‘Chorioamnionitis or Triple I’ – How Valid is the NICHD Guideline for the Diagnosis of Intrauterine Infection?

BACKGROUND AND PURPOSE:

• In 2015, NICHD recommended
  • Replace ‘chorioamnionitis’ with ‘Triple I’
    • Intrauterine Inflammation or Infection or both
    • Antibiotics given only for those meeting ‘Triple I’ criteria
    • Isolated fever would not necessarily be treated
  • Samsiya et al. (Obstetrics & Gynecology, 2019) sought to assess the diagnostic validity of the ‘Triple I’ approach for the intrauterine infection
    • Authors additionally measured rates of adverse outcomes in a cohort of febrile intrapartum women

METHODS:

• Retrospective cohort study
• Women included with the following
  • ≥24 weeks gestation
  • Temperature ≥100.4°F (38.0°C) during labor or within 1 hour postpartum
  • Available blood culture data
• Fever defined as
  • Single temperature ≥102.2°F (39.0°C) or
  • ≥100.4°F (38.0°C) but <102.2°F (39.0°C) on two measurements 45 minutes apart
• Two analysis groups were defined
  • Suspected triple I
    • Documented fever with clinical signs of infection
  • Isolated maternal fever
    • At least one temperature ≥100.4°F (38.0°C) in women who did not meet criteria for suspected triple I
  • NICHD test characteristics ability to predict suspected triple I was assessed
    • Confirmed triple I: Suspected triple I with placental pathology confirmation
  • Adverse clinical infectious outcome
    • Composite of maternal and neonatal adverse infectious outcomes

RESULTS:

• 339 women
  • 212 with suspected triple I | 127 with isolated maternal fever
• Incidence of adverse clinical infectious outcomes (P=.50)
  • Women with suspected triple I: 11.8%
  • Women with isolated maternal fever: 9.5%
• Performance characteristics of suspected triple I for confirmed triple I
  • Sensitivity: of 71.4% (95% CI 61.4–80.1%)
  • Specificity: 40.5% (95% CI 33.6–47.8%)
• Performance characteristics for predicting adverse clinical infectious outcomes
  • Sensitivity: 67.6% (95% CI 50.2–82.0%)
  • Specificity: 38.1% (95% CI 32.6–43.8%)

CONCLUSION:

• NICHD criteria may miss a significant proportion of laboring febrile women at risk for adverse infectious outcomes
• NICHD guideline had low sensitivity and specificity
• Women with isolated fever were at risk for adverse infectious outcomes
• The authors state

Following the publication of the triple I criteria, the American College of Obstetricians and Gynecologists issued a statement recommending consideration of treatment of women who fall under the umbrella of isolated maternal fever as defined by the NICHD, and our study supports this recommendation

Learn More – Primary Sources:

Diagnostic Validity of the Proposed Eunice Kennedy Shriver National Institute of Child Health and Human Development Criteria for Intrauterine Inflammation or Infection

Chorioamnionitis: ACOG Committee Opinion on Diagnosis and Management

CLINICAL ACTIONS:

The NICHD conducted a workshop in January 2015 to review evidence, with special consideration to avoid unnecessary treatment with antimicrobials and imprecise terminology. ACOG released a committee opinion, endorsed by SMFM, that agrees with 3 categories proposed by the workshop but differs regarding a single temperature of 39.0˚C.  While the workshop included this finding under ‘isolated maternal fever’, ACOG recommends that a single temperature of 39.0˚C be placed in the ‘suspected intraamniotic infection’ category to maximize sensitivity.

Categories

• Isolated maternal fever
  • Between 38.0˚C and 38.9˚C
  • With or without persistent temperature elavation
  • no other clinical criteria indicating intraamniotic infection
• Suspected intraamniotic infection
  • Fever of 39.0˚C or greater on any one occasion
  • Fever between 38.0˚C and 38.9˚C and at least one of the following clinical findings
    • Fetal tachycardia
    • Maternal leukocytosis
    • Definite purulent fluid from the cervical os
• Confirmed intraamniotic infection
  • Amniocentesis-proven infection through
    • Positive Gram stain, low glucose or positive amniotic fluid (AF) culture
  • Placental pathology revealing infection and/or inflammation of placenta, fetal membranes or cord (funisitis)

SYNOPSIS:

Intrauterine infection can have serious complications and include sepsis, prolonged labor, PPH, hysterectomy, endometritis, ICU admission and rarely maternal mortality. Communication with neonatology team is essential. The workshop determined that research is needed in almost all aspects, including biomarkers in AF and maternal and cord blood to aid in diagnosis and treatment.

KEY POINTS:

Overall Management

• Intraamniotic infection alone is rarely if ever a reason for immediate cesarean section
  • However, progress of labor should be monitored
  • Augmentation of protracted labor “appears prudent”
  • Base route of delivery on standard obstetric indications
• Antibiotics and antipyretics should be administered for suspected or confirmed intraamniotic infection
• Isolated maternal fever may be caused by epidural anesthesia, prostaglandin use, dehydration, hyperthyroidism or excess ambient heat
  • Antibiotics should be considered unless a secondary cause is apparent
  • Monitor closely for additional signs and/or symptoms of infection
• Postcesarean delivery: One additional dose of chosen antibiotic regimen is indicated
  • Recommended antibiotics: One additional dose is indicated
    • Add clindamycin 900 mg IV or metronidazole 500 mg IV for at least one additional dose
  • Alternative antibiotic regimen: One additional dose is indicated
    • Additional clindamycin is not required
• Postvaginal delivery: No additional doses required
  • If given, additional clindamycin is not required
• Consider other risk factors for postpartum endometritis such as bacteremia or persistent fever when deciding whether to continue antibiotics post delivery
  • Women who delivery vaginally are at a lower risk for endometritis
• Use vancomycin if the patient is colonized with group B strep that is resistant to clindamycin or erythromycin or if colonized and antibiotic sensitivities are unavailable

Recommended Antibiotics

Recommended

• Ampicillin 2 g IV q6hr

and

• Gentamicin
  • 2 mg/kg IV load followed by 1.5 mg/kg q8hr or
  • 5 mg/kg IV q24hr

Mild Penicillin Allergy

• Cefazolin 2 g IV q8hr

and

• Gentamicin
  • 2 mg/kg IV load followed by 1.5 mg/kg q8hr or
  • 5 mg/kg IV q24hr

Severe Penicillin Allergy

• Clindamycin 900 mg IV q8hr or Vancomycin 1 g IV q12 hours

and

• Gentamicin
  • 2 mg/kg IV load followed by 1.5 mg/kg q8hr or
  • 5 mg/kg IV q24hr

Alternative Regimens

• Ampicillin-sulbactam 3 g IV q6hr
• Piperacillin-tazobactam 3.375 g IV q6hr or 4.5 g IV q8hr
• Cefotetan 2 g IV q12hr
• Cefoxitin 2 g IV q8hr
• Ertapenem 1 g IV q24hr

Learn More – Primary Sources:

ACOG Committee Opinion 712: Intrapartum Management of Intraamniotic Infection

Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop

Current Management and Long-term Outcomes Following Chorioamnionitis

Maternal fever in labor: etiologies, consequences, and clinical management