Katherine T. Chen, MD, MPH

THE CASE: SIGNS AND SYMPTOMS

A 29–year–old nullipara at 18 weeks’ gestation complains of fevers and back pain. She had a diagnosis of urinary tract infection with sulfonamide-resistant Escherichia coli at 9 weeks of gestation, which was treated with nitrofurantoin, 100 mg by mouth twice a day for 7 days. A test of cure by urine culture was negative.

Now her temperature is 101°F and she has right costovertebral angle tenderness.

How should you proceed?

Anatomy is destiny, in the case of susceptibility to urinary tract infection (UTI). The female urethra is only 3 cm to 4 cm long, and its proximity to the vagina, anus, and rectum facilitates colonization of normal gastrointestinal flora in the bladder.¹

Sexual activity also facilitates migration of normal gastrointestinal flora to the female urethra.²

Anatomical features of pregnancy exacerbate the female predisposition to urinary tract infection. In pregnancy, hormonal and mechanical changes that occur in the urinary tract lead to urinary stasis and ureterovesical reflux—setting the stage for urinary tract infection (FIGURE 1).

Who should be screened?

All pregnant women should be screened for UTI early in pregnancy, according to the American College of Obstetricians and Gynecologists.³

I recommend a urine culture screening for all pregnant women at their first prenatal visit.

Screen often if she has risk factors

I recommend frequent screening (at least every trimester) by urine culture, in pregnant women with any of these risk factors:

• diabetes mellitus, including gestational diabetes⁴;
  
• urologic abnormalities—specifically, neurogenic bladder;
  
• prepregnancy (for example, 2 to 3 infections per year) and antepartum history of UTI prior to initiation of prenatal care⁵;
  
• sickle cell hemoglobinopathy.⁵
  

Which test is best?

The gold standard for detecting bacteria in urine is by culture.

Which threshold to use?

The standard definition of a positive urine culture from a clean-catch, midstream, voided specimen is ≥100,000 colony forming units (CFU) per mL of a single organism. However, in symptomatic patients, the test’s sensitivity is increased by lowering the cut-off to 100 CFU/mL of a single organism.⁶ In women with urinary symptoms, only 50% of patients had 100,000 CFU/mL by urine culture collected from clean-catch, midstream, voided specimens, though all of them had positive cultures from suprapubic taps.

The clean-catch, midstream, voided specimen is the specimen of choice for practical purposes, since it is noninvasive and easily obtained in the office setting.

For the record: The presence of any organism represents UTI in specimens obtained via suprapubic aspiration of the bladder; 100 CFU/mL of a single organism is positive for specimens obtained by urethral catheterization.

I recommend that, when obtaining urine cultures via clean-catch, midstream, voided specimens:

• for asymptomatic patients, use ≥100,000 CFU/mL of a single organism.
  
• in symptomatic patients, use ≥100 CFU/mL of a single organism.
  

What about rapid tests?

Urinary sediment analysis and urine dipstick testing offer speed and low cost, but with lower accuracy than urine cultures, which require 24 to 48 hours for results and cost more.

Urinary sediment analysis can diagnose pyuria, defined as a clean-catch, midstream, voided specimen, which is spun and which has >10 leukocytes per high-power field.

Pyuria can occur without infection due to:

• previous treatment with antibiotics,
  
• contamination of urine sample by sterilizing solution,
  
• contamination of urine sample with vaginal leukocytes,
  
• chronic interstitial nephritis (such as analgesic abuse),
  
• uroepithelial tumor, and
  
• nephrolithiasis.
  

Pyuria on urinalysis has low sensitivity (25%) but high specificity (99%).

Bacteria visualized on microscopic examination is more sensitive (75%) but less specific (60%).⁷

Urinary dipstick testing—fast, convenient, and low in cost—is considered positive if it identifies either leukocyte esterase or nitrite. Positive leukocyte esterase signifies pyuria. Positive nitrite indicates the presence of enteric organisms that convert urinary nitrate to nitrite.

With either finding, dipstick sensitivity is only 50%, although specificity is 97%.⁷

I recommend:

• If a symptomatic patient’s rapid test is positive, obtain a urine culture, empirically treat for UTI, and then use urine culture results to decide whether to continue treatment.
  
• If an asymptomatic patient’s rapid test is positive, obtain a urine culture and treat only if the culture is positive.
  

What urinary tract disorders occur in pregnancy?

First, determine if the patient has urinary tract symptoms and, if so, whether the symptoms are typical of upper or lower urinary tract infections.

 

Lower urinary tract symptoms:

• dysuria
  
• frequency
  
• urgency
  
• suprapubic pain
  
• hematuria in the absence of fever and systemic symptoms
  

Frequency, of course, is difficult to ascertain in pregnancy, since most women experience this complication secondary to increased urinary output due to higher fluid intake, increased plasma volume expansion, and increases in renal blood flow and glomerular filtration rate.

Upper urinary tract symptoms:

• fever
  
• chills
  
• flank pain
  
• nausea and vomiting
  
• The patient may or may not have the symptoms of lower urinary tract infection, as well.
  

Positive culture and no symptoms

This profile is typical of asymptomatic bacteriuria, a lower urinary tract infection that occurs in 2% to 7% of pregnancies.¹

Positive culture with symptoms

This profile probably reflects either:

• Acute cystitis, a lower urinary tract infection affecting 1% to 2% of pregnancies,⁸ or
  
• Acute pyelonephritis, an upper urinary tract infection affecting 2% of pregnancies.⁹
  

What are the consequences of UTI in pregnancy?

Maternal complications

Asymptomatic bacteriuria does not plague the patient with bothersome effects, but if left untreated, asymptomatic bacteriuria will progress to symptomatic UTI: 25% will develop acute pyelonephritis, compared to 3% to 4% of treated patients¹⁰; 20% of women with severe pyelonephritis develop serious complications,¹¹ including:

• sepsis and septic shock,
  
• hemolysis and thrombocytopenia,¹²
  
• acute respiratory distress syndrome,¹³
  
• renal insufficiency.¹⁴
  

Adverse fetal outcomes

Untreated asymptomatic bacteriuria is associated with preterm delivery and low birthweight.^15-17

Acute pyelonephritis is linked to preterm birth.^18,19 Kaul et al,²⁰ in an experimental model of pyelonephritis in mice, confirmed that E. coli plays an important role in the pathogenesis of preterm delivery and low birthweight.

What is the best treatment regimen?

Data are insufficient to recommend any specific regimen.^21,22 The following strategies are based on evaluation of review articles.^3,23

Asymptomatic bacteriuria and acute cystitis

Nitrofurantoin monohydrate macrocrystals is my first-line treatment. Nitrofurantoin has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

If nitrofurantoin is not effective, I change antibiotics based on urine culture antibiotic sensitivity profiles (FIGURE 2).

Keep in mind the current resistance of E. coli to antibiotics: ampicillin, 28% to 39%; trimethoprim-sulfamethoxazole, 31%; and first-generation cephalosporins, 9% to 19%.²⁴

Single-dose treatment for pregnant women with asymptomatic bacteriuria has been evaluated, given its lower cost and better compliance. However, evidence is insufficient to determine whether single-dose or longer-duration regimens are more effective.²⁵

I recommend longer-duration dosages for now, until a large randomized controlled trial can derive conclusive data.

Remember that treatment success is not contingent upon duration of therapy—just be sure that the test-of-cure urine culture is negative 1 to 2 weeks after treatment is completed.

Acute pyelonephritis

Management should include the following:

• hospitalization
  
• urine and blood cultures
  
• laboratory studies of complete blood cell count, electrolytes, creatinine, and liver function
  
• monitoring of vital signs and urine output
  
• intravenous (IV) crystalloid fluid to maintain urine output
  
• IV antibiotics (FIGURE 3).
  

If symptoms persist after 48 hours despite adequate IV antibiotic therapy, consider other causes such as resistant organisms, nephrolithiasis, perinephric abscesses, renal obstruction, or other infections.

Consider imaging by renal ultrasound to assess the presence of nephrolithiasis, perinephric abscess, or obstruction.

I recommend inpatient treatment for pregnant women with acute pyelonephritis at this time, until further studies are available.

To evaluate outpatient treatment, Millar and colleagues randomized 120 women under 24 weeks’ gestation either to inpatient IV cefazolin until 48 hours afebrile or to outpatient ceftriaxone intramuscularly. (Both treatment arms completed a course of oral cephalexin.) There were no differences in therapeutic response or birth outcomes, but 6 patients in the outpatient arm required hospitalization for IV therapy and 1 woman developed sepsis.²⁶

The same researchers studied 92 patients of more than 24 weeks’ gestation who received 2 doses of ceftriaxone intramuscularly, then were randomized to either continued inpatient therapy until 48 hours afebrile or discharge with reevaluation as an outpatient in 48 to 72 hours. Again, there were no differences in therapeutic response or birth outcomes; however, almost two-thirds of patients were excluded from the study as they did not meet criteria for outpatient management, due to sepsis, preterm labor, or concurrent medical conditions.²⁷

Adequate antibiotic coverage is crucial

To ensure adequate antibiotic coverage when treating UTI, it is important to understand which organisms cause these infections in pregnancy.

E. coli causes 75% to 90% of UTIs in nonpregnant women.²⁸Staphylococcus saprophyticus causes 10% to 15% of UTIs in nonpregnant women, but less in pregnant women.

Group B Streptococcus (GBS)—another gram-positive organism—has important implications for pregnant women: Intrapartum prophylaxis is important, to prevent neonatal GBS disease.²⁹

Klebsiella, Enterobacter, Proteus, and Enterococcus species²⁸ infrequently cause UTI in pregnancy.

What about prophylaxis and follow-up cultures?

 

Expect recurrence

One third of pregnant women diagnosed with UTI will have recurrence.¹ Recurrence is either relapse (same strain, within 2 weeks of completing initial treatment for the original infection) or reinfection (different strain or same strain after more than 2 weeks).

2 UTIs or pyelonephritis warrant suppressive therapy

I recommend suppressive therapy if a pregnant woman is diagnosed with 2 lower urinary tract infections or acute pyelonephritis (TABLE).

Nitrofurantoin is the preferred agent, as it has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

Start only after eradication of the acute infection, as evidenced by a negative test-of-cure urine culture at least 1 to 2 weeks after treatment is discontinued.²³

Monthly urine cultures until delivery

I recommend monthly follow-up urine cultures until delivery.

Periodic follow-up screening is often recommended, but opinions differ on which test to use or how often to screen.

THE CASE: DIAGNOSIS, TREATMENT, FOLLOW-UP, AND OUTCOME

The patient with upper urinary tract symptoms had a white blood cell count of 15, a urine dipstick positive for leukocyte esterase and nitrites, and a urine sediment analysis indicating pyuria.

She was diagnosed with acute pyelonephritis and started on ampicillin and gentamicin intravenously. Her urine culture drawn upon admission grew >100,000 CFU/mL of sulfonamide-resistant E. coli.

Within 48 hours, she showed clinical improvement and was discharged home with a 10-day course of nitrofurantoin. One week after completing treatment, her test-of-cure urine culture was negative and she was started on nitrofurantoin 50 mg every night at bedtime.

For the rest of pregnancy, she underwent monthly screening urine cultures, which remained negative. She had an uncomplicated delivery at 38 weeks of gestation.

TABLE

Suppressive therapy to prevent UTI recurrence

Suppressive therapy is recommended for any pregnant woman with:
2 lower urinary tract infections or acute pyelonephritis.
Do not initiate suppressive therapy until a negative test-of-cure urine culture confirms eradication of the acute infection.
ANTIBIOTIC	DOSE (ORAL)
Nitrofurantoin monohydrate macrocrystals	50 mg at bedtime
or
Cephalexin	250 mg at bedtime

Dr. Chen reports support from a Women’s Reproductive Health Research Career Development Center grant from the National Institutes of Child Health and Human Development.

THE CASE: SIGNS AND SYMPTOMS

A 29–year–old nullipara at 18 weeks’ gestation complains of fevers and back pain. She had a diagnosis of urinary tract infection with sulfonamide-resistant Escherichia coli at 9 weeks of gestation, which was treated with nitrofurantoin, 100 mg by mouth twice a day for 7 days. A test of cure by urine culture was negative.

Now her temperature is 101°F and she has right costovertebral angle tenderness.

How should you proceed?

Anatomy is destiny, in the case of susceptibility to urinary tract infection (UTI). The female urethra is only 3 cm to 4 cm long, and its proximity to the vagina, anus, and rectum facilitates colonization of normal gastrointestinal flora in the bladder.¹

Sexual activity also facilitates migration of normal gastrointestinal flora to the female urethra.²

Anatomical features of pregnancy exacerbate the female predisposition to urinary tract infection. In pregnancy, hormonal and mechanical changes that occur in the urinary tract lead to urinary stasis and ureterovesical reflux—setting the stage for urinary tract infection (FIGURE 1).

Who should be screened?

All pregnant women should be screened for UTI early in pregnancy, according to the American College of Obstetricians and Gynecologists.³

I recommend a urine culture screening for all pregnant women at their first prenatal visit.

Screen often if she has risk factors

I recommend frequent screening (at least every trimester) by urine culture, in pregnant women with any of these risk factors:

• diabetes mellitus, including gestational diabetes⁴;
  
• urologic abnormalities—specifically, neurogenic bladder;
  
• prepregnancy (for example, 2 to 3 infections per year) and antepartum history of UTI prior to initiation of prenatal care⁵;
  
• sickle cell hemoglobinopathy.⁵
  

Which test is best?

The gold standard for detecting bacteria in urine is by culture.

Which threshold to use?

The standard definition of a positive urine culture from a clean-catch, midstream, voided specimen is ≥100,000 colony forming units (CFU) per mL of a single organism. However, in symptomatic patients, the test’s sensitivity is increased by lowering the cut-off to 100 CFU/mL of a single organism.⁶ In women with urinary symptoms, only 50% of patients had 100,000 CFU/mL by urine culture collected from clean-catch, midstream, voided specimens, though all of them had positive cultures from suprapubic taps.

The clean-catch, midstream, voided specimen is the specimen of choice for practical purposes, since it is noninvasive and easily obtained in the office setting.

For the record: The presence of any organism represents UTI in specimens obtained via suprapubic aspiration of the bladder; 100 CFU/mL of a single organism is positive for specimens obtained by urethral catheterization.

I recommend that, when obtaining urine cultures via clean-catch, midstream, voided specimens:

• for asymptomatic patients, use ≥100,000 CFU/mL of a single organism.
  
• in symptomatic patients, use ≥100 CFU/mL of a single organism.
  

What about rapid tests?

Urinary sediment analysis and urine dipstick testing offer speed and low cost, but with lower accuracy than urine cultures, which require 24 to 48 hours for results and cost more.

Urinary sediment analysis can diagnose pyuria, defined as a clean-catch, midstream, voided specimen, which is spun and which has >10 leukocytes per high-power field.

Pyuria can occur without infection due to:

• previous treatment with antibiotics,
  
• contamination of urine sample by sterilizing solution,
  
• contamination of urine sample with vaginal leukocytes,
  
• chronic interstitial nephritis (such as analgesic abuse),
  
• uroepithelial tumor, and
  
• nephrolithiasis.
  

Pyuria on urinalysis has low sensitivity (25%) but high specificity (99%).

Bacteria visualized on microscopic examination is more sensitive (75%) but less specific (60%).⁷

Urinary dipstick testing—fast, convenient, and low in cost—is considered positive if it identifies either leukocyte esterase or nitrite. Positive leukocyte esterase signifies pyuria. Positive nitrite indicates the presence of enteric organisms that convert urinary nitrate to nitrite.

With either finding, dipstick sensitivity is only 50%, although specificity is 97%.⁷

I recommend:

• If a symptomatic patient’s rapid test is positive, obtain a urine culture, empirically treat for UTI, and then use urine culture results to decide whether to continue treatment.
  
• If an asymptomatic patient’s rapid test is positive, obtain a urine culture and treat only if the culture is positive.
  

What urinary tract disorders occur in pregnancy?

First, determine if the patient has urinary tract symptoms and, if so, whether the symptoms are typical of upper or lower urinary tract infections.

 

Lower urinary tract symptoms:

• dysuria
  
• frequency
  
• urgency
  
• suprapubic pain
  
• hematuria in the absence of fever and systemic symptoms
  

Frequency, of course, is difficult to ascertain in pregnancy, since most women experience this complication secondary to increased urinary output due to higher fluid intake, increased plasma volume expansion, and increases in renal blood flow and glomerular filtration rate.

Upper urinary tract symptoms:

• fever
  
• chills
  
• flank pain
  
• nausea and vomiting
  
• The patient may or may not have the symptoms of lower urinary tract infection, as well.
  

Positive culture and no symptoms

This profile is typical of asymptomatic bacteriuria, a lower urinary tract infection that occurs in 2% to 7% of pregnancies.¹

Positive culture with symptoms

This profile probably reflects either:

• Acute cystitis, a lower urinary tract infection affecting 1% to 2% of pregnancies,⁸ or
  
• Acute pyelonephritis, an upper urinary tract infection affecting 2% of pregnancies.⁹
  

What are the consequences of UTI in pregnancy?

Maternal complications

Asymptomatic bacteriuria does not plague the patient with bothersome effects, but if left untreated, asymptomatic bacteriuria will progress to symptomatic UTI: 25% will develop acute pyelonephritis, compared to 3% to 4% of treated patients¹⁰; 20% of women with severe pyelonephritis develop serious complications,¹¹ including:

• sepsis and septic shock,
  
• hemolysis and thrombocytopenia,¹²
  
• acute respiratory distress syndrome,¹³
  
• renal insufficiency.¹⁴
  

Adverse fetal outcomes

Untreated asymptomatic bacteriuria is associated with preterm delivery and low birthweight.^15-17

Acute pyelonephritis is linked to preterm birth.^18,19 Kaul et al,²⁰ in an experimental model of pyelonephritis in mice, confirmed that E. coli plays an important role in the pathogenesis of preterm delivery and low birthweight.

What is the best treatment regimen?

Data are insufficient to recommend any specific regimen.^21,22 The following strategies are based on evaluation of review articles.^3,23

Asymptomatic bacteriuria and acute cystitis

Nitrofurantoin monohydrate macrocrystals is my first-line treatment. Nitrofurantoin has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

If nitrofurantoin is not effective, I change antibiotics based on urine culture antibiotic sensitivity profiles (FIGURE 2).

Keep in mind the current resistance of E. coli to antibiotics: ampicillin, 28% to 39%; trimethoprim-sulfamethoxazole, 31%; and first-generation cephalosporins, 9% to 19%.²⁴

Single-dose treatment for pregnant women with asymptomatic bacteriuria has been evaluated, given its lower cost and better compliance. However, evidence is insufficient to determine whether single-dose or longer-duration regimens are more effective.²⁵

I recommend longer-duration dosages for now, until a large randomized controlled trial can derive conclusive data.

Remember that treatment success is not contingent upon duration of therapy—just be sure that the test-of-cure urine culture is negative 1 to 2 weeks after treatment is completed.

Acute pyelonephritis

Management should include the following:

• hospitalization
  
• urine and blood cultures
  
• laboratory studies of complete blood cell count, electrolytes, creatinine, and liver function
  
• monitoring of vital signs and urine output
  
• intravenous (IV) crystalloid fluid to maintain urine output
  
• IV antibiotics (FIGURE 3).
  

If symptoms persist after 48 hours despite adequate IV antibiotic therapy, consider other causes such as resistant organisms, nephrolithiasis, perinephric abscesses, renal obstruction, or other infections.

Consider imaging by renal ultrasound to assess the presence of nephrolithiasis, perinephric abscess, or obstruction.

I recommend inpatient treatment for pregnant women with acute pyelonephritis at this time, until further studies are available.

To evaluate outpatient treatment, Millar and colleagues randomized 120 women under 24 weeks’ gestation either to inpatient IV cefazolin until 48 hours afebrile or to outpatient ceftriaxone intramuscularly. (Both treatment arms completed a course of oral cephalexin.) There were no differences in therapeutic response or birth outcomes, but 6 patients in the outpatient arm required hospitalization for IV therapy and 1 woman developed sepsis.²⁶

The same researchers studied 92 patients of more than 24 weeks’ gestation who received 2 doses of ceftriaxone intramuscularly, then were randomized to either continued inpatient therapy until 48 hours afebrile or discharge with reevaluation as an outpatient in 48 to 72 hours. Again, there were no differences in therapeutic response or birth outcomes; however, almost two-thirds of patients were excluded from the study as they did not meet criteria for outpatient management, due to sepsis, preterm labor, or concurrent medical conditions.²⁷

Adequate antibiotic coverage is crucial

To ensure adequate antibiotic coverage when treating UTI, it is important to understand which organisms cause these infections in pregnancy.

E. coli causes 75% to 90% of UTIs in nonpregnant women.²⁸Staphylococcus saprophyticus causes 10% to 15% of UTIs in nonpregnant women, but less in pregnant women.

Group B Streptococcus (GBS)—another gram-positive organism—has important implications for pregnant women: Intrapartum prophylaxis is important, to prevent neonatal GBS disease.²⁹

Klebsiella, Enterobacter, Proteus, and Enterococcus species²⁸ infrequently cause UTI in pregnancy.

What about prophylaxis and follow-up cultures?

 

Expect recurrence

One third of pregnant women diagnosed with UTI will have recurrence.¹ Recurrence is either relapse (same strain, within 2 weeks of completing initial treatment for the original infection) or reinfection (different strain or same strain after more than 2 weeks).

2 UTIs or pyelonephritis warrant suppressive therapy

I recommend suppressive therapy if a pregnant woman is diagnosed with 2 lower urinary tract infections or acute pyelonephritis (TABLE).

Nitrofurantoin is the preferred agent, as it has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

Start only after eradication of the acute infection, as evidenced by a negative test-of-cure urine culture at least 1 to 2 weeks after treatment is discontinued.²³

Monthly urine cultures until delivery

I recommend monthly follow-up urine cultures until delivery.

Periodic follow-up screening is often recommended, but opinions differ on which test to use or how often to screen.

THE CASE: DIAGNOSIS, TREATMENT, FOLLOW-UP, AND OUTCOME

The patient with upper urinary tract symptoms had a white blood cell count of 15, a urine dipstick positive for leukocyte esterase and nitrites, and a urine sediment analysis indicating pyuria.

She was diagnosed with acute pyelonephritis and started on ampicillin and gentamicin intravenously. Her urine culture drawn upon admission grew >100,000 CFU/mL of sulfonamide-resistant E. coli.

Within 48 hours, she showed clinical improvement and was discharged home with a 10-day course of nitrofurantoin. One week after completing treatment, her test-of-cure urine culture was negative and she was started on nitrofurantoin 50 mg every night at bedtime.

For the rest of pregnancy, she underwent monthly screening urine cultures, which remained negative. She had an uncomplicated delivery at 38 weeks of gestation.

TABLE

Suppressive therapy to prevent UTI recurrence

Suppressive therapy is recommended for any pregnant woman with:
2 lower urinary tract infections or acute pyelonephritis.
Do not initiate suppressive therapy until a negative test-of-cure urine culture confirms eradication of the acute infection.
ANTIBIOTIC	DOSE (ORAL)
Nitrofurantoin monohydrate macrocrystals	50 mg at bedtime
or
Cephalexin	250 mg at bedtime

Dr. Chen reports support from a Women’s Reproductive Health Research Career Development Center grant from the National Institutes of Child Health and Human Development.

THE CASE: SIGNS AND SYMPTOMS

A 29–year–old nullipara at 18 weeks’ gestation complains of fevers and back pain. She had a diagnosis of urinary tract infection with sulfonamide-resistant Escherichia coli at 9 weeks of gestation, which was treated with nitrofurantoin, 100 mg by mouth twice a day for 7 days. A test of cure by urine culture was negative.

Now her temperature is 101°F and she has right costovertebral angle tenderness.

How should you proceed?

Anatomy is destiny, in the case of susceptibility to urinary tract infection (UTI). The female urethra is only 3 cm to 4 cm long, and its proximity to the vagina, anus, and rectum facilitates colonization of normal gastrointestinal flora in the bladder.¹

Sexual activity also facilitates migration of normal gastrointestinal flora to the female urethra.²

Anatomical features of pregnancy exacerbate the female predisposition to urinary tract infection. In pregnancy, hormonal and mechanical changes that occur in the urinary tract lead to urinary stasis and ureterovesical reflux—setting the stage for urinary tract infection (FIGURE 1).

Who should be screened?

All pregnant women should be screened for UTI early in pregnancy, according to the American College of Obstetricians and Gynecologists.³

I recommend a urine culture screening for all pregnant women at their first prenatal visit.

Screen often if she has risk factors

I recommend frequent screening (at least every trimester) by urine culture, in pregnant women with any of these risk factors:

• diabetes mellitus, including gestational diabetes⁴;
  
• urologic abnormalities—specifically, neurogenic bladder;
  
• prepregnancy (for example, 2 to 3 infections per year) and antepartum history of UTI prior to initiation of prenatal care⁵;
  
• sickle cell hemoglobinopathy.⁵
  

Which test is best?

The gold standard for detecting bacteria in urine is by culture.

Which threshold to use?

The standard definition of a positive urine culture from a clean-catch, midstream, voided specimen is ≥100,000 colony forming units (CFU) per mL of a single organism. However, in symptomatic patients, the test’s sensitivity is increased by lowering the cut-off to 100 CFU/mL of a single organism.⁶ In women with urinary symptoms, only 50% of patients had 100,000 CFU/mL by urine culture collected from clean-catch, midstream, voided specimens, though all of them had positive cultures from suprapubic taps.

The clean-catch, midstream, voided specimen is the specimen of choice for practical purposes, since it is noninvasive and easily obtained in the office setting.

For the record: The presence of any organism represents UTI in specimens obtained via suprapubic aspiration of the bladder; 100 CFU/mL of a single organism is positive for specimens obtained by urethral catheterization.

I recommend that, when obtaining urine cultures via clean-catch, midstream, voided specimens:

• for asymptomatic patients, use ≥100,000 CFU/mL of a single organism.
  
• in symptomatic patients, use ≥100 CFU/mL of a single organism.
  

What about rapid tests?

Urinary sediment analysis and urine dipstick testing offer speed and low cost, but with lower accuracy than urine cultures, which require 24 to 48 hours for results and cost more.

Urinary sediment analysis can diagnose pyuria, defined as a clean-catch, midstream, voided specimen, which is spun and which has >10 leukocytes per high-power field.

Pyuria can occur without infection due to:

• previous treatment with antibiotics,
  
• contamination of urine sample by sterilizing solution,
  
• contamination of urine sample with vaginal leukocytes,
  
• chronic interstitial nephritis (such as analgesic abuse),
  
• uroepithelial tumor, and
  
• nephrolithiasis.
  

Pyuria on urinalysis has low sensitivity (25%) but high specificity (99%).

Bacteria visualized on microscopic examination is more sensitive (75%) but less specific (60%).⁷

Urinary dipstick testing—fast, convenient, and low in cost—is considered positive if it identifies either leukocyte esterase or nitrite. Positive leukocyte esterase signifies pyuria. Positive nitrite indicates the presence of enteric organisms that convert urinary nitrate to nitrite.

With either finding, dipstick sensitivity is only 50%, although specificity is 97%.⁷

I recommend:

• If a symptomatic patient’s rapid test is positive, obtain a urine culture, empirically treat for UTI, and then use urine culture results to decide whether to continue treatment.
  
• If an asymptomatic patient’s rapid test is positive, obtain a urine culture and treat only if the culture is positive.
  

What urinary tract disorders occur in pregnancy?

First, determine if the patient has urinary tract symptoms and, if so, whether the symptoms are typical of upper or lower urinary tract infections.

 

Lower urinary tract symptoms:

• dysuria
  
• frequency
  
• urgency
  
• suprapubic pain
  
• hematuria in the absence of fever and systemic symptoms
  

Frequency, of course, is difficult to ascertain in pregnancy, since most women experience this complication secondary to increased urinary output due to higher fluid intake, increased plasma volume expansion, and increases in renal blood flow and glomerular filtration rate.

Upper urinary tract symptoms:

• fever
  
• chills
  
• flank pain
  
• nausea and vomiting
  
• The patient may or may not have the symptoms of lower urinary tract infection, as well.
  

Positive culture and no symptoms

This profile is typical of asymptomatic bacteriuria, a lower urinary tract infection that occurs in 2% to 7% of pregnancies.¹

Positive culture with symptoms

This profile probably reflects either:

• Acute cystitis, a lower urinary tract infection affecting 1% to 2% of pregnancies,⁸ or
  
• Acute pyelonephritis, an upper urinary tract infection affecting 2% of pregnancies.⁹
  

What are the consequences of UTI in pregnancy?

Maternal complications

Asymptomatic bacteriuria does not plague the patient with bothersome effects, but if left untreated, asymptomatic bacteriuria will progress to symptomatic UTI: 25% will develop acute pyelonephritis, compared to 3% to 4% of treated patients¹⁰; 20% of women with severe pyelonephritis develop serious complications,¹¹ including:

• sepsis and septic shock,
  
• hemolysis and thrombocytopenia,¹²
  
• acute respiratory distress syndrome,¹³
  
• renal insufficiency.¹⁴
  

Adverse fetal outcomes

Untreated asymptomatic bacteriuria is associated with preterm delivery and low birthweight.^15-17

Acute pyelonephritis is linked to preterm birth.^18,19 Kaul et al,²⁰ in an experimental model of pyelonephritis in mice, confirmed that E. coli plays an important role in the pathogenesis of preterm delivery and low birthweight.

What is the best treatment regimen?

Data are insufficient to recommend any specific regimen.^21,22 The following strategies are based on evaluation of review articles.^3,23

Asymptomatic bacteriuria and acute cystitis

Nitrofurantoin monohydrate macrocrystals is my first-line treatment. Nitrofurantoin has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

If nitrofurantoin is not effective, I change antibiotics based on urine culture antibiotic sensitivity profiles (FIGURE 2).

Keep in mind the current resistance of E. coli to antibiotics: ampicillin, 28% to 39%; trimethoprim-sulfamethoxazole, 31%; and first-generation cephalosporins, 9% to 19%.²⁴

Single-dose treatment for pregnant women with asymptomatic bacteriuria has been evaluated, given its lower cost and better compliance. However, evidence is insufficient to determine whether single-dose or longer-duration regimens are more effective.²⁵

I recommend longer-duration dosages for now, until a large randomized controlled trial can derive conclusive data.

Remember that treatment success is not contingent upon duration of therapy—just be sure that the test-of-cure urine culture is negative 1 to 2 weeks after treatment is completed.

Acute pyelonephritis

Management should include the following:

• hospitalization
  
• urine and blood cultures
  
• laboratory studies of complete blood cell count, electrolytes, creatinine, and liver function
  
• monitoring of vital signs and urine output
  
• intravenous (IV) crystalloid fluid to maintain urine output
  
• IV antibiotics (FIGURE 3).
  

If symptoms persist after 48 hours despite adequate IV antibiotic therapy, consider other causes such as resistant organisms, nephrolithiasis, perinephric abscesses, renal obstruction, or other infections.

Consider imaging by renal ultrasound to assess the presence of nephrolithiasis, perinephric abscess, or obstruction.

I recommend inpatient treatment for pregnant women with acute pyelonephritis at this time, until further studies are available.

To evaluate outpatient treatment, Millar and colleagues randomized 120 women under 24 weeks’ gestation either to inpatient IV cefazolin until 48 hours afebrile or to outpatient ceftriaxone intramuscularly. (Both treatment arms completed a course of oral cephalexin.) There were no differences in therapeutic response or birth outcomes, but 6 patients in the outpatient arm required hospitalization for IV therapy and 1 woman developed sepsis.²⁶

The same researchers studied 92 patients of more than 24 weeks’ gestation who received 2 doses of ceftriaxone intramuscularly, then were randomized to either continued inpatient therapy until 48 hours afebrile or discharge with reevaluation as an outpatient in 48 to 72 hours. Again, there were no differences in therapeutic response or birth outcomes; however, almost two-thirds of patients were excluded from the study as they did not meet criteria for outpatient management, due to sepsis, preterm labor, or concurrent medical conditions.²⁷

Adequate antibiotic coverage is crucial

To ensure adequate antibiotic coverage when treating UTI, it is important to understand which organisms cause these infections in pregnancy.

E. coli causes 75% to 90% of UTIs in nonpregnant women.²⁸Staphylococcus saprophyticus causes 10% to 15% of UTIs in nonpregnant women, but less in pregnant women.

Group B Streptococcus (GBS)—another gram-positive organism—has important implications for pregnant women: Intrapartum prophylaxis is important, to prevent neonatal GBS disease.²⁹

Klebsiella, Enterobacter, Proteus, and Enterococcus species²⁸ infrequently cause UTI in pregnancy.

What about prophylaxis and follow-up cultures?

 

Expect recurrence

One third of pregnant women diagnosed with UTI will have recurrence.¹ Recurrence is either relapse (same strain, within 2 weeks of completing initial treatment for the original infection) or reinfection (different strain or same strain after more than 2 weeks).

2 UTIs or pyelonephritis warrant suppressive therapy

I recommend suppressive therapy if a pregnant woman is diagnosed with 2 lower urinary tract infections or acute pyelonephritis (TABLE).

Nitrofurantoin is the preferred agent, as it has high concentrations in the urinary tract but induces minimal resistance in gram-negative organisms.

Start only after eradication of the acute infection, as evidenced by a negative test-of-cure urine culture at least 1 to 2 weeks after treatment is discontinued.²³

Monthly urine cultures until delivery

I recommend monthly follow-up urine cultures until delivery.

Periodic follow-up screening is often recommended, but opinions differ on which test to use or how often to screen.

THE CASE: DIAGNOSIS, TREATMENT, FOLLOW-UP, AND OUTCOME

The patient with upper urinary tract symptoms had a white blood cell count of 15, a urine dipstick positive for leukocyte esterase and nitrites, and a urine sediment analysis indicating pyuria.

She was diagnosed with acute pyelonephritis and started on ampicillin and gentamicin intravenously. Her urine culture drawn upon admission grew >100,000 CFU/mL of sulfonamide-resistant E. coli.

Within 48 hours, she showed clinical improvement and was discharged home with a 10-day course of nitrofurantoin. One week after completing treatment, her test-of-cure urine culture was negative and she was started on nitrofurantoin 50 mg every night at bedtime.

For the rest of pregnancy, she underwent monthly screening urine cultures, which remained negative. She had an uncomplicated delivery at 38 weeks of gestation.

TABLE

Suppressive therapy to prevent UTI recurrence

Suppressive therapy is recommended for any pregnant woman with:
2 lower urinary tract infections or acute pyelonephritis.
Do not initiate suppressive therapy until a negative test-of-cure urine culture confirms eradication of the acute infection.
ANTIBIOTIC	DOSE (ORAL)
Nitrofurantoin monohydrate macrocrystals	50 mg at bedtime
or
Cephalexin	250 mg at bedtime

Dr. Chen reports support from a Women’s Reproductive Health Research Career Development Center grant from the National Institutes of Child Health and Human Development.

The hepatitis C virus (HCV) was first identified in 1989 as the cause of non-A, non-B hepatitis infections. Since its discovery, HCV has become the most common chronic blood-borne infection in the United States: Approximately 2.7 to 3.5 million people have chronic HCV infection,^1,2 as compared with 1.25 million people with chronic hepatitis B virus infection and 1 million with the human immunodeficiency virus (HIV). In addition, HCV infection is the leading cause of chronic liver disease and the leading indication for liver transplantation in the United States. Some call HCV infection “the silent epidemic,” since 75% of people infected are asymptomatic and chronic manifestations don’t appear for 1 to 2 decades.

In 1998, the Centers for Disease Control and Prevention (CDC) issued guidelines for screening for HCV infection ( Table 1).³ The American College of Obstetricians and Gynecologists (ACOG) advocates screening for HCV infection at the annual exam if the patient belongs to one of the CDC’s routine-screening categories.⁴ Although ACOG has not issued separate screening guidelines for obstetric patients, some practitioners have advocated screening based on risk factors, as listed in the CDC’s routine-screening categories.⁵

HCV accounts for about 20% of acute hepatitis cases in the U.S.

Because Ob/Gyns are increasingly likely to encounter patients with positive HCV blood-screening results, they should be prepared to answer the following inquiries: What is hepatitis C? How is it diagnosed and transmitted? What is the natural history of the infection? Is there a treatment for it? How will HCV infection affect pregnancy?

This review addresses those questions.

What is hepatitis C?

Hepatitis C is a liver disease caused by the HCV, an RNA virus of the Flavivirus family, which includes the dengue and yellow fever viruses. Worldwide, approximately 170 million people are infected with HCV, with a prevalence ranging from a low of 0.15% in Scandinavia to a high of 38% in northern Egypt.^6,7 In the United States, 3.9 million people have been infected with HCV, with an overall prevalence of 1.8%.¹ U.S. prevalence rates by gender and age reveal that more males are infected than females and that, in females, prevalence is highest during the childbearing years, peaking at age 35.

TABLE 1

Recommendations for hepatitis C virus screening

PEOPLE WHO SHOULD BE TESTED ROUTINELY
Persons who have ever injected illegal drugs Persons with selected medical conditions, including: persons who have ever undergone chronic hemodialysis persons with evidence of liver disease, such as persistently abnormal ALT levels Prior recipients of transfusions or organ transplants, including: recipients of clotting factor concentrates produced before 1987 persons who received a transfusion of blood or blood components before July 1992 persons who received an organ transplant before July 1992 persons who were notified that they received clotting factor concentrates, blood components, or organ transplants from a donor who later tested positive for HCV infection Persons with a recognized exposure, including: health-care, emergency medical, and public safety workers after sticks with needles or sharps or mucosal exposure to HCV-positive blood children born to HCV-positive women
PEOPLE FOR WHOM ROUTINE TESTING IS OF UNCERTAIN NEED
Recipients of transplanted tissue, e.g., corneal or musculoskeletal tissue, skin, ova, or sperm Users of intranasal cocaine or other noninjected illegal drugs Persons with a history of tattooing or body piercing Persons with a history of multiple sex partners or sexually transmitted diseases Long-term sex partners of HCV-positive persons
PEOPLE FOR WHOM ROUTINE TESTING IS NOT RECOMMENDED*
Health-care, emergency medical, and public safety workers Pregnant women Nonsexual household contacts of HCV-positive persons The general population
* Except in cases where risk factors are present ALT=alanine aminotransferase; HCV=hepatitis C virus
Source: Centers for Disease Control and Prevention

How is HCV infection diagnosed?

The initial screening test is an enzyme immunoassay (EIA) for the antibody to HCV. Currently, a third-generation EIA is used, with a sensitivity and specificity of 99% in immunocompetent people. If the EIA is positive, the practitioner may proceed to a confirmatory recombinant immunoblot assay (RIBA) in individuals with a low pretest probability, or to direct measurement of HCV RNA by reverse-transcription polymerase chain reaction (PCR) in individuals with a high pretest probability. Figure 1 depicts the HCV testing algorithm recommended by the CDC.

 

FIGURE 1 HCV infection testing algorithm

ALT=alanine aminotransferase; EIA=enzyme immunoassay; PCR=polymerase chain reaction; RIBA=recombinant immunoblast assay Source: Centers for Disease Control and Prevention

How is HCV transmitted?

HCV spreads primarily through blood or fluids containing blood. Injection-drug use accounts for 60% of infections;1 a person who has used injection drugs for 5 years has a 60% to 90% chance of becoming infected with HCV. In fact, among injection-drug users, HCV infection is 4 times more common than HIV infection.8 The transfusion of blood or blood products accounts for another 10% of HCV cases. However, the transfusion-related risk has decreased markedly since the introduction of HCV screening in the blood banks in 1992. Figure 2 shows additional sources of HCV infection.

Although sexual transmission of HCV does occur, the virus is inefficiently spread in this manner. Evidence for this route of transmission has been accumulated from case-control and partner studies. Case-control studies have reported an association between HCV infection and exposure to a sex partner with a history of hepatitis or exposure to multiple sex partners.^9,10 Cross-sectional studies suggest that the probability of HCV infection in the sexual partner of an HCV-positive patient is 0% to 3% in northern Europe or North America. Higher probabilities are found in southern Europe and the Far East.¹¹ One prospective study showed no cases of sexual transmission of HCV from 94 HCV-positive females to their male part-ners.¹² Another prospective study found a low incidence—12 infections per 1,000 per-son-years—among 449 sexual partners of HCV-positive individuals.¹³

Since the risk of spreading HCV through sexual contact is relatively low, individuals in long-term, stable relationships with an infected partner need not change their sexual practices. However, they may choose to use barrier methods to lower the chance of transmission even further. Individuals with high-risk sexual practices, such as having multiple sexual partners, should definitely use barrier methods.

FIGURE 2 Sources of infection for persons with hepatitis C

*Nosocomial, occupational, perinatal

Source: Centers for Disease Control and Prevention

What is the natural history of HCV infection?

HCV accounts for approximately 20% of cases of acute hepatitis in the United States.¹⁴ The incubation period is approximately 6 weeks. Children and adults who acquire the infection usually are asymptomatic or have nonspecific symptoms of fatigue, malaise, anorexia, and weight loss. Some patients may present with jaundice. Serum aminotransferases can fluctuate during acute infection, and normalization occurs in 40% of individuals. However, this normalization does not necessarily represent a clearance of infection. Only 15% of patients clear the virus; the rest develop chronic infection.

Only 15% of patients clear the virus; the rest develop chronic infection.

During chronic infection, most patients are unaware that they are HCV-positive because, as with acute infection, they are asymptomatic or have mild, nonspecific symptoms such as fatigue. Again, serum aminotransferases typically fluctuate and are normal 30% of the time. Clinical progression to cirrhosis occurs in 20% of cases over a span of about 20 years. Once cirrhosis develops, the risk of decompensated cirrhosis or liver failure is about 3% to 4% per year. The annual risk of primary hepatocellular carcinoma in patients with cirrhosis is 1% to 4%. Data suggest that alcohol use is a predictive factor for progressive liver disease and liver cancer. Figure 3 summarizes the natural history of HCV infection.

FIGURE 3 Natural history of HCV infection

Is there a treatment for hepatitis C?

Over the past decade, there have been incremental improvements in hepatitis C therapy. The original mainstay of treatment was interferon alpha, with an initial response rate of 50% and a sustained response rate of only 10% to 15%.^15-17 Later, combination therapy with interferon alpha and ribavirin raised the sustained response rate to 40%.^18,19 However, both these therapies have substantial side effects and require frequent dosing schedules.

In January 2001, a new therapy, pegylated interferon alpha, was introduced. This modified form of traditional interferon alpha has fewer side effects and requires less frequent dosing. In addition, initial studies showed that it had a greater sustained-response rate than traditional interferon alpha alone.²⁰ The Food and Drug Administration (FDA) recently approved it for the treatment of chronic hepatitis not previously treated with standard interferon alpha. A recent trial showed that the combination of pegylated interferon alpha with ribavirin had a sustained virologic response rate of 54%.²¹ None of these medications are approved for use in pregnancy or childhood.

To prevent progressive liver disease, patients chronically infected with HCV should avoid alcohol and other hepatotoxins and get vaccinated against hepatitis A and B. To reduce the risk of transmission to others, they should be advised not to donate blood and tissues; not to share toothbrushes, razors, or other personal-care items that may have blood on them; and to cover cuts and sores on the skin.

 

TABLE 2

Characteristics of hepatitis viral infection in the U.S. population

	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS
	A	B	C	D	E
Source/route of transmission	Feces/Fecal-oral	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Feces/Fecal-oral
No. of acute infections (per year)	125,000-200,000	140,000-320,000	35,000-180,000	6,000-13,000	Rare in the the United States
No. of chronic infections	0	1-1.25 million	3.5 million	70,000	0
Deaths from chronic liver disease (per year)	0	5,000	8,000-10,000	1,000	NA
Symptoms	Fatigue, nausea, pain near liver or in upper-abdominal area, dark urine, light stools, fever, jaundice	Same as hepatitis A. However, almost 50% of people infected with hepatitis B are asymptomatic.	Same as hepatitis A. However,most people are asymptomatic	Similar to other types of viral hepatitis	Similar to other types of viral hepatitis
Prevention	Good personal hygiene and proper sanitation. Also pre- or postexposure immunization	Pre- or post-exposure immunization	Blood donor screening; risk behavior modification	Pre- or post-exposure immunization	Ensure safe drinking water
Comments	Typically lasts about 3 weeks, but may persist for as long as 6 months	—	Originally defined in the 1970s as non-A non-B hepatitis. Renamed hepatitis C in 1989.	Requires the hepatitis B virus to exist*	Usually associated with fecally contaminated drinking water. U.S. cases usually involve a history of travel to areas with endemic hepatitis E infection
*Hepatitis D infection can be acquired either as a co-infection with the hepatitis B virus or as a superinfection in persons with chronic hepatitis B infection. Persons coinfected with the B and D viruses may have more severe acute disease and a higher risk of fulminant hepatitis (2% to 20%) compared with those infected with hepatitis B alone. However, chronic hepatitis B infection appears to occur less frequently in persons coinfected with the B and D viruses. Chronic hepatitis B carriers who acquire hepatitis D superinfection usually develop chronic hepatitis D infection. In long-term studies of chronic hepatitis B carriers with hepatitis D superinfection, 70% to 80% have developed evidence of chronic liver diseases with cirrhosis compared with 15% to 30% of patients with chronic hepatitis B infection alone.
Source: American Liver Foundation, Centers for Disease Control and Prevention

How will hepatitis C affect my pregnancy?

Perinatal transmission occurs in women with chronic HCV infection at an average rate of 5%.^22-24 Small studies suggest that the level of HCV viremia may affect the risk of viral transmission.^22,25 However, in 2 large studies, no significant difference in HCV viremia levels was found between women who transmitted the virus to their children and women who did not.^23,24 Women co-infected with HIV have 2 to 3 times the rate of HCV transmission compared with women infected only with HCV.^26,27 The natural history of HCV infection in children is not well understood, but 50% to 80% of HCV-positive children develop chronic infection.²⁸

Currently, no intervention is available to decrease perinatal HCV transmission.

Currently, no intervention is available to decrease perinatal HCV transmission, although an unclear association with mode of delivery exists. One study of 441 mother-infant pairs showed that elective cesarean delivery may be associated with a lower transmission risk.²⁹ However, another study of 370 mother-infant pairs found no difference in risk.²⁴

The effect of pregnancy on the progression of hepatitis C infection also is unclear. In studies of HCV-positive pregnant women—as compared to HCV-positive non-pregnant women—researchers reported a decrease in serum alanine aminotransferase (ALT) and an increase in HCV RNA during pregnancy,³⁰ as well as a deterioration of hepatitis C disease after pregnancy, as confirmed by liver biopsy.³¹ In prospective cohort studies comparing infected and uninfected pregnant women, serum aminotrans-ferases flared postpartum in one study³² but remained normal in another.³³

Not much is known regarding the effect of chronic hepatitis C infection on pregnancy outcome, although 1 case-control study reported an association between hepatitis C infection and cholestasis of pregnancy.³⁴

Although HCV RNA has been detected in colostrum,³⁵ studies of breastfed infants with HCV-positive mothers have found no cases of transmission secondary to breastfeeding.^35,36 Thus, both the American Academy of Pediatrics and ACOG conclude that breastfeeding does not appreciably increase the risk of transmission to the neonate and should not be prohibited.^37,38 However, pending further studies, practitioners may choose to advise against breastfeeding if nipples are cracked and bleeding.

 

Conclusion

Chronic HCV infection can lead to serious medical consequences, such as cirrhosis, liver failure, hepatocellular cancer, and death. Unfortunately, 75% of individuals infected with HCV are asymptomatic. By the time symptoms do occur, the disease often is in its advanced stages. Thus, both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups. The early identification of chronic HCV infection is important, as it enables women to take advantage of increasingly effective treatments and alerts them to the need for preconception counseling.

Both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups.

Although perinatal HCV transmission is a known risk, we lack strategies to prevent it. In addition, the effects of pregnancy on the progression of chronic HCV infection, and the effects of chronic HCV infection on pregnancy outcome, are unknown. However, the identification of HCV-positive pregnant women will lead to screening of their infants and earlier identification of infected children.

The hepatitis C virus (HCV) was first identified in 1989 as the cause of non-A, non-B hepatitis infections. Since its discovery, HCV has become the most common chronic blood-borne infection in the United States: Approximately 2.7 to 3.5 million people have chronic HCV infection,^1,2 as compared with 1.25 million people with chronic hepatitis B virus infection and 1 million with the human immunodeficiency virus (HIV). In addition, HCV infection is the leading cause of chronic liver disease and the leading indication for liver transplantation in the United States. Some call HCV infection “the silent epidemic,” since 75% of people infected are asymptomatic and chronic manifestations don’t appear for 1 to 2 decades.

In 1998, the Centers for Disease Control and Prevention (CDC) issued guidelines for screening for HCV infection ( Table 1).³ The American College of Obstetricians and Gynecologists (ACOG) advocates screening for HCV infection at the annual exam if the patient belongs to one of the CDC’s routine-screening categories.⁴ Although ACOG has not issued separate screening guidelines for obstetric patients, some practitioners have advocated screening based on risk factors, as listed in the CDC’s routine-screening categories.⁵

HCV accounts for about 20% of acute hepatitis cases in the U.S.

Because Ob/Gyns are increasingly likely to encounter patients with positive HCV blood-screening results, they should be prepared to answer the following inquiries: What is hepatitis C? How is it diagnosed and transmitted? What is the natural history of the infection? Is there a treatment for it? How will HCV infection affect pregnancy?

This review addresses those questions.

What is hepatitis C?

Hepatitis C is a liver disease caused by the HCV, an RNA virus of the Flavivirus family, which includes the dengue and yellow fever viruses. Worldwide, approximately 170 million people are infected with HCV, with a prevalence ranging from a low of 0.15% in Scandinavia to a high of 38% in northern Egypt.^6,7 In the United States, 3.9 million people have been infected with HCV, with an overall prevalence of 1.8%.¹ U.S. prevalence rates by gender and age reveal that more males are infected than females and that, in females, prevalence is highest during the childbearing years, peaking at age 35.

TABLE 1

Recommendations for hepatitis C virus screening

PEOPLE WHO SHOULD BE TESTED ROUTINELY
Persons who have ever injected illegal drugs Persons with selected medical conditions, including: persons who have ever undergone chronic hemodialysis persons with evidence of liver disease, such as persistently abnormal ALT levels Prior recipients of transfusions or organ transplants, including: recipients of clotting factor concentrates produced before 1987 persons who received a transfusion of blood or blood components before July 1992 persons who received an organ transplant before July 1992 persons who were notified that they received clotting factor concentrates, blood components, or organ transplants from a donor who later tested positive for HCV infection Persons with a recognized exposure, including: health-care, emergency medical, and public safety workers after sticks with needles or sharps or mucosal exposure to HCV-positive blood children born to HCV-positive women
PEOPLE FOR WHOM ROUTINE TESTING IS OF UNCERTAIN NEED
Recipients of transplanted tissue, e.g., corneal or musculoskeletal tissue, skin, ova, or sperm Users of intranasal cocaine or other noninjected illegal drugs Persons with a history of tattooing or body piercing Persons with a history of multiple sex partners or sexually transmitted diseases Long-term sex partners of HCV-positive persons
PEOPLE FOR WHOM ROUTINE TESTING IS NOT RECOMMENDED*
Health-care, emergency medical, and public safety workers Pregnant women Nonsexual household contacts of HCV-positive persons The general population
* Except in cases where risk factors are present ALT=alanine aminotransferase; HCV=hepatitis C virus
Source: Centers for Disease Control and Prevention

How is HCV infection diagnosed?

The initial screening test is an enzyme immunoassay (EIA) for the antibody to HCV. Currently, a third-generation EIA is used, with a sensitivity and specificity of 99% in immunocompetent people. If the EIA is positive, the practitioner may proceed to a confirmatory recombinant immunoblot assay (RIBA) in individuals with a low pretest probability, or to direct measurement of HCV RNA by reverse-transcription polymerase chain reaction (PCR) in individuals with a high pretest probability. Figure 1 depicts the HCV testing algorithm recommended by the CDC.

 

FIGURE 1 HCV infection testing algorithm

ALT=alanine aminotransferase; EIA=enzyme immunoassay; PCR=polymerase chain reaction; RIBA=recombinant immunoblast assay Source: Centers for Disease Control and Prevention

How is HCV transmitted?

HCV spreads primarily through blood or fluids containing blood. Injection-drug use accounts for 60% of infections;1 a person who has used injection drugs for 5 years has a 60% to 90% chance of becoming infected with HCV. In fact, among injection-drug users, HCV infection is 4 times more common than HIV infection.8 The transfusion of blood or blood products accounts for another 10% of HCV cases. However, the transfusion-related risk has decreased markedly since the introduction of HCV screening in the blood banks in 1992. Figure 2 shows additional sources of HCV infection.

Although sexual transmission of HCV does occur, the virus is inefficiently spread in this manner. Evidence for this route of transmission has been accumulated from case-control and partner studies. Case-control studies have reported an association between HCV infection and exposure to a sex partner with a history of hepatitis or exposure to multiple sex partners.^9,10 Cross-sectional studies suggest that the probability of HCV infection in the sexual partner of an HCV-positive patient is 0% to 3% in northern Europe or North America. Higher probabilities are found in southern Europe and the Far East.¹¹ One prospective study showed no cases of sexual transmission of HCV from 94 HCV-positive females to their male part-ners.¹² Another prospective study found a low incidence—12 infections per 1,000 per-son-years—among 449 sexual partners of HCV-positive individuals.¹³

Since the risk of spreading HCV through sexual contact is relatively low, individuals in long-term, stable relationships with an infected partner need not change their sexual practices. However, they may choose to use barrier methods to lower the chance of transmission even further. Individuals with high-risk sexual practices, such as having multiple sexual partners, should definitely use barrier methods.

FIGURE 2 Sources of infection for persons with hepatitis C

*Nosocomial, occupational, perinatal

Source: Centers for Disease Control and Prevention

What is the natural history of HCV infection?

HCV accounts for approximately 20% of cases of acute hepatitis in the United States.¹⁴ The incubation period is approximately 6 weeks. Children and adults who acquire the infection usually are asymptomatic or have nonspecific symptoms of fatigue, malaise, anorexia, and weight loss. Some patients may present with jaundice. Serum aminotransferases can fluctuate during acute infection, and normalization occurs in 40% of individuals. However, this normalization does not necessarily represent a clearance of infection. Only 15% of patients clear the virus; the rest develop chronic infection.

Only 15% of patients clear the virus; the rest develop chronic infection.

During chronic infection, most patients are unaware that they are HCV-positive because, as with acute infection, they are asymptomatic or have mild, nonspecific symptoms such as fatigue. Again, serum aminotransferases typically fluctuate and are normal 30% of the time. Clinical progression to cirrhosis occurs in 20% of cases over a span of about 20 years. Once cirrhosis develops, the risk of decompensated cirrhosis or liver failure is about 3% to 4% per year. The annual risk of primary hepatocellular carcinoma in patients with cirrhosis is 1% to 4%. Data suggest that alcohol use is a predictive factor for progressive liver disease and liver cancer. Figure 3 summarizes the natural history of HCV infection.

FIGURE 3 Natural history of HCV infection

Is there a treatment for hepatitis C?

Over the past decade, there have been incremental improvements in hepatitis C therapy. The original mainstay of treatment was interferon alpha, with an initial response rate of 50% and a sustained response rate of only 10% to 15%.^15-17 Later, combination therapy with interferon alpha and ribavirin raised the sustained response rate to 40%.^18,19 However, both these therapies have substantial side effects and require frequent dosing schedules.

In January 2001, a new therapy, pegylated interferon alpha, was introduced. This modified form of traditional interferon alpha has fewer side effects and requires less frequent dosing. In addition, initial studies showed that it had a greater sustained-response rate than traditional interferon alpha alone.²⁰ The Food and Drug Administration (FDA) recently approved it for the treatment of chronic hepatitis not previously treated with standard interferon alpha. A recent trial showed that the combination of pegylated interferon alpha with ribavirin had a sustained virologic response rate of 54%.²¹ None of these medications are approved for use in pregnancy or childhood.

To prevent progressive liver disease, patients chronically infected with HCV should avoid alcohol and other hepatotoxins and get vaccinated against hepatitis A and B. To reduce the risk of transmission to others, they should be advised not to donate blood and tissues; not to share toothbrushes, razors, or other personal-care items that may have blood on them; and to cover cuts and sores on the skin.

 

TABLE 2

Characteristics of hepatitis viral infection in the U.S. population

	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS
	A	B	C	D	E
Source/route of transmission	Feces/Fecal-oral	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Feces/Fecal-oral
No. of acute infections (per year)	125,000-200,000	140,000-320,000	35,000-180,000	6,000-13,000	Rare in the the United States
No. of chronic infections	0	1-1.25 million	3.5 million	70,000	0
Deaths from chronic liver disease (per year)	0	5,000	8,000-10,000	1,000	NA
Symptoms	Fatigue, nausea, pain near liver or in upper-abdominal area, dark urine, light stools, fever, jaundice	Same as hepatitis A. However, almost 50% of people infected with hepatitis B are asymptomatic.	Same as hepatitis A. However,most people are asymptomatic	Similar to other types of viral hepatitis	Similar to other types of viral hepatitis
Prevention	Good personal hygiene and proper sanitation. Also pre- or postexposure immunization	Pre- or post-exposure immunization	Blood donor screening; risk behavior modification	Pre- or post-exposure immunization	Ensure safe drinking water
Comments	Typically lasts about 3 weeks, but may persist for as long as 6 months	—	Originally defined in the 1970s as non-A non-B hepatitis. Renamed hepatitis C in 1989.	Requires the hepatitis B virus to exist*	Usually associated with fecally contaminated drinking water. U.S. cases usually involve a history of travel to areas with endemic hepatitis E infection
*Hepatitis D infection can be acquired either as a co-infection with the hepatitis B virus or as a superinfection in persons with chronic hepatitis B infection. Persons coinfected with the B and D viruses may have more severe acute disease and a higher risk of fulminant hepatitis (2% to 20%) compared with those infected with hepatitis B alone. However, chronic hepatitis B infection appears to occur less frequently in persons coinfected with the B and D viruses. Chronic hepatitis B carriers who acquire hepatitis D superinfection usually develop chronic hepatitis D infection. In long-term studies of chronic hepatitis B carriers with hepatitis D superinfection, 70% to 80% have developed evidence of chronic liver diseases with cirrhosis compared with 15% to 30% of patients with chronic hepatitis B infection alone.
Source: American Liver Foundation, Centers for Disease Control and Prevention

How will hepatitis C affect my pregnancy?

Perinatal transmission occurs in women with chronic HCV infection at an average rate of 5%.^22-24 Small studies suggest that the level of HCV viremia may affect the risk of viral transmission.^22,25 However, in 2 large studies, no significant difference in HCV viremia levels was found between women who transmitted the virus to their children and women who did not.^23,24 Women co-infected with HIV have 2 to 3 times the rate of HCV transmission compared with women infected only with HCV.^26,27 The natural history of HCV infection in children is not well understood, but 50% to 80% of HCV-positive children develop chronic infection.²⁸

Currently, no intervention is available to decrease perinatal HCV transmission.

Currently, no intervention is available to decrease perinatal HCV transmission, although an unclear association with mode of delivery exists. One study of 441 mother-infant pairs showed that elective cesarean delivery may be associated with a lower transmission risk.²⁹ However, another study of 370 mother-infant pairs found no difference in risk.²⁴

The effect of pregnancy on the progression of hepatitis C infection also is unclear. In studies of HCV-positive pregnant women—as compared to HCV-positive non-pregnant women—researchers reported a decrease in serum alanine aminotransferase (ALT) and an increase in HCV RNA during pregnancy,³⁰ as well as a deterioration of hepatitis C disease after pregnancy, as confirmed by liver biopsy.³¹ In prospective cohort studies comparing infected and uninfected pregnant women, serum aminotrans-ferases flared postpartum in one study³² but remained normal in another.³³

Not much is known regarding the effect of chronic hepatitis C infection on pregnancy outcome, although 1 case-control study reported an association between hepatitis C infection and cholestasis of pregnancy.³⁴

Although HCV RNA has been detected in colostrum,³⁵ studies of breastfed infants with HCV-positive mothers have found no cases of transmission secondary to breastfeeding.^35,36 Thus, both the American Academy of Pediatrics and ACOG conclude that breastfeeding does not appreciably increase the risk of transmission to the neonate and should not be prohibited.^37,38 However, pending further studies, practitioners may choose to advise against breastfeeding if nipples are cracked and bleeding.

 

Conclusion

Chronic HCV infection can lead to serious medical consequences, such as cirrhosis, liver failure, hepatocellular cancer, and death. Unfortunately, 75% of individuals infected with HCV are asymptomatic. By the time symptoms do occur, the disease often is in its advanced stages. Thus, both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups. The early identification of chronic HCV infection is important, as it enables women to take advantage of increasingly effective treatments and alerts them to the need for preconception counseling.

Both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups.

Although perinatal HCV transmission is a known risk, we lack strategies to prevent it. In addition, the effects of pregnancy on the progression of chronic HCV infection, and the effects of chronic HCV infection on pregnancy outcome, are unknown. However, the identification of HCV-positive pregnant women will lead to screening of their infants and earlier identification of infected children.

The hepatitis C virus (HCV) was first identified in 1989 as the cause of non-A, non-B hepatitis infections. Since its discovery, HCV has become the most common chronic blood-borne infection in the United States: Approximately 2.7 to 3.5 million people have chronic HCV infection,^1,2 as compared with 1.25 million people with chronic hepatitis B virus infection and 1 million with the human immunodeficiency virus (HIV). In addition, HCV infection is the leading cause of chronic liver disease and the leading indication for liver transplantation in the United States. Some call HCV infection “the silent epidemic,” since 75% of people infected are asymptomatic and chronic manifestations don’t appear for 1 to 2 decades.

In 1998, the Centers for Disease Control and Prevention (CDC) issued guidelines for screening for HCV infection ( Table 1).³ The American College of Obstetricians and Gynecologists (ACOG) advocates screening for HCV infection at the annual exam if the patient belongs to one of the CDC’s routine-screening categories.⁴ Although ACOG has not issued separate screening guidelines for obstetric patients, some practitioners have advocated screening based on risk factors, as listed in the CDC’s routine-screening categories.⁵

HCV accounts for about 20% of acute hepatitis cases in the U.S.

Because Ob/Gyns are increasingly likely to encounter patients with positive HCV blood-screening results, they should be prepared to answer the following inquiries: What is hepatitis C? How is it diagnosed and transmitted? What is the natural history of the infection? Is there a treatment for it? How will HCV infection affect pregnancy?

This review addresses those questions.

What is hepatitis C?

Hepatitis C is a liver disease caused by the HCV, an RNA virus of the Flavivirus family, which includes the dengue and yellow fever viruses. Worldwide, approximately 170 million people are infected with HCV, with a prevalence ranging from a low of 0.15% in Scandinavia to a high of 38% in northern Egypt.^6,7 In the United States, 3.9 million people have been infected with HCV, with an overall prevalence of 1.8%.¹ U.S. prevalence rates by gender and age reveal that more males are infected than females and that, in females, prevalence is highest during the childbearing years, peaking at age 35.

TABLE 1

Recommendations for hepatitis C virus screening

PEOPLE WHO SHOULD BE TESTED ROUTINELY
Persons who have ever injected illegal drugs Persons with selected medical conditions, including: persons who have ever undergone chronic hemodialysis persons with evidence of liver disease, such as persistently abnormal ALT levels Prior recipients of transfusions or organ transplants, including: recipients of clotting factor concentrates produced before 1987 persons who received a transfusion of blood or blood components before July 1992 persons who received an organ transplant before July 1992 persons who were notified that they received clotting factor concentrates, blood components, or organ transplants from a donor who later tested positive for HCV infection Persons with a recognized exposure, including: health-care, emergency medical, and public safety workers after sticks with needles or sharps or mucosal exposure to HCV-positive blood children born to HCV-positive women
PEOPLE FOR WHOM ROUTINE TESTING IS OF UNCERTAIN NEED
Recipients of transplanted tissue, e.g., corneal or musculoskeletal tissue, skin, ova, or sperm Users of intranasal cocaine or other noninjected illegal drugs Persons with a history of tattooing or body piercing Persons with a history of multiple sex partners or sexually transmitted diseases Long-term sex partners of HCV-positive persons
PEOPLE FOR WHOM ROUTINE TESTING IS NOT RECOMMENDED*
Health-care, emergency medical, and public safety workers Pregnant women Nonsexual household contacts of HCV-positive persons The general population
* Except in cases where risk factors are present ALT=alanine aminotransferase; HCV=hepatitis C virus
Source: Centers for Disease Control and Prevention

How is HCV infection diagnosed?

The initial screening test is an enzyme immunoassay (EIA) for the antibody to HCV. Currently, a third-generation EIA is used, with a sensitivity and specificity of 99% in immunocompetent people. If the EIA is positive, the practitioner may proceed to a confirmatory recombinant immunoblot assay (RIBA) in individuals with a low pretest probability, or to direct measurement of HCV RNA by reverse-transcription polymerase chain reaction (PCR) in individuals with a high pretest probability. Figure 1 depicts the HCV testing algorithm recommended by the CDC.

 

FIGURE 1 HCV infection testing algorithm

ALT=alanine aminotransferase; EIA=enzyme immunoassay; PCR=polymerase chain reaction; RIBA=recombinant immunoblast assay Source: Centers for Disease Control and Prevention

How is HCV transmitted?

HCV spreads primarily through blood or fluids containing blood. Injection-drug use accounts for 60% of infections;1 a person who has used injection drugs for 5 years has a 60% to 90% chance of becoming infected with HCV. In fact, among injection-drug users, HCV infection is 4 times more common than HIV infection.8 The transfusion of blood or blood products accounts for another 10% of HCV cases. However, the transfusion-related risk has decreased markedly since the introduction of HCV screening in the blood banks in 1992. Figure 2 shows additional sources of HCV infection.

Although sexual transmission of HCV does occur, the virus is inefficiently spread in this manner. Evidence for this route of transmission has been accumulated from case-control and partner studies. Case-control studies have reported an association between HCV infection and exposure to a sex partner with a history of hepatitis or exposure to multiple sex partners.^9,10 Cross-sectional studies suggest that the probability of HCV infection in the sexual partner of an HCV-positive patient is 0% to 3% in northern Europe or North America. Higher probabilities are found in southern Europe and the Far East.¹¹ One prospective study showed no cases of sexual transmission of HCV from 94 HCV-positive females to their male part-ners.¹² Another prospective study found a low incidence—12 infections per 1,000 per-son-years—among 449 sexual partners of HCV-positive individuals.¹³

Since the risk of spreading HCV through sexual contact is relatively low, individuals in long-term, stable relationships with an infected partner need not change their sexual practices. However, they may choose to use barrier methods to lower the chance of transmission even further. Individuals with high-risk sexual practices, such as having multiple sexual partners, should definitely use barrier methods.

FIGURE 2 Sources of infection for persons with hepatitis C

*Nosocomial, occupational, perinatal

Source: Centers for Disease Control and Prevention

What is the natural history of HCV infection?

HCV accounts for approximately 20% of cases of acute hepatitis in the United States.¹⁴ The incubation period is approximately 6 weeks. Children and adults who acquire the infection usually are asymptomatic or have nonspecific symptoms of fatigue, malaise, anorexia, and weight loss. Some patients may present with jaundice. Serum aminotransferases can fluctuate during acute infection, and normalization occurs in 40% of individuals. However, this normalization does not necessarily represent a clearance of infection. Only 15% of patients clear the virus; the rest develop chronic infection.

Only 15% of patients clear the virus; the rest develop chronic infection.

During chronic infection, most patients are unaware that they are HCV-positive because, as with acute infection, they are asymptomatic or have mild, nonspecific symptoms such as fatigue. Again, serum aminotransferases typically fluctuate and are normal 30% of the time. Clinical progression to cirrhosis occurs in 20% of cases over a span of about 20 years. Once cirrhosis develops, the risk of decompensated cirrhosis or liver failure is about 3% to 4% per year. The annual risk of primary hepatocellular carcinoma in patients with cirrhosis is 1% to 4%. Data suggest that alcohol use is a predictive factor for progressive liver disease and liver cancer. Figure 3 summarizes the natural history of HCV infection.

FIGURE 3 Natural history of HCV infection

Is there a treatment for hepatitis C?

Over the past decade, there have been incremental improvements in hepatitis C therapy. The original mainstay of treatment was interferon alpha, with an initial response rate of 50% and a sustained response rate of only 10% to 15%.^15-17 Later, combination therapy with interferon alpha and ribavirin raised the sustained response rate to 40%.^18,19 However, both these therapies have substantial side effects and require frequent dosing schedules.

In January 2001, a new therapy, pegylated interferon alpha, was introduced. This modified form of traditional interferon alpha has fewer side effects and requires less frequent dosing. In addition, initial studies showed that it had a greater sustained-response rate than traditional interferon alpha alone.²⁰ The Food and Drug Administration (FDA) recently approved it for the treatment of chronic hepatitis not previously treated with standard interferon alpha. A recent trial showed that the combination of pegylated interferon alpha with ribavirin had a sustained virologic response rate of 54%.²¹ None of these medications are approved for use in pregnancy or childhood.

To prevent progressive liver disease, patients chronically infected with HCV should avoid alcohol and other hepatotoxins and get vaccinated against hepatitis A and B. To reduce the risk of transmission to others, they should be advised not to donate blood and tissues; not to share toothbrushes, razors, or other personal-care items that may have blood on them; and to cover cuts and sores on the skin.

 

TABLE 2

Characteristics of hepatitis viral infection in the U.S. population

	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS	HEPATITIS
	A	B	C	D	E
Source/route of transmission	Feces/Fecal-oral	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Blood and blood-derived body fluids/Percutaneous, permucosal	Feces/Fecal-oral
No. of acute infections (per year)	125,000-200,000	140,000-320,000	35,000-180,000	6,000-13,000	Rare in the the United States
No. of chronic infections	0	1-1.25 million	3.5 million	70,000	0
Deaths from chronic liver disease (per year)	0	5,000	8,000-10,000	1,000	NA
Symptoms	Fatigue, nausea, pain near liver or in upper-abdominal area, dark urine, light stools, fever, jaundice	Same as hepatitis A. However, almost 50% of people infected with hepatitis B are asymptomatic.	Same as hepatitis A. However,most people are asymptomatic	Similar to other types of viral hepatitis	Similar to other types of viral hepatitis
Prevention	Good personal hygiene and proper sanitation. Also pre- or postexposure immunization	Pre- or post-exposure immunization	Blood donor screening; risk behavior modification	Pre- or post-exposure immunization	Ensure safe drinking water
Comments	Typically lasts about 3 weeks, but may persist for as long as 6 months	—	Originally defined in the 1970s as non-A non-B hepatitis. Renamed hepatitis C in 1989.	Requires the hepatitis B virus to exist*	Usually associated with fecally contaminated drinking water. U.S. cases usually involve a history of travel to areas with endemic hepatitis E infection
*Hepatitis D infection can be acquired either as a co-infection with the hepatitis B virus or as a superinfection in persons with chronic hepatitis B infection. Persons coinfected with the B and D viruses may have more severe acute disease and a higher risk of fulminant hepatitis (2% to 20%) compared with those infected with hepatitis B alone. However, chronic hepatitis B infection appears to occur less frequently in persons coinfected with the B and D viruses. Chronic hepatitis B carriers who acquire hepatitis D superinfection usually develop chronic hepatitis D infection. In long-term studies of chronic hepatitis B carriers with hepatitis D superinfection, 70% to 80% have developed evidence of chronic liver diseases with cirrhosis compared with 15% to 30% of patients with chronic hepatitis B infection alone.
Source: American Liver Foundation, Centers for Disease Control and Prevention

How will hepatitis C affect my pregnancy?

Perinatal transmission occurs in women with chronic HCV infection at an average rate of 5%.^22-24 Small studies suggest that the level of HCV viremia may affect the risk of viral transmission.^22,25 However, in 2 large studies, no significant difference in HCV viremia levels was found between women who transmitted the virus to their children and women who did not.^23,24 Women co-infected with HIV have 2 to 3 times the rate of HCV transmission compared with women infected only with HCV.^26,27 The natural history of HCV infection in children is not well understood, but 50% to 80% of HCV-positive children develop chronic infection.²⁸

Currently, no intervention is available to decrease perinatal HCV transmission.

Currently, no intervention is available to decrease perinatal HCV transmission, although an unclear association with mode of delivery exists. One study of 441 mother-infant pairs showed that elective cesarean delivery may be associated with a lower transmission risk.²⁹ However, another study of 370 mother-infant pairs found no difference in risk.²⁴

The effect of pregnancy on the progression of hepatitis C infection also is unclear. In studies of HCV-positive pregnant women—as compared to HCV-positive non-pregnant women—researchers reported a decrease in serum alanine aminotransferase (ALT) and an increase in HCV RNA during pregnancy,³⁰ as well as a deterioration of hepatitis C disease after pregnancy, as confirmed by liver biopsy.³¹ In prospective cohort studies comparing infected and uninfected pregnant women, serum aminotrans-ferases flared postpartum in one study³² but remained normal in another.³³

Not much is known regarding the effect of chronic hepatitis C infection on pregnancy outcome, although 1 case-control study reported an association between hepatitis C infection and cholestasis of pregnancy.³⁴

Although HCV RNA has been detected in colostrum,³⁵ studies of breastfed infants with HCV-positive mothers have found no cases of transmission secondary to breastfeeding.^35,36 Thus, both the American Academy of Pediatrics and ACOG conclude that breastfeeding does not appreciably increase the risk of transmission to the neonate and should not be prohibited.^37,38 However, pending further studies, practitioners may choose to advise against breastfeeding if nipples are cracked and bleeding.

 

Conclusion

Chronic HCV infection can lead to serious medical consequences, such as cirrhosis, liver failure, hepatocellular cancer, and death. Unfortunately, 75% of individuals infected with HCV are asymptomatic. By the time symptoms do occur, the disease often is in its advanced stages. Thus, both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups. The early identification of chronic HCV infection is important, as it enables women to take advantage of increasingly effective treatments and alerts them to the need for preconception counseling.

Both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups.

Although perinatal HCV transmission is a known risk, we lack strategies to prevent it. In addition, the effects of pregnancy on the progression of chronic HCV infection, and the effects of chronic HCV infection on pregnancy outcome, are unknown. However, the identification of HCV-positive pregnant women will lead to screening of their infants and earlier identification of infected children.