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Keywords:

  • Complications;
  • diagnostic tests;
  • pre-eclampsia;
  • systematic review;
  • uric acid.

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

Background  Pre-eclampsia is one of the largest causes of maternal and fetal mortality and morbidity. Hyperuricemia is often associated with pre-eclampsia.

Objective  To determine the accuracy with which serum uric acid predicts maternal and fetal complications in women with pre-eclampsia.

Study design  Systematic quantitative review of test accuracy studies.

Search strategy  We conducted electronic searches in MEDLINE (1951–2004), EMBASE (1980–2004), the Cochrane Library (2004:4) and the MEDION database to identify relevant articles. A hand-search of selected specialist journals and reference lists of articles obtained was then carried out. There were no language restrictions for any of these searches.

Selection criteria  Two reviewers independently selected the articles in which the accuracy of serum uric acid was evaluated to predict maternal and fetal complications of pre-eclampsia.

Data collection and analysis  Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standard. Summary likelihood ratios for positive (LR+) and negative LR(−) test results are generated for various threshold levels of uric acid.

Main results  There were 18 primary articles that met the selection criteria, including a total of 3913 women and forty-one 2 × 2 tables. In women with pre-eclampsia, a positive test result of uric acid greater than or equal to a 350-μmol/l threshold predicted eclampsia with a pooled likelihood ratio (LR) of 2.1 (95% CI 1.4–3.5), while a negative test result had a pooled LR of 0.38 (95% CI 0.18–0.81). For severe hypertension as the outcome measure, the LRs were 1.7 (95% CI 1.3–2.2) and 0.49 (95% CI 0.38–0.64) for positive and negative test results, respectively, and for caesarean section the LRs were 2.4 (95% CI 1.3–4.7) and 0.39 (95% CI 0.20–0.76). For stillbirths and neonatal deaths the respective LRs were 1.5 (95% CI 0.91–2.6) and 0.51 (95% CI 0.20–1.3). For the prediction of small-for-gestational-age fetus, the pooled LRs were 1.3 (95% CI 1.1–1.7) and 0.60 (95% CI 0.43–0.83) for positive and negative results, respectively.

Author's conclusion  Serum uric acid is a poor predictor of maternal and fetal complications in women with pre-eclampsia.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

Pre-eclampsia affects approximately 2–8% of all pregnancies and is associated with several complications.1 It remains one of the largest single causes of maternal and fetal mortality and morbidity.1,2 Clinical prediction of disease complications may facilitate instigation of timely management to avert mortality and morbidity in the mother and baby. Hyperuricemia is one of the characteristic findings in pre-eclampsia. In clinical practice, uric acid determination is considered to be a part of the workup in women with pre-eclampsia to monitor disease severity and aid management of these women. The association between raised serum uric acid and pre-eclamptic pregnancy was first reported in 1917.3 Reduced uric acid clearance secondary to reduced glomerular filtration rate, increased reabsorption and decreased secretion may be the reasons for elevated serum uric acid levels in women with pre-eclampsia.4,5 The pathophysiologic mechanisms of pre-eclampsia comprising increased trophoblastic tissue shedding, endothelial dysfunction, and reduced blood flow in the fetomaternal unit have also been hypothesised as the underlying cause of hyperuricemia in this condition.6

Several studies have reported a positive correlation between elevated maternal serum uric acid levels and adverse maternal and fetal outcomes.7–10 However, these primary diagnostic studies have not generally been conducted with large enough sample size to provide precise accuracy estimates and they vary widely in their definition of pre-eclampsia, maternal and fetal outcomes and optimal cutoff levels of uric acid in predicting maternal and fetal complications. There are no systematic reviews exploring the accuracy of uric acid to predict complications of pre-eclampsia. We therefore conducted a comprehensive systematic review to obtain precise estimates of maternal serum uric acid levels to predict maternal and fetal complications in women with pre-eclampsia.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

The review was carried out with a prospective protocol using widely recommended methods.11–14

Identification of studies

We searched MEDLINE (1951–2004), EMBASE (1974–2004), Cochrane Library (2004:4) and MEDION (a database of diagnostic test reviews set up by Dutch and Belgian researchers) for relevant citations. The reference lists of all known primary and review articles were examined to identify cited articles not captured by electronic searches. Details of the search strategy are available from the authors. Language restrictions were not applied. A comprehensive database of relevant articles was constructed.

Study selection and data extraction procedures

Studies that evaluated the accuracy of maternal serum uric acid in women with pre-eclampsia for the prediction of maternal or fetal complications were selected in a two-stage process. First, the electronic searches were scrutinised and full articles of all citations that were likely to meet the predefined selection criteria were obtained by two independent reviewers (S.T. and K.M.K.I.). Second, final inclusion or exclusion decisions were made by the reviewers (S.T. and K.M.K.I.) after examination of these articles. Studies that met the predefined and explicit criteria regarding population, tests, outcomes and study design (1Table 1) were selected for inclusion in the review. When disagreements occurred, they were resolved by consensus. In cases of duplicate publication, the most recent and complete versions were selected. There were no language restrictions.

Table 1.  Study characteristics of the trials included in the systematic review of accuracy of serum uric acid in predicting complications in women with pre-eclampsia
StudyPopulationTest (uric acid), cutoffOutcome
Study (Year)QualityNumber of patientsInclusion criteria 
  1. LDH, Lactal dehydration; SGOT, Serum glutamic oxaloacetic transaminase

Yassaee (2003)15Cohort, not blind, enrolment method not known, direction of data collection not known, test not described103Severe pre-eclampsia350 μmol/lEclampsia, maternal death, caesarean section, intrauterine death, intrauterine growth restriction
Williams and Galerneau (2002)16Cross-sectional, not blind, prospective, test described, enrolment method not known194Blood pressure (BP) ≥140/90 after 20 weeks and proteinuria ≥1+ or 300 mg/24 hour450 and 540 μmol/lHELLP syndrome (SGOT > 40 iu/l, LDH >600 iu/l, haemolysis on blood film, platelets ≤150 × 109/l), small for gestational age (birthweight <10th centile), severe hypertension (systolic BP ≥160 and/or diastolic BP ≥110 on two occasions)
D’Anna et al. (2000)17Cross-sectional, not blind, retrospective, enrolment not known, test described94National Working Group on Hypertension in Pregnancy criteria for pre-eclampsia340 μmol/lIntrauterine growth restriction
Martin et al. (1999)18Cross-sectional, not blind, retrospective, not consecutive enrolment, test not described568Severe pre-eclampsia380 and 460 μmol/lSignificant maternal morbidity, renal, hepatic and/or gastrointestinal
Odendaal and Pienaar (1997)19Cross-sectional, not blind, prospective, enrolment method not known, test described229Severe pre-eclampsia520 μmol/lSmall for gestational age (Tygerberg hospital growth curves), intrauterine death, neonatal death, perinatal mortality (within 7days), caesarean section, preterm delivery
Shah and Reed (1996)20Cross-sectional, not blind, retrospective, consecutive enrolment, test description not adequate271Pre-eclampsia (de novo development of hypertensive disorder in second half of pregnancy). It includes proteinuric pre-eclampsia >300 mg/dl in 24 hour or ≥1+ 6 hour apart and nonproteinuric pre-eclampsia with increased BP in second-half of pregnancy and elevated uric acid or other systemic involvement markers350 μmol/lAdverse perinatal outcome that includes: 1. perinatal death; 2. perinatal morbidity of prematurity due to hypertensive disease, moderate or severe hyaline membrane disease, patent ductus arteriosus, intraventricular haemorrhage; 3. perinatal morbidity due to uteroplacental vasculopathy, intrauterine growth restriction, abruption, fetal distress needing caesarean section
Magann et al. (1993)21Cross-sectional, not blind, retrospective data collection, not consecutive enrolment, test described454Severe pre-eclampsia330, 460 and 600 μmol/lClass I HELLP syndrome (Platelets <50 000, elevated LDH, haemolysis and hepatic dysfunction)
Voto et al. (1988)22Cross-sectional, not blind, enrolment not known, direction of data collection not known, test not described125BP ≥140/90 in third trimester, mild pre-eclampsia (BP 140–159/90–99), severe pre-eclampsia (BP ≥160/100)350 μmol/lSevere hypertension BP ≥160/100, intrauterine growth restriction
Sagen et al. (1984)23Cross-sectional, not blind, prospective, test described, not consecutive enrolment72Severe pre-eclampsia, BP ≥160/110 and proteinuria ≥5 g/24 hoursUrate increment ≥50 μmol/l in last 3 days prior to delivery, ≥350 μmol/lPerinatal distress (perinatal death, Apgar, 7 at 1 or 5 mins, later development of neonatal asphyxia, respiratory distress syndrome, hypoglycaemia or fits), small for gestational age (<10th centile), perinatal death
Liedholm et al. (1984)7Cross-sectional, not blind, retrospective, test described, consecutive enrolment26BP ≥140/90 after 20 weeks, proteinuria ≥1+ on two or more occasions350 μmol/lCaesarean section, use of any one antihypertensive, use of two antihpertensives (hydralazine added on to beta blocker)
Varma (1982)24Cross-sectional, not blind, prospective, not consecutive enrolment, test described200BP ≥140/90 after 24 weeks on two or more occasions 24 hours apart.≥60 μmol/l on ≥2 consecutive samples or maximum ≥330 μmol/lIntrauterine growth restriction (birthweight <10th centile), fetal distress in labour, neonatal death, stillbirth
Mathews et al. (1980)25Cross-sectional, not blind, prospective, not consecutive enrolment, test described40Diastolic BP ≥90, >trace protein240 μmol/l before 34 weeks, 350 μmol/l after 34 weeksPerinatal death
Dequiedt et al. (1979)26Cross-sectional, not blind, prospective data collection, enrolment not known, test described43BP ≥140/80 with proteinuria in third trimester and blood pressure returned to normal postnatally300 μmol/lIntrauterine growth restriction, stillbirth, caesarean section
Fadel et al. (1969)27Cross-sectional, not blind, prospective, test described, enrolment not known62Pre-eclamptic women BP >140/90 and/or proteinuria in latter half of pregnancy240 and 350 μmol/lEclampsia
Connon and Wadsworth (1968)28Cross-sectional, not blind, retrospective data collection, not consecutive enrolment, test described124BP ≥140/90 with proteinuria350 μmol/lSevere pre-eclampsia
Lancet and Fisher (1956)9Cross-sectional, not blind, enrolment not known, direction of data collection not known, test not described469Not available350 μmol/lSevere pre-eclampsia, eclampsia
Seitchik (1953)29Cross-sectional, not blind, retrospective data collection, enrolment not known, test described14BP ≥140/90 mmHg350 μmol/lSevere pre-eclampsia

Information was extracted from each selected article on study characteristics, quality and accuracy results. Accuracy data were used to construct 2 × 2 tables of uric acid result (test positive if uric acid levels were above a threshold as defined in the primary study, and test negative if these were below the threshold) and maternal (eclampsia, severe hypertension, HELLP [haemolysis, elevated liver enzymes and low platelet count] syndrome, caesarean section) and fetal (stillbirths and neonatal deaths, intrauterine death, small-for-gestational-age fetus) outcomes.

Methodological quality assessment

All articles meeting the selection criteria were assessed for their methodological quality. Quality was defined as the confidence that the study design, conduct and analysis minimised bias in the estimation of test accuracy. Based on existing check-lists,11,12,14,30,31 quality assessment involved scrutinising study design and relevant features of the population, test and outcomes of the study. A study was considered to be of good quality if it used a prospective design, consecutive enrolment, full verification of the test result with reference standard and had adequate test description.11,14,30,31 We excluded studies with case–control design as these are known to result in statistical bias.30

Data synthesis

Likelihood ratios (LRs) for positive and negative test results were calculated for each study, separately for each test threshold. Summary LRs32 were then computed for positive and negative test results for each individual test threshold and for each outcome of interest. This information is clinically more relevant than traditional summaries of accuracy such as sensitivity and specificity, as LRs allow the estimation of post-test probabilities of various complications for women at different risk levels.33 The LR indicates by how much a given test result raises or lowers the probability of having the disease. The higher the LR of an abnormal test, the greater is the value of the test. Conversely, the lower the LR of a normal test, the greater the value of the test. An LR >10 for an abnormal test or <0.1 for a normal test is regarded as ‘very useful’ test accuracy, LR of 5–10 or 0.1–0.2 is regarded as ‘moderately useful’ and LR of 2–5 or 0.5–0.2 is regarded as ‘somewhat useful’. An LR of 1–2 or 0.5–1 is only regarded as ‘little useful’ and LR of 1 as ‘useless’. Although, this categorisation is useful for interpretation of LRs, it should be noted that the value of a test may vary depending on the pre-test probability of the condition and the consequences of treatment.

Heterogeneity of diagnostic odds ratio was assessed graphically using forest plot34 (not shown) and statistically using chi-square test35 to aid in decisions on how to proceed with quantitative synthesis.36 As, for some tests and outcomes, there was either graphical or statistically significant heterogeneity, we used random effects model meta-analysis.35 All statistical analyses were performed using Stata 7.0 statistical package.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

Literature identification and study quality

1Figure 1 summarises the process of literature identification and selection. There were 18 primary articles7,9,15–29,37 that met the selection criteria, consisting of 41 accuracy studies (16 studies evaluating accuracy of serum uric acid in severe pre-eclampsia, and 25 studies evaluating accuracy in various grades of pre-eclampsia), including a total of 3913 women (Figure 1). Each study's salient features according to the population subgroups, test characteristics and reference standards can be obtained from the authors. The definition of pre-eclampsia differed widely between the studies. The test thresholds varied from 240 to 600 μmol/l in individual studies. The most common was 350 μmol/l, which was the threshold in 21 studies. The commonest maternal and fetal outcomes assessed were severity of hypertension (in eight studies) and small for gestational age (in ten studies), respectively. The methodological quality of the included studies is given in 2Figure 2.

image

Figure 1. Study selection process for systematic review of uric acid to predict maternal and fetal complications.

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image

Figure 2. Quality of the included studies in the systematic review of accuracy of uric acid in predicting maternal and fetal complications.

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Uric acid to predict maternal outcomes

The pooled accuracy estimates for uric acid in predicting maternal outcomes using different test thresholds and stratified by different population subgroups are presented in 2Table 2 as LR (LR+ and LR−). Eclampsia was evaluated as an outcome in three studies using a cutoff level of 350 μmol/l. The pooled estimates of LR+ and LR− of uric acid levels for this threshold level were 2.1 (95% CI 1.4–3.5) and 0.38 (95% CI 0.18–0.81), respectively (3Figure 3a).

Table 2.  LRs for predicting maternal outcomes in women with pre-eclampsia using serum uric acid
Subgroups and test thresholds (μmol/l)Maternal outcomes
EclampsiaSevere hypertensionCaesarean sectionHELLP syndrome
nLR+ (95% CI)LR− (95% CI)nLR+ (95% CI)LR− (95% CI)nLR+ (95% CI)LR− (95% CI)nLR+ (95% CI)LR− (95% CI)
  • n = number of studies.

  • *

    Pooling was performed using a random effects model.

Overall accuracy across all studies*
35032.1 (1.4–3.5)0.38 (0.18–0.81)61.7 (1.3–2.2)0.49 (0.38–0.64)22.4 (1.3–4.7)0.39 (0.20–0.76) 
Subgroup in which study participants had varying degrees of pre-eclampsia
300 12.6 (0.82–8.5)0.29 (0.06–1.4) 
35023.0 (0.89–9.8)0.43 (0.19–1.0)61.7 (1.3–2.2)0.49 (0.38–0.64)12.2 (0.59–7.9)0.19 (0.02–1.7) 
450 11.8 (0.86–3.7)0.87 (0.56–1.4) 11.6 (0.73–3.3)0.90 (0.56–1.4)
540 11.8 (0.71–4.3)0.93 (0.60–1.4) 11.9 (0.85–4.2)0.92 (0.81–1.0)
Subgroup in which study participants had severe pre-eclampsia
330
35012.0 (0.85–4.8)0.14 (0.02–1.1) 12.6 (1.2–5.4)0.42 (0.21–0.84) 
520 11.3 (0.53–3.3)0.97 (0.65–1.4) 
image

Figure 3. LRs for predicting maternal outcomes using 350-μmol/l threshold level of serum uric acid. (a) Prediction of eclampsia, (b) prediction of severe hypertension, (c) prediction of caesarean section.

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Six studies estimated the accuracy of uric acid levels more than or equal to 350 μmol/l to predict severe hypertension. The pooled LR for positive test in this group was 1.7 (95% CI 1.3–2.2) and for negative test was 0.49 (95% CI 0.38–0.64) (Figure 3b).

Caesarean section was studied as an outcome in four studies. The pooled LRs for a threshold level of 350 μmol/l were 2.4 (95% CI 1.3–4.7) and 0.39 (95% CI 0.20–0.76) for positive and negative test results, respectively (Figure 3c).

Two studies evaluated the prediction of HELLP syndrome using 450 μmol/l and 540-μmol/l threshold levels. The LRs for predicting HELLP syndrome with a threshold of 450 μmol/l were 1.6 (95% CI 0.73–3.3) and 0.90 (95% CI 0.56–1.4), and with a threshold of 540 μmol/l were 1.9 (95% CI 0.85–4.2) and 0.92 (95% CI 0.81–1.0).

Uric acid to predict fetal outcomes

Ten studies evaluated the accuracy of uric acid to predict small-for-gestational-age fetus for various threshold levels (3Table 3). The pooled LRs for positive and negative tests for threshold level of 350 μmol/l (n= 5) to predict small-for-gestational-age fetus are 1.3 (95% CI 1.1–1.7) and 0.60 (95% CI 0.43–0.83), respectively (4Figure 4a).

Table 3.  LRs for predicting fetal outcomes in women with pre-eclampsia using serum uric acid
Subgroups and test thresholds (μmol/l)Fetal outcomes
 Small for gestational ageStillbirths and neonatal deathsIntrauterine death
 nLR+ (95% CI)LR− (95%CI)nLR+ (95% CI)LR− (95% CI)nLR+ (95% CI)LR− (95% CI)
  • n = number of studies.

  • *

    Pooling was performed using a random effects model; LR+ Likelihood ratio for positive test; LR− Likelihood ratio for negative text.

Overall accuracy across all studies*
35051.3 (1.1–1.7)0.60 (0.43–0.83)41.5 (0.91–2.6)0.51 (0.20–1.3) 
Subgroup in which study participants had varying degrees of pre-eclampsia
30012.2 (0.63–7.6)0.38 (0.07–2.0)12.7 (0.68–10.4)0.14 (0.01–2.6)12.7 (0.71–9.8)0.13 (0.01–2.4)
33012.3 (1.2–4.3)0.62 (0.35–1.1)12.8 (0.42–18.3)0.28 (0.01–5.9)12.8 (0.42–18.3)0.28 (0.01–5.9)
35031.4 (1.1–1.8)0.65 (0.50–0.86)21.4 (0.92–2.0)0.63 (0.30–1.3) 
45010.89 (0.38–2.1)1.0 (0.63–1.7) 
54010.71 (0.23–2.2)1.0 (0.65–1.7) 
Subgroup in which study participants had severe pre-eclampsia
35021.0 (0.08–11.9)0.68 (0.24–1.9)21.65 (0.82–3.3)0.21 (0.03–1.7)12.1 (0.89–5.1)0.07 (0.01–1.3)
52010.65 (0.28–1.5)1.1 (0.72–1.5)11.6 (0.68–3.9)0.94 (0.61–1.5)11.5 (0.40–5.3)0.93 (0.46–1.9)
image

Figure 4. LRs for predicting fetal outcomes using 350-μmol/l threshold level of serum uric acid. (a) Prediction of small-for-gestational-age fetus, (b) prediction of stillbirth and neonatal death.

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Stillbirths and neonatal deaths were evaluated as an outcome measure in seven studies. The pooled estimates of LR+ and LR− for uric acid levels more than or equal to 350 μmol/l were 1.5 (95% CI 0.91–2.6) and 0.51 (95% CI 0.20–1.3), respectively (Figure 4b). In the subgroup of women with severe pre-eclampsia, the LR+ of uric acid for the above cutoff and outcome was 1.65 (95% CI 0.82–3.3) and the corresponding LR− was 0.21 (95% CI 0.03–1.7).

Four studies evaluated the accuracy of uric acid to predict intrauterine death for various threshold levels of uric acid: 300 μmol/l (n= 1), 330 μmol/l (n= 1), 350 μmol/l (n= 2) and 520 μmol/l (n= 1). Meta-analyses were not performed since the studies could not be pooled due to the varied threshold levels. The positive LRs for uric acid levels more than or equal to 300 and 330 μmol/l were 2.7 (95% CI 0.71–9.8) and 2.8 (95% CI 0.42–18.3), respectively. The negative LRs for the above thresholds were 0.13 (95% CI 0.01–2.4) and 0.28 (95% CI 0.01–5.9).

All the above results were statistically homogenous.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

This review presents the best available evidence so far in addressing the question of significance of uric acid levels as a predictor of maternal and fetal complications in pre-eclampsia. Although uric acid as a marker may be of value in detecting pre-eclampsia,38 it has been identified as a poor predictor of any complications of pre-eclampsia. The provision of LRs stratified by the severity of pre-eclampsia and test thresholds will enable clinicians to understand the poor clinical value of this test in predicting complications in women with pre-eclampsia.

The validity of our review findings depends on the methodology of the systematic review and the quality of the individual studies included.12,30 An extensive literature search was performed in relevant databases without any language restrictions to minimise the possibility of missing any studies. Methodological deficiencies like verification bias, differential use of reference standards and case–control design did not apply to the studies in the review, ensuring inclusion of acceptable quality studies. We used summary LRs to report the accuracy of tests in preference to summary receiver operating characteristics curve39 that has limited value in clinical interpretation of diagnostic information. A significant limitation of this review is the heterogeneity noticed between individual studies with regard to population, definition of pre-eclampsia, test thresholds, frequency of testing, interval between the test and outcome and reference standards. This led us to analyse data within subgroups defined by severity of pre-eclampsia and threshold levels, resulting in the inclusion of a small number of studies in the subgroup meta-analyses.

Caution is needed in interpreting quantitative estimation of uric acid levels in relation to outcome. Apart from the variations in the methods for estimating uric acid levels, levels of uric acid could be raised due to the use of antihypertensives.19 The outcomes could also be influenced by the different therapeutic interventions such as use of antenatal steroids in reducing respiratory distress syndrome40 and antihypertensives41 that might help to reduce fetal and maternal complications. Moreover, it is not possible to be certain of the finding where only a small number of studies exist in a subgroup, due to imprecision.

Our review has consistently observed poor performance of uric acid in predicting various maternal and fetal outcomes, across various studies, settings and population. The consistency of such poor performance of uric acid in predicting complications in those with pre-eclampsia cannot be ignored. The predictive value of a positive test was particularly poor for some fetal outcomes like stillbirths and neonatal deaths. The confidence intervals of the pooled LRs for a positive result extended to 1 or less than 1, suggesting the possibility of finding the same or more number of complications in those with normal urate levels compared with raised levels. The same anomaly was seen for a negative test result in predicting stillbirths and neonatal deaths (Figure 4b).

Given our results, uric acid test does not seem to be a clinically useful test to predict maternal or fetal complications in women with pre-eclampsia. There is no strong evidence to justify the use of therapeutic measures like magnesium sulphate use42 or early delivery aimed at reducing maternal and fetal complications based on the levels of uric acid.

TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

Shakila Thangaratinam (specialist registrar), Khaled MK Ismail (senior lecturer/consultant), Fidelma O’Mahony (senior lecturer/consultant), Shaughn O’Brien (professor in obstetrics and gynaecology) affiliated to Academic Unit of Obstetrics and Gynaecology, Keele University School of Medicine, University Hospital of North Staffordshire, Stoke-on-Trent, ST4 6QG, UK.

Steve Sharp (electronic information librarian) affiliated to NeLH Specialist Library for ENT and Audiology, Radcliffe Infirmary, Oxford, OX2 6HE, UK.

Arri Coomarasamy (clinical lecturer/specialist registrar), Khalid S Khan (professor in obstetrics and gynaecology) affiliated to Education Resource Centre, Birmingham Women's Hospital, Birmingham, B15 2TG, UK.

Contributors

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

K.S.K. conceived the idea of the review and developed the protocol with K.M.K.I., F.O.’M., A.C. and S.T. S.S. searched the electronic databases to identify the studies. K.M.K.I., F.O.’M. and S.O.’B. obtained funding for S.T. from University Hospital North Staffordshire Research and Development Department, Stoke-on-Trent, UK.

Funding

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References

University Hospital North Staffordshire Research and Development Department, Stoke-on-Trent, UK (Ref No. R 5177680).

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. TIPPS (Tests in Prediction of Pre-eclampsia Severity) review group
  8. Contributors
  9. Funding
  10. References
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