chorio
TRANSCRIPT
ChorioamnionitisAKA 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/Neurologic injury
3. Developmental plasticity disorders
4. Pulmonary disease
Significance
Maternal Morbidity associated with IAI:
Septic shock
Coagulopathy
ARDS
Labor abnormalities, increased C/S rate
Uterine atony, PP hemorrhage inc X 2
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 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 duration of labor increases.
Obstetric risk factors for IAI
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.
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 of the Length of Gestation among Women Presenting in Spontaneous Labour with
Intact Foetal Membranes and Who Deliver Their Infants by Caesarean Section
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Potential Pathways from Choriodecidual Bacterial Colonization to Preterm Delivery
Goldenberg R et al. N Engl J Med 2000;342:1500-1507
Markers of Intrauterine Infection in Pregnant Women
•Microbiology:
PolymicrobialPolymicrobial
BacterialViral
Fungal
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 :
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
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
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
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 is evaluated with Chemstrip 9 Reagent Strips (abnormal result = trace or greater).
WBC/LE
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 medicine
From Proteogenix.com
Michael G. Gravett, M.D.Chair, Clinical Advisory Board & Co-Founder
Michael Gravett’s research has focused on the association of maternal genital tract infections and preterm birth. Among the first investigators in the nation to describe the association of maternal genital infections or intrauterine infections and preterm birth, Dr. Gravett has now developedthe first non-human primate model to study the mechanisms by which infection leads to prematurity. Dr. Gravett is an internationally-recognized expert on prematurity and serves on both a prematurity panel for the Institute of Medicine and on NIH Study Sections related to prematurity. He is currently Professor and Vice-Chair of Obstetrics & Gynecology and Director of Maternal-Fetal Medicine at the University of Washington. He is President of and serves on the Executive Council for the Infectious Disease Society for Obstetrics and Gynecology, and is listed in Who’s Whofor both Medicine and Science & Engineering and in the Best Doctors in America. He received his M.D. from UCLA.
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
JAMA, July 28, 2004—Vol 292, No. 4 (Reprinted)
Diagnosis of Intra-amniotic Infectionby Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infectionby Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infectionby Proteomic Profiling and
Identification of Novel Biomarkers
Diagnosis of Intra-amniotic Infectionby Proteomic Profiling and
Identification of Novel Biomarkers
Neonatal and later Effectsof
perinatal sepsis
Mechanisms of Disease
Effect of In Utero and Early-Life Conditionson 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
current concepts
Chronic Lung Disease after Premature BirthEugenio Baraldi, M.D., and Marco Filippone, M.D.N Engl J Med
2007;357:1946-55.Copyright © 2007 Massachusetts Medical Society
Causes of chronic lung disease
Premature newbornsBronchopulmonary dysplasia PrematurityStatus after respiratory distress syndromeTerm and near-term newbornsPneumonia or sepsisAspiration syndromesPersistent pulmonary hypertension of the newbornPulmonary hypoplasiaDiaphragmatic herniaCongenital heart disease
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
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
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
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
Neonatal Brain InjuryReview
Donna M. Ferriero, M.D.
• N Engl J Med 2004;351:1985-95.
• Copyright © 2004 Massachusetts Medical Society.
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
American Journal of Obstetrics & Gynecology. 201(3):230-40, 2009 Sep.
Premature ROM
PROM flow chart
Premature Labor
Group B Strep
Leading cause of neonatal infectionMajor cause of neonatal sepsis
Treatment of IAI
ACOG recommendations
Ampicillin + GentamycinAdd Clindamycin if C/S
Recent increase in clindamycin resistant c. Difficille colitis has caused some centers toSwitch to Timentin or Zosyn
Other pathogens
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
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
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
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 & GynecologyJanuary 2008 (Vol. 198, Issue 1, Pages 1-3)
MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIESRESEARCH 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
UreaplasmaCertain type of chronic lung disease of newborns is associatedwith Ureaplasma urealyticum infection in uteroYOKO HONMA , 1 YUKARI YADA , 2 NAOTO TAKAHASHI , 2 MARIKO Y MOMOI 2AND YOSHIKAZU NAKAMURA 2Departments of 1 Pediatrics and 2 Public Health, Jichi Medical School, Tochigi, Japan
PEDIATRICS Volume 123, Number 5, May 2009
Perinatal Correlates of Ureaplasma urealyticum inPlacenta Parenchyma of Singleton PregnanciesThatEnd 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
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 Chorioamnionitis, Preterm Delivery, and Fetal Pneumonia in Rhesus Macaques
Miles J. Novy, MD et al
American Journal of Obstetrics & GynecologyJanuary 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
American Journal of Obstetrics & GynecologyJanuary 2008 (Vol. 198, Issue 1, Pages 1-3)
• ConclusionU 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.
American Journal of Obstetrics & GynecologyDOI: 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
American Journal of Obstetrics & GynecologyDOI: 10.1016/j.ajog.2010.03.037
Noninvasive diagnosis of intraamniotic infection: proteomic biomarkers in vaginal fluid
Azithromycin
• 500 mg IV, then 250 po qd X 10-14 days