This document discusses chorioamnionitis (intra-amniotic infection), including its pathogenesis, risk factors, clinical findings, diagnosis, and evaluation. Chorioamnionitis occurs when pathogens ascend from the vagina and infect the amniotic fluid and fetal membranes. It complicates 40-70% of preterm births and 1-4% of term births. Diagnosis is based on maternal fever and may include leukocytosis, fetal tachycardia, and uterine tenderness. Evaluation of amniotic fluid can confirm infection through culture, Gram stain, or glucose/white blood cell counts. Histologic examination after birth also helps diagnosis.

1. Chorioamnionitis
DR .Tesema Eshete
OBGYN resident at SPMMC
Notes

2. INTRODUCTION
• Historically, infection of the chorion, amnion, or both was termed
"chorioamnionitis."
• Although this term remains in common use, the term "intra-
amniotic infection" (IAI) is also commonly used since infection often
involves the amniotic fluid, fetus, umbilical cord, or placenta as well
as the fetal membranes.
• Adding to the complexity, the term "histologic chorioamnionitis"
has been used to describe cases without the typical clinical or
microbiological findings associated with acute infection.
• These cases may be the result of sterile inflammation or use of
insensitive microbiologic techniques.

4. PATHOGENESIS
• Migration of cervicovaginal flora through the cervical canal is the
most common pathway to IAI.
• Uncommonly, the pathway to IAI is hematogenous as a result of
maternal bacteremia(eg, Listeria monocytogenes) infecting the
intervillous space or from contamination of the amniotic cavity as a
result of an invasive procedure (eg, fetoscopy).
• Infection from the peritoneum via the fallopian tubes has also been
postulated but is likely rare.
• Subsequent activation of the maternal and fetal inflammatory
response systems generally leads to labor and/or rupture of
membranes.

5. PATHOGENESIS
• Local host factors likely play a role in facilitating or preventing infection.
• The cervical mucus plug, membranes, and placenta provide barriers to
ascending and transplacental infection, while rupture of membranes
removes barriers.
• There is some evidence that the fetal membranes have antimicrobial
activity.
• 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.
• Lactobacilli in the vagina may induce changes in the flora that impair the
virulence of pathogenic organisms.

6. INCIDENCE
• The variation 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.
• The frequency of IAI ranges from 40 to 70 percent among pregnancies delivered preterm because
of preterm labor or preterm premature rupture of membranes (PPROM).
• In a systematic review, 20 to 25 percent of pregnancies with PPROM not treated with antibiotics
developed IAI.
• At term, IAI complicates approximately 1 to 4 percent of deliveries overall.
• However, at term it has been diagnosed in 7 percent of women with rupture of membranes before
onset of labor (PROM) (40 percent of those with PROM >24 hours), 12 percent of women in labor
who undergo a primary cesarean delivery after labor, and 20 percent of women who have more
than eight digital vaginal examinations.

7. RISK FACTORS
• Longer length of labor and length of ruptured membranes may be the most important risk
factors for IAI.
• Several other obstetric factors have been associated with an increased risk for IAI, including
multiple digital vaginal examinations (especially with ruptured membranes), cervical
insufficiency, nulliparity, meconium-stained amniotic fluid, internal fetal or uterine
monitoring, presence of genital tract pathogens (eg, sexually transmitted infections, group
B Streptococcus, bacterial vaginosis), alcohol and tobacco use, and previous IAI.
• An increasing number of digital examinations may be a consequence of longer labor rather
than an independent risk factor, particularly prior to membrane rupture.
• There is no strong evidence of an increased risk of IAI in pregnancies exposed to mechanical
methods of cervical ripening versus prostaglandins; however, trials typically excluded women
with ruptured membranes.

8. MICROBIOLOGY
• IAI is typically polymicrobial, often involving vaginal or enteric flora.
• 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 are other frequent pathogens.
• Anaerobes appear to be more frequently involved in preterm IAI than term IAI.
• 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 for their pathogenicity, including induction of a
robust inflammatory response with clinical consequences for both mother and neonate.

11. CLINICAL FINDINGS
• IAI often occurs in women with premature rupture of membranes (PROM) but can occur with intact
membranes, especially in laboring women.
• The key clinical findings, which are nonspecific, and their frequencies are as follows :
• Fever (100 percent).
• Maternal leukocytosis (variously defined as white blood cell count >12,000/mm3 or >15,000/mm3) (70 to
90 percent).
• Maternal tachycardia >100/min (50 to 80 percent).
• Fetal tachycardia >160/min (40 to 70 percent).
• Uterine tenderness (4 to 25 percent).
• Bacteremia (5 to 10 percent). Bacteremia is most common when IAI is associated with group
B Streptococcus or Escherichia coli infection (bacteremia in 18 and 15 percent of cases, respectively).
• Purulent or malodorous amniotic fluid.
• IAI may be subclinical, which by definition does not present with the above clinical findings. Subclinical
infection may manifest as preterm labor with intact membranes or as preterm premature rupture of
membranes (PPROM).
• Computerized analysis of the fetal heart rate may show reduced variability.

12. Potential maternal sequelae
• Dysfunctional labor – IAI is associated with an increased risk of labor abnormalities, which increase
the risk for cesarean delivery, uterine atony, postpartum bleeding, and need for blood transfusion.
• The type of bacteria appears to play a role:
• Women with persistent high-virulence organisms(eg, Enterobacteriaceae, Group A and B
Streptococci, Mycoplasma hominis) in their amniotic fluid have more labor abnormalities than
women with low-virulence organisms (Ureaplasma urealyticum, Lactobacilli, Staphylococcus
epidermidis).
• 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 bleeding suggests dysfunctional myometrial
contractility due to inflammation.

13. Cont..
• Localized infection – Patients with IAI who undergo cesarean delivery, which is
common, are at increased risk for wound infection, endomyometritis, septic pelvic
thrombophlebitis, and pelvic abscess.
• ●Sepsis – In a population-based study of maternal sepsis in the United States, 18
percent of cases were associated with IAI.
• 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.
• An elevated lactic acid concentration can be a sign of sepsis and is associated
with an adverse maternal outcome.
• 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 despite use of a modified obstetric early warning scoring
system.

15. Histology
• The maternal immune response to IAI leads to neutrophilic inflammation of the chorioamnion
(chorioamnionitis); the fetal immune response leads to neutrophilic inflammation of the umbilical cord
(funisitis) and/or fetal vessels in the chorionic plate (chorionic vasculitis).
• Chorioamnionitis is more common than funisitis:
• Funisitis is observed in up to 60 percent of cases of chorioamnionitis, while chorioamnionitis is observed in
almost 100 percent of cases of funisitis.
• Microorganisms should be present in infection.
• The histologic diagnosis of chorioamnionitis may not correlate with clinical findings or microorganisms in
the placenta, membranes, or amniotic fluid.
• In these cases, 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 sensitive.
• Antibiotic therapy prior to delivery could also play a role. In one study, histologic and bacteriologic results
were concordant in approximately 70 percent of the 376 examined placentas.
• When the diagnosis of chorioamnionitis was based on culture-positive amniotic fluid, sensitivity and
specificity of histology were 83 to 100 percent and 23 to 52 percent, respectively

16. Histologic criteria for chorioamnionitis
and funisitis

17. Differential diagnosis
• Most of the clinical findings associated with IAI are nonspecific.
• Intrapartum fever can be related to epidural anesthesia.
• Maternal tachycardia during labor may be physiologic or related to
pain, epidural anesthesia, or medications.
• Maternal leukocytosis occurs with both labor and antenatal
corticosteroid therapy as well as infections other than IAI.
• Fetal tachycardia can be related to fetal hypoxemia, maternal fever
of any etiology, or transplacental passage of some maternal
medications.

18. DDX
• Labor – Labor can be associated with fever (if the patient has an epidural anesthetic), maternal
tachycardia, leukocytosis, and uterine tenderness.
• Diagnosis of clinical IAI is difficult in laboring patients with epidural anesthesia because fever is
common in this setting and may be related to the anesthetic itself.
• In addition, epidural anesthesia masks uterine tenderness and may induce maternal or fetal
tachycardia.
• Lastly, prolonged labor is a risk factor for both requesting epidural anesthesia and developing IAI.
• Abruptio placenta – Abruption can cause uterine tenderness and maternal tachycardia but is
usually associated with vaginal bleeding and absence of fever.
• Other infections – Extrauterine infections associated with fever and abdominal pain (with or
without labor) include pyelonephritis, influenza, appendicitis, and pneumonia.
• These infections can cause maternal tachycardia and leukocytosis, and fetal tachycardia; however,
they can usually be differentiated from IAI by the clinical setting (eg, respiratory or gastrointestinal
symptoms suggest an extrauterine source of fever) and laboratory tests (pyuria in urine obtained
via a catheter suggests pyelonephritis).

19. DIAGNOSIS OF INTRA-AMNIOTIC
INFECTION
• Diagnostic criteria — The diagnosis of IAI is commonly based on clinical findings. The key
criterion is maternal fever, which is a manifestation of systemic inflammation; other
criteria are insensitive.
• Of note, for treatment purposes, ACOG further suggests that patients with isolated fever ≥39.0°C
(102.2°F) should be managed as having suspected intra-amniotic infection.
• A presumptive diagnosis of IAI (suspected triple I) can be made in women with:
• ●Fever – ≥39.0°C [102.2°F] or 38.0°C [100.4°F] to 38.9°C [102.02°F] on two occasions 30 minutes
apart, without another clear source PLUS one or more of the following:
• •Baseline fetal heart rate >160 beats/min for ≥10 minutes, excluding accelerations, decelerations,
and periods of marked variability
• •Maternal white cell count >15,000/mm3 in the absence of corticosteroids and ideally showing a
left shift (bandemia)
• •Purulent-appearing fluid coming from the cervical os visualized by speculum examination

20. Cont..
• The presumptive diagnosis of IAI in febrile laboring patients is
strengthened by the presence of risk factors for the disease, especially
ruptured membranes, and by excluding other potential sources of fever.
• Measurement of C-reactive protein (CRP) in maternal serum is not part of
the diagnostic evaluation.
• Meta-analyses concluded that an elevated maternal CRP level did not
appear to be useful for early diagnosis of IAI or predicting neonatal sepsis,
but was moderately predictive of histologic chorioamnionitis.
• Available studies were very heterogeneous, with a wide variety of
sensitivity and specificity of CRP at various thresholds.
• We do not obtain blood cultures in women with IAI, except in rare atypical
cases, such as septic shock.

21. Cont..
• A confirmed diagnosis of IAI can be made in women with:
• ●All of the above PLUS one or more of the following objective laboratory
findings:
• •Positive Gram stain of amniotic fluid >100 colony forming units/mL bacteria
• •Low glucose level in amniotic fluid<15mg/dl
• •Positive amniotic fluid culture
• •High white cell (WBC) count in amniotic fluid in the absence of a bloody
tap>30cells/ml
• •Histopathologic evidence of infection or inflammation or both in the placenta,
fetal membranes, or the umbilical cord vessels (funisitis)
• Laboratory studies should be performed on amniotic fluid obtained by
amniocentesis. Histopathology is obtained after delivery.

22. Cont..
• Laboratory studies should be performed on amniotic fluid obtained
by amniocentesis. Histopathology is obtained after delivery.
• The rationale for these criteria are the temperature and fetal heart
rate criteria exceed the 90 to 95th percentile for normal pregnancies
and the WBC count exceeds the 80th percentile.
• In addition, 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, aerobic gram-negative
rods, anaerobes, and Mycoplasma hominis).

23. Evaluation of amniotic fluid
• A presumptive diagnosis of IAI is adequate for initiating maternal therapy in most
cases.
• However, when the presumptive diagnosis of IAI is uncertain because of absence
of typical clinical findings or overlap with other disorders, evaluation of amniotic
fluid can confirm or exclude the diagnosis of IAI.
• 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 obtain definitive results, which is too long to be clinically useful.
• Results from 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 and even lower ability to predict neonatal sepsis

24. Cont..
• 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.
• In an individual patient-level meta-analysis based on two studies with a total of 288 women with
preterm labor and intact membranes (11.8 percent with culture-confirmed IAI), sensitivity and
specificity of positive Gram stain were 65 and 99 percent, respectively.
• Glucose concentration is measured with an autoanalyzer (abnormal result <15 mg/dL).
• In the individual patient-level meta-analysis discussed above, sensitivity and specificity of glucose
≤14 mg/dL were 85 and 87 percent, respectively .
• A combination of positive Gram stain or glucose ≤14 mg/dL afforded a sensitivity of 88 percent and
specificity of 87 percent – not much different from a low glucose level alone

25. Cont..
• WBC concentration can be determined using a Coulter
counter (abnormal result >30 cells/mm3).
• In a study of 120 patients with preterm labor and intact
membranes, sensitivity was 64 percent and specificity was
95 percent.
• Leukocyte esterase activity can be evaluated with a urine
dipstick reagent strip (eg, Chemstrip 9 Reagent Strips, an
abnormal result is trace or greater).
• Sensitivity ranges from 85 to 91 percent; specificity ranges
from 95 to 100 percent.

26. Cont..
• 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 (approximately 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/mm3).
• Interleukin-6 (IL-6) – 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.
• Elevated cytokine levels (eg, IL-6, matrix metalloproteinase in amniotic fluid and fetal blood are
associated with infection, preterm birth, and systemic fetal inflammatory syndrome .

27. Cont..
• Evidence of IAI by elevated IL-6 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.
• 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).
• 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).

28. MATERNAL MANAGEMENT
• Delivery — Women with IAI (including suspected or confirmed "triple I" should be given antibiotics
and delivered.
• Antimicrobial therapy provides bactericidal concentrations of antibiotics to the fetus, membranes,
and amniotic fluid within one-half to one hour after infusion, but IAI can only be cured by delivery
of the infected products of conception.
• The lack of efficacy of antibiotics alone may be because amniotic fluid bacteria can form biofilms,
which are resistant to antibiotic treatment.
• We suggest prompt induction or augmentation of labor, as appropriate, with cesarean delivery
reserved for standard obstetric indications.
• In women receiving antibiotics, there is no evidence that the duration of labor correlates with
adverse neonatal outcome ; therefore, cesarean delivery should be reserved for standard obstetric
indications.
• Cesarean delivery in the presence of IAI increases the risk of wound infection, endomyometritis,
and venous thrombosis.

29. Antibiotic therapy
• Broad-spectrum antibiotics should be given promptly following a diagnosis of IAI to initiate treatment of both the
mother and fetus.
• We administer antibiotics to women with a presumptive diagnosis of IAI even if epidural-related fever cannot be
excluded.
• Early initiation of antibiotic therapy may reduce the frequency and severity of neonatal infection.
• ntrapartum regimen — Administration of broad spectrum parenteral antibiotics with coverage for beta-lactamase-
producing aerobes and anaerobes is the preferred therapy of both IAI and postpartum endometritis. Our
preference is:
• ●Ampicillin 2 g intravenously every six hours PLUS
• ●Gentamicin 5 mg/kg once daily
• A single daily gentamicin dose is equally or more effective and more convenient than thrice-daily dosing and safe
when used intrapartum or postpartum .
• It 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 (1.5 mg/kg every
eight hours: fetal level 2.9 microg/mL).
• Routine monitoring of gentamicin levels is unnecessary for women who are healthy except for IAI.
• 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.

30. Alternatives
• Some reasonable alternative intravenous antibiotic regimens include:
• ●Ampicillin 2 g every six hours PLUS gentamicin 1.5 mg/kg every eight
hours for patients with normal renal function. Some centers use a
gentamicin load (eg, 2 mg/kg) with thrice-daily dosing, but objective data
to support its superiority are lacking.
• ●Ampicillin-sulbactam 3 g every six hours.
• ●Ticarcillin-clavulanate 3.1 g every four hours.
• ●Cefoxitin 2 g every 8 hours.
• ●Cefotetan 2 g every 12 hours
• ●Piperacillin-tazobactam 3.375 g every 6 hours or 4.5 g every 8 hours.
• ●Ertapenem 1 g every 24 hours

31. Cont..
• Postpartum regimens — The optimal duration of antibiotic therapy after delivery has not been
determined conclusively.
• ●Vaginal delivery, the author administers one additional dose of antibiotics, but believes
discontinuing antibiotics is a reasonable alternative, given low quality evidence of available
evidence.
• ●Cesarean delivery, in women with IAI undergoing cesarean delivery, anaerobic coverage should
be added to the regimen used for vaginal delivery because anaerobes play a major role in
complications associated with postcesarean endometritis.
• The addition of anaerobic coverage has reduced failure rates of postcesarean endometritis. Our
preference is:
• •Ampicillin 2 g every six hours PLUS
• •Gentamicin 5.0 mg/kg once daily PLUS
• •Either clindamycin 900 mg or metronidazole 500 mg
• The author administers additional doses of the antibiotic regimen postpartum until the patient is
afebrile and asymptomatic for at least 48 hours, but believes one additional dose only (particularly
for non-obese patients) is a reasonable alternative, given low-quality of available evidence.

32. Cont..
• 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 retrospective 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 versus 1 percent
after vaginal delivery).
• There is no evidence that oral antibiotics are beneficial after
discontinuation of parenteral therapy .

33. Cont ...
• 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.
• Penicillin-allergic patients- vancomycin 1 g intravenously every 12
hours for ampicillin (ie, gentamicin 5 mg/kg once daily plus
vancomycin 1 g every 12 hours).
• vancomycin 1 g intravenously every 12 hours
for ampicillin (ie, gentamicin 5 mg/kg once daily plus vancomycin 1
g every 12 hours).

34. Cont..
• Fetal monitoring during labor — Use of continuous electronic fetal monitoring is appropriate in
these patients to detect development of fetal compromise due to sequelae of IAI (villous edema,
hyperthermic stress, fetal infection) or other factors.
• Fetal infection is not associated with a specific pattern of periodic fetal heart rate changes, except
mild baseline tachycardia in some cases, which is a category II tracing.
• Management of category II tracings is reviewed separately.
• Antipyretics — The combination of maternal fever and fetal acidosis conferred a 12.5 percent risk
of neonatal encephalopathy.
• Reduction of intrapartum fever with antipyretics may also reduce fetal tachycardia, thereby
avoiding the tendency to perform a cesarean delivery because of an abnormal fetal heart rate
pattern.
• Acetaminophen is the preferred drug.

35. Cont..
• Postpartum care — Postpartum care is routine as
IAI resolves after delivery in most women,
particularly after vaginal delivery. Women with
persistent fever and/or pelvic pain should be
evaluated for postpartum endometritis, wound
infection after cesarean delivery, and, rarely,
septic pelvic thrombophlebitis.

36. FETAL AND NEONATAL OUTCOME
• Adverse effects of intra-amniotic infection —
Adverse fetal/neonatal outcomes include perinatal death, asphyxia,
early-onset neonatal sepsis, septic shock, pneumonia, meningitis,
intraventricular hemorrhage (IVH), cerebral white matter damage,
and long-term disability including cerebral palsy, as well as
morbidity related to preterm birth.
• Overall, IAI is associated with up to 40 percent of cases of early-
onset neonatal sepsis.
• fetal exposure to inflammation can induce interleukin-1 production,
which enhances surfactant protein and lipid synthesis thereby
promoting lung maturation.

37. Cont..
• Neurodevelopmental impairment — Most studies have found that neurodevelopmental delay and
cerebral palsy are potential long-term disabilities resulting from IAI, especially at or near term, but
also at extremely preterm gestational ages.
• Fetal infection/inflammation is likely a more important predictor of neonatal outcome than isolated
maternal, amniotic fluid, or amniochorionic infection/inflammation.
• 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.
• Funisitis and chorionic vasculitis appear to be the placental histologic manifestations of fetal
inflammatory response syndrome and markers for adverse outcome.
• Laboratory findings include fetal plasma interleukin-6 (IL-6) concentration IL-6 >11 pg/mL.

38. Cont..
• Neuroinflammation during the perinatal period can increase the risk of
long-term neurologic and neuropsychiatric disease.
• High fetal/neonatal levels of cytokines and chemokines, especially tumor
necrosis factor , appear to mediate fetal/neonatal brain injury.
• These inflammatory substances can cause cerebral ischemia and damage,
ultimately leading to intraventricular hemorrhage and periventricular
leukomalacia.
• Intervention to prevent these outcomes is an active area of investigation.
• Neurodevelopmental impairment associated with IAI may involve multiple
factors, including asphyxia and toxic injury by bacterial products.

39. PREVENTION
• The main strategy to prevent IAI is administration of prophylactic
antibiotics to women with preterm premature rupture of
membranes (PPROM), which reduces the incidence of clinical
chorioamnionitis, prolongs latency, and improves neonatal
outcomes.
• For term PROM, we prefer delivery to expectant management with
antibiotic prophylaxis.
• Modifiable risk factors that pertain to the health care provider
include conduct of labor (eg, minimizing the number of vaginal
examinations) and use of prophylactic antibiotics in women with
group B Streptococcuscolonization.

40. Thanks
Questions ???