Dataset Information

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review.

ABSTRACT:

Background

Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies.

Methods

We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 x 2 tables with maternal and fetal complications as reference standards.

Results

Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission.

Conclusion

Measure of proteinuria is a poor predictor of either maternal or fetal complications in women with pre-eclampsia.

SUBMITTER: Thangaratinam S

PROVIDER: S-EPMC2670320 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review.

Thangaratinam Shakila S Coomarasamy Arri A O'Mahony Fidelma F Sharp Steve S Zamora Javier J Khan Khalid S KS Ismail Khaled M K KM

BMC medicine 20090324

<h4>Background</h4>Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies.<h4>Methods</h4>We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (19 ...[more]

PMID: 19317889

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Project description:BackgroundIn the past, progesterone has been advocated for prevention of pre-eclampsia and its complications. Although progestogens are not used for this purpose in current clinical practice, it remains relevant to assess the evidence on their possible benefits and harms.ObjectivesTo assess the effects of progesterone during pregnancy on the risk of developing pre-eclampsia and its complications.Search strategyWe searched the Cochrane Pregnancy and Childbirth Group's Trials Register (April 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2), and EMBASE (1974 to August 2005).Selection criteriaRandomised trials evaluating progesterone or any other progestogen during pregnancy for prevention of pre-eclampsia and its complications were included.Data collection and analysisTwo review authors independently assessed studies for inclusion and extracted data.Main resultsTwo trials of uncertain quality were included (296 women). These trials compared progesterone injections with no progesterone. There was insufficient evidence to demonstrate any clear differences between the two groups on the risk of pre-eclampsia (one trial, 128 women; relative risk (RR) 0.21, 95% confidence interval (CI) 0.03 to 1.77), death of the baby (two trials, 296 women; RR 0.72, 95% CI 0.21 to 2.51), preterm birth (one trial, 168 women; RR 1.10, 95% CI 0.33 to 3.66), small-for-gestational-age babies (one trial, 168 women; RR 0.83, 95% CI 0.19 to 3.57) or major congenital defects (one trial, 168 women; RR 1.65, 95% CI 0.28 to 9.62). There were no reported cases of masculinisation of female babies (one trial, 128 women). Long-term follow up for the children has been reported in one trial, but the data are excluded from the review as 54% were lost to follow up at one year and 80% at 16 years.Authors' conclusionsThere is insufficient evidence for reliable conclusions about the effects of progesterone for preventing pre-eclampsia and its complications. Therefore, progesterone should not be used for this purpose in clinical practice at present. Unless new and plausible hypotheses emerge for the role of progesterone in development of pre-eclampsia, further trials of progesterone are unlikely to be a priority.

Project description:BACKGROUND:Pre-term pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality worldwide. A multi-centre randomized-controlled trial has shown that first-trimester screening followed by treatment of high-risk women with aspirin reduces the risk of pre-term pre-eclampsia. However, the biomarkers currently employed in risk prediction are only weakly associated with the outcome. METHODS:We conducted a case-cohort study within the Pregnancy Outcome Prediction study to analyse untargeted maternal serum metabolomics in samples from 12, 20, 28 and 36?weeks of gestational age (wkGA) in women with pre-eclampsia delivering at term (n?=?165) and pre-term (n?=?29), plus a random sample of the cohort (n?=?325). We used longitudinal linear mixed models to identify candidate metabolites at 20/28?wkGA that differed by term pre-eclampsia status. Candidates were validated using measurements at 36?wkGA in the same women. We then tested the association between the 12-, 20- and 28-wkGA measurements and pre-term pre-eclampsia. We externally validated the association using 24- to 28-wkGA samples from the Born in Bradford study (25 cases and 953 controls). RESULTS:We identified 100 metabolites that differed most at 20/28?wkGA in term pre-eclampsia. Thirty-three of these were validated (P?<?0.0005) at 36?wkGA. 4-Hydroxyglutamate and C-glycosyltryptophan were independently predictive at 36?wkGA of term pre-eclampsia. 4-Hydroxyglutamate was also predictive (area under the receiver operating characteristic curve, 95% confidence interval) of pre-term pre-eclampsia at 12 (0.673, 0.558-0.787), 20 (0.731, 0.657-0.806) and 28?wkGA (0.733, 0.627-0.839). The predictive ability of 4-hydroxyglutamate at 12?wkGA was stronger than two existing protein biomarkers, namely PAPP-A (0.567, 0.439-0.695) and placenta growth factor (0.589, 0.463-0.714). Finally, 4-hydroxyglutamate at 24-28?wkGA was positively associated with pre-eclampsia (term or pre-term) among women from the Born in Bradford study. CONCLUSIONS:4-hydroxyglutamate is a novel biochemical predictor of pre-eclampsia that provides better first-trimester prediction of pre-term disease than currently employed protein biomarkers.

Project description:BACKGROUND:Proteinuria has emerged as an important vascular risk factor for adverse cardiovascular events including stroke. Hypertension has been proposed as the principal confounder of this relationship but its role has not been systematically examined. AIM:We aimed to determine if proteinuria remains an independent predictor of stroke after more complete adjustment for blood pressure. SUMMARY OF REVIEW:We performed a systematic review, searching MEDLINE and EMBASE (to February 2018) for cohort studies or randomized controlled trials that reported stroke incidence in adults according to baseline proteinuria?±?glomerular filtration rate. Study and participant characteristics and relative risks were extracted. Estimates were combined using a random effects model. Heterogeneity was assessed by ? 2 statistics and I2, and by subgroup strata and meta-regression, with a particular focus on the impact of more complete adjustment for blood pressure on the association. The quality of cohort studies and post hoc analyses was assessed using the Newcastle-Ottawa Scale. We identified 38 studies comprising 1,735,390 participants with 26,405 stroke events. Overall, the presence of any level of proteinuria was associated with greater stroke risk (18 studies; pooled crude relative risk 2.00, 95%CI 1.63-2.46; p?<?0.001) even after adjustment for established cardiovascular risk factors (33 studies; pooled adjusted relative risk 1.72, 1.51-1.95; p?<?0.001), albeit with considerable heterogeneity between studies (p?<?0.001; I2?=?77.3%). Moreover, the association did not substantially attenuate with more thorough adjustment for hypertension: single baseline blood pressure measure (10 studies; pooled adjusted relative risk?=?1.92, 1.39-2.66; p?<?0.001); history or treated hypertension (four studies; pooled adjusted relative risk?=?1.76, 1.13-2.75, p?=?0.013); multiple blood pressure measurements over months to years (four studies; relative risk?=?1.68, 1.33-2.14; p?<?0.001). CONCLUSIONS:Even after extensive adjustment for hypertension, proteinuria is strongly and independently associated with incident stroke risk, possibly indicating a shared renal and cerebral susceptibility to vascular injury that is not fully explained by traditional vascular risk factors.

Project description:BackgroundThe risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods.MethodsElectronic searches using the terms "troponin I" or "troponin T", and "pregnancy", "pregnancy complications" or "obstetrics". cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia.ResultsThe search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia.ConclusionTnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology.

Project description:ObjectiveA model that can predict reliably the risk of pre-eclampsia (PE)-related pregnancy complications does not exist. The aim of this study was to develop and validate internally a clinical prediction model to predict the risk of a composite outcome of PE-related maternal and fetal complications within 7, 14 and 30 days of testing in women with suspected or confirmed PE.MethodsThe data for this study were derived from a prospective, multicenter, observational cohort study on women with a singleton pregnancy and suspected or confirmed PE at 20 to < 37 weeks' gestation. For the development of the prediction model, the possible contribution of clinical and standard laboratory variables, as well as the biomarkers soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and their ratio, in the prediction of a composite outcome of PE-related complications, consisting of maternal and fetal adverse events within 7, 14 and 30 days, was explored using multivariable competing-risks regression analysis. The discriminative ability of the model was assessed using the concordance (c-) statistic. A bootstrap validation procedure with 500 replications was used to correct the estimate of the prediction model performance for optimism and to compute a shrinkage factor for the regression coefficients to correct for overfitting.ResultsAmong 384 women with suspected or confirmed PE, 96 (25%) had an adverse PE-related outcome at any time after hospital admission. Important predictors of adverse PE-related outcome included sFlt-1/PlGF ratio, gestational age at the time of biomarker measurement and protein-to-creatinine ratio as continuous variables. The c-statistics (corrected for optimism) for developing a PE-related complication within 7, 14 and 30 days were 0.89, 0.88 and 0.87, respectively. There was limited overfitting, as indicated by a shrinkage factor of 0.91.ConclusionsWe propose a simple clinical prediction model with good discriminative performance to predict PE-related complications. Determination of its usefulness in clinical practice awaits further investigation and external validation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dataset Information

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review.

Background

Methods

Results

Conclusion

Publications

Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review.

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