Intra-amniotic infection

Intra-amniotic infection, also called chorioamnionitis, is confirmed infection and inflammation of intrauterine structures of pregnancy (e.g., fetus, placenta, amniotic fluid). Intra-amniotic infection most commonly occurs during labor due to ascending vaginal flora. Intra-amniotic infection is presumptively diagnosed based on maternal and fetal signs and symptoms (i.e., maternal fever, fetal tachycardia, prurulent cervical discharge) and presence of maternal leukocytosis; confirmatory diagnostic studies (e.g., amniotic fluid studies, placental pathology) are typically not available until after delivery. Management includes immediate empiric antibiotic therapy for intra-amniotic infection and delivery of the fetus. Serious complications include sepsis, postpartum hemorrhage, and intrauterine fetal demise.

• Intra-amniotic infection (chorioamnionitis) ^[1][2]
  • Confirmed microbial invasion of the amniotic cavity causing infection and inflammation of the fetus, amniotic fluid, fetal membranes, placenta, and/or endometrial decidua
  • Usually only diagnosed after delivery, from studies performed on amniotic fluid or placenta
• Clinical chorioamnionitis: a clinical syndrome comprising maternal fever and signs of maternal and/or fetal inflammation, usually caused by intra-amniotic infection or, less commonly, sterile intra-amniotic inflammation ^[2]

Although intra-amniotic infection and clinical chorioamnionitis are distinct entities, they cannot usually be distinguished from one another before delivery. ^[2]

• Affects 1–6% of pregnancies at term ^[2]
• Most frequently occurs intrapartum or in patients with prelabor rupture of membranes (PROM) ^[1][2][3]

Epidemiological data refers to the US, unless otherwise specified.

Route of spread ^[1][2]

• Most common: ascending vaginal flora, particularly during labor ^[4]
• Rarely
  • After invasive prenatal diagnostic testing or fetal procedures
  • Through hematogenous spread via the placenta (e.g., Listeria monocytogenes)

Risk factors ^[1]

• Prolonged labor and/or PROM ^[2]
• Repeated digital cervical examinations
• Use of internal intrapartum monitoring (e.g., fetal scalp monitor)
• Maternal colonization with group B Streptococcus or STIs
• Presence of meconium
• Low parity
• History of intra-amniotic infection ^[2]

Common organisms ^[1][2]

Polymicrobial infection with aerobic and anaerobic bacteria is most common.

• Ureaplasma urealyticum (> 60% of infections) ^[2]
• Mycoplasma hominis
• Bacteroides spp.
• E. coli
• Group B Streptococcus
• Gardnerella vaginalis
• Staphylococcus aureus
• Listeria monocytogenes
• Species commonly found in the oral microbiota (e.g., Porphyromonas spp., Fusobacterium spp., Streptococcus oralis)
• Candida spp.

The following features indicate clinical chorioamnionitis. ^[1][2][5]

• Fever
• Tachycardia
• Uterine tenderness
• Malodorous amniotic fluid
• Purulent cervical discharge
• Fetal tachycardia
• Maternal or neonatal complications of intra-amniotic infection

Fever is not always present in intra-amniotic infection. ^[5]

• Other causes of clinical chorioamnionitis, e.g.: ^[2]
  • Sterile intra-amniotic inflammation
  • Systemic maternal inflammation (e.g., from epidural anesthesia)
• Sepsis from nonobstetric causes (e.g., UTI)

The differential diagnoses listed here are not exhaustive.

Approach

• Check CBC to evaluate for leukocytosis. ^[1][2]
• Start immediate treatment if the criteria for suspected intra-amniotic infection are met.
  • Start empiric antibiotics for intra-amniotic infection.
  • Treat sepsis if present.
  • Give antipyretics.
• Consult with specialists.
  • Consult obstetrics and/or maternal-fetal medicine for pregnant patients. ^[1][5]
    • Manage as high-risk pregnancy.
    • Delivery is required to resolve the infection; begin augmentation of labor if protracted. ^[1][5]
  • Consult pediatrics for neonatal management; see also: ^[1]
    • "Approach to suspected neonatal bacterial infection"
    • "Neonatal risk assessment for early-onset GBS infection"
• Obtain confirmatory diagnostic studies for intra-amniotic infection.

The route of delivery is determined by standard indications; infection alone is not typically an indication for cesarean delivery. ^[1]

Intra-amniotic infection before the third trimester is uncommon. Consult a specialist, as management is based on gestation and pathogen. ^[1][6]

Criteria for suspected intra-amnitoic infection ^[1][2][5]

• Maternal temperature 38.0–38.9°C and ≥ 1 of the following:
  • Maternal leukocytosis > 15,000 cells/μL
  • Purulent cervical drainage
  • Fetal tachycardia > 160 beats/minute
• OR isolated maternal temperature ≥ 39.0 °C ^[1]
• OR clinical features of intra-amniotic infection in the absence of maternal fever ^[5]

Empiric antibiotic therapy for intra-amniotic infection ^[1][7]

• First-line therapy
  • Ampicillin (off-label) ^[1]
  • PLUS gentamicin (off-label) ^[1]
  • Following cesarean delivery
    • At least one additional dose of ampicillin and gentamicin
    • PLUS clindamycin OR metronidazole (off-label)
• Nonsevere penicillin allergy^[1]
  • Cefazolin (off-label) ^[1]
  • PLUS gentamicin (off-label)
• Severe penicillin allergy ^[1]
  • Clindamycin OR vancomycin (off-label) ^[1]
  • PLUS gentamicin (off-label)

After cesarean delivery, one additional dose of the antibiotic regimen is recommended; after vaginal delivery, discontinue antibiotics unless there is evidence of ongoing infection. ^[1]

Confirmatory diagnostic studies for intra-amniotic infection

The following results, combined with clinical features of infection, confirm the diagnosis; however, results are typically unavailable until after delivery.

• Analysis of amniotic fluid: Obtain via amniocentesis or transcervical amniotic fluid collector. ; ^[1][2]
  • Gram stain and culture showing bacteria
  • White cells: ≥ 50 cells/mm³
  • Glucose: < 1–4 mg/dL at term ^[2]
  • If available, consider the following: ^[2]
    • IL–6 and IL–8: elevated
    • Matrix metalloproteinase-8 (MMP–8): > 23 ng/mL
    • Molecular diagnostics (e.g., PCR)
• Placental histopathology consistent with infection and/or inflammation ^[1][2]

If there are no signs of infection on confirmatory diagnostic studies, consider differential diagnoses for intra-amniotic infection.

Maternal ^[1][2]

• Protracted labor leading to interventions
• Postpartum uterine atony, hemorrhage
• Additional infections (e.g., endometritis, peritonitis, wound infection)
• Complications of severe infection, e.g.:
  • Sepsis in pregnancy and postpartum ^[7]
  • Disseminated intravascular coagulation ^[7]
  • Acute respiratory distress syndrome
  • Hypercoagulable state (e.g., thromboembolic disease, septic pelvic thrombophlebitis)
  • Death

Neonatal ^[2]

• Infection and/or sepsis ^[1]
• Asphyxia, intraventricular hemorrhage, cerebral palsy ^[1][8][9]
• Premature birth ^[10]
• Meconium aspiration syndrome
• Encephalopathy
• Bronchopulmonary dysplasia ^[1]
• Fetal death ^[1]

We list the most important complications. The selection is not exhaustive.

• Reduce the risk of group B Streptococcus infection with the following:
  • Prenatal group B streptococcus screening ^[11]
  • Prevention of neonatal group B streptococcal infections ^[11]˚
• Screen for sexually transmitted infections in pregnancy. ^[12]
  • First trimester
    • All patients: Screen for syphilis and HIV.
    • Patients with risk factors for STIs : Perform prenatal gonorrhea screening and prenatal syphilis screening.
  • Third trimester: Perform third-trimester screening for STIs in patients with risk factors for STIs.