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Chorioamnionitis
AKA Intraamniotic infection
(IAI)
What’s bugging you?
John Buckmaster MD
Legacy Maternal Fetal Medicine
Significance
Fetal Morbidity associated with intra-
amniotic infection include:
1. Prematurity
2. Fetal/Neonatal brain/Neu...
Significance
Maternal Morbidity associated with IAI:
Septic shock
Coagulopathy
ARDS
Labor abnormalities, increased C/S rat...
Incidence
• Occurs in 1-5% of term deliveries, and
up to 25-50+% of preterm deliveries.
Definition
• Infection of amniotic fluid, membranes,
and/or placental tissue before, during or
within 24 hours of birth.
- nulliparity
- longer length of labor and membrane rupture
- multiple digital vaginal examinations
(especially with ruptu...
Prematurity
• The major problem in obstetrics
• Accounts for 70% of perinatal mortality
• 40+% of long term neurologic mor...
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Potential Sites of Bacterial
Infection within the Uterus
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Frequency of Positive Cultures of Chorioamnionic Tissue as a Function ...
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Potential Pathways from Choriodecidual Bacterial Colonization to Prete...
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Markers of Intrauterine Infection in Pregnant Women
•Microbiology:
PolymicrobialPolymicrobial
Bacterial
Viral
Fungal
Diagnosis-
Clinical
The diagnosis of IAI is typically based
upon the presence of maternal fever of
greater than 38 degrees...
IAI signs/symptoms
• Maternal leukocytosis (greater than
15,000 cells/cubic millimeter)
• Maternal tachycardia (greater th...
Diagnosis-
Sub clinical
• Amniocentesis for amniotic fluid culture is the
best method for diagnosis of sub clinical IAI in...
Gram stain is performed on an unspun specimen of amniotic fluid;
centrifugation does not significantly improve the sensiti...
Glucose concentration is measured with an auto analyzer
(abnormal result <15 mg/dL).
Glucose Concentration
WBC concentration can be determined using a Coulter counter
(abnormal result >30 cells/mm(3)).
Leukocyte esterase activity...
PCR
Species specific PCR on AF samples now
Available with 24h turnaround
Introducing ProteoGenix
CLIA-certified Clinical
Laboratory, dedicated to
advancing
maternal/fetal/neonatal
diagnostic medi...
Using proteomics in perinatal and neonatal sepsis:
hopes and challenges for the future.
Buhimschi CS; Bhandari V; Han YW; ...
JAMA, July 28, 2004—Vol 292,
No. 4 (Reprinted)
Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infection
by Proteomic Profiling and
Identification of Novel Biomarkers
Neonatal and later Effects
of
perinatal sepsis
Mechanisms of Disease
Effect of In Utero and Early-Life
Conditions
on Adult Health and Disease
Peter D. Gluckman, M.D., D....
current concepts
Chronic Lung Disease after Premature Birth
Eugenio Baraldi, M.D., and Marco Filippone,
N Engl J Med
2007;...
Causes of chronic lung disease
Premature newborns
Bronchopulmonary dysplasia
Prematurity
Status after respiratory distress...
Neonatal Neurologic Damage
Ferriero D. N Engl J Med 2004;351:1985-1995
2
Figure 1
Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Curr...
Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Current Opinion...
Neonatal infection and long-term neurodevelopment
outcome in the preterm infant.
Adams-Chapman I; Stoll BJ
Current Opinion...
Neonatal Brain Injury
Review
Donna M. Ferriero, M.D.
• N Engl J Med 2004;351:1985-95.
• Copyright © 2004 Massachusetts
Med...
Ferriero D. N Engl J Med 2004;351:1985-1995
Selective Regional Vulnerability Determined According to Age at Insult
Ferriero D. N Engl J Med 2004;351:1985-1995
Evolution of Brain Injury as Seen with MRI
Ferriero D. N Engl J Med 2004;351:1985-1995
Mechanisms of Brain Injury in
the Term Neonate
The management of preterm premature rupture of the membranes
near the limit of fetal viability.
Waters TP; Mercer BM
Ameri...
PROM flow chart
Premature Labor
Group B Strep
Leading cause of neonatal infection
Major cause of neonatal sepsis
Treatment of IAI
ACOG recommendations
Ampicillin + Gentamycin
Add Clindamycin if C/S
Recent increase in clindamycin resist...
Other pathogens
Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):120-4,
2...
Table 1
Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):...
Perinatal infections and fetal/neonatal brain injury.
Ledger WJ
Current Opinion in Obstetrics & Gynecology. 20(2):120-4,
2...
Mycoplasma
Twenty percent of very preterm neonates
(23-32 weeks of gestation)
are born with bacteremia caused by genital M...
MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES
RESEARCH REVIEWS 8: 3–13 (2002)
• INTRAUTERINE INFECTION AND
PREMATURITY...
Ureaplasma
Certain type of chronic lung
disease of newborns is
associated
with Ureaplasma urealyticum
infection in utero
Y...
PEDIATRICS Volume 123,
Number 5, May 2009
Perinatal Correlates of Ureaplasma urealyticum in
Placenta Parenchyma of Singlet...
Perinatal Correlates of
Ureaplasma urealyticum
Perinatal Correlates of
Ureaplasma urealyticum
Perinatal Correlates of
Ureaplasma urealyticum
Perinatal Correlates of
Ureaplasma urealyticum
Perinatal Correlates of
Ureaplasma urealyticum
Reproductive Sciences, Vol. 16,
No. 1, 56-70 (2009)
Ureaplasma parvum or Mycoplasma
hominis as Sole Pathogens Cause
Chorio...
American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 1-3)
• The Alabama Preterm Birth Study:...
American Journal of Obstetrics & Gynecology
January 2008 (Vol. 198, Issue 1, Pages 1-3)
• Conclusion
U urealyticum and/or ...
American Journal of Obstetrics & Gynecology
DOI: 10.1016/j.ajog.2010.03.037
Noninvasive diagnosis of intraamniotic infecti...
American Journal of Obstetrics & Gynecology
DOI: 10.1016/j.ajog.2010.03.037
Noninvasive diagnosis of intraamniotic infecti...
Azithromycin
• 500 mg IV, then 250 po qd X 10-14
days
Chorio
Chorio
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Chorio
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Chorio
Chorio
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  • Sites of infection
  • Organisms isolated
  • Proteomics
  • Proteomics
  • Neonatal outcomes
  • Gluckman et al
  • Causes of chronic lung disease
  • Figure 1. Selective Regional Vulnerability Determined According to Age at Insult. Panel A shows an image of a neonate who was born at 24 weeks of gestation. The T1-weighted, spin-echo MRI was performed at 28 weeks and reveals sub acute white-matter injury with cystic changes and volume loss. A T2-weighted, spin-echo image of the brain of a two-year-old child who had a documented ischemic insult at term shows chronic injury to the basal ganglia and thalamus (Panel B). A T1-weighted image on day 2 of life revealed hyper intensity in the scarred regions shown in Panel B. In Panel C, a T2-weighted, spin-echo image of a term newborn who presented with seizures reveals multiple acute arterial infarcts. In Panel D, a T2-weighted, spin-echo image shows a thrombosed left transverse sinus and hemorrhagic venous infarction in a six-day-old term newborn who presented with focal seizures.
  • Figure 3. Evolution of Brain Injury as Seen with MRI. A normal structural image (Panel A), a diffusion-weighted MRI (Panel B), and lactate accumulation in the basal ganglia on magnetic resonance spectroscopy (Panel C, arrow) are shown in the same newborn at 1 day of life. At day 8, T1-weighted MRI (Panel D) and T2-weighted MRI (Panel E) reveal extensive damage to the deep gray nuclei, and magnetic resonance spectroscopy shows diminution of the lactate peak (Panel F, arrow).
  • Oxidative stress and excitotoxicity, through downstream intracellular signaling, produce both inflammation and repair. Cell death begins immediately and continues during a period of days to weeks. The cell-death phenotype changes from an early necrotic morphology to a pathology resembling apoptosis. This evolution is called the necrosis– apoptosis continuum.
  • Toxo flow chart
  • Transcript of "Chorio"

    1. 1. Chorioamnionitis AKA Intraamniotic infection (IAI) What’s bugging you? John Buckmaster MD Legacy Maternal Fetal Medicine
    2. 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. 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. 4. Incidence • Occurs in 1-5% of term deliveries, and up to 25-50+% of preterm deliveries.
    5. 5. Definition • Infection of amniotic fluid, membranes, and/or placental tissue before, during or within 24 hours of birth.
    6. 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. 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. 8. Goldenberg R et al. N Engl J Med 2000;342:1500-1507 Potential Sites of Bacterial Infection within the Uterus
    9. 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. 10. Goldenberg R et al. N Engl J Med 2000;342:1500-1507 Potential Pathways from Choriodecidual Bacterial Colonization to Preterm Delivery
    11. 11. Goldenberg R et al. N Engl J Med 2000;342:1500-1507 Markers of Intrauterine Infection in Pregnant Women
    12. 12. •Microbiology: PolymicrobialPolymicrobial Bacterial Viral Fungal
    13. 13. 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 :
    14. 14. 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
    15. 15. 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
    16. 16. 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
    17. 17. Glucose concentration is measured with an auto analyzer (abnormal result <15 mg/dL). Glucose Concentration
    18. 18. 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
    19. 19. PCR Species specific PCR on AF samples now Available with 24h turnaround
    20. 20. Introducing ProteoGenix CLIA-certified Clinical Laboratory, dedicated to advancing maternal/fetal/neonatal diagnostic medicine From Proteogenix.com
    21. 21. 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
    22. 22. JAMA, July 28, 2004—Vol 292, No. 4 (Reprinted)
    23. 23. Diagnosis of Intra-amniotic Infection by Proteomic Profiling and Identification of Novel Biomarkers
    24. 24. Diagnosis of Intra-amniotic Infection by Proteomic Profiling and Identification of Novel Biomarkers
    25. 25. Diagnosis of Intra-amniotic Infection by Proteomic Profiling and Identification of Novel Biomarkers
    26. 26. Diagnosis of Intra-amniotic Infection by Proteomic Profiling and Identification of Novel Biomarkers
    27. 27. Neonatal and later Effects of perinatal sepsis
    28. 28. 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
    29. 29. 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
    30. 30. 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
    31. 31. Neonatal Neurologic Damage
    32. 32. Ferriero D. N Engl J Med 2004;351:1985-1995
    33. 33. 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
    34. 34. 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
    35. 35. 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
    36. 36. Neonatal Brain Injury Review Donna M. Ferriero, M.D. • N Engl J Med 2004;351:1985-95. • Copyright © 2004 Massachusetts Medical Society.
    37. 37. Ferriero D. N Engl J Med 2004;351:1985-1995 Selective Regional Vulnerability Determined According to Age at Insult
    38. 38. Ferriero D. N Engl J Med 2004;351:1985-1995 Evolution of Brain Injury as Seen with MRI
    39. 39. Ferriero D. N Engl J Med 2004;351:1985-1995 Mechanisms of Brain Injury in the Term Neonate
    40. 40. 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
    41. 41. PROM flow chart
    42. 42. Premature Labor
    43. 43. Group B Strep Leading cause of neonatal infection Major cause of neonatal sepsis
    44. 44. 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
    45. 45. Other pathogens
    46. 46. 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
    47. 47. 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
    48. 48. 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
    49. 49. 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)
    50. 50. 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
    51. 51. 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
    52. 52. 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
    53. 53. Perinatal Correlates of Ureaplasma urealyticum
    54. 54. Perinatal Correlates of Ureaplasma urealyticum
    55. 55. Perinatal Correlates of Ureaplasma urealyticum
    56. 56. Perinatal Correlates of Ureaplasma urealyticum
    57. 57. Perinatal Correlates of Ureaplasma urealyticum
    58. 58. 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
    59. 59. 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
    60. 60. 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.
    61. 61. 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
    62. 62. American Journal of Obstetrics & Gynecology DOI: 10.1016/j.ajog.2010.03.037 Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid
    63. 63. Azithromycin • 500 mg IV, then 250 po qd X 10-14 days
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