsöversikt (refereegranskat)abstract
- Background: Genital Chlamydia trachomatis (C.trachomatis) infection may lead to pregnancy complications such as miscarriage, preterm labour, low birthweight, preterm rupture of membranes, increased perinatal mortality, postpartum endometritis, chlamydial conjunctivitis and C.trachomatis pneumonia.This review supersedes a previous review on this topic. Objectives: To establish the most efficacious and best-tolerated therapy for treatment of genital chlamydial infection in preventing maternal infection and adverse neonatal outcomes. Search methods: We searched the Cochrane Pregnancy and Childbirth Group"s Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (26 June 2017) and reference lists of retrieved studies. Selection criteria: Randomised controlled trials (RCTs) as well as studies published in abstract form assessing interventions for treating genital C.trachomatis infection in pregnancy. Cluster-RCTs were also eligible for inclusion but none were identified. Quasi-randomised trials and trials using cross-over design are not eligible for inclusion in this review. Data collection and analysis: Two review authors independently assessed studies for inclusion, assessed trial quality and extracted the data using the agreed form. Data were checked for accuracy. Evidence was assessed using the GRADE approach. Main results: We included 15 trials (involving 1754 women) although our meta-analyses were based on fewer numbers of studies/women. All of the included studies were undertaken in North America from 1982 to 2001. Two studies were low risk of bias in all domains, all other studies had varying risk of bias. Four other studies were excluded and one study is ongoing. Eight comparisons were included in this review; three compared antibiotic (erythromycin, clindamycin, amoxicillin) versus placebo; five compared an antibiotic versus another antibiotic (erythromycin, clindamycin, amoxicillin, azithromycin). No study reported different antibiotic regimens. Microbiological cure (primary outcome) Antibiotics versus placebo: Erythromycin (average risk ratio (RR) 2.64, 95% confidence interval (CI) 1.60 to 4.38; two trials, 495 women; I2 = 68%; moderate-certainty evidence), and clindamycin (RR 4.08, 95% CI 2.35 to 7.08; one trial, 85 women;low-certainty evidence) were associated with improved microbiological cure compared to a placebo control. In one very small trial comparing amoxicillin and placebo, the results were unclear, but the evidence was graded very low (RR 2.00, 95% CI 0.59 to 6.79; 15 women). One antibiotic versus another antibiotic: Amoxicillin made little or no difference in microbiological cure in comparison to erythromycin (RR 0.97, 95% CI 0.93 to 1.01; four trials, 466 women; high-certainty evidence), probably no difference compared to clindamycin (RR 0.96, 95% CI 0.89 to 1.04; one trial, 101 women; moderate-quality evidence), and evidence is very low certainty when compared to azithromycin so the effect is not certain (RR 0.89, 95% CI 0.71 to 1.12; two trials, 144 women; very low-certainty evidence). Azithromycin versus erythromycin (average RR 1.11, 95% CI 1.00 to 1.23; six trials, 374 women; I2 = 53%; moderate-certainty evidence) probably have similar efficacy though results appear to favour azithromycin. Clindamycin versus erythromycin (RR 1.06, 95% CI 0.97 to 1.15; two trials, 173 women; low-certainty evidence) may have similar numbers of women with a microbiological cure between groups. Evidence was downgraded for design limitations, inconsistency, and imprecision in effect estimates. Side effects of the treatment (maternal) (secondary outcome) Antibiotics versus placebo: side effects including nausea, vomiting, and abdominal pain, were reported in two studies (495 women) but there was no clear evidence whether erythromycin was associated with more side effects than placebo and a high level of heterogeneity (I2 = 78%) was observed (average RR 2.93, 95% CI 0.36 to 23.76). There was no clear difference in the number of women experiencing side effects when clindamycin was compared to placebo in one small study (5/41 versus 1/44) (RR 6.35, 95% CI 0.38 to 107.45, 62 women). The side effects reported were mostly gastrointestinal and also included resolving skin rashes. One antibiotic versus another antibiotic: There was no clear difference in incidence of side effects (including nausea, vomiting, diarrhoea and abdominal pain) when amoxicillin was compared to azithromycin based on data from one small study (36 women) (RR 0.56, 95% CI 0.24 to 1.31). However, amoxicillin was associated with fewer side effects compared to erythromycin with data from four trials (513 women) (RR 0.31, 95% CI 0.21 to 0.46; I2 = 27%). Side effects included nausea, vomiting, diarrhoea, abdominal cramping, rash, and allergic reaction. Both azithromycin (RR 0.24, 95% CI 0.17 to 0.34; six trials, 374 women) and clindamycin (RR 0.44, 95% CI 0.22 to 0.87; two trials, 183 women) were associated with a lower incidence of side effects compared to erythromycin. These side effects included nausea, vomiting, diarrhoea and abdominal cramping. One small study (101 women) reported there was no clear difference in the number of women with side effects when amoxicillin was compared with clindamycin (RR 0.57, 95% CI 0.14 to 2.26; 107 women). The side effects reported included rash and gastrointestinal complaints. Other secondary outcomes Single trials reported data on repeated infections, preterm birth, preterm rupture of membranes, perinatal mortality and low birthweight and found no clear differences between treatments. Many of this review's secondary outcomes were not reported in the included studies. Authors' conclusions: Treatment with antibacterial agents achieves microbiological cure from C.trachomatis infection during pregnancy. There was no apparent difference between assessed agents (amoxicillin, erythromycin, clindamycin, azithromycin) in terms of efficacy (microbiological cure and repeat infection) and pregnancy complications (preterm birth, preterm rupture of membranes, low birthweight). Azithromycin and clindamycin appear to result in fewer side effects than erythromycin. All of the studies in this review were conducted in North America, which may limit the generalisability of the results. In addition, study populations may differ in low-resource settings and these results are therefore only applicable to well-resourced settings. Furthermore, the trials in this review mainly took place in the nineties and early 2000's and antibiotic resistance may have changed since then. Further well-designed studies, with appropriate sample sizes and set in a variety of settings, are required to further evaluate interventions for treating C.trachomatis infection in pregnancy and determine which agents achieve the best microbiological cure with the least side effects. Such studies could report on the outcomes listed in this review.
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| 11. |
- 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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| 12. |
- Friis, Therese, et al.
(författare)
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Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia
- 2022
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood-brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 mu g/L, p < 0.001 and 0.08 vs. 0.05 mu g/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.
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| 13. |
- Hastie, Roxanne, 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. - : John Wiley & Sons. - 2047-9980. ; 11:16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe 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 ResultsWe 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.ConclusionsFurther angiogenic imbalance among women with preeclampsia is likely a pathogenic disease driver responsible for the life‐threatening maternal complications.
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| 14. |
- 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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| 15. |
- Hastie, Roxanne, et al.
(författare)
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Predictive Value of the Signs and Symptoms Preceding Eclampsia : A Systematic Review
- 2019
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Ingår i: Obstetrics and Gynecology. - 0029-7844 .- 1873-233X. ; 134:4, s. 677-684
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: To estimate the predictive value of signs and symptoms that occur before onset of eclampsia among pregnant women.DATA SOURCES: Electronic databases, including MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov were searched from inception to 2018. Search terms included eclampsia, predict, likelihood ratio, predictive value, and risk.METHODS OF STUDY SELECTION: Abstracts and later full texts were selected for review if a diagnosis of eclampsia was made, a comparator arm included (women without a diagnosis of eclampsia), and predictors of imminent eclampsia 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).TABULATION, INTEGRATION, AND RESULTS: 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 eclampsia nor rule out eclampsia in their absence, with moderate specificity (83-94%) and poor sensitivity (29-56%).CONCLUSION: There is a dearth of high-quality studies investigating the predictive value of imminent signs and symptoms of eclampsia. 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 eclampsia. Of the most commonly reported symptoms-visual disturbances, epigastric pain, and headache-none were able to accurately predict, nor rule out, imminent eclampsia.
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| 16. |
- Joubert, Lloyd H., et al.
(författare)
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Cardiac magnetic resonance imaging in preeclampsia complicated by pulmonary edema shows myocardial edema with normal left ventricular systolic function
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 227:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Preeclampsia complicates approximately 5% of all pregnancies. When pulmonary edema occurs, it accounts for 50% of preeclampsia-related mortality. Currently, there is no consensus on the degree to which left ventricular systolic dysfunction contributes to the development of pulmonary edema. OBJECTIVE: This study aimed to use cardiac magnetic resonance imaging to detect subtle changes in left ventricular systolic function and evidence of acute left ventricular dysfunction (through tissue characterization) in women with preeclampsia complicated by pulmonary edema compared with both preeclamptic and normotensive controls. STUDY DESIGN: Cases were postpartum women aged >= 18 years presenting with preeclampsia complicated by pulmonary edema. Of note, 2 control groups were recruited: women with preeclampsia without pulmonary edema and women with normotensive pregnancies. All women underwent echocardiography and 1.5T cardiac magnetic resonance imaging with native T1 and T2 mapping. Gadolinium contrast was administered to cases only. Because of small sample sizes, a nonparametric test (Kruskal-Wallis) with pairwise posthoc analysis using Bonferroni correction was used to compare the differences between the groups. Cardiac magnetic resonance images were interpreted by 2 independent reporters. The intraclass correlation coefficient was calculated to assess interobserver reliability. RESULTS: Here, 20 women with preeclampsia complicated by pulmonary edema, 13 women with preeclampsia (5 with severe features and 8 without severe features), and 6 normotensive controls were recruited. There was no difference in the baseline characteristics between groups apart from the expected differences in blood pressure. Left atrial sizes were similar across all groups. Women with preeclampsia complicated by pulmonary edema had increased left ventricular mass (P=.01) but had normal systolic function compared with the normotensive controls. Furthermore, they had elevated native T1 values (P=.025) and a trend toward elevated T2 values (P=.07) in the absence of late gadolinium enhancement consistent with myocardial edema. Moreover, myocardial edema was present in all women with eclampsia or hemolysis, elevated liver enzymes, and low platelet count. Women with preeclampsia without severe features had similar findings to the normotensive controls. All cardiac magnetic resonance imaging measurements showed a very high level of interobserver correlation. CONCLUSION: This study focused on cardiac magnetic resonance imaging in women with preeclampsia complicated by pulmonary edema, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count. We have demonstrated normal systolic function with myocardial edema in women with preeclampsia with these severe features. These findings implicate an acute myocardial process as part of this clinical syndrome. The pathogenesis of myocardial edema and its relationship to pulmonary edema require further elucidation. With normal left atrial sizes, any hemodynamic component must be acute.
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| 17. |
- Kandel, Manju, et al.
(författare)
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PSG7 and 9 (Pregnancy-Specific beta-1 Glycoproteins 7 and 9) : Novel Biomarkers for Preeclampsia
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 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 beta-1 glycoprotein 7) and PSG9 (pregnancy-specific beta-1 glycoprotein 9) in preeclampsia.Methods and Results: At 36 weeks 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 32 weeks 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 <34 weeks 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 TNF alpha (tumor necrosis factor alpha) 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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| 18. |
- 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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