3 centres collaboration

Urinalysis By Dipstick For Proteinuria

The aim of these guidelines is to assist midwives and doctors in their decisions about methods to detect pre-eclampsia, chronic renal disease and urinary tract infections.

This guideline should be read in conjunction with the guideline for antenatal screening for asymptomatic bacteriuria.

Introduction

In Australia, analysis of urine by dipstick for proteinuria is one of the most common antenatal tests, usually performed at every antenatal visit. Proteinuria may be used to screen for asymptomatic urinary infection, renal disease and pre-eclampsia. The presence of proteinuria is central to the diagnosis of pre-eclampsia in a hypertensive pregnancy and a component of classification systems for hypertensive disorders in pregnancy. Hypertension with proteinuria is associated with an increased rate of fetal growth restriction, perinatal mortality and poorer maternal prognosis. The gold standard for assessing proteinuria is laboratory biochemical measurement of total protein excretion over 24 hours. However, this method is unsuitable for use as a universal-screening tool. The most commonly employed method for screening for proteinuria is dipstick urinalysis of a randomly voided specimen.

The 3centres Collaboration contracted the Royal Women's Hospital (RWH) Clinical Practice Improvement Unit (CPIU) to conduct a comprehensive search and critical appraisal of publications addressing the topic of "urinalysis by dipstick for proteinuria", published between January 2000 and March 2005, to inform the proposed review of the 2001 3centres Consensus Guidelines on Antenatal Care.

The new evidence was discussed by the Guideline Advisory Group and a new draft guideline produced. The Guideline Advisory Group, an expert multidisciplinary group, was appointed by the 3 Centres Steering Group to review the evidence produced by the CPIU, debate issues and to draft guidelines. Members of the Guideline Advisory Group were: 3 midwives, 3 obstetricians, 2 consumers and a general practitioner from a rural practice. Guidelines drafted by the Antenatal Care Guideline Advisory group were approved by the 3centres Steering Group.

Research Questions Addressed

  1. Does the practice of testing urine for increased proteinuria by dipstick lead to better detection of pre- eclampsia, other hypertensive disorders and chronic renal disease than not testing urine (by dipstick) at all?
  2. Does the practice of testing urine (for increased proteinuria) by dipstick throughout pregnancy lead to better detection of pre-eclampsia, other hypertensive disorders and chronic renal disease than no further urinalysis until after 26 weeks?
  3. Does the practice of women interpreting the results of their dipstick testing lead to worse outcomes (detection of pre- eclampsia, hypertension and chronic renal disease) than if carers interpret the results?
  4. Does the practice of women interpreting the results of their dipstick testing lead to better satisfaction with care or perceptions of the procedure than if carers interpret the results?

Evidence

1. Does the practice of testing urine for increased proteinuria by dipstick lead to better detection of pre- eclampsia, other hypertensive disorders and chronic renal disease than not testing urine (by dipstick) at all?

The Australasian Society for the Study of Hypertension in Pregnancy (ASSHP) Consensus statement (1) and the Royal College of Obstetricians and Gynaecologists (RCOG) (2) guidelines state that dipstick for proteinuria is a screening test only with very high false positive rates and recommend that dipstick proteinuria should always be confirmed with either 24 hour urine collection or spot protein creatinine ratio. In addition, RCOG comment that the considerable observer error in dipstick urinalysis for proteinura can be overcome by automated readers with significantly improved false positive and false negative rates. (2,10) The RCOG Evidence Based Guidelines for Antenatal Care (3) recommend routine dipstick urinalysis for protein at every antenatal assessment where blood pressure is taken, but conclude that further research is required to determine the role of screening for proteinuria.

In a 1995 US study, Gribble et al examined the routine use of the dipstick test in antenatal care and subsequent outcome in 3,217 low risk women. They found no statistically significant differences in the rates of pregnancy associated hypertension, fetal distress, or neonatal outcomes in those with absent, mild or marked proteinuria by dipstick. The authors concluded that the test provided no clinically important information regarding pregnancy outcome when used in a low risk population (3a).

One significant 2002 Australian study conducted by Murray, Homer et al, evaluated the outcomes for 1000 antenatal women with routine dipstick urinalysis throughout pregnancy. They concluded that in the absence of hypertension routine dipstick urinalysis during pregnancy did not result in better detection of pre-eclampsia. Six women developed proteinuria prior to development of hypertension, half of whom had recognized risk factors for pre- eclampsia. They comment that their study was underpowered for significant maternal and perinatal outcomes but question the benefit of the detection of 3/1000 with proteinuria in whom pre-eclampsia would be diagnosed at a subsequent antenatal visit (4).

Murphy and Redman comment that this potentially leaves proteinuria undetected for up to 4 weeks between antenatal visits and reinforces the need for randomized controlled data powered to detect relevant maternal and perinatal outcomes (5).

Regarding the detection of chronic renal disease, an Australian population study by Chadban (3) revealed a prevalence of 16% in a non-pregnant mix-gender cohort6. No evidence was identified to support routine screening in young adults for proteinuria to detect chronic renal disease (7). In addition, Boulware found it is not cost effective to screen for chronic renal disease in a low risk population8. The CPIU team noted there was a lack of studies specifically relating to pregnant women and screening for renal disease.

There are two studies that support dipstick urinalysis to detect proteinuria when hypertension has been diagnosed (9,10).

There is a significant correlation between a formal 24 hour total protein excretion and 2 hour urinary protein quantification (11, 12).

Recommendations (Grade B)

  • Further studies are required to specifically answer this question.
  • There may be improved detection of chronic renal disease, but this is not supported by evidence of improved outcomes (maternal, perinatal or cost).
  • Dipstick for proteinuria in the presence of hypertension appears to be of benefit in detection of pre- eclampsia. There are cost and safety concerns for routine dipstick testing otherwise.

2. Does the practice of testing urine (for increased proteinuria) by dipstick throughout pregnancy lead to better detection of pre-eclampsia, other hypertensive disorders and chronic renal disease than no further urinalysis until after 26 weeks?

The evidence is not conclusive. When dipstick urinalysis for proteinuria is undertaken at the first antenatal assessment there is a possibility of improved detection of chronic renal diseasem (19).

Recommendation (Grade B)

Further studies are required to ascertain the value of routine dipstick urinalysis for proteinuria prior to 26 weeks gestation.

3. Does the practice of women interpreting the results of their dipstick testing lead to worse outcomes (detection of pre- eclampsia, hypertension and chronic renal disease) than if carers interpret the results?

One recent study concludes women interpreting the results of their dipstick urinalysis have an equivalent false negative and higher false positive detection rate than of dedicated midwifery / nursing staff performing the same test. However, the authors suggest women self testing of urine during the antenatal phase can be:

  • practicable
  • easily implemented
  • taught to women using verbal instructions at their first antenatal clinic visit
  • less confusing for women if the dipstick tests only for protein (not a multiple analysis dipstick), and
  • checked or retested by a trained member of staff if there is significant proteinuria (1+ or more) (20).

There is no evidence regarding outcomes for mother and baby.

Recommendation (Grade B)

There is insufficient evidence to not support a guideline for women to self-test.

4. Does the practice of women interpreting the results of their dipstick testing lead to better satisfaction with care or perceptions of the procedure than if carers interpret the results?

There is no new evidence to support or discourage the practice of women interpreting their own urine dipstick results in terms of perceptions of care.

Methods of Search and Appraisal

Search strategy

  • The OVID interface was used to search the following electronic databases:
    • MEDLINE: 2000 – January 2005
    • CINAHL: 2000 – January 2005
    • EBM Reviews: June 2000 – January 2005
  • Cochrane Database: 2005 Issue 1
  • Review of article citations and Cochrane Library references for additional citations
  • Guidelines developed by specific Colleges of Obstetricians and Gynaecologists were searched including:
    • Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG)
    • Royal College of Obstetricians and Gynaecologists (RCOG)
    • Society of Obstetricians and Gynaecologists Canada (SOGC), and
    • American College of Obstetricians and Gynecologists.
  • Guidelines developed by other groups were searched for via the internet, on the:
    • United States National Guidelines Clearinghouse, and
    • TRIP database.

Search terms

The search was conducted in three sections:

  • Pregnancy/antenatal
  • Dipstick
  • Satisfaction

The initial search retrieved 125 citations and 8 guidelines.

These citations were triaged into those:

  • Possibly containing relevant evidence or authoritative opinion (48 publications – Appendix III), and
  • Unlikely to contain relevant evidence or authoritative opinion (85 publications). These were not considered further.

The abstracts and publications from the 48 citations were retrieved and further screened to identify those studies with respect to quality of methodology and relevance to Australian obstetric practice. As a result of this exercise 20 articles were classified as key citations, and were subjected to systematic critical appraisal by the Project Team (Appendix IV).

The evidence within these 20 key citations fell into the following levels (see Appendix IV for definitions):

  • Level I evidence: 0 publications
  • Level II evidence: 0 publications
  • Level III evidence: 15 publications
  • Level IV evidence: 3 publications, and
  • One letter

References

1. Brown MA, Hague WM, Higgins J, Lowe S, McCowan L, Oats J, et al. The detection, investigation and management of hypertension in pregnancy: full consensus statement. Australian & New Zealand Journal of Obstetrics & Gynaecology 2000;40(2):139-55. (Level IV)
1 a. Bell SC, Halligan A, Martin A et al. The diagnosis of pre eclampsia: effect of alternative methods for the detection of proteinuria. Hypertension in Pregnancy 1997;16:138. (Level IV)

2. Royal College of Obstetricians and Gynaecologists (RCOG). Study group ecommendations: Pre-eclampsia. 2003 (Level IV) (http://www.rcog.org.uk/mainpages .asp?PageID=1215)

2 a. Canadian Task Force on the Periodic Health Examination. The Canadian guide to clinical preventive health care. Ottawa: Canada Publishing Group, 1994.(Level IV)

3. Royal College of Obstetricians and Gynaecologists (RCOG). Evidence based guidelines Antenatal care: routine care for the healthy pregnant woman. 2003 (Level IV) (http://www.rcog.org.ukhttp://3centres.com.au/resources/ Public/Antenatal_Care.pdf)

3 a. Gribble RK, Fee SC, Berg RL. The value of routine urine dipstick screening for protein at each prenatal visit. American Journal of Obstetrics and Gynecology 1995;173:214-7. (Level III)

4. Murray N, Homer CS, Davis GK, Curtis J, Mangos G, Brown MA. The clinical utility of routine urinalysis in pregnancy: a prospective study.[see comment]. Medical Journal of Australia 2002;177(9):477-80. (Level III-2)

4 a. US Preventive Services Task Force. Guide to clinical preventive services. 2nd ed. Baltimore: Williams and Wilkins, 1996. (Level IV)

5. Murphy DJ, Redman CW. The clinical utility of routine urinalysis in pregnancy [comment]. Medical Journal of Australia 2003;178(10):524; author reply 524-5.

5 a. Kuo VS, Koumantakis G, Gallery ED. Proteinuria and its assessment in normal and hypertensive pregnancy. American Journal of Obstetrics and Gynecology 1999;167:723-8. (Level II)

6. Chadban SJ, Briganti EM, Kerr PG, Dunstan DW, Welborn TA, Zimmet PZ, et al. Prevalence of kidney damage in Australian adults: The AusDiab kidney study. Journal of the American Society of Nephrology 2003;14(7 Suppl 2):S131-8. (Level III-2)

6 a. Meyer NL, Mercer BM, Friedman SA, Sibai BM. Urinary dipstick protein: a poor predictor of absent or severe proteinuria. American Journal of Obstetrics and Gynecology 1994;170:137-41. (Level III)

7. Topham PS, Jethwa A, Watkins M, Rees Y, Feehally J. The value of urine screening in a young adult population. Family Practice 2004;21(1):18-21. (Level III-2)

7 a. Brown MA, Buddle ML. Inadequacy of dipstick proteinuria in hypertensive pregnancy. ANZJOG 1995;35:366-9. (Level III)

8. Boulware LE, Jaar BG, Tarver-Carr ME, Brancati FL, Powe NR. Screening for proteinuria in US adults: a cost-effectiveness analysis. JAMA 2003;290(23):3101-14.

8 a. Jazayeri A, Chez RA, Porter KB, Jayazeri M, Spellac WN. Urine protein dipstick measurements. A screen for a standard, 24-hour urine collection. Journal of Reproductive Medicine 1998;43:687-90. (Level III)

9. Barton JR, O'Brien J M, Bergauer NK, Jacques DL, Sibai BM. Mild gestational hypertension remote from term: progression and outcome. American Journal of Obstetrics & Gynecology 2001;184(5):979-83. (Level III-3)

9 a. Phelan LK, Brown MA, Davis GK, Mangos G. (Un)reliability of dipstick testing in hypertensive pregnancy Paper A48 presented at PSANZ Conference, Canberra 2001. Available from www.psanz.org. (Level III)

10. Phelan LK, Brown MA, Davis GK, Mangos G. A prospective study of the impact of automated dipstick urinalysis on the diagnosis of preeclampsia. Hypertension in Pregnancy 2004;23(2):135-42. (Level III-2)

10 a. Bell SC, Halligan AW, Martin A, et al. The role of observer error in antenatal dipstick proteinuria analysis. BJOG 1999;106:1177-80. (Level IV)

11. Evans W, Lensmeyer JP, Kirby RS, Malnory ME, Broekhuizen FF. Two- hour urine collection for evaluating renal function correlates with 24- hour urine collection in pregnant patients. Journal of Maternal-Fetal Medicine 2000;9(4):233-7. (Level III-2)

11 a. Lumley J. What do women really want? Satisfaction with care in pregnancy, birth and the postnatal hospital stay. A summary of current evidence to April 2000. Unpublished report commissioned by The Royal Women's Hospital, Melbourne from the Centre for Studies on Mother's and Children's Health, La Trobe University, Melbourne 2000. (Level IV)

12. Somanathan N, Farrell T, Galimberti A. A comparison between 24-hour and 2-hour urine collection for the determination of proteinuria. Journal of Obstetrics & Gynaecology 2003;23(4):378-80. (Level III-2)

12. a Lind T, Anderson J. Does random blood glucose sampling outdate testing for glycosuria in the detection of diabetes during pregnancy? BMJ 1984;289:1569- 1571.(Level IV)

13. Waugh J, Bell SC, Kilby MD, Lambert PC, Blackwell CN, Shennan A, et al. Urinary microalbumin/creatinine ratios: reference range in uncomplicated pregnancy. Clinical Science 2003;104(2):103-7. (Level III-2)

13 a. McLellan A. Is traditional antenatal care worthwhile? Healthright 1986;5(4): 22-27. (Level IV)

14. Risberg A, Larsson A, Olsson K, Lyrenas S, Sjoquist M. Relationship between urinary albumin and albumin/creatinine ratio during normal pregnancy and pre- eclampsia. Scandinavian Journal of Clinical & Laboratory Investigation 2004;64(1):17-23. (Level III-2)

15. Neithardt AB, Dooley SL, Borensztajn J. Prediction of 24-hour protein excretion in pregnancy with a single voided urine protein-to- creatinine ratio. American Journal of Obstetrics & Gynecology 2002;186(5):883-6. (Level III-2)

16. Yamasmit W, Wongkitisophon K, Charoenvidhya D, Uerpairojkit B, Chaithongwongwatthana S. Correlation between random urinary protein-to-creatinine ratio and quantitation of 24-hour proteinuria in preeclampsia. Journal of the Medical Association of Thailand 2003;86(1):69 (Level III-2)

17. Yamasmit W, Chaithongwongwatthana S, Charoenvidhya D, Uerpairojkit B, Tolosa J. Random urinary protein-to- creatinine ratio for prediction of significant proteinuria in women with preeclampsia. Journal of Maternal-Fetal & Neonatal Medicine 2004;16(5):275-9. (Level III-2)

18. Durnwald C, Mercer B. A prospective comparison of total protein/creatinine ratio versus 24- hour urine protein in women with suspected preeclampsia. American Journal of Obstetrics & Gynecology 2003;189(3):848-52. (Level III-2)

19. Murakami S, Saitoh M, Kubo T, Koyama T, Kobayashi M. Renal disease in women with severe preeclampsia or gestational proteinuria. Obstetrics & Gynecology 2000;96(6):945-9. (Level III-2)

20. Goh JT, Krause H. A prospective observational study on the accuracy of patient self-testing of urine at an antenatal clinic. Australian & New Zealand Journal of Obstetrics & Gynaecology 2002;42(1):67-8. (Level III-2)

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