Intraamniotic infection (chorioamnionitis)

Author
Alan Thevenet N Tita, MD, PhD
Section Editor
Susan M Ramin, MD
Deputy Editor
Vanessa A Barss, MD, FACOG
Disclosures: Alan Thevenet N Tita, MD, PhD Nothing to disclose. Susan M Ramin, MD Nothing to
disclose. Vanessa A Barss, MD, FACOG Nothing to disclose.
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All topics are updated as new evidence becomes available and our peer review process is
complete.
Literature review current through: Aug 2015. | This topic last updated: Apr 17, 2015.
INTRODUCTION Intraamniotic infection (IAI) refers to infection of the amniotic fluid,
membranes, placenta, and/or decidua. Other terms that have been used to describe this
condition include chorioamnionitis, amnionitis, and amniotic fluid infection. Based on the
presence or absence of overt clinical signs and the results of diagnostic tests, IAI may be subgrouped into clinical or subclinical infection, and/or histologic chorioamnionitis (which may be
noninfectious).
IAI is a cause of maternal febrile morbidity in the peripartum period. It is associated with 20 to
40 percent of cases of early neonatal sepsis and pneumonia. In addition, a growing body of
research has suggested that an exuberant fetal immune response to IAI is associated with white
matter brain injury and cerebral palsy [1]. (See "Neonatal pneumonia" and "Epidemiology,
etiology, and prevention of cerebral palsy".)
PATHOGENESIS Intraamniotic infection (IAI) usually results from migration of cervicovaginal
flora through the cervical canal to infect the fetal membranes, placenta, amniotic fluid, and fetus.
Rupture of membranes facilitates this process. Uncommonly, the gateway is transplacental as a
result of placental infection related to bacteremia (eg, Listeria monocytogenes) or the
amniotic fluid/placenta is inoculated with bacteria during invasive procedures (eg,
amniocentesis, chorionic villus sampling, fetal surgery). Regardless of the origin of the infection,
activation of the maternal and fetal inflammatory response often leads to labor and/or rupture of
membranes. (See "Pathogenesis of spontaneous preterm birth".)
Specific local host factors likely play a role in preventing infection. The cervical mucus plug,
placenta, and membranes provide a barrier to infection of the amniotic fluid and fetus. There is
some evidence that the fetal membranes have antimicrobial activity, which may help protect
them from rupture [2,3]. Cells within fetal membranes appear to mediate innate immune
responses through activation of toll-like receptors, key modulators of the innate immune
response that recognize components of bacteria and viruses [4,5]. Lactobacilli in the vagina
may induce changes in the flora that impair the virulence of pathogenic organisms.
INCIDENCE The reported incidence of intraamniotic infection (IAI) in the United States varies
widely among publications, but consistently shows a decline as pregnancy advances toward
term. The variation in incidence is due to several factors, including differences in ascertainment

(prospective studies report higher rates than retrospective studies), differences in prevalence of
risk factors in the populations studied, use of different diagnostic criteria (eg, clinical versus
histologic), and temporal changes in obstetric practice [6-8].
Preterm The frequency of IAI is highest in preterm deliveries. In one review, the incidence of
IAI in women with premature rupture of membranes (PROM) at less than 27 weeks of gestation,
28 to 36 weeks of gestation, and term was 41, 15, and 2 percent, respectively [9]. IAI is
associated with one-third of cases of preterm labor with intact membranes and is present in 40
percent of women with preterm PROM admitted with contractions and 75 percent of those who
develop labor after admission for preterm PROM [10]. (See "Pathogenesis of spontaneous
preterm birth" and "Preterm premature (prelabor) rupture of membranes".)
Term At term, IAI typically occurs in the setting of labor and membrane rupture, complicating
approximately 2 to 4 percent of term deliveries overall [9]. As many as 12 percent of women in
labor at term who undergo a primary cesarean have clinically-diagnosed IAI [11].
RISK FACTORS Several obstetric factors have been associated with intraamniotic infection
(IAI), including prolonged labor, prolonged membrane rupture, multiple digital vaginal
examinations (especially with ruptured membranes), nulliparity, previous IAI, meconium-stained
amniotic fluid, internal fetal or uterine monitoring, presence of genital tract pathogens (eg,
sexually transmitted infections, group B streptococcus [GBS], bacterial vaginosis), and alcohol
and tobacco use [7,12-18]. Longer length of labor and length of ruptured membranes appear to
be important risk factors, whereas an increasing number of digital examinations may be a
consequence of longer labor rather than an independent risk factor, particularly prior to
membrane rupture [19]. In a retrospective population-based cohort study, women with a history
of IAI in their first pregnancy had a significantly higher risk of IAI in their second pregnancy than
women without IAI in their first pregnancy (OR 3.43, 95% CU 2.67-4.42) [18].
It is noteworthy that IAI can be either a risk factor for, or a result of, preterm labor or premature
rupture of membranes (PROM), particularly at early gestational ages.
MICROBIOLOGY Intraamniotic infection (IAI) is polymicrobial; amniotic fluid culture in
pregnancies complicated by IAI reveals multiple organisms, usually from the vaginal or enteric
flora (table 1). Two-thirds of women with IAI have at least two isolates per specimen of amniotic
fluid. Regardless of gestational age, genital mycoplasmas (Ureaplasma and mycoplasma
species) are the most common isolates. Anaerobes (including Gardnerella vaginalis), enteric
gram-negative bacilli and group B streptococcus (GBS) are other frequent pathogens.
Anaerobes appear to be more frequently involved in preterm IAI than term IAI [20].
Genital mycoplasmas are the most frequent organisms detected in cases of culture-confirmed
chorioamnionitis and are highly prevalent (>70 percent) in the lower genital tract. For this
reason, some authors attribute their isolation from patients with IAI to contamination or
colonization from the lower tract, rather than a true infection. However, as data accrue, there is
increasing support of their pathogenicity, including induction of a robust inflammatory response
with clinical consequences for both mother and neonate [21,22].
CLINICAL FINDINGS
Patient presentation Intraamniotic infection (IAI) typically occurs in the setting of premature
rupture of membranes (PROM), but can occur with intact membranes. The key clinical findings
are fever, uterine tenderness, maternal tachycardia (>100/min), fetal
tachycardia (>160/min) and purulent or foul amniotic fluid. Fever is present in all cases of
clinical chorioamnionitis, as it is required for the clinical diagnosis. Maternal tachycardia (>100

beats per minute) and fetal tachycardia (>160 beats per minute) are reported in 50 to 80 percent
and 40 to 70 percent of cases, respectively [23]. Uterine tenderness and a foul odor to the
amniotic fluid are reported in 4 to 25 percent of cases [9].
Maternal leukocytosis (variously defined as white blood cell [WBC]
count >12,000/mm3 or >15,000/mm3) is reported in 70 to 90 percent of cases.
Bacteremia occurs in 5 to 10 percent of cases overall, but is most common when IAI is
associated with group B streptococcus (GBS) or Escherichia coli (bacteremia in 18 and 15
percent of cases, respectively).
IAI may be subclinical, which by definition does not present with the above clinical findings.
Subclinical infection may manifest as preterm labor or as PROM, especially when preterm.
Clinical course IAI is associated with an increased risk of labor abnormalities, uterine atony,
postpartum hemorrhage, and endometritis [11,24,25]. The type of infection appears to play a
role: women with persistent high-virulence organisms in their amniotic fluid have more labor
abnormalities than women with low-virulence organisms [9]. The pathophysiologic mechanisms
for labor abnormalities related to IAI are poorly understood and often complicated by other
factors (eg, epidural anesthesia), but the link between IAI and both labor abnormalities and
postpartum hemorrhage suggests dysfunctional myometrial contractility due to inflammation
[11,24-26]. Patients who undergo cesarean delivery in the presence of IAI, which is common,
are at increased risk of wound infection, endomyometritis, and venous thrombosis [11,27].
The risk of life-threatening maternal sequelae, such as sepsis, coagulopathy, and adult
respiratory distress syndrome related to IAI, are low if treatment with broad spectrum antibiotics
is initiated (see 'Maternal management' below). Review of a database including 364 women with
IAI showed that five developed severe sepsis (1.4 percent) and that it was difficult to identify
these women upon initial presentation using modified obstetric early warning scoring systems
[28].
Placental histology and culture The maternal and fetal immune response to IAI is
manifested by inflammation of the chorioamnion (chorioamnionitis) and umbilical cord (funisitis),
respectively [29,30]. Although chorioamnionitis is present in nearly all cases of funisitis, funisitis
is present in only up to 60 percent of cases of chorioamnionitis [31].
Histologic criteria for chorioamnionitis and funisitis are reviewed separately. (See "The placental
pathology report", section on 'Neutrophilic (acute) and immune mediated (lympho-histiocytic or
"chronic") inflammation' and "The placental pathology report", section on 'Inflammation'.)
In one study, histological and bacteriological results were concordant in about 70 percent of the
376 examined placentas [32]. When the diagnosis of chorioamnionitis is based on culturepositive amniotic fluid, histology has sensitivity of 83 to 100 percent and specificity of 23 to 52
percent [33]. When histology is positive, cultures may be negative because inflammatory
changes in the membranes can result from noninfectious insults (hypoxic injury, trauma,
meconium, allergens). Another reason for negative cultures is that cultures for fastidious
organisms such as genital mycoplasmas, the most common organisms associated with
chorioamnionitis, are not very sensitive. Antibiotic therapy prior to delivery could also play a role.
DIAGNOSIS OF CLINICAL CHORIOAMNIONITIS The essential criterion for clinical
diagnosis of intraamniotic infection (IAI) is maternal fever (variably defined as 37.8 C [100 F]
or 38 C [100.4 F]) [9,11,34], which is a manifestation of systemic inflammation; other criteria
are insensitive. The presumptive clinical diagnosis is strengthened by the presence of risk

factors for the disease, especially ruptured membranes, and by excluding other potential
sources of fever and the nonspecific clinical signs and symptoms (eg, uterine tenderness,
maternal and fetal tachycardia, malodorous amniotic fluid, leukocytosis).
For clinical research, the diagnosis of overt IAI is typically based upon the presence of maternal
fever 38 degrees C (100.4 F) and at least two of the following conditions [9], while in clinical
practice, the diagnosis of overt IAI is commonly based on the presence of maternal fever plus
one additional finding from this list [35].
Maternal leukocytosis (greater than 15,000 cells/mm3)
Maternal tachycardia (greater than 100 beats/minute)
Fetal tachycardia (greater than 160 beats/minute)
Uterine tenderness
Foul odor of the amniotic fluid
The criteria for temperature, maternal heart rate, and fetal heart rate exceed the 90 to 95th
percentile for normal pregnancies and the white blood cell (WBC) count exceeds the 80th
percentile. These thresholds are associated with higher rates of neonatal and maternal
morbidity and, in preterm gestations, define a population whose amniotic fluid contains higher
concentrations of organisms (>100 colony forming units/mL bacteria) and high-virulence isolates
(group B streptococcus [GBS], aerobic gram negative rods, anaerobes, and Mycoplasma
hominis).
Differential diagnosis Differential diagnosis includes, but is not limited to:
Labor, which can cause leukocytosis, tachycardia, uterine tenderness, and fever (if the
patient has an epidural anesthetic)
Abruption, which can cause uterine tenderness and tachycardia, but is usually associated
with vaginal bleeding and absence of fever
Extrauterine infections that can cause fever and abdominal pain (with or without labor),
such as pyelonephritis, influenza, appendicitis, and pneumonia.
In one study of 139 pregnancies with clinical diagnosis of IAI, histologic examination of the
placenta did not support the clinical diagnosis in approximately one-third of cases [29]. Fever is
common in the setting of epidural anesthesia, particularly among nulliparous women with
prolonged labor, and may be related to the anesthetic itself. It is usually low-grade. Diagnosis of
clinical IAI is difficult in these patients because epidural anesthesia masks other signs of
chorioamnionitis such as uterine tenderness, medications given during epidural anesthesia may
induce maternal or fetal tachycardia, and prolonged labor is a risk factor for both requesting
epidural anesthesia and developing IAI. It is also possible that the pathologic basis for epidural
fever might be chorioamnionitis. The diagnostic evaluation of patients with intrapartum fever,
including those with epidural-related fever, is reviewed separately. (See "Intrapartum fever".)
In the absence of fever, individual signs and symptoms are not specific for IAI. Maternal
tachycardia may be physiologic or related to pain, epidural anesthesia, or medications
(ephedrine); fetal tachycardia may be due to maternal medication or fetal hypoxemia; and
uterine pain and tenderness also occur with placental abruption. Maternal WBC count is high in
the presence of infection, but high values are frequently found in the absence of overt infection
(eg, in association with labor or antenatal corticosteroids). When clinical concern about infection
is high, leukocytosis (especially when accompanied by a left shift or bandemia) supports the
diagnosis.

Ancillary tests when the clinical diagnosis is uncertain When the diagnosis is uncertain
because of absence of typical clinical findings or overlap with other disorders, ancillary tests
may support the clinical impression of IAI.
Amniocentesis Amniocentesis for amniotic fluid culture establishes a microbiologic
diagnosis of IAI when culture results are positive. This procedure has been used primarily in
women with refractory preterm labor to determine whether continued tocolysis is appropriate
and in women with preterm premature rupture of membranes (PPROM) to determine whether
induction is indicated. Occasionally, amniocentesis is used to discriminate between IAI and
other causes of abdominal pain, uterine tenderness, or maternal fever (eg, maternal viral
syndrome, abruption, appendicitis). (See "Preterm premature (prelabor) rupture of
membranes" and "Diagnostic amniocentesis".)
Culture of amniotic fluid remains the "gold standard" and most specific test for documentation of
IAI, but is limited by the fact that it may take days to get definitive results, which is too long to be
clinically useful. Several other tests, including Gram stain, glucose concentration, WBC
concentration, and leukocyte esterase level, can be obtained more rapidly. The majority of these
tests have relatively low predictive value for a positive amniotic fluid culture (25 to 75 percent)
and even lower ability to predict neonatal sepsis [36,37].
Gram stain is performed on an unspun specimen of amniotic fluid; centrifugation does not
significantly improve the sensitivity of the technique. Twenty to 30 high power fields should
be examined. The presence of any bacteria and leukocytes (at least six leukocytes per
high-power field) is suspicious for infection. Sensitivity 24 percent, specificity 99 percent
[38].
Glucose concentration is measured with an autoanalyzer (abnormal result <15 mg/dL).
Sensitivity 57 percent, specificity 74 percent [38].
WBC concentration can be determined using a Coulter counter (abnormal result
>30 cells/mm3). Sensitivity 57 percent, specificity 78 percent [38].
Leukocyte esterase activity is evaluated with Chemstrip 9 Reagent Strips (abnormal
result = trace or greater). Sensitivity 85 to 91 percent, specificity 95 to 100 percent [39,40].
In patients with preterm labor, the combined result of positive gram stain, positive leukocyte
esterase, low glucose concentration, and elevated WBC concentration has sensitivity of 90
percent and specificity of 80 percent for predicting positive results of amniotic fluid culture.
However, since the prevalence of IAI is relatively low (about 10 percent), this combination of
tests has a false positive rate of 67 percent, thus the clinician should use caution in acting prior
to obtaining culture results, particularly when the intervention involves delivery of an immature
fetus. In addition, an elevated WBC concentration is less predictive of infection if the
amniocentesis is traumatic (defined as amniotic fluid containing 1000 red blood
cells [RBCs]/mm3) [41].
Some clinicians perform amniocentesis to exclude subclinical IAI in patients with preterm labor
or cervical insufficiency before attempts are made to prolong pregnancy. We do not recommend
routine amniocentesis in patients with preterm labor or cervical insufficiency because of the poor
predictive value of the combined test, the 48-hour delay in obtaining definitive culture results,
and the lack of data proving that this approach reduces maternal/neonatal morbidity.
Inflammatory markers Elevated cytokine levels (eg, interleukin-6, matrix metalloproteinase
[38,42]) in amniotic fluid and fetal blood are associated with infection, preterm birth, and
systemic fetal inflammatory syndrome [10,36]. Evidence of intraamniotic inflammation may be a
more important prognostic factor for adverse outcomes than a positive amniotic fluid culture

alone, which may represent only colonization. In a study of 305 women with preterm labor and
intact membranes, median latency was similar in pregnancies with and without positive
microbial culture [43]. Pregnancies with and without positive microbial culture and IL-6 levels
<2.6 ng/mL had longer median latency (23 to 25 days) compared with pregnancies with or
without positive microbial culture but IL-6 >11.3 ng/mL (latency <1 to 2 days) [43]. Regardless of
microbial culture results, composite perinatal morbidity/mortality rates were lower in pregnancies
with IL-6 levels <2.6 ng/mL (morbidity/mortality 21 to 25 percent) than in pregnancies with IL-6
levels >11.3 ng/mL (morbidity/mortality 72 to 81 percent). The technical complexity of the
assays, lack of standards across laboratories, and limited data on test characteristics currently
restrict this testing to research settings in the United States. However, a rapid test has become
available in some countries and provides results within 20 minutes [44].
A high level of IL-6 in cervicovaginal fluid appears to be predictive of microbial invasion of the
amniotic cavity in women with preterm labor and intact membranes [45]. Measurement of
maternal C-reactive protein >2 mg/dL is not useful for prediction of early IAI [46,47].
Evaluation of proteomic biomarkers in the amniotic fluid and maternal serum are under
investigation in an attempt to identify unique proteins diagnostic of subclinical IAI [48,49].
Preliminary studies show promise in the diagnosis of early IAI [48-51]. (See "Overview of gene
expression profiling, proteomics, and microRNA profiling in clinical oncology", section on
'Proteomics'.)
MATERNAL MANAGEMENT Antibiotics are administered to control intrauterine infection,
but intraamniotic infection (IAI) can only be considered cured after delivery of the infected
products of conception.
Antibiotics Broad spectrum antibiotics should be given promptly following a diagnosis of IAI
to initiate treatment of both the mother and fetus. We administer antibiotics for presumed
chorioamnionitis even if epidural-related fever cannot be excluded. In a 2014 systematic review
of one trial (n = 45 patients with IAI) comparing intrapartum versus postpartum antibiotic
therapy, intrapartum treatment was associated with a reduction in early neonatal sepsis (RR
0.08; 95% CI 0.00-1.44) and pneumonia or sepsis (RR 0.06; CI 0.00-0.95); however, the trial
was underpowered to show statistical significance [52].
Regimen Administration of broad spectrum parenteral antibiotics with coverage for betalactamase producing aerobes and anaerobes is the preferred therapy of both chorioamnionitis
and postpartum endometritis. There are few good comparative trials of antibiotic regimens on
which to base treatment recommendations. In the previously mentioned small systematic review
[52], there was no clear difference in the incidence of postpartum endometritis between women
who received treatment with ampicillin and gentamicin alone versus those who received
ampicillin, gentamicin and clindamycin (RR 1.86; 95% CI 0.67-5.14; one trial, n = 133) and no
randomized trials of comparing other regimens.
The standard treatment of ampicillin 2 g intravenously every six hours
plus gentamicin 1.5 mg/kg every eight hours for patients with normal renal function is safe and
effective. Some centers use a gentamicin load (eg, 2 mg/kg) with thrice daily dosing, but
objective data to support its superiority are lacking. Instead of thrice daily dosing, we prefer to
administer a single daily dose of gentamicin 5.0 mg/kg once daily because it is equally or more
effective, safe, and more convenient when used intrapartum or postpartum [53,54]. This single
daily dose does not result in toxic maternal levels (peak 18.2 microg/mL and <2 microg/mL by
10 hours) and results in appropriate fetal serum levels (peak 6.9 microg/mL); fetal levels are
lower with standard dosing (1.5mg/kg every eight hours: fetal level 2.9 microg/mL) [55]. Routine

monitoring of gentamicin levels is not indicated for the otherwise healthy woman with
chorioamnionitis. For women with renal insufficiency, we adjust the gentamicin dose with the
assistance of a clinical pharmacist; serum levels and creatinine clearance are monitored to
guide dosing. (See "Dosing and administration of parenteral aminoglycosides".)
Some alternative antibiotic regimens include:
Ampicillin-sulbactam (3 grams intravenously every six hours)
Ticarcillin-clavulanate (3.1 grams intravenously every four hours)
Cefoxitin (2 grams intravenously every six hours)
Cesarean delivery Anaerobes play a major role in the pathogenesis of preterm birth, the
amniotic fluid flora of IAI (table 1), and complications associated with postcesarean
endometritis. The addition of anaerobic coverage has reduced failure rates of postcesarean
endometritis and, because of this finding, we add clindamycin (900 mg intravenously)
ormetronidazole (500 mg intravenously) to the primary antibiotic regimen if the patient is
undergoing a cesarean delivery [54]. Traditionally, anaerobic coverage has been initiated after
umbilical cord clamping at delivery. However, given the recent shift to preincision initiation of
antibiotic prophylaxis for cesarean delivery, it may be prudent to initiate anaerobic coverage as
soon as possible or 30 to 60 minutes prior to incision to prevent subsequent wound infection.
Penicillin-allergic patients Evidence-based data to guide the treatment of IAI in penicillin
allergic patients are lacking (see "Penicillin allergy: Immediate reactions"). At our institution, we
substitute vancomycin 1 g intravenously every 12 hours for ampicillin.
Group B streptococcus-positive women Patients receiving intrapartum penicillin G for
group B streptococcus (GBS) prophylaxis need broader antibiotic coverage if they develop IAI.
An appropriate option is ampicillin and gentamicin.
Duration The optimal duration of continuing antibiotic therapy postpartum has not been
determined conclusively. Clindamycin or metronidazole should be added to the postcesarean
antibiotic regimen for anaerobic coverage. We suggest continuing intrapartum antibiotics for one
additional postpartum dose. This approach is based on data from a few small randomized trials
and observational studies of women treated for chorioamnionitis before delivery that compared
the outcomes of women treated with no [56] or one [57-59] postpartum dose of antibiotics with
the outcomes of those who received multiple postpartum antibiotic doses. In all of these studies,
postpartum treatment with multiple doses of antibiotics was not associated with a significant
reduction in treatment failure (usually defined as persistent fever) compared with less intensive
therapy.
Some clinicians continue the administration of antibiotics after delivery until the patient is
afebrile and asymptomatic for at least 24 hours. This is a reasonable alternative approach,
given the small number of subjects and postpartum febrile events in the available studies and
differences among the studies in patient characteristics and treatment regimens. In one study,
patients most likely to benefit from this approach were those who underwent cesarean delivery
since they had a higher prevalence of persistent fever after delivery (15 percent versus 1
percent after vaginal delivery) [59].
There is no evidence that oral antibiotics are beneficial after discontinuation of parenteral
therapy [60].
Treatment of women with postpartum endometritis is discussed separately. (See "Postpartum
endometritis".)

Route of delivery Some clinicians believe that the longer the fetus stays in an infected
environment, the greater the likelihood of developing neonatal infection and short-term and
long-term complications. This concern may contribute to the greater rate of intervention in IAI by
cesarean birth. However, an expedited delivery does not appear to be warranted.
Intrapartum antimicrobial therapy provides bactericidal concentrations of antibiotics to the fetus,
membranes, and amniotic fluid within one-half to one hour after infusion. Since the average time
between diagnosis of IAI and delivery is three to five hours [61,62], it is unlikely that shortening
this period will affect neonatal outcome if the fetus is receiving adequate antibiotic therapy
transplacentally and labor is progressing. Finally, overall, there is no evidence that the duration
of infection or labor correlates with adverse neonatal outcome [11,62]; therefore, cesarean
delivery should be reserved for standard obstetrical indications.
Fetal monitoring during labor The use of continuous electronic fetal monitoring is
appropriate for detecting the development of fetal compromise due to villous edema,
hyperthermic stress, fetal infection, or other factors. Although no particular pattern of periodic
heart rate changes signifies fetal infection, a category III tracing (eg, one with absent variability
and late decelerations) is predictive of fetal acidosis and poor short-term outcomes [63] and
should be cause for expedited delivery. Fetal tachycardia is common in the setting of IAI, but
mild tachycardia alone (category II tracing) is not highly predictive of fetal acidemia.
(See "Management of intrapartum category I, II, and III fetal heart rate tracings".)
Antipyretics In human studies, the combination of maternal fever and fetal acidosis
conferred a 12.5 percent risk of neonatal encephalopathy (OR 94, 95% CI 29-307), and each of
these factors also appeared to have an independent effect (fever OR 8.1, 95% CI 3.5-18.6;
neonatal acidosis OR 11.5, 95% CI 5.0-26.5) [64]. These observations support the adjunctive
use of antipyretics in IAI. Reduction of intrapartum fever with antipyretics may also reduce fetal
tachycardia, thereby avoiding the tendency to perform cesarean for a non-reassuring fetal
status.
FETAL AND NEONATAL OUTCOME Adverse outcomes may include perinatal death,
asphyxia, early onset neonatal sepsis, septic shock, pneumonia, meningitis, intraventricular
hemorrhage (IVH), cerebral white matter damage, long-term disability including cerebral palsy,
as well as morbidity related to preterm birth [65-70]. Preterm infants have a higher rate of shortterm complications from chorioamnionitis than term infants, including in one study: perinatal
death (25 versus 6 percent in preterm and term infants), neonatal sepsis (28 versus 6 percent),
pneumonia (20 versus 3 percent), grades 3 or 4 IVH (24 versus 8 percent) and respiratory
distress (62 versus 35 percent) [67]. Overall, chorioamnionitis is associated with up to 40
percent of cases of early-onset neonatal sepsis [23]. (See "Assessment of the newborn
infant" and "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm
infants" and "Short-term complications of the premature infant".)
There is some evidence that fetal exposure to inflammation can induce interleukin-1 production,
which enhances surfactant protein and lipid synthesis, thereby promoting lung maturation;
however, adverse effects on fetal lung development and outcome can also occur [71]. These
adverse effects include structural changes and alterations in growth factor expression and the
immune system. Preterm ventilated infants from pregnancies with histologic chorioamnionitis
have been reported to have less respiratory distress syndrome (RDS) than unexposed preterm
infants [72], but also may have a higher risk of developing bronchopulmonary dysplasia [73].
(See "Pathogenesis and clinical features of bronchopulmonary dysplasia", section on
'Chorioamnionitis' and "Pathogenesis and clinical features of bronchopulmonary dysplasia",
section on 'Inflammation'.)

Neurodevelopmental impairment Most studies have found that neurodevelopmental delay

and cerebral palsy are potential long-term disabilities resulting from chorioamnionitis, especially
at or near term [74-76], but also at extremely preterm gestational ages [77,78]. In a 2010 metaanalysis of the relationship between chorioamnionitis and cerebral palsy, there were significant
associations between cerebral palsy and both clinical chorioamnionitis (pooled OR 2.42; 95% CI
1.52-3.84) and histological chorioamnionitis (pooled OR 1.83; 95% CI 1.17-2.89) [76]. However,
this analysis was limited by many potential biases, such as differences in the definitions across
studies, extent of blinding in determining exposure status, and whether the study controlled for
potential confounders.
Fetal involvement is likely a more important predictor of neonatal outcome than isolated
maternal or intrauterine inflammation [77].The term systemic fetal inflammatory syndrome (also
known as fetal inflammatory response syndrome) refers to the fetal immune response to
intrauterine infection and the potential consequences of this response: preterm labor, fetal
growth restriction, severe neonatal morbidity, brain injury, and development of chronic lung
disease in the child [75,79-88]. High levels of fetal/neonatal cytokines and chemokines,
especially tumor necrosis factor [85], appear to mediate the fetal/neonatal brain injury
[81,83,85,89,90]. These inflammatory substances can cause cerebral ischemia and damage,
ultimately leading to intraventricular hemorrhage and periventricular leukomalacia. An
interesting pilot study in rats showed that intrapartum maternal treatment with an antiinflammatory cytokine (eg, interleukin-10) could prevent severe cerebral injury in the pups of
mothers with intrauterine infection [86]. (See "Pathogenesis of spontaneous preterm birth",
section on 'Bacteria'.) Asphyxia and toxic injury by bacterial products may also play a role in
neurodevelopmental impairment associated with IAI.
Funisitis and chorionic vasculitis appear to be the placental histological manifestations of fetal
inflammatory response syndrome [87,91,92]. Funisitis is an independent risk factor for a lower
median Bayley psychomotor index [93]. Vasculitis probably reduces perfusion and adds hypoxic
injury. We send the placenta for pathologic evaluation.
PREVENTION The main preventive strategy is administration of antibiotics to women with
preterm premature rupture of membranes (PPROM), which reduces the incidence of clinical
chorioamnionitis, prolongs latency, and improves neonatal outcomes. (See "Preterm premature
(prelabor) rupture of membranes", section on 'Antibiotic therapy'.)
Attention to modifiable risk factors may also reduce the incidence of intraamniotic infection (IAI).
(See 'Risk factors' above.)
SUMMARY AND RECOMMENDATIONS
Intraamniotic infection (IAI, also called chorioamnionitis) refers to infection of the amniotic
fluid, membranes, placenta, and/or decidua. It may be sub-grouped as clinical (overt) or
subclinical infection, or as histologic chorioamnionitis (which may be noninfectious).
(See 'Introduction' above and 'Placental histology and culture' above.)
IAI is polymicrobial (table 1), and usually results from migration of cervicovaginal flora
through the cervical canal in women with ruptured membranes. Other causes include
transplacental infection associated with bacteremia and bacterial contamination during
invasive procedures. (See 'Microbiology' above and 'Pathogenesis' above.)
Clinically, the diagnosis of IAI is based upon the presence of maternal fever 38 degrees
C (100.4 F). The presumptive clinical diagnosis is strengthened by the presence of risk
factors for the disease, especially ruptured membranes, and by excluding other potential
sources of fever and the nonspecific clinical signs and symptoms (leukocytosis, maternal

and fetal tachycardia, uterine tenderness, malodorous amniotic fluid). A positive amniotic
fluid culture is diagnostic, but takes too long to be clinically useful. (See 'Diagnosis of
clinical chorioamnionitis' above.)
Amniocentesis for Gram stain, glucose and leukocyte concentration, and leukocyte
esterase activity may be helpful in cases of diagnostic uncertainty. (See 'Ancillary tests
when the clinical diagnosis is uncertain' above.)
In addition to maternal infectious complications (eg, postpartum endometritis), IAI may
impair myometrial contractility, which can result in labor abnormalities, need for cesarean
delivery, and postpartum hemorrhage. Cesarean delivery in the presence of IAI increases
the risk of wound infection, endomyometritis, and venous thrombosis. (See 'Clinical
course' above.)
Broad spectrum antibiotics should be started at diagnosis to minimize maternal and fetal
morbidity. A typical regimen is ampicillin (2 g intravenously every six hours)
plus gentamicin(1.5 mg/kg intravenously every eight hours for patients with normal renal
function). Clindamycin (900 mg intravenously) is added to this regimen to reduce
postsurgical infections related to anaerobes in patients undergoing cesarean delivery. For
most patients, we suggest a single dose of antibiotics after delivery rather than no or
multiple doses (Grade 2B). For patients delivered by cesarean with other risk factors for
postcesarean infection, such as obesity, continuing antibiotics until the patient is afebrile
for at least 24 hours is acceptable. (See'Antibiotics' above.)
IAI cannot be cured without delivery. We suggest prompt induction or augmentation of
labor, as appropriate, with cesarean delivery reserved for standard obstetrical indications
(Grade 2C). Immediate (cesarean) delivery in the presence of reassuring intrapartum fetal
testing, adequate progress of labor, and administration of antibiotics does not improve
neonatal or maternal outcome. (See 'Route of delivery' above.)
Adverse neonatal outcomes associated with IAI include perinatal death, asphyxia, early
onset neonatal sepsis, septic shock, pneumonia, meningitis, intraventricular hemorrhage
(IVH), cerebral white matter damage, long-term neurodevelopmental disability including
cerebral palsy, as well as morbidity related to preterm birth. (See 'Fetal and neonatal
outcome' above.)
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