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

Screen for:

Gestational diabetes

Preeclampsia

Urinary tract infection

Traditional Purpose of Prenatal Urine Testing

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 ConsiderationsNo 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: • 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 RecommendationsACOG

• BP measurements at initial visit• Every 4 weeks until 28 weeks gestation• Every 2-3 weeks until 36 weeks gestation• Every week thereafterCanadian Task Force on Periodic Health Examination• Systolic & diastolic BP at the first prenatal visit

and periodically throughout the rest of pregnancyGuide 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 DefinitionsTerm Definition Formula

Sensitivity Proportion of persons with acondition who test positive a + c

Specificity Proportion of persons without dcondition who test negative b + d

Positive predictive value Proportion of persons with positive test awho have condition a + b

Negative predictive value Proportion of persons with negative test dwho do not have condition c + d

Condition Condition Legend:Present Absent

a = true positivePositive test a b

b = false positiveNegative test c d

c = false negative

d = true negative

From: U.S. Preventive Task Force Guide to Clinical Preventive Services, 3 rd. Ed.

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 Sensitivity Specificity + predictive valueCulture 100

Gram stain 83-92 % 89-95 17-28

Urinalysis 8 -25 % 99 37-40

Urinalysis w/ 75-83 59-60 4.5bacteria or leukocytes

Nitrites 19-68 99 69-90

Leukocyte 17 97 12 esterase

LE and nitrites 13 100 100

LE or nitrites 50 97 27

Protein, nitrites 8-33 91 18blood, LE

* From: Bachman, Tincello, and Etherington, rounded to nearest whole percentage point

Sources of False Positive Results

• 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

• 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

• Dehydration

• Emotional status

• Fever

• Heat injury

• 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 beensuggested 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.

• Acute renal failure in pregnancy - 1 : 20,000

• 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 StudiesLenke 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 stripsUrine cultures should be universally used to detect ASBChance 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 StudiesStudy Year Type of Study Focus N

Watson 1990 Observational glycosuria 500

Gribble 1995 Retrospective chart review glucosuria 2965

Gribble 1995 Retrospective chart review proteinuria 3104

Hooper 1996 Retrospective chart review glycosuria 600 proteinuria

Murray 2002 Prospective observational proteinuria 913

Rhode 2006 Retrospective, non-inferiority proteinuria 1952cohort design glycosuria

ASB

Study ConclusionsWatson 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), atweeks gestation and a repeat at 28 weeks if risk factorspresent

• 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 PracticeChanging 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. Noadditional follow-up needed

• If positive - persistent proteinuria. Needs24 hr. urine or urine protein/creatinine ratio

Indicated prenatal urine testing is

• Safe

• Patient-centered

• Reduces cost of clinic operation

• Improves clinic flow

• Improves patient satisfaction.