CLINICAL ACTIONS: The NICHD conducted a workshop in January to review evidence, with special consideration to avoid unnecessary. The American College of Obstetricians and Gynecologists (ACOG) published a Intraamniotic infection, also known as chorioamnionitis, is an. Historically, infection of the chorion, amnion, or both was termed ” chorioamnionitis.” Although this term remains in common use, the term.
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Chorioamnionitis is a common complication of pregnancy associated with significant maternal, perinatal, and long-term adverse outcomes. Adverse maternal outcomes include postpartum infections and sepsis while adverse infant outcomes include stillbirth, premature birth, neonatal sepsis, acgo lung disease and brain injury leading to cerebral palsy and other neurodevelopmental disabilities.
Research in the last two decades has expanded our understanding of the mechanistic links between intraamniotic infection and preterm delivery as well as morbidities of preterm and term infants. Recent and ongoing clinical research into better methods for diagnosing, treating and preventing chorioamnionitis is likely to have a substantial impact on short and long-term outcomes in the neonate.
Chorioamnionitis or intraamniotic infection is an acute inflammation of the membranes and chorion of the placenta, typically due to ascending polymicrobial bacterial infection in the setting of membrane rupture. Only rarely is hematogeneous spread implicated in chorioamnionitis, as occurs with Listeria monocytogenes [ 2 ].
When characteristic clinical signs are present, the condition is referred to as clinical chorioamnionitis or clinical intraamniotic infection. Although there is significant overlap between clinical and histologic chorioamnionitis, the latter is a more common diagnosis based on pathologic findings on microscopic examination of the placenta that encompasses clinically unapparent sub-clinical chorioamnionitis as well as clinical chorioamnionitis.
Funisitis, also a histopathologic diagnosis, is the extension of infection or inflammation to the umbilical cord. Overall the definition of chorioamnionitis varies according to key diagnostic criteria, choriowmnionitis can be clinical presence of typical clinical findingsmicrobiologic culture of microbes from appropriately collected amniotic fluid or chorioamnion or histopathologic microscopic evidence of infection or inflammation on examination of the placenta or chorioamnionic specimens.
Twelve percent of primary cesarean births at term involve clinical chorioamnionitis, with the most common indication for cesarean in these cases being failure to progress usually after membrane rupture [ 12 ].
Multiple studies have reported risk factors for chorioamnionitis, including longer duration of membrane rupture, prolonged labor, nulliparity, African American ethnicity, internal monitoring of labor, multiple vaginal exams, meconium-stained amniotic fluid, smoking, alcohol or drug abuse, immune-compromised states, epidural anesthesia, colonization with group B streptococcus, bacterial vaginosis, sexually transmissible genital infections and vaginal colonization with ureaplasma [ 3 — 7 chorioamnionltis, 13 — 18 ].
A strong association between untreated GBS bacteriuria and chorioamnionitis may reflect the high concentration of GBS in the genital tract [ 19 ]. After adjusting for potential confounding variables and depending on the specific confounders considered, some of the risk factors for chorioamnionitis identified in older studies no longer demonstrate an association in recent studies. Select factors independently associated with chorioamnionitis and their strength of association are summarized in Table 1 [ 3 — 713 — 17 ].
Contrary to most obstetric conditions, chorioamnionitis in a previous pregnancy may not be associated with an increased risk of chorioamnionitis in a subsequent pregnancy [ 20 ].
Although PPROM is a major risk factor for clinical chorioamnionitis, it is noteworthy that together with preterm labor, PPROM frequently is the consequence of sub-clinical chorioamanionitis [ 21 ].
This passage occurs most commonly by retrograde or ascending infection chorioamnionitid the lower genital tract cervix and vagina Figure 1. Anterograde infection from the peritoneum via the fallopian tubes has also been postulated [ 22 ]. The presence of infectious agents in the chorioamnion engenders a maternal and fetal inflammatory response characterized by the release of a combination of proinflammatory and inhibitory cytokines and chemokines in the maternal and fetal compartments Figure 2.
Aside from the risk of direct fetal infection and chorioaamnionitis, the fetal inflammatory response may induce cerebral white matter injury, which may result in cerebral palsy and other short and long-term neurological deficits Figure 2.
Host defense mechanisms preventing intraamniotic infection remain poorly elucidated, but specific local host factors likely play an important role. The cervical mucous plug as well as the placenta and membranes provide a barrier to infection of the amniotic fluid and fetus.
Peroxide-producing lactobacilli in the birth canal may induce changes in the flora that impair the virulence of pathogenic organisms. Maternal fever is the most chorioamnionitid clinical sign of chorioamnionitis. This is because i in addition to fever, the two conditions share other major risk factors low parity and prolonged labor chorjoamnionitis, ii epidural anesthesia masks signs of chorioamnionitis such as fundal tenderness, chorloamnionitis iii medications given during epidural anesthesia may induce maternal or fetal tachycardia and therefore confound the diagnosis of chorioamnionitis [ 24 ].
The exact mechanism of epidural fever is unknown, but it is thought to be the result of epidural sympathetic blockade of thermoregulatory processes such as sweating [ 24 ].
This suggests that the pathologic basis for epidural fever is chorioamnionitis [ 23 ]. In sum, the concept of epidural fever remains controversial and warrants additional studies. Tachycardia may be present in the absence of chorioamnionitis and requires careful assessment for alternative etiologies. Medications such as ephedrine, choruoamnionitis, and beta agonists may raise maternal or fetal heart rate.
Aside from the objective measurements of maternal fever and tachycardia, other signs of chorioamnionitis are highly subjective. Fundal tenderness is difficult to interpret in the context of the pain of labor and may be masked by analgesics including epidural or confounded by the pain associated with placental abruption. Purulence or foul odor of amniotic fluid are more likely to be present with severe or prolonged infection and may be organism-specific, but in any case may or may not be appreciated by clinicians.
Chorioamnionitis that is subclinical by definition does not present the above clinical signs but may manifest as preterm labor or, even more commonly, as preterm premature rupture of membranes PPROM. As suggested by the name, clinical chorioamnionitis is diagnosed solely based on clinical signs since access to uncontaminated amniotic fluid or placenta for culture is invasive and usually avoided.
Individual clinical criteria have variable sensitivity and low specificity for chorioamnionitis see table 2. Because of the low specificity of clinical findings a consideration of other potential sources of fever and other causes of clinical symptoms is essential for the diagnosis of chorioamnionitis [ 26 ]. In the absence of other etiologies the combination of cgorioamnionitis clinical criteria provides a highly accurate diagnosis of chorioamnionitis.
The presence of risk factors of chorioamnionitis, especially membrane rupture, further strengthens the diagnosis. Chorioamninoitis from laboratory or bedside testing may aid in ruling in or out the diagnosis of chorioamnionitis, particularly when the clinical signs and symptoms are equivocal Table 2 [ 227 — 32 ].
Recent research on proteomic analysis for diagnosing intraamniotic infection is discussed vhorioamnionitis in this series. However, isolated leucocytosis in the absence of other signs or symptoms is of limited value since it may be induced by several other conditions including labor and steroid use. Therefore routine monitoring of CBC in high-risk women e.
Other laboratory parameters including high levels of C-reactive protein CRPlipopolysacharide binding protein LBPsoluble intercellular adhesion molecule 1 sICAM 1 and interleukin 6 have been associated with a higher risk of chorioamnionitis in the setting of PPROM or preterm delivery [ 33 — 37 ].
However, their utility for the diagnosis or prediction of choriamnionitis as part of routine clinical practice is not established. Tests on amniotic fluid, usually obtained by amniocentesis, have been used for the diagnosis of chorioamnionitis table 2 [ 2630 — 32 ]. Culture of amniotic fluid is the most reliable test but is of limited utility since culture results may not be available for up to 3 days. In addition, because of the invasive nature of the procedure, amniocentesis is not performed in the majority of cases, which occur during labor.
However, the value of this practice has recently been questioned [ 38 ]. Their role in the pathogenesis of chorioamnionitis and neonatal complications, once controversial, is now increasingly accepted [ 41 ]. These fastidious organisms provoke a robust inflammatory reaction affecting both maternal and fetal compartments, particularly in preterm gestations [ 40 — 42 ].
They are commonly isolated from amniotic fluid in the setting of preterm birth or premature membrane rupture with or without clinical chorioamnionitis [ 41 ]. These organisms are commonly part of the vaginal flora especially in women with bacterial vaginosis or the enteric flora E. Occasionally chorioamnionitis is the result of hematogenous spread of bacterial or viral infection to the placenta.
Listeria monocytogenes infection of the fetus, which presents a pattern of both early onset and late onset neonatal sepsis similar to GBS, is presumed to be due to a hematogenous route rather than an ascending infection [ 45 ].
More research is needed to clarify the significance of individual microbes and their potential interactions in the pathogenesis of chorioamnionitis.
For clinical decision-making and management, however, knowing the exact organisms involved in chorioamnionitis is not generally useful. Other tests on amniotic fluid table 2 are limited in their overall predictive abilities for chorioamnionitis although the interleukin 6 and matrix metalloproteinase are more promising because of higher sensitivity and specificity [ 30 — 32 ].
The use of vaginal pool fluid after premature membrane rupture for these assessments e. Histologic chorioamnionitis captures sub-clinical as well as clinical chorioamnionitis, thus it is not surprising that overall histologic chorioamnionitis at term is up to 3 times as frequent as clinical chorioamnionitis confirmed by amniotic fluid culture [ 47 ].
This is in part because cultures for genital mycoplasmas, the most common organisms associated with chorioamnionitis, are not very sensitive. Subclinical chorioamnionitis and non-infectious inflammation also contribute to this discrepancy. Consequently, depending on the criteria used and maternal characteristics including ethnicity and type of laborthe prevalence of chorioamnionitis based on placental pathology varies widely. On the other hand, clinical chorioamnionitis is not uniformly confirmed on pathologic evaluation.
For these reasons, placental pathology should be performed to confirm suspected chorioamnionitis even if amniotic fluid culture is negative. The pathologic finding of funisitis inflammation of the umbilical cord is even more concerning than chorioamnionitis alone as it represents a fetal response to infection.
Several other conditions should be considered in the differential diagnosis of chorioamnionitis. In the intrapartum patient with an epidural and low-grade fever without tachycardia maternal or fetal or other clinical signs of intrauterine inflammation, epidural-associated fever is a strong consideration.
Extrauterine infections can cause fever and abdominal pain, either during or in absence of labor, including urinary tract infection pyelonephritisinfluenza, appendicitis, and pneumonia. Non-infectious conditions associated with abdominal pain usually in absence of fever include thrombophlebitis, round ligament pain, colitis, connective tissue disorders and placental abruption.
Clinical chorioamnionitis carries adverse consequences affecting both the woman and her infant Figure 2. Chorioamnionitis leads to a 2 to 3-fold increased risk for cesarean delivery and 2 to 4-fold increase in endomyometritis, wound infection, pelvic abscess, bacteremia and postpartum hemorrhage [ 1253 — 56 ]. The increase in postpartum hemorrhage appears to be due to dysfunctional uterine muscle contractions as a result of inflammation [ 54 — 55 ].
Ten percent of women with chorioamnionitis have positive blood cultures bacteremia most commonly involving GBS and E.
Fortunately, however, septic shock, disseminated intravascular coagululation, adult respiratory distress syndrome and maternal death are only rarely encountered[ 57 ]. Fetal exposure to infection may lead to fetal death, neonatal sepsis and numerous other postnatal complications Figure 2. The histopathologic hallmarks of FIRS are funisitis and chorionic vasculitis [ 60 ]. FIRS is now recognized to represent the fetal immune response to infection or injury mediated by the release of cytokines and chemokines such as interleukins, TNF-alpha, C-reactive protein, and matrix melloproteinases [ 59 ].
FIRS has also been linked to preterm labor culminating in perinatal death Figure 2 and is associated, particularly among preterm neonates, with multi-organ injury, including chronic lung disease, periventricular leucomalacia and cerebral palsy, [ 62 — 64 ] Although FIRS may occur in the setting of non-infectious inflammation, its magnitude tends to be significantly more robust with documented infection [ 61 ] Although somewhat controversial, fetal exposure to genital mycoplasmas U.
The neonate exposed to intrauterine infection and inflammation may show adverse effects at or shortly after birth. Adverse outcomes may include perinatal death, asphyxia, early onset neonatal sepsis, septic shock, pneumonia, intraventricular hemorrhage IVHcerebral white matter damage, and long-term disability including cerebral palsy [ 69 — 74 ]. Preterm infants have an even higher rate of complications of chorioamnionitis than term infants, including perinatal death 25 vs.
Chorioamnionitis is also well-established as a risk factor for long-term neurodevelopmental disability especially when it occurs prior to term [ 275 — 79 ]. In term and near-term infants it is associated with a 4-fold increase in the frequency of cerebral palsy [ 76 — 77 ]. Prompt initiation of antibiotic therapy is essential to prevent both maternal and fetal complications in the setting of clinical chorioamnionitis [ 2 ].
Time -to-delivery after institution of antibiotic therapy has been shown to not affect morbidities; therefore cesarean section to expedite delivery is not indicated for chorioamnionitis unless there are other obstetric indications [ 125378 ].
Evidence from randomized trials and observational studies demonstrate that immediate intrapartum use of broad-spectrum antibiotics significantly reduces maternal and fetal complications of chorioamnionitis [ 79 — 83 ]. The optimal antibiotic regimen for treatment of clinical chorioamnionitis has not been well-studied and current recommendations are based largely on clinical consensus [ 83 ]. Intravenous administration of ampicillin every 6 hours and gentamicin every 8—24 hours until delivery is the typical regimen [ 83 — 84 ].
If cesarean delivery is performed, clindamycin every 8 hours or metronidazole is often added for anaerobic coverage.
Interestingly, although genital mycoplasmas are the most commonly isolated organisms associated with chorioamnionitis, the standard antibiotic regimens used for clinical chorioamnionitis do not provide optimal cohrioamnionitis against these organisms.
Clindamycin does provide coverage against mycoplasma hominis but none of the 3 standard antibiotics is effective against ureaplasma species which is the most common group associated with infection.
Supportive measures include acob use of antipyretics acetaminophen. This is particularly important during the intrapartum period since fetal acidosis in the setting of fever has been associated with a marked increase in the incidence of neonatal encephalopathy [ 87 ].
Maternal fever even in the absence of documented fetal acidosis is associated with adverse neonatal choriomnionitis, particularly neonatal encephalopathy, though it is unclear to what extent the etiology of the fever rather than the fever itself is choriosmnionitis [ 88 ]. Treating intrapartum fever with antipyretics may also be helpful in reducing fetal tachycardia thereby avoiding the tendency to perform cesarean for a non-reassuring fetal status.
Antibiotics have also been shown to reduce the incidence of clinical or pathologic chorioamnionitis and neonatal sepsis and to prolong time-to-delivery among women with preterm membrane rupture managed expectantly but not among those in active preterm labor with intact membranes in whom maternal infection was reduced [ 89 — 91 ].
The authors speculated that the findings could be due to chance or to maintenance of the fetus in a milieu with suppressed not eradicated subclinical infection given the low dose and oral route of antibiotics [ 92 choriaomnionitis 93 ].