Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis

Abstract

Objective: To determine the diagnostic accuracy of two "spot urine" tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia.

Design: Systematic review and meta-analysis.

Data sources: Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts.

Inclusion criteria: Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed.

Data extraction: Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods.

Results: Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67).

Conclusion: The maternal "spot urine" estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome.

Fig 1 Process from initial search to final inclusion for albumin to creatinine ratio or protein to creatinine ratio in management of pre-eclampsia (up to January 2011)

Fig 2 Bar chart showing quality assessment using QUADAS criteria of included papers in systematic review of albumin to creatinine ratio and protein to creatinine ratio in management of pre-eclampsia. Availability of clinical data refers to “Were the same clinical data available when test results were interpreted as would be available when the test is used in practice?”

Fig 3 Summary receiver operating characteristics curve for constrained estimates of sensitivity and specificity for protein to creatinine ratio. Open circles indicate most promising thresholds for use, as they optimise both sensitivity and specificity (and thus give largest rectangular area below paired point to right)