1. Chorioamnionitis
AKA Intraamniotic infection
(IAI)
What’s bugging you?
John Buckmaster MD
Legacy Maternal Fetal Medicine

2. Significance
Fetal Morbidity associated with intra-
amniotic infection include:
1. Prematurity
2. Fetal/Neonatal brain/Neurologic injury
3. Developmental plasticity disorders
4. Pulmonary disease

3. Significance
Maternal Morbidity associated with IAI:
Septic shock
Coagulopathy
ARDS
Labor abnormalities, increased C/S rate
Uterine atony, PP hemorrhage inc X 2

4. Incidence
• Occurs in 1-5% of term deliveries, and
up to 25-50+% of preterm deliveries.

5. Definition
• Infection of amniotic fluid, membranes,
and/or placental tissue before, during or
within 24 hours of birth.

6. - nulliparity
- longer length of labor and membrane rupture
- multiple digital vaginal examinations
(especially with ruptured membranes),
-meconium-stained amniotic fluid,
-internal fetal or uterine monitoring, and
-presence of genital tract pathogens
(eg, sexually transmitted infections, group B Streptococcus,
bacterial vaginosis)
-The two most important risk factors for IAI are
-number of digital examinations and length of labor,
with the risk increasing as the number of digital examinations and
Obstetric risk factors for IAI

7. Prematurity
• The major problem in obstetrics
• Accounts for 70% of perinatal mortality
• 40+% of long term neurologic morbidity
• 10% of births occur < 37 weeks, but
majority of serious morbidity and
mortality is in the 1-2% of births at < 32
weeks and < 1500 g.

8. Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Potential Sites of Bacterial
Infection within the Uterus

9. Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Frequency of Positive Cultures of Chorioamnionic Tissue as a Function of the
Length of Gestation among Women Presenting in Spontaneous Labour with
Intact Foetal Membranes and Who Deliver Their Infants by Caesarean Section

10. Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Potential Pathways from Choriodecidual Bacterial Colonization to Preterm
Delivery

11. Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Markers of Intrauterine Infection in Pregnant Women

12. •Microbiology:
PolymicrobialPolymicrobial
Bacterial
Viral
Fungal

14. Diagnosis-
Clinical
The diagnosis of IAI is typically based
upon the presence of maternal fever of
greater than 38 degrees C (100.4 F)
and at least two of the following
conditions :

15. IAI signs/symptoms
• Maternal leukocytosis (greater than
15,000 cells/cubic millimeter)
• Maternal tachycardia (greater than
100 beats/minute)
• Fetal tachycardia (greater than 160
beats/minute)
• Uterine tenderness
• Foul odor of the amniotic fluid

16. Diagnosis-
Sub clinical
• Amniocentesis for amniotic fluid culture is the
best method for diagnosis of sub clinical IAI in
preterm gestations.
• Gram stain, glucose concentration, white
blood cell concentration, leukocyte esterase
• Relatively low predictive value for a positive
amniotic fluid culture (25 to 75 percent) and
even lower ability to predict neonatal sepsis

17. 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.
Gram Stain

18. Glucose concentration is measured with an auto analyzer
(abnormal result <15 mg/dL).
Glucose Concentration

19. WBC concentration can be determined using a Coulter counter
(abnormal result >30 cells/mm(3)).
Leukocyte esterase activity is evaluated with
Chemstrip 9 Reagent Strips (abnormal result = trace or greater).
WBC/LE

20. PCR
Species specific PCR on AF samples now
Available with 24h turnaround

21. Introducing ProteoGenix
CLIA-certified Clinical
Laboratory, dedicated to
advancing
maternal/fetal/neonatal
diagnostic medicine
From Proteogenix.com

23. Using proteomics in perinatal and neonatal sepsis:
hopes and challenges for the future.
Buhimschi CS; Bhandari V; Han YW; Dulay AT;
Baumbusch MA; Madri JA; Buhimschi IA
Current Opinion in Infectious Diseases. 22(3):235-43, 2009 Jun.
Future Directions

27. JAMA, July 28, 2004—Vol 292,
No. 4 (Reprinted)

28. Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers

29. Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers

30. Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers

31. Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers

32. Neonatal and later Effects
of
perinatal sepsis

34. Mechanisms of Disease
Effect of In Utero and Early-Life
Conditions
on Adult Health and Disease
Peter D. Gluckman, M.D., D.Sc., Mark
A. Hanson, D.Phil., Cyrus Cooper,
M.D.,
and Kent L. Thornburg, Ph.D.From
New Engl J Med 2008;359:61-73.
Copyright © 2008 Massachusetts Medical Society

35. current concepts
Chronic Lung Disease after Premature Birth
Eugenio Baraldi, M.D., and Marco Filippone,
N Engl J Med
2007;357:1946-55.
Copyright © 2007
Massachusetts
Medical Society

36. Causes of chronic lung disease
Premature newborns
Bronchopulmonary dysplasia
Prematurity
Status after respiratory distress syndrome
Term and near-term newborns
Pneumonia or sepsis
Aspiration syndromes
Persistent pulmonary hypertension of the newborn
Pulmonary hypoplasia
Diaphragmatic hernia
Congenital heart disease

37. Neonatal Neurologic Damage

38. Ferriero D. N Engl J Med 2004;351:1985-1995

39. 2
Figure 1
Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Current Opinion in Infectious Diseases. 19(3):290-7, 2006
Jun.
Figure 1 Schematic representation of events associated
with the formation of deep cortical white matter lesions
in per ventricular leukomalacia

40. Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Current Opinion in Infectious Diseases. 19(3):290-7, 2006
Jun.
Table 1 Neurodevelopment outcomes from university
analyses by infection group compared with uninfected
infants
Infection and Neurologic
impairment

41. Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Current Opinion in Infectious Diseases. 19(3):290-7, 2006
Jun.
Figure 2
OR CP and NEC

42. Neonatal Brain Injury
Review
Donna M. Ferriero, M.D.
• N Engl J Med 2004;351:1985-95.
• Copyright © 2004 Massachusetts
Medical Society.

43. Ferriero D. N Engl J Med 2004;351:1985-1995
Selective Regional Vulnerability Determined According to Age at Insult

44. Ferriero D. N Engl J Med 2004;351:1985-1995
Evolution of Brain Injury as Seen with MRI

45. Ferriero D. N Engl J Med 2004;351:1985-1995
Mechanisms of Brain Injury in
the Term Neonate

47. The management of preterm premature rupture of the membranes
near the limit of fetal viability.
Waters TP; Mercer BM
American Journal of Obstetrics & Gynecology. 201(3):230-40, 2009 Sep.
Premature ROM

48. PROM flow chart

49. Premature Labor

50. Group B Strep
Leading cause of neonatal infection
Major cause of neonatal sepsis

51. Treatment of IAI
ACOG recommendations
Ampicillin + Gentamycin
Add Clindamycin if C/S
Recent increase in clindamycin resistant
c. Difficille colitis has caused some centers to
Switch to Timentin or Zosyn

53. Other pathogens

54. Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):120-4,
2008 Apr.
Figure 1 Cytomegalovirus flow chart
CMV

55. Table 1
Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):120-4,
2008 Apr.
Table 1 Recommendations for
the toxoplasmosis-antibody-
negative pregnant patient
Recommendations for
Toxoplasmosis AB negative
patients

56. Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):120-4,
2008 Apr.
Figure 2 Toxoplasmosis
flow chart
Toxoplasmosis

57. Mycoplasma
Twenty percent of very preterm neonates
(23-32 weeks of gestation)
are born with bacteremia caused by genital Mycoplasmas
Roberto Romero, MD, Thomas J. Garite, MD
American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 1-3)

58. MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES
RESEARCH REVIEWS 8: 3–13 (2002)
• INTRAUTERINE INFECTION AND
PREMATURITY
• Luı´s F. Gonc¸alves, Tinnakorn
Chaiworapongsa, and Roberto Romero*
• Perinatology Research Branch, NICHD,
Hutzel Hospital, Department of Obstetrics and
Gynecology, Detroit, Michigan

59. Ureaplasma
Certain type of chronic lung
disease of newborns is
associated
with Ureaplasma urealyticum
infection in utero
YOKO HONMA , 1 YUKARI
YADA , 2 NAOTO
TAKAHASHI , 2 MARIKO Y
MOMOI 2
AND YOSHIKAZU NAKAMURA
2
Departments of 1 Pediatrics and
2 Public Health, Jichi Medical
School, Tochigi, Japan

60. PEDIATRICS Volume 123,
Number 5, May 2009
Perinatal Correlates of Ureaplasma urealyticum in
Placenta Parenchyma of Singleton PregnanciesThat
End Before 28 Weeks of Gestation
I. Nicholas Olomu, MDa, Jonathan L. Hecht, MD,
PhDb,c,d, Andrew O. Onderdonk, PhDb,d,e,
Elizabeth N. Allred, MSd,f,g,h, Alan Leviton, MD,
MSd,f,g, for the Extremely Low Gestational Age
Newborn Study Investigators

61. Perinatal Correlates of
Ureaplasma urealyticum

62. Perinatal Correlates of
Ureaplasma urealyticum

63. Perinatal Correlates of
Ureaplasma urealyticum

64. Perinatal Correlates of
Ureaplasma urealyticum

65. Perinatal Correlates of
Ureaplasma urealyticum

66. Reproductive Sciences, Vol. 16,
No. 1, 56-70 (2009)
Ureaplasma parvum or Mycoplasma
hominis as Sole Pathogens Cause
Chorioamnionitis, Preterm Delivery, and
Fetal Pneumonia in Rhesus Macaques
Miles J. Novy, MD et al

67. American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 1-3)
• The Alabama Preterm Birth Study: Umbilical
cord blood Ureaplasma urealyticum and
Mycoplasma hominis cultures in very preterm
newborn infants
• Robert L. Goldenberg, MDa, William W.
Andrews, PhD, MDb, Alice R. Goepfert, MDb,
Ona Faye-Petersen, MDc, Suzanne P. Cliver,
BSb, Waldemar A. Carlo, MDd, John C.
Hauth, MDb

68. American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 1-3)
• Conclusion
U urealyticum and/or M hominis were present in
23% of cord blood cultures.
• U urealyticum and M hominis cord blood
infections are far more common in
spontaneous vs indicated preterm deliveries
and are strongly associated with markers of
acute placental inflammation. Positive
cultures are associated with neonatal
systemic inflammatory response syndrome
and probably bronchopulmonary dysplasia.

69. American Journal of Obstetrics & Gynecology
DOI: 10.1016/j.ajog.2010.03.037
Noninvasive diagnosis of intraamniotic infection:
proteomic biomarkers in vaginal fluid
Jane Hitti, MD, Jodi A. Lapidus, PhD, Xinfang Lu, MS, Ashok
P. Reddy, PhD, Thomas Jacob, PhD, Surendra Dasari,
PhD, David A. Eschenbach, MD, Michael G. Gravett, MD
and Srinivasa R. Nagalla, MD

70. American Journal of Obstetrics & Gynecology
DOI: 10.1016/j.ajog.2010.03.037
Noninvasive diagnosis of intraamniotic infection:
proteomic biomarkers in vaginal fluid

71. Azithromycin
• 500 mg IV, then 250 po qd X 10-14
days