Prenatal Urine Testing
Mary Ann Rhode MS, CNM
Exempla Certified Nurse Midwives
Denver, Colorado
A Sacred Cow of Obstetrics
History of Urine Testing Practices
1843
Relationship between urinary protein and eclampsia noted
1903
Protein testing suggested by Edgar in The Practice of
Obstetrics
1917 Screening for glycosuria proposed in Williams
Obstetrics
1948
Urine testing was being taught to granny midwives in the
movie "All My Babies" produced by Columbia University
1970
Nearly universal, expanded to include other substances such
as nitrites and leukocyte esterase
Traditional Purpose of
Prenatal Urine Testing
Screen for:
Gestational diabetes
Preeclampsia
Urinary tract infection
Gestational Diabetes Considerations
Urine testing for GDM, as the primary screening test,
not used for decades
Diabetics no longer regulate insulin based on urine
testing
Glucose tolerance testing is widely accepted as
the best screening method
Pre-eclampsia Considerations
No current effective screening method for early detection
Many early markers identified but either impractical to use or not
predictive enough
Urinary placental growth factor (PlGF)
Most recently studied marker for preeclampsia
Tested between 21-32 weeks gestation
"Decreased urinary PIGF at mid gestation is strongly associated
with subsequent early development of preeclampsia." Levine 2005
Pre-eclampsia Considerations
Protein testing is for diagnosis, 24 hour urine collection is
preferred method
Proteinuria rarely precedes an elevation in blood pressure
"Dipstick urinalysis cannot be relied on either to
detect or to exclude the presence of proteinuria
in pregnant women."
Kuo 1992
Urinary Tract Infection Considerations
Type of infection
Cystitis - 1 - 2 % incidence
Pyelonephritis - 1-2 % incidence
Asymptomatic bacteriuria
•2 - 7 % incidence
•20-30 % progress to pyelonephritis without treatment
Less than 1 % acquire bacteriuria in pregnancy after initial
screening
Symptomatic vs asymptomatic
• Sensitivities of tests vary based on presence or
absence of symptoms
Pregnant vs non-pregnant
• Sensitivities vary by patient population
• Many symptoms of pregnancy and UTI are similar
• Prenatal urine screening is mostly for
asymptomatic bacteriuria
• Urine culture is considered the "gold standard" for
ASB
Current Standard Screening Practices
BP check each prenatal visit
Urine dipstick testing each visit
Glucose challenge test at 24-29 weeks
Urinalysis or urine culture at first visit
Recommended Guidelines
“During each regularly scheduled visit, the health care provider
should evaluate the woman’s blood pressure, weight, urine for
the presence of protein and glucose levels, uterine size for
progressive growth and consistency with the estimated date of
delivery, and fetal heart rate.”
Guidelines for Perinatal Care, 2002
Routine testing:
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•
•
•
•
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Hct or Hgb levels
Urinalysis, including microscopic examination
Urine testing to detect asymptomatic bacteriuria (eg, urine culture)
Determination of blood group and CDE (Rh) type
ABS
Determination of immunity to rubella virus
Syphilis screen
Cervical cytology (as needed)
Hepatitis B virus surface antigen
HIV antibody testing
GDM Screening Recommendations
ACOG and AAP
• Do not recommend universal screening for GDM but strongly
recommend screening pregnant women in high-prevalence
populations
ACP, ADA, & Third International Workshop Conference on
Gestational Diabetes
• Recommend universal screening for GDM at 24-28 weeks using
a 1-hour glucose tolerance test
Guide to Clinical Preventive Services 3rd edition, 2002
• Insufficient evidence to recommend for or against routine
screening for GDM
Preeclampsia Screening
Recommendations
ACOG
• BP measurements at initial visit
• Every 4 weeks until 28 weeks gestation
• Every 2-3 weeks until 36 weeks gestation
• Every week thereafter
Canadian Task Force on Periodic Health Examination
• Systolic & diastolic BP at the first prenatal visit
and periodically throughout the rest of pregnancy
Guide to Clinical Preventive Services. 3rd edition, 2002
• BP measurement at each visit
• Further diagnostic evaluation, including BP monitoring
and urine testing for protein when indicated
Asymptomatic Bacteriuria Screening
Recommendations
ACOG and AAP
• Urinalysis, including microscopic examination and infection screen at
first visit
• Additional evaluation such as culture, as needed, based on history and
physical exam
Canadian Task Force on Periodic Health Examination
• Urine culture at 12-16 weeks of pregnancy
(based on research that showed identification of 80 % who will
eventually have ASB in pregnancy)
Guide to Clinical Preventive Services
3rd edition, 2002
• Urine culture for all pregnant women at 12-16 weeks gestation
• Routine screening for ASB with LE or nitrite testing in pregnant
women not recommended
Questions about Urine
Reagent Strip Testing
• Redundant testing
• Lack of evidence of improved
pregnancy outcome with routine testing
• Testing sources of error - tests need to
be accurate and reliable, i.e. sensitive
and specific
Problems with Urine Reagent Strip Testing
• Different thresholds between dipstick urinalysis and 24
hour urinary protein excretion
(Thresholds for dipstick test and standard 24 hour urine assay are only
equivalent if the 24 hour urine specimen is about 1000 mL)
• Sensitivity and specificity
• Varying concentration of protein in random specimens
• Observer error
Sensitivity and Specificity Definitions
Term
Definition
Formula
Sensitivity
Proportion of persons with
condition who test positive
a
a+c
Specificity
Proportion of persons without
condition who test negative
d
b+d
Positive predictive value
Proportion of persons with positive test
who have condition
a
a+b
Negative predictive value
Proportion of persons with negative test
who do not have condition
Condition
Present
Condition
Absent
Legend:
a = true positive
Positive test
a
b
b = false positive
Negative test
c
d
c = false negative
d = true negative
From: U.S. Preventive Task Force Guide to Clinical Preventive Services, 3rd. Ed.
d
c+d
Poor sensitivity
• Misses cases - the false negative rate
• Leads to delayed treatment
Poor specificity
• Identifies healthy people as having a
condition - the false positive rate
• Leads to over-investigation, over-treatment
Urine Reagent Strip Sensitivities*
Test
Culture
Sensitivity
100
Specificity
+ predictive value
Gram stain
83-92 %
89-95
17-28
Urinalysis
8 -25 %
99
37-40
Urinalysis w/
bacteria or
leukocytes
75-83
59-60
4.5
Nitrites
19-68
99
69-90
Leukocyte
esterase
17
97
12
LE and nitrites
13
100
100
LE or nitrites
50
97
27
Protein, nitrites
blood, LE
8-33
91
18
*
From: Bachman, Tincello, and Etherington, rounded to nearest whole percentage point
Sources of False Positive Results
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Dipstick left too long in concentrated urine
Gross hematuria
Pus, semen, vaginal secretions
Penicillin, sulfonamides, tolbutamide use
False + for protein if refrigerated > 24 hours
Sources of False Negative Results
• Nonalbumin or LMW proteins
• High levels of ascorbic acid or aspirin
• Dilute urine ( > 1.015)
• Nitrite false negatives are common due to: Lack of dietary
nitrates, insufficient urinary nitrate levels due to diuretics, low
urinary retention, infection due to organisms that don't produce
nitrites, Staphyloccocus sp. , Enterococcus sp., Pseudomonas
sp.
• Increased for WBC’s/RBC’s if refrigerated > 24
hours
Variation in Protein Concentration in
Random Specimens
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Contamination (false positive)
Exercise
(increased excretion)
Posture
(increased excretion in upright position)
Osmolality
(increased false positives)
Urinary pH ( pH > 7.5)
Timing of collection - sensitivity improved with first
morning specimen
• Different assay methods, pattern of urinary protein
composition (some proteins may be associated more with
preeclampsia)
Observer Error
• More false positives with less trained staff
• Most common error is to "round up"
• Training can reduce false positive rate
• Specificity may deteriorate if strips stored in open containers
• False negative rate unchanged by training, possibly due to
concentration
• Use of automated devices can improve accuracy
Obstacles to Changing Current Practice
• We might miss something
• It’s too slow if we have to get a specimen
later
• Somebody might die
• What will the other care providers think
• We’ve always done it that way
• Remember, there are legal issues to consider
• What about renal disease?
Sources of Benign Proteinuria
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Dehydration
Emotional status
Fever
Heat injury
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Inflammatory process
Intense activity
Acute illness
Orthostatic disorder
Corral MF. Proteinuria in adults: a diagnostic approach. American Family
Physician, 2000.
Some Pathologic Causes of Proteinuria
• Primary glomerulonephropathy
– ex. glomerulonephritis
• Secondary glomerulonephropathy
– ex. diabetes
collagen vascular disease
preeclampsia
• Drug associated
• Hemoglobulinuria
• Multiple myeloma
Renal Disease Considerations
•
“Fewer than 2 % of positive dipsticks have serious and treatable urinary tract
disorders.” Corral MF. Proteinuria in adults: a diagnostic approach. American Family Physician, 2000.
•
“It is likely that this occurrence of mild, intermittent proteinuria in the general
population makes routine screening ineffective. It has been
suggested that screening of urine be reserved for populations at high
risk of renal disease such as patients with diabetes or hypertension.”
Woolhandler S. Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders. JAMA, 1989.
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Acute renal failure in pregnancy
- 1 : 20,000
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Microalbuminuria – excretion below detection level of urine dipsticks
•
Persistent rates of 20 micrograms/minute predictive of diabetic neuropathy &
chronic renal disease
Routine prenatal urine screening
• Done at every prenatal visit
Indicated prenatal urine testing
• First prenatal visit
• Whenever clinical symptoms are present
• High risk conditions
Why Continue Urine
Reagent Strip Testing?
• Only testing available for many years
• Easy and quick, compared to 24 hour urine
collection
• Requires little technical expertise
• Less expensive than urine culture or 24 hour urine
tests
• No "absolute" proof of safety of indicated testing
• Sometimes the information is needed, i.e. there is
an indication for the test
Evidence to Discontinue Routine Screening
• Changing practice at other institutions
• Public Health Service Expert Panel on
the Content of Prenatal Care, 1989
• US Preventive Services Task Force Guide to
Clinical Preventive Services, 1996, 2004
• Previous research
Asymptomatic Bacteriuria Studies
Lenke
1981
Recommended use of routine culture for women at risk of
for recurrent pyelonephritis because positive cultures aren't
accurately predicted by microscopic urinalysis or nitrite testing
Robertson
1988
Nitrite or leukocyte esterase alone not sensitive enough to detect
ASB, nitrites plus LE may be better
Etherington
1993
Combination of leukocyte esterase, nitrite, protein and blood gives
highest predictive value of negative culture (99.3) so conclude is
reliable for screening to avoid culture for all. (Sensitivity - 8.2 %,
specificity - 79 %, positive predictive value - 10.5 %)
Bachman
1993
Screening with urinalysis cost more than cultures for all
Reagent strips missed 50 % of ASB on initial exam
Tincello
1998
Reagent strips OK to use to determine need for culture
of symptomatic women. Not sensitive enough to screen for ASB
McNair
2000
High false negative rates with urinalysis & reagent strips
Urine cultures should be universally used to detect ASB
Chance of detecting ASB best in first trimester
"Urine culture remains the gold standard, and all pregnant women should have a
screening culture during their early prenatal care."
Gilstrap 2001
Proteinuria & Glycosuria Studies
Study
Year
Watson
1990
Gribble
Type of Study
Focus
N
Observational
glycosuria
500
1995
Retrospective chart review
glucosuria
2965
Gribble
1995
Retrospective chart review
proteinuria
3104
Hooper
1996
Retrospective chart review
glycosuria
proteinuria
600
Murray
2002
Prospective observational
proteinuria
913
Rhode
2006
Retrospective, non-inferiority proteinuria
cohort design
glycosuria
ASB
1952
Study Conclusions
Watson Routine screening for glycosuria does not appear to be clinically useful
Gribble 3rd trimester testing for glycosuria is not predictive of any clinically
important pregnancy outcome
Routine screening for glycosuria before the 3rd trimester may identify
women at increased risk of GDM
Gribble
In low risk women with no signs of hypertensive disease, routine
screening for proteinuria did not provide any clinically important
information about pregnancy outcome
Hooper
Oral glucose diabetes screening and careful monitoring of blood
pressure (and symptomatology) are better screens for GDM and
preeclampsia than routine urinalysis
Murray After an initial screening urinalysis, routine urinalysis could be
eliminated without adverse outcomes for women
Research Setting & Population
Aurora Nurse Midwives Clinic, Aurora Colorado.
Started to provide care to medically underserved.
Approximately 1000 visits per month, mostly obstetric
Predominately Hispanic
Population considered high risk due to low socio-economic status
Only two bathrooms in the clinic
Study Objective
To determine if asymptomatic bacteriuria, elevated blood
pressure, and gestational diabetes are underdiagnosed if
routine prenatal urine screening is replaced with clinically
indicated testing.
Methodology
Prior to August 2002
• Initial urinalysis, urine culture, BP
• One-hour 50-g load glucose challenge test at about 28 weeks
gestation, (130 mg/dL threshold used for 3 hour GTT), at
weeks gestation and a repeat at 28 weeks if risk factors
present
• Urine dipstick testing and BP at each follow-up visit
After August 15, 2002
• Same initial visit and GDM regimen
• Urine dipstick testing done only when established criteria*
were present
Antepartum and intrapartum charts were reviewed after delivery
Study Conclusion
A change to indicated urine reagent strip
testing does not result in under-diagnosis of
high blood pressure, urinary tract infection, or
gestational diabetes.
Implications for Clinical Practice
Changing long-standing clinical practices is
difficult!
• Conduct a prospective, randomized trial and publish
the results
• Have documentation articles available
• Make sure all involved are on-board, no saboteurs
• Give advance notice, educate everyone involved,
including patients
We are making a change
we hope you will like!
Starting August 15, you will NOT need to give a
urine specimen every time you come to the clinic.
We will ask for a urine specimen ONLY if you
have a problem. This change is based on scientific
information that says urine testing of healthy
women is not necessary every visit.
We are always trying to improve the way we give
you the best care. This does not mean you are
getting less care.
Compliance with established criteria is
essential to patient safety!
Must get urine specimen whenever criteria are present
No skipping, "just this one time"
No repeating a blood pressure to avoid getting a urine specimen
Must document
No reason for 18.1% of indicated tests
No urine testing done on some subjects in each group
Not documented or not done?
Pay more attention to preeclampsia symptomatology since blood
pressures may be labile
Common Themes in Medico-legal Claims
• Assuming proteinuria is from contamination or
UTI
• Failing to appreciate the significance of patient
complaints on the phone
Sibai, BM. Cutting the legal risks of hypertension in pregnancy. OBG
Management. 2003.
Follow-up for Trace to 2 + Proteinuria
• Repeat dipstick twice in the next month with
a first morning specimen
• If negative - transient proteinuria. No
additional follow-up needed
• If positive - persistent proteinuria. Needs
24 hr. urine or urine protein/creatinine ratio
Indicated prenatal urine testing is
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Safe
Patient-centered
Reduces cost of clinic operation
Improves clinic flow
Improves patient satisfaction.