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Steven Lovrich, Gundersen Lutheran Medical Foundation
ASSOCIATION BETWEEN MYCOPLASMA INFECTION
AND COMPLICATIONS DURING PREGNANCY
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Mollicutes: “soft skin” Intracellular parasite Lack cell wall Trilayered external membranes
2 genera:Mycoplasma
14 human species; three pathogenic M. hominis M. genitalium M. pneumoniae
Ureaplasma 2 human species; both pathogenic
U. urealyticum U. parvum
(Taylor-Robinson et al., An International Journal of Obstetrics and Gynecology, 2010)
MYCOPLASMA
Microscopic view of Mycoplamsas
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Facultative anaerobes
Pleomorphic
Limited genome
Unable to gram stain
Culture?
(Larsen et al., Infectious Diseases in Obstetrics and Gynecology, 2010)
LABORATORY CHARACTERISTICS
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Normal Flora/Non-pathogenic colonizers?
Pathogenic?
Opportunistic pathogen Location of colonization Host immune response Conditions of pregnancy Co-infections Genetic factors Environmental factors
VIRULENCE
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Adherence to host cell by mycoplasmal adhesion proteins/lipoproteins
Stimulate secretion of pro-inflammatory cytokines (tumor necrosis factor-, interleukin, & interferon-γ)
Stimulate release of prostaglandins which leads to protease production
Protease can cause adverse pregnancy outcomes miscarriage, pre-term labor, bacterial vaginosis, chorioamnionitis,
spontaneous abortion, perinatal morbidity & mortality, PROM, etc.
PATHOGENICITY DURING PREGNANCY
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Problems:Genital tract infections associated with approximately 50% of
preterm deliveries
13% of pregnancies in the U.S. result in preterm delivery or low infant birth weight
60% of mortality among infants (with no anatomic/chromosomal defects) is low birth weight
(Kataoka, Journal of Clinical Microbiology, 2006), (Taylor-Robinson, An International Journal of Obstetrics and Gynecology, 2010)
PRE-TERM BIRTH
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Strongly associated with: Chorioamnionitis Pelvic inflammatory disease Bacterial vaginosis
Pregnancy Lower gestational age at delivery Lower birth weight Increased neonatal morbidity & mortality Increase risk for miscarriage at 14 weeks
Infant Pneumonia
MYCOPLASMA HOMINIS
Mycoplasma hominis on agar plate
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Causative agent of urethritis
Associated with cervicitis, PID, and endometritis in women
Pregnancy- Unknown
(Taylor-Robinson, An International Journal of Obstetrics and Gynecology, 2010)
MYCOPLASMA GENITALIUM
Electron micrograph of M. genitalium
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In 2002, U. urealyticum & U. parvum distinguished as separate species
Therefore, studies pre-2002 confounded
UREAPLASMA SPP.
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Colonization of placenta= increases risk for fetal & maternal inflammation Increase risk of preterm labor Increase risk for miscarriage (@14 weeks)
Vertically transmitted to fetus potentially causing: Bacteremia Pneumonia Chronic lung disease Nervous system infections
UREAPLASMA UREALYTICUM
Electron micrograph of U. urealyticum
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Vertically transmitted to fetus in utero or during delivery Bacteremia, pneumonia, chronic lung disease, & nervous
system infections
More prevalent in amniotic fluid of preterm pregnancies than U. urealyticum
If colonization occurs can cause: PROM Preterm labor Chorioamnionitis (in mother) Early onset sepsis & BPD (bronchopulmonary dysplasia) in
baby
(Larsen et al., Infectious Diseases in Obstetrics and Gynecology, 2010)
UREAPLASMA PARVUM
Electron micrograph of U. parvum
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Objectives:
1. Determine if colonization of either Ureaplasma species had association with miscarriage or preterm labor
2. To perfect detection methods and discrimination of species
Methods: Tested 239 pregnant women (PCR) from the
La Crosse area for colonization with Ureaplasma
urealyticum & parvum during early prenatal period
ASSOCIATION OF UREAPLASMA WITH PRETERM BIRTH
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239 patient samples at start
192 follow ups at Gundersen Lutheran 47 lost
27 adverse events 23 preterm birth (≤36 weeks) or miscarriage 4 preterm labor (stopped)
Significance of Colonization P-value ≤ 0.05
SUMMARY OF RESULTS
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RESULTS
Bacterial characteristics and cause of early delivery for the preterm birth group. Presence (+/-) of: Cause of
Subject Gestational wk at delivery U. parvum U. urealyticum preterm deliverya
1 6 + - Miscarriage 2 9 + - Miscarriage 3 18 + - Miscarriage 4 26 + - PROM 5 30 + - Preeclampsia 6 31 - - PROM 7 34 + - FSUA 8 35 + + Preeclampsia 9 35 + - Preeclampsia 10 35 + - FSUA 11 35 + - FSUA 12 35 + - FSUA 13 36 + - FSUA 14 36 + - FSUA 15 36 - + FSUA 16 36 - - FSUA 17 36 - - FSUA 18 36 + - FSUA 19 36 + - FGR 20 36 + - Preeclampsia 21 36 + - Preeclampsia 22 36 - - FSUA 23 36 + - FSUA
a PROM, premature rupture of the membranes; FSUA, failure to suppress uterine activity; FGR, fetal growth restriction.
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Table 2. Association between urogenital infection with ureaplasmas and miscarriage, preterm
labor controlled by treatment, and/or preterm birth.
Pregnancy outcome (no.) No. (%) U. urealyticum p value No. (%) U. parvum p value Normal (165) 16 (10) NA 84 (51) NA Abnormal (27) 2 (7) 0.999 22 (81) 0.003
Miscarriage (3) 0 0.999 3 (100) 0.245 Preterm birth (20) 2 (10) 0.999 15 (75) 0.057 Preterm labor (4) 0 0.999 4 (100) 0.122
RESULTS
•27 abnormal pregnancy outcomes -25 associated with U. parvum•U. parvum strongly associated with their occurrence (p=0.003)
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Previous study Small population sample Little diversity & limited risk factors
Parameters:Project collaboration with WiNHR
(Wisconsin Network for Healthcare Research)
4 different hospital sites: 200 samples per site Aurora Health, Gundersen Lutheran, UW-Hospital (Madison), Marshfield Cinic
Test for 4 Mycoplasma species
*Objective: To determine if any of the 4 Mycoplasma species correlate with pregnancy abnormalities or adverse outcomes Examine multiple risk factors
CURRENT STUDY
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Normal healthy pregnant women targeted in 4 sites across Wisconsin
Swabs of urogenital tract (~12 weeks)
Samples blinded
DNA extracted and forwarded to Gundersen Lutheran
Polymerase Chain Reaction (PCR)
Hybridization assay
EXPERIMENTAL DESIGN
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HYBRIDIZATION ASSAY
Aminated probe(4 species specific probes used)
Biotinylatedamplification product
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HYBRIDIZATION ASSAY
Aminated probe(4 species specific probes used)
Biotinylatedamplification product
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HYBRIDIZATION ASSAY
E
Aminated probe(4 species specific probes used)
Biotinylatedamplification product
Strepavidin-HPO conjugate
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HYBRIDIZATION ASSAY
E(S)
Aminated probe(4 species specific probes used)
Biotinylatedamplification product
Strepavidin-HPO conjugate
Substrate
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PCR hybridization assay completed on samples
Correlations between species and adverse pregnancy outcomes
STUDY PROGRESS
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Thanks to: Microbiology Research Laboratory Gundersen Lutheran Medical Foundation Dr. Steve Callister Dean Jobe
ACKNOWLEDGEMENTS