User login
What should you tell pregnant women about exposure to parvovirus?
TELL PATIENTS that parvovirus infections before 20 weeks’ gestation confer a risk of fetal morbidity and mortality as high as 16%, but don’t significantly increase long-term developmental sequelae (strength of recommendation [SOR]: B, prospective cohort studies).
Parvovirus infection rates are similar in a variety of maternal workplace environments (SOR: A, prospective cohort studies); routinely excluding pregnant women from the workplace is unwarranted (SOR: C, expert opinion).
Physicians should order immunologic assays for women who may have been exposed to parvovirus to assess maternal immunity and determine whether evaluation for fetal hydrops is necessary (SOR: C, expert opinion).
Evidence summary
Although most parvovirus infections in pregnant women don’t harm the fetus, human parvovirus B19 (B19V) may cause severe fetal anemia and cardiac failure, potentially leading to nonimmune fetal hydrops. Transplacental transmission occurs in as many as 33% of cases, with the highest risk of fetal infection occurring between the 9th and 20th weeks of gestation and within 2 to 4 weeks of maternal infection.1,2
A quarter of infections are asymptomatic; the remainder present as a self-limited flu-like syndrome. Infected people may transmit the virus for 5 to 10 days before developing symptoms.1-3
Infection raises risk of death, but not later developmental delay
First- and second-trimester parvovirus infections carry an excess fetal loss risk of 10% above baseline (5%), but a low risk of long-term sequelae during childhood.4 A prospective cohort study of 1018 pregnant German women, confirmed to be immunoglobulin M-positive and followed by targeted ultrasound for 10 weeks, found a 6.3% incidence of fetal death and a 3.9% incidence of hydrops fetalis.3 Fetal death occurred only with B19V infection before 20 weeks’ gestation. Although more cases (67.5%) of fetal hydrops occurred before 20 weeks, cases were seen throughout all gestational periods.
A similar prospective cohort study of 427 pregnant women from England and Wales reported 14% and 1.7% incidences of fetal death and hydrops fetalis, respectively.4 In following up on 182 infants (1 year of age) and 129 children (7-10.5 years of age), investigators found 3 children (2%) with developmental delays in each cohort—consistent with expected numbers for any unselected group of children. They found no congenital abnormalities attributable to B19V infections.
Occupational exposure doesn’t pose significant danger
Few prospective studies have examined prevention of parvovirus infection because of the difficulty of detecting infection during the initial asymptomatic phase. In an effort to determine potential modifiable risk factors, a prospective cohort study of a convenience sample at a referral clinic with no power analysis examined infection rates among 618 pregnant women in various occupations who were exposed to infected children.5
Exposure to children in the household produced the highest risk of infection (29.4% vs 16.7% overall incidence; P<.001). Primary school teachers and daycare workers had an increased risk of infection that didn’t reach statistical significance (23%, P=.5).5 None of the occupations examined (school teacher, daycare worker, office professional, homemaker, and health care worker) demonstrated significantly increased risk (P=.5). Because of the lack of difference in infection rates among studied occupations, the authors recommended against routine workplace exclusion.5 Subsequent Danish population-based cohort studies (N=32,300) found that nursery school teachers had an odds ratio of 3.0 for acute infection, but it was reduced to 1.82 after accounting for infections in their own children.6
The TABLE summarizes current consensus guidelines for initial evaluation, clinical surveillance, and management of pregnant women potentially exposed to B19V.2
TABLE
Managing suspected parvovirus B19 infections in pregnancy: Consensus recommendations
| Antibody results | Status | Clinical follow-up |
|---|---|---|
| IgG-positive, IgM-negative | Immune | Reassurance |
| IgG-negative, IgM-negative | Susceptible | Repeat immunologic assay in 2-4 wk |
| IgG-negative, IgM-positive | Infection in previous 7 days | Refer to MFM for consultation and targeted ultrasound every 4 wk for 12 wk to evaluate for fetal hydrops |
| IgG-positive, IgM-positive | Infection within previous 7-120 days | |
| IgG, immunoglobulin G; IgM, immunoglobulin M; MFM, maternal-fetal-medicine specialist. Adapted from: Goff M. J Midwifery Women’s Health. 2005.2 | ||
Recommendations
The Centers for Disease Control and Prevention and a 2000 practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) don’t recommend routinely excluding pregnant women from the workplace during endemic outbreaks of parvovirus to reduce exposure risk. They do, however, encourage women to discuss their individual risk with their physician.7,8
ACOG and the Society of Obstetricians and Gynaecologists of Canada concur with consensus guidelines for evaluating and managing women suspected of exposure or infection.1,7
1. Crane J. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can. 2002;24:727-734.
2. Goff M. Parvovirus B19 in pregnancy. J Midwifery Women’s Health. 2005;50:536-538.
3. Enders M, Weidner A, Zoellner I, et al. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn. 2004;24:513-518.
4. Miller E, Fairley CK, Cohen BJ, et al. Immediate and long-term outcome of human parvovirus in pregnancy. Br J Obstet Gynaecol. 1998;105:174-178.
5. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
6. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
7. Centers for Disease Control and Prevention. Parvovirus B19 infection and pregnancy. Available at: www.cdc.gov/ncidod/dvrd/revb/respiratory/b19&preg.htm. Accessed August 2, 2010.
8. American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infections. ACOG Practice Bulletin No. 20. September 2000. Available at: www.acog.org/publications/educational_bulletins/pb020.cfm. Accessed August 2, 2010.
TELL PATIENTS that parvovirus infections before 20 weeks’ gestation confer a risk of fetal morbidity and mortality as high as 16%, but don’t significantly increase long-term developmental sequelae (strength of recommendation [SOR]: B, prospective cohort studies).
Parvovirus infection rates are similar in a variety of maternal workplace environments (SOR: A, prospective cohort studies); routinely excluding pregnant women from the workplace is unwarranted (SOR: C, expert opinion).
Physicians should order immunologic assays for women who may have been exposed to parvovirus to assess maternal immunity and determine whether evaluation for fetal hydrops is necessary (SOR: C, expert opinion).
Evidence summary
Although most parvovirus infections in pregnant women don’t harm the fetus, human parvovirus B19 (B19V) may cause severe fetal anemia and cardiac failure, potentially leading to nonimmune fetal hydrops. Transplacental transmission occurs in as many as 33% of cases, with the highest risk of fetal infection occurring between the 9th and 20th weeks of gestation and within 2 to 4 weeks of maternal infection.1,2
A quarter of infections are asymptomatic; the remainder present as a self-limited flu-like syndrome. Infected people may transmit the virus for 5 to 10 days before developing symptoms.1-3
Infection raises risk of death, but not later developmental delay
First- and second-trimester parvovirus infections carry an excess fetal loss risk of 10% above baseline (5%), but a low risk of long-term sequelae during childhood.4 A prospective cohort study of 1018 pregnant German women, confirmed to be immunoglobulin M-positive and followed by targeted ultrasound for 10 weeks, found a 6.3% incidence of fetal death and a 3.9% incidence of hydrops fetalis.3 Fetal death occurred only with B19V infection before 20 weeks’ gestation. Although more cases (67.5%) of fetal hydrops occurred before 20 weeks, cases were seen throughout all gestational periods.
A similar prospective cohort study of 427 pregnant women from England and Wales reported 14% and 1.7% incidences of fetal death and hydrops fetalis, respectively.4 In following up on 182 infants (1 year of age) and 129 children (7-10.5 years of age), investigators found 3 children (2%) with developmental delays in each cohort—consistent with expected numbers for any unselected group of children. They found no congenital abnormalities attributable to B19V infections.
Occupational exposure doesn’t pose significant danger
Few prospective studies have examined prevention of parvovirus infection because of the difficulty of detecting infection during the initial asymptomatic phase. In an effort to determine potential modifiable risk factors, a prospective cohort study of a convenience sample at a referral clinic with no power analysis examined infection rates among 618 pregnant women in various occupations who were exposed to infected children.5
Exposure to children in the household produced the highest risk of infection (29.4% vs 16.7% overall incidence; P<.001). Primary school teachers and daycare workers had an increased risk of infection that didn’t reach statistical significance (23%, P=.5).5 None of the occupations examined (school teacher, daycare worker, office professional, homemaker, and health care worker) demonstrated significantly increased risk (P=.5). Because of the lack of difference in infection rates among studied occupations, the authors recommended against routine workplace exclusion.5 Subsequent Danish population-based cohort studies (N=32,300) found that nursery school teachers had an odds ratio of 3.0 for acute infection, but it was reduced to 1.82 after accounting for infections in their own children.6
The TABLE summarizes current consensus guidelines for initial evaluation, clinical surveillance, and management of pregnant women potentially exposed to B19V.2
TABLE
Managing suspected parvovirus B19 infections in pregnancy: Consensus recommendations
| Antibody results | Status | Clinical follow-up |
|---|---|---|
| IgG-positive, IgM-negative | Immune | Reassurance |
| IgG-negative, IgM-negative | Susceptible | Repeat immunologic assay in 2-4 wk |
| IgG-negative, IgM-positive | Infection in previous 7 days | Refer to MFM for consultation and targeted ultrasound every 4 wk for 12 wk to evaluate for fetal hydrops |
| IgG-positive, IgM-positive | Infection within previous 7-120 days | |
| IgG, immunoglobulin G; IgM, immunoglobulin M; MFM, maternal-fetal-medicine specialist. Adapted from: Goff M. J Midwifery Women’s Health. 2005.2 | ||
Recommendations
The Centers for Disease Control and Prevention and a 2000 practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) don’t recommend routinely excluding pregnant women from the workplace during endemic outbreaks of parvovirus to reduce exposure risk. They do, however, encourage women to discuss their individual risk with their physician.7,8
ACOG and the Society of Obstetricians and Gynaecologists of Canada concur with consensus guidelines for evaluating and managing women suspected of exposure or infection.1,7
TELL PATIENTS that parvovirus infections before 20 weeks’ gestation confer a risk of fetal morbidity and mortality as high as 16%, but don’t significantly increase long-term developmental sequelae (strength of recommendation [SOR]: B, prospective cohort studies).
Parvovirus infection rates are similar in a variety of maternal workplace environments (SOR: A, prospective cohort studies); routinely excluding pregnant women from the workplace is unwarranted (SOR: C, expert opinion).
Physicians should order immunologic assays for women who may have been exposed to parvovirus to assess maternal immunity and determine whether evaluation for fetal hydrops is necessary (SOR: C, expert opinion).
Evidence summary
Although most parvovirus infections in pregnant women don’t harm the fetus, human parvovirus B19 (B19V) may cause severe fetal anemia and cardiac failure, potentially leading to nonimmune fetal hydrops. Transplacental transmission occurs in as many as 33% of cases, with the highest risk of fetal infection occurring between the 9th and 20th weeks of gestation and within 2 to 4 weeks of maternal infection.1,2
A quarter of infections are asymptomatic; the remainder present as a self-limited flu-like syndrome. Infected people may transmit the virus for 5 to 10 days before developing symptoms.1-3
Infection raises risk of death, but not later developmental delay
First- and second-trimester parvovirus infections carry an excess fetal loss risk of 10% above baseline (5%), but a low risk of long-term sequelae during childhood.4 A prospective cohort study of 1018 pregnant German women, confirmed to be immunoglobulin M-positive and followed by targeted ultrasound for 10 weeks, found a 6.3% incidence of fetal death and a 3.9% incidence of hydrops fetalis.3 Fetal death occurred only with B19V infection before 20 weeks’ gestation. Although more cases (67.5%) of fetal hydrops occurred before 20 weeks, cases were seen throughout all gestational periods.
A similar prospective cohort study of 427 pregnant women from England and Wales reported 14% and 1.7% incidences of fetal death and hydrops fetalis, respectively.4 In following up on 182 infants (1 year of age) and 129 children (7-10.5 years of age), investigators found 3 children (2%) with developmental delays in each cohort—consistent with expected numbers for any unselected group of children. They found no congenital abnormalities attributable to B19V infections.
Occupational exposure doesn’t pose significant danger
Few prospective studies have examined prevention of parvovirus infection because of the difficulty of detecting infection during the initial asymptomatic phase. In an effort to determine potential modifiable risk factors, a prospective cohort study of a convenience sample at a referral clinic with no power analysis examined infection rates among 618 pregnant women in various occupations who were exposed to infected children.5
Exposure to children in the household produced the highest risk of infection (29.4% vs 16.7% overall incidence; P<.001). Primary school teachers and daycare workers had an increased risk of infection that didn’t reach statistical significance (23%, P=.5).5 None of the occupations examined (school teacher, daycare worker, office professional, homemaker, and health care worker) demonstrated significantly increased risk (P=.5). Because of the lack of difference in infection rates among studied occupations, the authors recommended against routine workplace exclusion.5 Subsequent Danish population-based cohort studies (N=32,300) found that nursery school teachers had an odds ratio of 3.0 for acute infection, but it was reduced to 1.82 after accounting for infections in their own children.6
The TABLE summarizes current consensus guidelines for initial evaluation, clinical surveillance, and management of pregnant women potentially exposed to B19V.2
TABLE
Managing suspected parvovirus B19 infections in pregnancy: Consensus recommendations
| Antibody results | Status | Clinical follow-up |
|---|---|---|
| IgG-positive, IgM-negative | Immune | Reassurance |
| IgG-negative, IgM-negative | Susceptible | Repeat immunologic assay in 2-4 wk |
| IgG-negative, IgM-positive | Infection in previous 7 days | Refer to MFM for consultation and targeted ultrasound every 4 wk for 12 wk to evaluate for fetal hydrops |
| IgG-positive, IgM-positive | Infection within previous 7-120 days | |
| IgG, immunoglobulin G; IgM, immunoglobulin M; MFM, maternal-fetal-medicine specialist. Adapted from: Goff M. J Midwifery Women’s Health. 2005.2 | ||
Recommendations
The Centers for Disease Control and Prevention and a 2000 practice bulletin from the American College of Obstetricians and Gynecologists (ACOG) don’t recommend routinely excluding pregnant women from the workplace during endemic outbreaks of parvovirus to reduce exposure risk. They do, however, encourage women to discuss their individual risk with their physician.7,8
ACOG and the Society of Obstetricians and Gynaecologists of Canada concur with consensus guidelines for evaluating and managing women suspected of exposure or infection.1,7
1. Crane J. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can. 2002;24:727-734.
2. Goff M. Parvovirus B19 in pregnancy. J Midwifery Women’s Health. 2005;50:536-538.
3. Enders M, Weidner A, Zoellner I, et al. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn. 2004;24:513-518.
4. Miller E, Fairley CK, Cohen BJ, et al. Immediate and long-term outcome of human parvovirus in pregnancy. Br J Obstet Gynaecol. 1998;105:174-178.
5. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
6. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
7. Centers for Disease Control and Prevention. Parvovirus B19 infection and pregnancy. Available at: www.cdc.gov/ncidod/dvrd/revb/respiratory/b19&preg.htm. Accessed August 2, 2010.
8. American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infections. ACOG Practice Bulletin No. 20. September 2000. Available at: www.acog.org/publications/educational_bulletins/pb020.cfm. Accessed August 2, 2010.
1. Crane J. Parvovirus B19 infection in pregnancy. J Obstet Gynaecol Can. 2002;24:727-734.
2. Goff M. Parvovirus B19 in pregnancy. J Midwifery Women’s Health. 2005;50:536-538.
3. Enders M, Weidner A, Zoellner I, et al. Fetal morbidity and mortality after acute human parvovirus B19 infection in pregnancy: prospective evaluation of 1018 cases. Prenat Diagn. 2004;24:513-518.
4. Miller E, Fairley CK, Cohen BJ, et al. Immediate and long-term outcome of human parvovirus in pregnancy. Br J Obstet Gynaecol. 1998;105:174-178.
5. Harger JH, Adler SP, Koch WC, et al. Prospective evaluation of 618 pregnant women exposed to parvovirus B19: risks and symptoms. Obstet Gynecol. 1998;91:413-420.
6. Valeur-Jensen AK, Pedersen CB, Westergaard T, et al. Risk factors for parvovirus B19 infection in pregnancy. JAMA. 1999;281:1099-1105.
7. Centers for Disease Control and Prevention. Parvovirus B19 infection and pregnancy. Available at: www.cdc.gov/ncidod/dvrd/revb/respiratory/b19&preg.htm. Accessed August 2, 2010.
8. American College of Obstetricians and Gynecologists. Perinatal viral and parasitic infections. ACOG Practice Bulletin No. 20. September 2000. Available at: www.acog.org/publications/educational_bulletins/pb020.cfm. Accessed August 2, 2010.
Evidence-based answers from the Family Physicians Inquiries Network
What treatment approach to intrapartum maternal fever has the best fetal outcomes?
A combination of beta-lactam and aminoglycoside antibiotics are the recommended empiric agents for the treatment of acute chorioamnionitis, given that no head-to-head trials exist (strength of recommendation [SOR]: C, based on expert opinion). Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia (SOR: C, based on patient-oriented, underpowered randomized trials).
Carefully follow laboring patients with fever for other signs of chorioamnionitis
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
The data on the best antibiotic treatment of clinical chorioamnionitis remains as slim as ever, it appears. But since experts continue to recommend potentially toxic gentamicin as part of therapy, you should carefully monitor laboring patients at term who develop a fever for the development of other diagnostic signs of chorioamnionitis. While maternal and fetal tachycardia are frequently caused by conditions other than infection, their appearance in a febrile gravida should prompt full chorioamnionitis therapy (even in patients already on empiric antibiotics for group B streptococci). With epidural anesthesia, uterine tenderness is an unreliable sign of infection. Purulent amniotic fluid is a late sign and rarely contributes clinically.
Evidence summary
Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;1 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.1,2
Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.
Intrapartum antibiotics probably reduce sepsis
Although few well-designed trials stand out, a Cochrane review4 summarizing 2 relevant studies is available. Gibbs et al3 performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.3 Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.
Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.4
The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).1 There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).4
Recommendations from others
A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics5 recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).6 Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.
Acknowledgments
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
1. Maberry MC, Gilstrap LC, 3rd. Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate. Clin Obstet Gyn 1991;34:345-351.
2. Hauth JC, Gilstrap LC, Hankins GD, Conner KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gyn 1985;66:59-62.
3. Gibbs RS, Dinsmoor MJ, Newton ER, et al. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gyn 1988;72:823-828.
4. Hopkins L, Smaill F. Antibiotic regimens for management of intraamniotic infection. Cochrane Database Syst Rev 2002;(3):CD003254.-
5. American College of Obstetricians and Gynecologists, American Academy of Pediatrics. Guidelines for Perinatal Care. 5th ed. Washington, DC: ACOG;2002:165-166.
6. Hayman R, Kean L. Guidelines for the Prevention of Neonatal Group B Streptococcal Infection. Nottingham: Nottingham City Hospital, National Health Service; 2002. Revised 2005. Available at: www.nuh.nhs.uk/nch/antibiotics. Accessed on March 30, 2007.
A combination of beta-lactam and aminoglycoside antibiotics are the recommended empiric agents for the treatment of acute chorioamnionitis, given that no head-to-head trials exist (strength of recommendation [SOR]: C, based on expert opinion). Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia (SOR: C, based on patient-oriented, underpowered randomized trials).
Carefully follow laboring patients with fever for other signs of chorioamnionitis
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
The data on the best antibiotic treatment of clinical chorioamnionitis remains as slim as ever, it appears. But since experts continue to recommend potentially toxic gentamicin as part of therapy, you should carefully monitor laboring patients at term who develop a fever for the development of other diagnostic signs of chorioamnionitis. While maternal and fetal tachycardia are frequently caused by conditions other than infection, their appearance in a febrile gravida should prompt full chorioamnionitis therapy (even in patients already on empiric antibiotics for group B streptococci). With epidural anesthesia, uterine tenderness is an unreliable sign of infection. Purulent amniotic fluid is a late sign and rarely contributes clinically.
Evidence summary
Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;1 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.1,2
Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.
Intrapartum antibiotics probably reduce sepsis
Although few well-designed trials stand out, a Cochrane review4 summarizing 2 relevant studies is available. Gibbs et al3 performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.3 Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.
Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.4
The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).1 There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).4
Recommendations from others
A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics5 recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).6 Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.
Acknowledgments
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
A combination of beta-lactam and aminoglycoside antibiotics are the recommended empiric agents for the treatment of acute chorioamnionitis, given that no head-to-head trials exist (strength of recommendation [SOR]: C, based on expert opinion). Intrapartum antibiotic treatment is not superior to postpartum antibiotics for reducing neonatal sepsis and pneumonia (SOR: C, based on patient-oriented, underpowered randomized trials).
Carefully follow laboring patients with fever for other signs of chorioamnionitis
Jon O. Neher, MD
Valley Family Medicine, Renton, Wash
The data on the best antibiotic treatment of clinical chorioamnionitis remains as slim as ever, it appears. But since experts continue to recommend potentially toxic gentamicin as part of therapy, you should carefully monitor laboring patients at term who develop a fever for the development of other diagnostic signs of chorioamnionitis. While maternal and fetal tachycardia are frequently caused by conditions other than infection, their appearance in a febrile gravida should prompt full chorioamnionitis therapy (even in patients already on empiric antibiotics for group B streptococci). With epidural anesthesia, uterine tenderness is an unreliable sign of infection. Purulent amniotic fluid is a late sign and rarely contributes clinically.
Evidence summary
Acute chorioamnionitis (or intra-amniotic infection) poses a high risk of maternal and neonatal morbidity. Neonatal sepsis or pneumonia occurs in up to 24% of infants born to mothers with chorioamnionitis;1 1% to 2% of pregnancies complicated by chorioamnionitis end in neonatal death.1,2
Acute chorioamnionitis is defined as intrapartum maternal fever and maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent amniotic fluid.1,3 Antibiotic treatment of acute chorioamnionitis is widely accepted, yet in vivo studies to determine the most effective empiric antibiotic regimens are lacking.
Intrapartum antibiotics probably reduce sepsis
Although few well-designed trials stand out, a Cochrane review4 summarizing 2 relevant studies is available. Gibbs et al3 performed an underpowered, randomized comparative trial of intrapartum vs postpartum treatment of chorioamnionitis, with both groups (45 patients total) receiving ampicillin 2 g IV every 6 hours plus gentamicin 1.5 mg/kg IV every 8 hours.3 Those women who underwent cesarean section also received clindamycin 900 mg IV every 8 hours starting at cord clamping. In this study, investigators reported neonatal sepsis was significantly reduced with intrapartum treatment (0 vs 21%; P=.03, number needed to treat=4.8), as were neonatal hospital stays (3.8 vs 5.7 days; P=.02), regardless of delivery method. The study had been planned for 92 patients; it was stopped early (n=48) after an interim analysis.
Because of the small sample size, other findings from the study must be viewed with caution. Intrapartum treatment with antibiotics was associated with a “significant” clinical reduction in neonatal sepsis (relative risk [RR]=0.08; 95% confidence interval [CI], 0.00–1.44) and pneumonia (RR=0.15; 95% CI, 0.01–2.92) compared with treatment given immediately postpartum; however, neither value was truly statistically significant according to the Cochrane review.4
The research suggests a potential benefit to adding clindamycin to ampicillin and gentamicin. In an effort to test this, 1 study randomized 133 women into 2 arms—treatment with ampicillin, gentamicin, and clindamycin compared with ampicillin and gentamicin alone—and found no additional benefit in regards to neonatal sepsis (RR=2.16; 95% CI, 0.20–23.21) or neonatal death (RR=0.72; 95% CI, 0.12–4.16).1 There was a trend towards a decrease in the incidence of postpartum endometritis in women who received ampicillin, gentamicin, and clindamycin, but this did not reach statistical significance (RR=0.54; 95% CI, 0.19–1.49).4
Recommendations from others
A 2002 bulletin from American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics5 recommended the combination of ampicillin 2 gm IV every 4 to 6 hours or penicillin 5 million units IV every 4 to 6 hours, plus an aminoglycoside (such as gentamicin 1.5 mg/kg IV every 8 hours), since this regimen provides appropriate coverage for typical organisms associated with acute chorioamnionitis. At the time the bulletin was published, the use of single daily dosing of aminoglycoside did not have sufficient studies to back its use. In addition, ACOG recommends adding clindamycin, metronidazole, or an extended-spectrum third-generation cephalosporin to the treatment regimen if cesarean section is required, to provide coverage for anaerobic organisms. They recommend clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. The Nottingham Guideline Development Group recommends amoxicillin 2 gm IV initially then 1 gm every 8 hours, and in place of gentamicin, recommends metronidazole 500 mg IV, every 8 hours (or 1 gm PR twice a day).6 Both recommendations suggest clindamycin 900 mg IV every 8 hours to replace amoxicillin in penicillin-allergic patients. For patients with nonanaphylactic reactions to penicillin, they recommend cefotaxime 1 g IV every 8 hours.
Acknowledgments
The opinions and assertions contained herein are the private views of the author and not to be construed as official, or as reflecting the views of the US Air Force Medical Service or the US Air Force at large.
1. Maberry MC, Gilstrap LC, 3rd. Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate. Clin Obstet Gyn 1991;34:345-351.
2. Hauth JC, Gilstrap LC, Hankins GD, Conner KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gyn 1985;66:59-62.
3. Gibbs RS, Dinsmoor MJ, Newton ER, et al. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gyn 1988;72:823-828.
4. Hopkins L, Smaill F. Antibiotic regimens for management of intraamniotic infection. Cochrane Database Syst Rev 2002;(3):CD003254.-
5. American College of Obstetricians and Gynecologists, American Academy of Pediatrics. Guidelines for Perinatal Care. 5th ed. Washington, DC: ACOG;2002:165-166.
6. Hayman R, Kean L. Guidelines for the Prevention of Neonatal Group B Streptococcal Infection. Nottingham: Nottingham City Hospital, National Health Service; 2002. Revised 2005. Available at: www.nuh.nhs.uk/nch/antibiotics. Accessed on March 30, 2007.
1. Maberry MC, Gilstrap LC, 3rd. Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate. Clin Obstet Gyn 1991;34:345-351.
2. Hauth JC, Gilstrap LC, Hankins GD, Conner KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gyn 1985;66:59-62.
3. Gibbs RS, Dinsmoor MJ, Newton ER, et al. A randomized trial of intrapartum versus immediate postpartum treatment of women with intra-amniotic infection. Obstet Gyn 1988;72:823-828.
4. Hopkins L, Smaill F. Antibiotic regimens for management of intraamniotic infection. Cochrane Database Syst Rev 2002;(3):CD003254.-
5. American College of Obstetricians and Gynecologists, American Academy of Pediatrics. Guidelines for Perinatal Care. 5th ed. Washington, DC: ACOG;2002:165-166.
6. Hayman R, Kean L. Guidelines for the Prevention of Neonatal Group B Streptococcal Infection. Nottingham: Nottingham City Hospital, National Health Service; 2002. Revised 2005. Available at: www.nuh.nhs.uk/nch/antibiotics. Accessed on March 30, 2007.
Evidence-based answers from the Family Physicians Inquiries Network