Obstetrics and Gynecology
- Amnionitis, amniotic fluid infection, intra-amniotic infection (IAI), intrapartum infection. For the purpose of this review, we will use the abbreviation IAI.
- 1. What every clinician should know
- 2. Diagnosis and differential diagnosis
- 3. Management
6. What is the evidence for specific management and treatment recommendations
Amnionitis, amniotic fluid infection, intra-amniotic infection (IAI), intrapartum infection. For the purpose of this review, we will use the abbreviation IAI.
1. What every clinician should know
Clinical features and incidence
Early-onset neonatal infections often originate in utero. Intrauterine exposure to bacteria may be the cause of important neonatal adverse outcomes, including cerebral palsy and respiratory distress syndrome. Correctly diagnosing and treating chorioamnionitis (i.e. intra-amniotic infection, or IAI) should result in improved neonatal outcomes.
Clinically evident IAI during the latter half of pregnancy develops in 1-10% of pregnant women. Older studies report rates in the 1-2% range, while newer studies report rates in the range of 4-10%. Because of numerous terms to describe IAI and differences in definitions it is difficult to obtain true incidence of this illness. For instance, histologic IAI is diagnosed following pathologic review of the placenta far more frequently than clinical IAI; this diagnosis is made in 20% of term deliveries and in more than 50% of preterm deliveries. IAI following preterm premature rupture of membranes has been reported in 40% of women admitted with contractions.
Most cases of IAI occur at term, and risk factors are mainly those of complicated or prolonged labor. Risk factors include:
Prolonged duration of labor, including longer length of membrane rupture.
Larger number of vaginal examinations, especially with ruptured membranes.
Duration of internal fetal monitoring.
The most important modifiable risk factors are number of digital examinations and length of labor. Active management of labor with early recognition of labor abnormalities and subsequent intervention, such as oxytocin augmentation, results in lower rates of IAI.
The amniotic cavity is nearly always sterile prior to labor and rupture of membranes. Intact placental membranes and cervical mucus usually are effective in preventing entry of bacteria. With onset of labor or rupture of membranes, bacteria from the lower genital tract, including the vagina and cervix, commonly ascend into the amniotic cavity. This ascending route is the most common pathway for developing IAI.
IAI in the absence of labor or rupture of membranes supports a presumed hematogenous or transplacental route of infection, as is seen with the bacteria Listeria monocytogenes. Group A streptococci (GAS), another virulent organism, also leads to a blood-borne infection. Both listeria and GAS may lead to significant maternal and fetal morbidity and occasionally mortality.
Rarely, IAI may occur as a complication of invasive diagnostic procedures, such as amniocentesis (rarely), intrauterine transfusion, chorionic villus sampling, percutaneous umbilical blood sampling and fetal shunting procedures.
The cause of IAI is often polymicrobial, involving both aerobic and anaerobic organisms. In 50% of patients with microbial invasion, more than one organism is isolated from the amniotic cavity. The following organisms are the most frequently organisms grown from culture of amniotic fluid:
Ureaplasma urealyticum 47-50%
Mycoplasma hominis 31-35%
Prevotella bivia 11-29%
Fusobacterium species 6-7%
Group Bstreptococci 12-19%
Escherichia coli 33%
Other aerobic gram-negative rods 5-10%
Gardnerella vaginalis 24%
Low-virulence organisms such as lactobacilli, diptheroids and Staphylococcus epidermidisare isolated in similar numbers from women with IAI and controls (uninfected women in labor), and are not thought to be diagnostic for infection. If these organisms are isolated from the amniotic fluid, such as when a woman with preterm labor has an amniocentesis to rule out IAI, do not treat the patient as though she has IAI and search for other clues to aid in the proper diagnosis to explain her symptoms.
Bacterial vaginosis (BV) is causally linked to IAI, but studies have shown that treatment of BV with antibiotics do not reduce the incidence of IAI.
2. Diagnosis and differential diagnosis
Clinical signs and symptoms consistent with IAI include fever, maternal or fetal tachycardia, uterine tenderness, foul odor of the amniotic fluid or from cervical os and leukocytosis. However, it is important to consider other diagnoses when these signs or symptoms are present. For instance, fever in the parturient may be caused by a urinary tract infection, viral illness or infection of another organ. Similarly, fetal tachycardia might be a consequence or prematurity, medications, arrhythmia, and perhaps hypoxia, while maternal tachycardia might be secondary to drugs, hypotension, dehydration or anxiety. These most common signs and symptoms have been reported in the following frequencies:
Maternal fever 85-99%
Fetal tachycardia 37-82%
Maternal tachycardia 19-37%
Uterine tenderness 13-16%
Foul amniotic fluid 9-22%
Some authors advocate that maternal fever greater than 38 degrees C (100.4 F) and two additional criteria (from the above list) are necessary for the diagnosis of IAI. Given the variable frequencies of these signs and symptoms, including the fact that maternal fever is not present in all cases, we rely on clinical suspicion with exclusion of other possible etiologies that might explain the clinical scenario we are encountering.
There is not a single test that reliably predicts the diagnosis of IAI. The clinical criteria that are available are neither specific nor sensitive, requiring a high index of suspicion when making this diagnosis. Laboratory criteria that are used in other clinical situations to diagnose infection, such as positive stains for organisms or leukocytes, are found more frequently than clinically evident infection. The best, most predictive test for IAI is a positive amniotic fluid culture. Since it may take days to receive a culture result, it is not reasonable to await such a result prior to making clinical decisions.
Similar to clinical criteria for the diagnosis of IAI, laboratory criteria aid in the diagnosis; however, there is no single test that has both high sensitivity and specificity for IAI.
Maternal blood draw
Maternal leukocytosis (peripheral white blood cell count greater than 15,000/mm3) supports the clinical diagnosis of IAI. This value exceeds the 80th percentile for normal leukocytosis in pregnancy. The presence of a left shift (i.e. an increase in the proportion of neutrophils, especially immature forms) further supports the diagnosis. Other etiologies for high maternal WBC counts include labor and recent administration of antenatal corticosteroids. Following steroid administration, leukocytosis occurs due to demargination of mature neutrophils and may exceed the 15,000/mm3 level seen with true IAI.
Amniotic fluid evaluation
Direct examination of the amniotic fluid may provide important diagnostic information. Transabdominal amniocentesis is the most common technique for obtaining amniotic fluid. Other methods for obtaining amniotic fluid include transvaginal collection by aspiration through an intrauterine pressure catheter or by needle aspiration of the forewaters, though both of these methods are usually utilized in research protocols only. Once amniotic fluid is collected, we recommend ordering the following studies:
Glucose concentration. Most specific rapid test for predicting a positive amniotic fluid culture. A value of 5 mg/dL or less has a positive predictive value of 90% and a value of 20 mg/dL or more has a negative predictive value of 98%. With intermediate values (14-15 mg/dL), the likelihood of a positive amniotic fluid culture is 30-50%. At the extremes of values (very low or very high), this test alone is quite useful for predicting IAI, while in the equivocal zone (6-19 mg/dL), this result in combination with other diagnostic tests and/or the clinical picture will lead one to make the proper diagnosis.
Gram stain. The presence of any bacteria and leukocytes is suspicious for infection.
Cell count. White blood cells are suspicious for IAI. Often, the cell count result will display total number of cells and percent epithelial cells. To calculate WBC count, subtract % epithelial cells from 100% to calculate %WBC, then multiple this % times total cells.
Culture, including Mycoplasma and Ureaplasma. The gold standard for diagnosing IAI is a positive amniotic fluid culture, though not practical for use in acute clinical situations due to the time involved in awaiting the results. This information is useful to confirm the diagnosis and aid in the care of the newborn.
Interleukin-6. This immunostimulatory cytokine and key mediator of fetal host response to infection is a more sensitive and specific test than is amniotic fluid glucose and gram stain; however, it is not typically availabe in clinical settings.
The sonographic finding of "sludge," or the presence of free-floating hyperechogenic material within the amniotic fluid in close proximity to the uterine cervix, has been associated with clinical IAI. This "sludge" often resembles pus when aspirated at needle amniotomy, and, by gram stain, shows an aggregation of epithelial and white blood cells as well as bacteria. In the presence of sludge, the frequency of both clinical IAI and spontaneous preterm delivery is increased.
In patients with preterm contractions and the ultrasound finding of sludge, we have increased concern for IAI. In this scenario, we have low threshold for performing a diagnostic amniocentesis.
Laboratory criteria in the placenta
It is recommended to send the placenta to pathology for evaluation. A pathologic evaluation that includes examination of the umbilical cord, placenta and membranes might identify infants at risk for infection, with leukocyte infiltrate being the most common histologic finding noted. However, placental inflammation and/or funisitis are found often in the absence of clinical evidence of infection in the mother or neonate.
Management of clinical chorioamnionitis includes antibiotic administration and delivery. As soon as the diagnosis of IAI is made, antibiotic therapy should be started. Prompt antibiotic initiation, in comparison to delaying antibiotics to the immediate postpartum treatment, results in a significant decrease in neonatal bacteremia and neonatal sepsis with subsequent shorter neonatal hospital days. For the mother, prompt antibiotic therapy results in decreased hospital stay, lower mean temperature postpartum and fewer febrile days postpartum.
We favor the following antibiotic regimen for IAI: Ampicillin 2 gm IV q6h plus gentamicin 1.5 mg/kg IV load followed by 1.0 mg/kg IV q8h. If cesarean delivery, add clindamycin 900 mg IV q8h
Alternative published regimens include ampicillin-sulbactam 3 gm IV q6h, ticarcillin-clavulanate 3.1 gm IV q4h, and cefoxitin 2 gm IV q6h.
There are many published recommendations for duration of antibiotic therapy following delivery. In some centers, broad-spectrum antibiotics, regardless of mode of delivery, are continued until the patient is afebrile for 24 hours. In other centers, antibiotics are discontinued following vaginal delivery (with the thought that "the abscess has been drained") and continued for 24 hours following cesarean delivery.
Another regimen includes one additional dose of a broad-spectrum antibiotic combination following delivery. At our center, we favor the first approach (continuation of broad-spectrum antibiotics until the patient is afebrile for 24 hours postpartum). No matter what regimen is used, the risk of postpartum endometritis approaches 10% in this population, and there should be a low threshold to restart antibiotics postpartum should the patient become febrile.
Mode of delivery
Despite a higher rate of cesarean delivery among women diagnosed with IAI, the presence of IAI is not reason in and of itself to proceed to an abdominal delivery. Cesarean delivery should be reserved for standard obstetric indications.
The cesarean delivery rate among women diagnosed with IAI in labor approaches 45% in some studies. This rate, approximately two to three times higher than in the general population, is due to patient selection (most cases occur in women with dystocia already diagnosed, and dystocia is a risk factor for both IAI and cesarean delivery) and a poor response to oxytocin in women with IAI.
Traditional complications of IAI include maternal sepsis, neonatal sepsis, neonatal pneumonia, neonatal meningitis and neonatal death. Recent studies indicate that complications of IAI should be expanded to include periventricular leukomalacia, cerebral palsy, RDS and other end-organ injury.
There are many maternal and neonatal complications of IAI. One should have a high index of suspicion, especially in preterm pregnancies, for diagnosing IAI. Amniocentesis should be used selectively, and broad-spectrum antibiotics should be initiated at time of diagnosis. Delivery timing and route should be determined by standard obstetric practices.
Maternal: There are ramifications for the pregnant patient diagnosed with IAI. Bacteremia occurs in only 2-6% of women. There is an increased rate of cesarean delivery with concomitant recovery issues (longer hospital stay, increased pain) related to abdominal surgery. In addition, IAI is a significant risk factor for uterine atony, need for blood transfusion, pelvic abscess and septic pelvic thrombophlebitis.
Neonatal: For the neonate, there is an increased risk of complications in the setting of prematurity. The risk of RDS and any diagnosis of neonatal infection is higher when the neonate is born to a woman diagnosed with IAI. In addition, seizures and 5-minute Apgar scores of 3 or less are significantly higher in the setting of IAI. Neonatal outcome is better when the infant weighs > 2500 gm, antibiotics are given in labor, and E. coli and group B streptococcusare not in the amniotic fluid.
6. What is the evidence for specific management and treatment recommendations
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Rouse, DJ, Landon, M, Leveno, KJ. "The maternal-fetal medicine units cesarean registry: chorioamnionitis at term and its duration-relationship to outcomes". Am J Obstet Gynecol. vol. 191. 2004. pp. 211-6.
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