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The urine spot albumin-creatinine ratio (which is done on a single, on-the-spot sample) reliably identified 99% of pregnant women with high blood pressure who went on to develop severe pre-eclampsia. The spot protein-creatinine ratio, as currently recommended by NICE, was slightly less sensitive identifying over 90% of women. Both spot tests were good value for money.
Nearly 1,000 women, suspected of having pre-eclampsia, took part in this NIHR-funded study, in 36 UK obstetric units. They had high blood pressure and protein detected in their urine (by dipstick) beyond 20 weeks of pregnancy. The study compared the diagnostic accuracy of newer ways of ‘spot’ testing a single sample of urine for predicting severe pre-eclampsia with traditional tests on a urine sample taken over 24-hours.
The findings suggest that spot albumin-creatinine or protein-creatinine ratios could be used in place of 24-hour urine collection and testing. Each can potentially rule-out women at risk of severe pre-eclampsia while being cheaper, quicker and more acceptable to women.
The study supports current NICE recommendations on the use of spot protein-creatinine ratio. Further guideline updates may consider the feasibility of the spot albumin-creatinine ratio test, though this test required analysis at a central laboratory.
Why was this study needed?
Pre-eclampsia is a serious complication of late pregnancy involving raised blood pressure (hypertension) and kidney dysfunction, detected by protein in the urine (proteinuria). It occurs in around 4-5% of pregnancies in the UK.
Pre-eclampsia is the second most common cause of maternal death and accounts for around 20% of stillbirths and up to 10% of preterm births. Early detection and active management are therefore essential.
Measuring the urine protein excreted over 24 hours is one way of quantifying the proteinuria. However, other tests on single samples, are more convenient and less time-consuming. They could also be a more accurate measure of protein excretion and better tests for ruling out pre-eclampsia.
This study aimed to see whether the spot protein-creatinine ratio (SPCR) and spot albumin-creatinine ratio (SACR) were more accurate at diagnosing severe pre-eclampsia than the 24-hour collection. Both tests only require a single urine sample. If these tests are more efficient and accurate, they may enable better management of pre-eclampsia, reduce adverse outcomes, and spare healthcare resources.
What did this study do?
Pregnant women (aged 16 and over) who were over 20 weeks were recruited from 36 UK centres. All had new hypertension (blood pressure of 140/90 mmHg or more) and at least a trace of proteinuria when tested by urine dipstick.
Participants provided a single urine spot sample and then collected urine for 24 hours in a container. SPCR was tested in three ways: at the local laboratory, and at the central laboratory using two different assays. SACR was tested at the central laboratory using an automated chemistry analyser. The 24-hour urine sample was tested at the central laboratory.
Tests were assessed for their ability to predict severe pre-eclampsia (the reference standard) according to the NICE definition, which includes severe hypertension (≥160/110), symptoms and/or blood abnormalities.
What did it find?
- Of 1,823 women with hypertension initially recruited, 959 had complete data available on all tests and could be included in the analysis. Half of these women (475) with pre-eclampsia, of which 417 cases were severe.
- The three SPCR tests (using a cut-off threshold of 30 mg/mmol) had good accuracy for reliably identifying those who would develop severe pre-eclampsia. Sensitivity (the proportion with the diagnosis correctly identified by the test) ranged from 93% to 95% depending on test assay and laboratory. However, not everyone testing positive would develop severe pre-eclampsia. Specificity (the proportion of women without the condition who correctly tested negative) was only 56% to 61% depending on the test.
- The SACR test (using a cut-off threshold of 2 mg/mmol) had a very high sensitivity of 99% so identified almost all women with severe pre-eclampsia. Specificity of SACR, however, was much poorer at 23%, so at this threshold the test would also pick up about three-quarters of women who wouldn’t develop severe pre-eclampsia (false positive results).
- All test strategies had similar overall costs.
What does current guidance say on this issue?
NICE guidelines on the diagnosis and management of hypertension in pregnancy (2010) recommend using SPCR to diagnose proteinuria in the hospital setting, alternatively 24-hour urine collection. NICE advise diagnosing significant proteinuria if the urinary protein:creatinine ratio is greater than 30 mg/mmol or a validated 24-hour urine collection result shows greater than 300 mg protein.
NICE does not currently give any recommendation about the use of SACR testing. Their 2010 guideline called for more research into the different tests for measuring proteinuria, including SACR.
What are the implications?
Spot testing using SACR or SPCR at the currently recommended threshold seem reliable for ruling out severe pre-eclampsia in pregnant women with new-onset hypertension.
The findings seem to support the withdrawal of 24-hour urine collection as a means to diagnose proteinuria. The spot tests are likely to be more acceptable and easier to carry and save time and resources.
While SACR, in particular, had excellent sensitivity, specificity was very poor at the 2mg/mmol threshold. The researchers suggest further evaluation of an 8mg/mmol threshold if the test is used to ”rule out” significant proteinuria and severe pre-eclampsia. This may reduce the number of women at low risk who are put through further testing.
Citation and Funding
Waugh J, Hooper R, Lamb E, et al. Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based economic evaluation and acceptability analysis. Health Technol Assess. 2017;21(61).
This project was funded by the National Institute for Health Research Health Technology Assessment (HTA) programme (project number 10/65/02).
Bibliography
NICE. Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. CG107. London: National Institute for Health and Care Excellence; 2010.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre
