9/21/04njm

Revised 9/4/05njm

**Q. Should we perform routine urine dipstick protein screening in our
prenatal clinic?**

A. No, the urine dipstick tests are not sensitive, nor specific enough
for routine screening for pre-eclampsia. There is more to the story,
though. See below

The old prenatal systems included performing routine urine dipstick
screening for pre-eclampsia and diabetes on all prenatal patients at all
visits. Upon further review by the 1989 PHS Expert Panel on the Content
of Prenatal Care neither of those two disorders were well screened by
urine dipstick testing.

Urinary protein dipstick values do not correlate well with 24-hour
urinary collection protein excretion values in hypertensive pregnant
women (Meyer, Kuo, Waugh). In one systematic review including six
studies, the posttest probability for urine dipstick of
![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}1+ for predicting 24-hour urine protein
excretion ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}300 mg ranged from 53 to 86 percent, and
was 23 to 40 percent when the dipstick was negative or trace (Waugh).
Thus, a negative dipstick does not necessarily exclude significant
proteinuria while many women with positive tests do not have it.
However, urine dipstick values of 3+ and 4+ are more helpful as, in one
series, all but 9 percent of patients with these dipstick values
excreted at least 3.5 g of protein per day (Mercer).

Another approach is to limit initial clinic screening pre-eclampsia
screening to patients at higher risk, e.g., BP greater then 140/90 mm
Hg, or mean arterial pressure greater than 105 mm Hg, symptoms of
pre-clampsia, multiple gestation, symptoms of UTI, or chronic
hypertension currently on hypertension medication. (see Guideline #2 a
bottom of page) Screening of this high risk group could be performed by
either a classic dipstick, or a total protein to creatinine ratio.

In any case, the best screen for pre-eclampsia remains a casual BP
reading performed in a sitting position after appropriate rest. (See
Screening Method bottom of document -- Guideline #1)

**[Background]{.underline}**

**Dipstick** --- Urinary protein dipstick values do not correlate well
with 24-hour urinary collection protein excretion values in hypertensive
pregnant women (Meyer, Kuo, Waugh). In one systematic review including
six studies, the posttest probability for urine dipstick of
![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}1+ for predicting 24-hour urine protein
excretion ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}300 mg ranged from 53 to 86 percent, and
was 23 to 40 percent when the dipstick was negative or trace (Waugh).
Thus, a negative dipstick does not necessarily exclude significant
proteinuria while many women with positive tests do not have it.
However, urine dipstick values of 3+ and 4+ are more helpful as, in one
series, all but 9 percent of patients with these dipstick values
excreted at least 3.5 g of protein per day (Mercer).

**Urine protein to creatinine ratio** --- Proteinuria can also be
measured by calculating the protein-to creatinine (P:C) ratio in a
random urine sample (Ginsberg, Robert). This minimizes collection and
laboratory errors, saves time in obtaining results, and is far more
convenient for the patient. However, there is no consensus on the best
threshold for identifying pregnant women with significant proteinuria.

One large study concluded that in the presence of stable renal function,
a P:C ratio ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}0.19 optimally predicted protein
excretion ![](media/image1.png){width="8.333333333333333e-2in"
height="9.236111111111112e-2in"}300 mg per day (sensitivity,
specificity, positive predictive value, negative predictive value: 90,
70, 75, and 87 percent, respectively) (Rodriguez-Thompson). Fifty
percent of this population had significant proteinuria and most of the
false-negative and false-positive test results were within 50 mg of the
cutoff of 300 mg for a 24-hour urine. A cut-off of 0.14 had sensitivity
and negative predictive values of 100 percent, but specificity dropped
to 51 percent. The P:C ratio appears to be most useful when quantitation
of proteinuria is desired quickly and in ambulatory patients with
hypertension and very low P:C values in whom the presence of significant
proteinuria (and thus preeclampsia) can be excluded confidently.

In another report in which hospitalized patients were followed with
serial tests, the P:C ratio correlated with changes in 24-hour protein
excretion over time. Therefore, the test could be used to evaluate for
progression of preeclampsia, along with other clinical parameters.

**Resources:**

Guidelines for Management of Hypertensive Disorders in Pregnancy

<http://www.ihs.gov/NonMedicalPrograms/nc4/Documents/HYPERT12004.doc>

**Hypertension in Pregnancy: Mild Pre-eclampsia - Indian Health CME /
CEU module**

<http://www.ihs.gov/MedicalPrograms/MCH/M/HP01.cfm>

Caring for Our Future: The Content of Prenatal Care - A Report of the
Public Health Service Expert Panel on the Content of Prenatal Care. 1989
U.S. Department of Health and Human Service. NIH Publication No. 90-3182
Reprinted 1990

[Rosen
MG](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Rosen+MG"%5BAuthor%5D),
[Merkatz
IR](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Merkatz+IR"%5BAuthor%5D),
[Hill
JG](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&term="Hill+JG"%5BAuthor%5D).
Caring for our future: a report by the expert panel on the content of
prenatal care. Obstet Gynecol. 1991 May;77(5):782-7.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=2014096&dopt=Abstract>

**[References:]{.underline}**

Meyer NL; Mercer BM; Friedman SA; Sibai BM. Urinary dipstick protein: a
poor predictor of absent or severe proteinuria. Am J Obstet Gynecol 1994
Jan;170(1 Pt 1):137-41

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8296815&dopt=MEDLINE>

OBJECTIVE: Our purpose was to compare urinary protein dipstick values
with standard 24-hour urinary protein excretion in women with
hypertension in pregnancy. STUDY DESIGN: Urinary protein dipstick
determinations and concurrent 24-hour urinary protein excretion
measurements were compared by review of 300 urine samples obtained from
women with hypertension in pregnancy. RESULTS: One hundred twenty-three
samples had negative to trace protein on dipstick on two occasions at
least 6 hours apart. Eight-one (66%) of these patients had significant
proteinuria (\> or = 300 mg per 24 hours). Seventy-six samples revealed
3+ to 4+ protein on dipstick in at least two samples. Of these, 27 (36%)
had heavy proteinuria (\> or = 5 gm per 24 hours), and 42 (55%) had
nephrotic range proteinuria of \> or = 3.5 gm per 24 hours. One hundred
one patients had urine dipstick values of 1+ to 2+, of whom 89 (88%) had
significant proteinuria. CONCLUSION: Urinary protein dipstick values \>
or = 1+ have a positive predictive value of 92% (162/177) for predicting
\> or = 300 mg per 24 hours. In contrast, a dipstick of negative to
trace should not be used to rule out significant proteinuria because its
negative predictive value is only 34% (42/123) in hypertensive patients.
Moreover, urine dipstick values of 3+ to 4+ should not be used to
diagnose severe preeclampsia because their positive predictive value is
only 36% (27/76).

Kuo VS; Koumantakis G; Gallery ED. Proteinuria and its assessment in
normal and hypertensive pregnancy. Am J Obstet Gynecol 1992
Sep;167(3):723-8.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1530030>

OBJECTIVES: The purposes of this study were (1) to determine 24-hour
urinary protein excretion rates in normal human pregnancy and (2) to
assess the reliability of assessment of proteinuria by dipstick
measurement. STUDY DESIGN: At 17 to 20 and 33 to 36 weeks of pregnancy,
174 normal volunteers collected a 24-hour urine sample; the volume and
the protein and creatinine concentrations were measured. The result for
protein was compared with dipstick analysis of an early morning
midstream urine sample collected at the conclusion of the 24-hour
period. Sixty-eight consecutive inpatients admitted to the antenatal
ward with hypertension and positive urine dipstick tests for protein
underwent the same procedure. The interobserver variability in dipstick
analyses of urine samples of known protein content was assessed with the
aid of 66 volunteers from the hospital staff. RESULTS: The upper 95%
confidence limit of the normal population was less than 200 mg per 24
hours, at both stages of pregnancy investigated. In these women and in
the hypertensive inpatients a high proportion of false-positive and
false-negative results was found with dipstick analyses. Interobserver
variation in assessment of proteinuria by dipstick was high, with an 18%
false-positive rate and a false-negative rate approaching 40% for
samples with 30 mg/dl. Even in the presence of 100 mg/dl the
false-negative rate was 7%, whereas the concentration of protein was
significantly underestimated in 20% of samples with 500 mg/dl.
CONCLUSION: Dipstick urinalysis cannot be relied on either to detect or
to exclude the presence of proteinuria in pregnant women.

Waugh JJ; Clark TJ; Divakaran TG; Khan KS; Kilby MD. Accuracy of
urinalysis dipstick techniques in predicting significant proteinuria in
pregnancy. Obstet Gynecol 2004 Apr;103(4):769-77.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=retrieve&db=pubmed&list_uids=15051572&dopt=Abstract>

OBJECTIVE: To estimate the accuracy of point-of-care dipstick urinalysis
in predicting significant proteinuria in pregnancy. DATA SOURCES:
Literature from 1970 to February 2002 was identified via 1). general
bibliographic databases, that is, MEDLINE and EMBASE, 2). Cochrane
Library and relevant specialist register of the Cochrane Collaboration,
and 3). checking the reference lists of known primary and review
articles. METHODS OF STUDY SELECTION: Studies were selected if the
accuracy of dipstick urinalysis techniques in predicting total protein
excretion was estimated compared with a reference standard (laboratory
estimation of protein excretion). The tests included visually read
color-change dipsticks and automated dipstick urinalysis. Study
selection, quality assessment, and data abstraction were performed
independently and in duplicate. TABULATION, INTEGRATION, AND RESULTS:
Data from selected studies were abstracted as 2 x 2 tables comparing the
test result with the reference standard. Test accuracy was expressed as
likelihood ratios. Summary likelihood ratios were generated as measures
of diagnostic accuracy to determine posttest probabilities. The
electronic search produced 1543 citations. After independent review of
published articles, a total of 34 articles was obtained for further
scrutiny, and 7 studies were considered eligible for inclusion in the
review. The 6 studies evaluating visual dipstick urinalysis produced a
pooled positive likelihood ratio of 3.48 (95% confidence interval 1.66,
7.27) and a pooled negative likelihood ratio of 0.6 (95% confidence
interval 0.45, 0.8) for predicting 300 mg/24-hour proteinuria at the 1+
or greater threshold. CONCLUSION: The accuracy of dipstick urinalysis
with a 1+ threshold in the prediction of significant proteinuria is poor
and therefore of limited usefulness to the clinician. Accuracy may be
improved at higher thresholds (greater than 1+ proteinuria), but
available data are sparse and of poor methodological quality. Therefore,
it is not possible to make meaningful inferences about accuracy at
higher urine dipstick thresholds. There is an urgent need for research
in this area of common obstetric practice.

Ginsberg JM; Chang BS; Matarese RA; Garella S Use of single voided urine
samples to estimate quantitative proteinuria. N Engl J Med 1983 Dec
22;309(25):1543-6.\
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=6656849>

Quantitation of urinary protein excretion is used extensively for
diagnostic and prognostic purposes and to assess the effects of therapy.
The method most commonly used to measure urinary protein relies on
24-hour urine collections, which are time consuming, cumbersome, and
often inaccurate. We reasoned that the urinary protein/creatinine ratio
in a single voided urine sample should correlate well with the quantity
of protein in timed urine collections. In a study of 46 specimens we
found an excellent correlation between the protein content of a 24-hour
urine collection and the protein/creatinine ratio in a single urine
sample. The best correlation was found when samples were collected after
the first voided morning specimen and before bedtime. We conclude that
the determination of the protein/creatinine ratio in single urine
samples obtained during normal daylight activity, when properly
interpreted by taking into consideration the effect of different rates
of creatinine excretion, can replace the 24-hour urine collection in the
clinical quantitation of proteinuria. In the presence of stable renal
function, a protein/creatinine ratio of more than 3.5 (mg/mg) can be
taken to represent \"nephrotic-range\" proteinuria, and a ratio of less
than 0.2 is within normal limits.

Robert M; Sepandj F; Liston RM; Dooley KC Random protein-creatinine
ratio for the quantitation of proteinuria in pregnancy.Obstet Gynecol
1997 Dec;90(6):893-5.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9397097>

OBJECTIVE: To compare random urine protein-creatinine ratios with
24-hour urine protein excretion rates in patients hospitalized with
hypertensive disorders in pregnancy. METHODS: All hospitalized,
hypertensive patients requiring 24-hour urine protein excretion
collections were eligible for the study. During the 24-hour urine
collection a separate 2-mL aliquot was taken for a protein and
creatinine determination. RESULTS: Seventy-one samples were collected
from patients with the following diagnoses: gestational hypertension (n
= 56), preexisting hypertension and superimposed gestational
hypertension (n = 11), and syndrome of hemolysis, elevated liver enzymes
and low platelets (n = 4). The correlation coefficient between the
random protein-creatinine ratio and the 24-hour urine protein excretion
was 0.94. Calculated excretion rates with at least 300 mg protein in 24
hours had a sensitivity of 0.93, specificity of 0.90, and positive and
negative predictive values of 0.87 and 0.95, respectively. For those
samples with calculated excretion rates at least 5 g protein in 24
hours, the sensitivity was 1.00, specificity was 0.99, and positive and
negative predictive values were 0.75 and 0.99, respectively. CONCLUSION:
In nonambulatory hypertensive pregnant patients, there is a strong
correlation between random voided protein-creatinine ratios and 24-hour
urine protein excretions.

Rodriguez-Thompson D; Lieberman ES Use of a random urinary
protein-to-creatinine ratio for the diagnosis of significant proteinuria
during pregnancy. Am J Obstet Gynecol 2001 Oct;185(4):808-11.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11641656>

OBJECTIVE: The purpose of this study was to evaluate whether a random
urinary protein-to-creatinine ratio is a clinically useful predictor of
significant proteinuria (300 mg/24 hour). STUDY DESIGN: The medical
records of 138 women who completed both a random urinary
protein-to-creatinine ratio and a 24-hour urine collection for the
evaluation of preeclampsia were reviewed. Urine samples for the random
protein-to-creatinine ratio were collected before the 24-hour urine
collection. With the use of a protein level of at least 300 mg in the
24-hour urine sample as the gold standard, the sensitivity and
specificity of the random protein-to-creatinine ratio for the diagnosis
of significant proteinuria were determined with a range of cutoffs.
RESULTS: Fifty percent of the study population had significant
proteinuria. The data suggest that a cutoff below 0.14 ruled out
significant proteinuria. The best cutoff of \> or = 0.19 yields a
sensitivity of 90% and 3a specificity of 70%. All of the false-negative
test results had 24-hour urine protein levels below 400 mg; 13 of the 21
false-positive results had levels that ranged from 250 to 300 mg.
CONCLUSION: The random urinary protein-to-creatinine ratio is strongly
associated with the 24-hour total protein excretion. A level below 0.14
can rule out significant proteinuria. A best cutoff of \> or = 0.19 is a
good predictor of significant proteinuria. With further study, the
random urinary protein-to-creatinine ratio could replace the 24-hour
urine collection as a simpler, faster, more useful method for the
diagnosis of significant proteinuria.

#1

GUIDELINES FOR MANAGEMENT OF HYPERTENSIVE DISORDERS IN PREGNANCY

<http://www.ihs.gov/NonMedicalPrograms/nc4/Documents/HYPERT12004.doc>

(Excerpt)

## Screening

-Screening for preeclampsia is recommended for all pregnant women at the
first prenatal

visit and throughout the remainder of pregnancy.

-To screen for preeclampsia, measure an upright sitting blood pressure
after a 10 minute rest. The BP should be repeated in a similar manner
4-6 hours later to confirm the diagnosis. (see below)

-There is no role for universal urine dipstick testing to screen for
preeclampsia in routine

prenatal care.

[Method of measuring blood pressure in pregnancy]{.underline}

The diastolic blood pressure is that pressure at which the sound
disappears (Korotkoff phase V) .

To reduce inaccurate readings, an appropriate size cuff should be used
(length 1.5 times upper arm circumference or a cuff with a bladder that
encircles 80% or more of the arm). The blood pressure level should be
taken with the patient in an upright position, after a 10-minute or
longer rest period.

For patients in the hospital, the blood pressure can be taken with
either the patient sitting up or in the left lateral recumbent position
with the patient\'s arm at the level of the heart. The patient should
not use tobacco or caffeine for 30 minutes preceding the measurement
Although validated electronic devices can be used, a mercury
sphygmomanometer is preferred because it is the most accurate device

#2

**[Guidelines for Urine Screening during Pregnancy]{.underline}**

Urine screening for pre-clampsia and gestational diabetes has a very
poor sensitivity and specifics. In conjunction with the PHS Expert Panel
on the Content of Prenatal Care we suggest:

Urine analysis and culture and sensitivity at the first visit, then
repeat urine dipstick only if

-   BP greater then 140/90 mm Hg or

> mean arterial pressure greater than 105 mm Hg

-   Symptoms of pre-clampsia

-   Multiple gestation

-   Symptoms of UTI

-   Chronic hypertension listed on problem list or currently on
    hypertension medication.