Chorioamnionitis

Chorioamnionitis, commonly referred to as intraamniotic infection (IAI), is a common obstetric complication involving infection and inflammation of the fetal membranes, amniotic fluid, placenta, or the fetus itself. Chorioamnionitis is typically caused by a polymicrobial infection that ascends from the lower genitourinary tract. Primary risk factors include prolonged rupture of membranes and prolonged labor. Chorioamnionitis is diagnosed by clinical findings, including maternal fever. Chorioamnionitis is managed with antibiotics, and by ensuring continued labor progress (or initiating progress) toward delivery. Chorioamnionitis typically resolves soon after delivery. Significant maternal and fetal complications are possible, warranting prompt diagnosis and treatment.

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Definition and Epidemiology

Definition

Also known as intraamniotic infection (IAI), chorioamnionitis is an infection, and resulting inflammation, of any combination of the fetal membranes (chorion and amnion), amniotic fluid, placenta, umbilical cord (funisitis), and/or the fetus.

Epidemiology

Chorioamnionitis is the most common cause of peripartum infection, with the following incidence rates:

  • Overall incidence: 3.9%
  • All term deliveries: 1%–5%
    • Term pre-labor rupture of membranes (PROM), any length: 7%
    • Term PROM > 24 hours: 40%
  • Preterm deliveries: 40%–70%
  • Extreme preterm deliveries (< 24 weeks gestation): up to 94%

Etiology

Intraamniotic infection and inflammation may be caused by the following mechanisms:

  • Ascending migration of cervicovaginal flora (primary mechanism)
  • Hematogenous spread to intervillous space, associated with maternal bacteremia
  • Direct infection after invasive procedures (e.g., amniocentesis)
  • Descending infection from the peritoneum via fallopian tubes (very rare)

Routes of chorioamnionitis/funisitis:
There are multiple routes of infection attributed to chorioamnionitis. Ascending infection by the cervicovaginal flora is the most common etiology.

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Risk factors:

  • Prolonged rupture of membranes (ROMs) > 18 hours
    • Most significant risk factor
    • In both term and preterm pregnancies
  • Prolonged labor
  • Preterm labor
  • Preterm PROMs (PPROMs)
  • Multiple digital examinations (especially after ROMs)
  • Use of internal uterine fetal monitors
  • Genital-tract pathogens present during labor:
    • Group B streptococcus colonization
    • STIs
  • Primiparous pregnancy
  • Meconium-stained fluid
  • Tobacco use
  • Alcohol use

Pathophysiology

By far, the most common cause of chorioamnionitis is the ascending migration of cervicovaginal flora.

  • Cervicovaginal flora introduced into the amniotic cavity → infection → maternal and fetal inflammation 
  • Can lead to:
    • Labor
    • ROMs
  • Maternal immune response: neutrophilic inflammation of membranes (chorion/amnion)
  • Fetal immune response: neutrophilic inflammation of the umbilical cord
  • Microbiology:
    • Polymicrobial
    • Includes both aerobes and anaerobes (especially in preterm gestation)
    • Most common organisms:
      • Genital mycoplasmas: Ureaplasma and Mycoplasma
      • Gardnerella vaginalis
      • Bacteroides species
      • Enteric gram-negative rods (e.g., Escherichia coli)
      • Group B Streptococcus
      • Listeria monocytogenes (hematogenous spread)
  • Host defense mechanisms: 
    • Cervical mucus plug
    • Intact fetal membranes:
      • Barrier function
      • Antimicrobial activity
      • Modulate immune response
    • Vaginal peroxide-producing lactobacilli → impair virulence of pathogens

Clinical Presentation

The vast majority of presenting women will either be in labor, have ruptured membranes, or both.

Primary manifestations:

  • Fever
  • Uterine fundal tenderness
  • Purulent or foul-smelling fluid from the cervical os
  • Maternal tachycardia (> 100 bpm)
  • Fetal tachycardia (> 160 bpm) 
  • Reduced fetal heart rate variability

Diagnosis

There are 3 categories of IAI:

  • Isolated maternal fever
  • Suspected IAI
  • Confirmed IAI

Isolated maternal fever

  • Fever (oral temperature):
    • > 39 °C (102.2 °F) once
    • 38.0–38.9 °C (100.4–102.2 °F) on 2 occasions, 30 minutes apart
  • Rule out other potential causes of fever: 
    • Urinalysis
    • Other testing based on associated signs and symptoms:
      • Blood cultures
      • Sputum testing
      • Influenza/COVID-19 testing
  • If no other source is found, expert opinion recommends considering patients with a fever > 39 °C (102.2 °F) as suspected IAI.

Suspected intraamniotic infection

Fever, and 1 of the following:

  • Fetal tachycardia: > 160 bpm for ≥ 10 minutes
  • Maternal leukocytosis: WBC > 15,000/mm3
  • Purulent cervical drainage on exam

Confirmed intraamniotic infection

Must meet criteria for “suspected IAI” and exhibit at least 1 of the following:

  • Positive amniotic-fluid test (obtained by amniocentesis):
    • Positive culture: 
      • Gold standard
      • Takes days to obtain results → ↓ clinical utility
    • Positive Gram stain 
    • ↓ Glucose 
    • ↑ WBC 
  • Histopathology (after delivery) showing inflammatory infiltrates in membranes

Management

The goal of management is to minimize the risks of maternal and fetal complications. 

  • Antibiotics:
    • Standard regimen: ampicillin-gentamicin
    • If patient undergoes cesarean delivery, add anaerobic coverage:
      • Clindamycin 
      • Azithromycin (single pre-op dose)
  • Antipyretics:
    • To prevent risk to the fetus associated with ↑ maternal temperature
    • Acetaminophen
  • Progress towards delivery:
    • Think of “delivery” like draining an abscess:
      • Removes infection from the mother
      • Removes baby from the infection
    • Augment labor if it is dysfunctional (common):
      • Oxytocin
      • IAI does not necessitate immediate delivery, but continued progress should be made.
    • In preterm patients:
      • IAI is an indication to initiate induction of labor (IOL).
      • Management is complex: based on gestational age and clinical scenario
  • Continuous fetal monitoring
  • Route of delivery: 
    • Based on routine obstetric indications
    • Vaginal delivery preferred (↓ morbidity/mortality compared to cesarean)
  • Postpartum care:
    • Usually routine care
    • Monitor for wound infection
    • IAI typically resolves quickly after delivery.

Complications

Maternal complications

  • Dysfunctional labor (infected uterus does not contract well)
  • Operative delivery
  • Postpartum hemorrhage (infected uterus does not clamp down well)
  • Maternal sepsis
  • Postpartum endometritis
  • Adult respiratory distress syndrome

Neonatal complications

The earlier the gestational age at delivery, the higher the risk for neonatal complications.

  • Meningitis
  • Intraventricular hemorrhage (IVH)
  • Pneumonia
  • Bronchopulmonary dysplasia
  • Cerebral palsy
  • Sepsis
  • Premature birth (with many of its own associated complications):
    • Respiratory distress syndrome
    • Neurological abnormalities
    • Retinopathy of prematurity (ROP)
    • Necrotizing enterocolitis (NEC)
  • Death

Differential Diagnosis

  • Urinary tract infection (UTI)/pyelonephritis: a common condition in pregnancy with an increased risk of pyelonephritis. Symptoms of pyelonephritis include fever, dysuria, suprapubic or flank pain, costovertebral angle tenderness, nausea, and vomiting. Diagnosis is made based on bacteriuria in the setting of the aforementioned symptoms. Treatment is with antibiotics.
  • Upper respiratory tract infection (URI): a common condition, especially in winter. Symptoms include nasal congestion, rhinorrhea, sore throat, cough, and fever. Patients should be tested for influenza and COVID-19. A chest X-ray is usually required to confirm the diagnosis of pneumonia, although the X-ray can often be delayed until after delivery, except in more severe cases.
  • Acute appendicitis: presents with severe abdominal pain, fever, nausea, and vomiting. The diagnosis may be confirmed with an ultrasound or CT scan (CT scan exposes the fetus to significant radiation and should be used extremely judiciously). Appendicitis rarely presents intrapartum, whereas IAI is rare outside of labor or when membranes are still intact. Management is surgical.
  • Epidural-associated fever: Evidence points to a frequent and significant association between a rise in maternal temperature and neuraxial anesthesia that typically occurs quickly. There are no reliable tests to identify neuraxial anesthesia as the cause of a fever; therefore, close observation and/or presumptive treatment for IAI may be appropriate.
  • Placental abruption: occurs when the placenta begins to separate prematurely, compromising fetal blood flow and oxygenation. Placental abruption typically presents with uterine cramping or pain and vaginal bleeding. Fever is usually not present. Lack of fever, the presence of bleeding, and characteristic findings on fetal monitoring make the diagnosis and help distinguish abruption from IAI. Placental abruption is an obstetrical emergency that requires prompt management, including urgent delivery in most cases.

References

  1. Tita, A.T. N. (2020). Intraamniotic infection (clinical chorioamnionitis or triple I). In Barss, V. A. (Ed.), UpToDate. Retrieved February 19, 2021, from https://www.uptodate.com/contents/intraamniotic-infection-clinical-chorioamnionitis-or-triple-i 
  2. Chen, K.T. (2021). Intrapartum fever. In Barss, V. A. (Ed.), UpToDate. Retrieved February 19, 2021, from https://www.uptodate.com/contents/intrapartum-fever
  3. Committee on Obstetric Practice (2017). Intrapartum management of intraamniotic infection. American College of Obstetrics and Gynecology Committee Opinion No. 712. Retrieved February 19, 2021, from https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2017/08/intrapartum-management-of-intraamniotic-infection 
  4. Bany-Mohammed, F. M. (2018). Chorioamnionitis. In Rosenkrantz, T. (Ed.). Medscape. Retrieved February 20, 2021, from https://emedicine.medscape.com/article/973237-overview 
  5. Tita, A. T., Andrews, W. W. (2010). Diagnosis and management of clinical chorioamnionitis. Clinics in Perinatology, 37(2), 339–354. Retrieved February 20, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008318/; https://doi.org/10.1016/j.clp.2010.02.003 
  6. Fowler J.R., Simon L.V. (2020). Chorioamnionitis. StatPearls. Retrieved February 20, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK532251/ 

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