Chorio

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