Browsing by Author "Cluver, Catherine"

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    Circulating Growth Differentiation Factor 15 Is Increased Preceding Preeclampsia Diagnosis: Implications as a Disease Biomarker
    (Wolters Kluwer, 2021-08-17) Cruickshank, Tess; MacDonald, Teresa M; Walker, Susan P; Keenan, Emerson; Dane, Kirsten; Middleton, Anna; Kyritsis, Valerie; Myers, Jenny; Cluver, Catherine; Hastie, Roxanne; Bergman, Lina; Garcha, Damanpreet; Cannon, Ping; Murray, Elizabeth; Nguyen, Tuong‐Vi; Hiscock, Richard; Pritchard, Natasha; Hannan, Natalie J; Tong, Stephen; Kaitu’u‐Lino, Tu’uhevaha J
    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 preeclampsia 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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    Evidence of neuroinflammation and blood–brain barrier disruption in women with preeclampsia and eclampsia
    (MDPI, 2021-11-05) Bergman, Lina; Hastie, Roxanne; Zetterberg, Henrik; Blennow, Kaj; Schell, Sonja; Langenegger, Eduard; Moodley, Ashley; Walker, Susan; Tong, Stephen; Cluver, Catherine
    ENGLISH 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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    Interventions for treating genital Chlamydia trachomatis infection in pregnancy
    (John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2017) Cluver, Catherine; Novikova, Natalia; Eriksson, David O. A.; Bengtsson, Kevin; Lingman, Goran K.
    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. 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.
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    Planned early delivery versus expectant management for hypertensive disorders from 34 weeks gestation to term
    (John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2017) Cluver, Catherine; Novikova, Natalia; Koopmans, Corine M.; West, Helen M.
    Background: Hypertensive disorders in pregnancy are significant contributors to maternal and perinatal morbidity and mortality. These disorders include well‐controlled chronic hypertension, gestational hypertension (pregnancy‐induced hypertension) and mild pre‐eclampsia. The definitive treatment for these disorders is planned early delivery and the alternative is to manage the pregnancy expectantly if severe uncontrolled hypertension is not present, with close maternal and fetal monitoring. There are benefits and risks associated with both, so it is important to establish the safest option. Objectives: To assess the benefits and risks of a policy of planned early delivery versus a policy of expectant management in pregnant women with hypertensive disorders, at or near term (from 34 weeks onwards). Search methods: We searched Cochrane Pregnancy and Childbirth Trials Register (12 January 2016) and reference lists of retrieved studies. Selection criteria: Randomised trials of a policy of planned early delivery (by induction of labour or by caesarean section) compared with a policy of delayed delivery ("expectant management") for women with hypertensive disorders from 34 weeks' gestation. Cluster‐randomised trials would have been eligible for inclusion in this review, but we found none. Studies using a quasi‐randomised design are not eligible for inclusion in this review. Similarly, studies using a cross‐over design are not eligible for inclusion, because they are not a suitable study design for investigating hypertensive disorders in pregnancy. Data collection and analysis: Two review authors independently assessed eligibility and risks of bias. Two review authors independently extracted data. Data were checked for accuracy. Main results: We included five studies (involving 1819 women) in this review. There was a lower risk of composite maternal mortality and severe morbidity for women randomised to receive planned early delivery (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83, two studies, 1459 women (evidence graded high)). There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with lower risk of HELLP syndrome (RR 0.40, 95% CI 0.17 to 0.93, 1628 women; three studies) and severe renal impairment (RR 0.36, 95% CI 0.14 to 0.92, 100 women, one study). There was not enough information to draw any conclusions about the effects on composite infant mortality and severe morbidity. We observed a high level of heterogeneity between the two studies in this analysis (two studies, 1459 infants, I2 = 87%, Tau2 = 0.98), so we did not pool data in meta‐analysis. There were no clear differences between subgroups based on our subgroup analysis by gestational age, gestational week or condition. Planned early delivery was associated with higher levels of respiratory distress syndrome (RR 2.24, 95% CI 1.20 to 4.18, three studies, 1511 infants), and NICU admission (RR 1.65, 95% CI 1.13 to 2.40, four studies, 1585 infants). There was no clear difference between groups for caesarean section (RR 0.91, 95% CI 0.78 to 1.07, 1728 women, four studies, evidence graded moderate), or in the duration of hospital stay for the mother after delivery of the baby (mean difference (MD) ‐0.16 days, 95% CI ‐0.46 to 0.15, two studies, 925 women, evidence graded moderate) or for the baby (MD ‐0.20 days, 95% CI ‐0.57 to 0.17, one study, 756 infants, evidence graded moderate). Two fairly large, well‐designed trials with overall low risk of bias contributed the majority of the evidence. Other studies were at low or unclear risk of bias. No studies attempted to blind participants or clinicians to group allocation, potentially introducing bias as women and staff would have been aware of the intervention and this may have affected aspects of care and decision‐making. The level of evidence was graded high (composite maternal mortality and morbidity), moderate (caesarean section, duration of hospital stay after delivery for mother, and duration of hospital stay after delivery for baby) or low (composite infant mortality and morbidity). Where the evidence was downgraded, it was mostly because the confidence intervals were wide, crossing both the line of no effect and appreciable benefit or harm. Authors' conclusions: For women suffering from hypertensive disorders of pregnancy after 34 weeks, planned early delivery is associated with less composite maternal morbidity and mortality. There is no clear difference in the composite outcome of infant mortality and severe morbidity; however, this is based on limited data (from two trials) assessing all hypertensive disorders as one group. Further studies are needed to look at the different types of hypertensive diseases and the optimal timing of delivery for these conditions. These studies should also include infant and maternal morbidity and mortality outcomes, caesarean section, duration of hospital stay after delivery for mother and duration of hospital stay after delivery for baby. An individual patient meta‐analysis on the data currently available would provide further information on the outcomes of the different types of hypertensive disease encountered in pregnancy.
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    PROVE—Pre-Eclampsia Obstetric Adverse Events: Establishment of a Biobank and Database for Pre-Eclampsia
    (MDPI, 2021-04) Bergman, Lina; Bergman, Karl; Langenegger, Eduard; Moodley, Ashley; Griffith-Richards, Stephanie; Wikström, Johan; Hall, David; Joubert, Lloyd; Herbst, Philip; Schell, Sonja; Van Veen, Teelkien; Belfort, Michael; Tong, Stephen Y. C.; Walker, Susan; Hastie, Roxanne; Cluver, Catherine
    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.