PLBW TAMANNA

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Periodontal infection andPeriodontal infection and

preterm low birth weightpreterm low birth weightinfantsinfants

Submitted by :

Tamanna(intern 2006 batch)


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IntroductionIntroduction

Preterm lowPreterm low--birth weight (PLBW), as defined bybirth weight (PLBW), as defined bythe 29th World Health assembly in 1976, is athe 29th World Health assembly in 1976, is abirth weight of less than 2500 g with abirth weight of less than 2500 g with agestational age of less than 37 weeksgestational age of less than 37 weeks..

very pretermvery preterm --Delivery at less than 32Delivery at less than 32 weeks,weeks, Extremely pretermExtremely preterm --delivery at less thandelivery at less than

2828 weeks .weeks .

Birth weights are considered to be:Birth weights are considered to be:

lowlow if


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Maternal age 34 yrsMaternal age 34 yrs

genetic factorsgenetic factors

the use of alcoholthe use of alcohol

poor prenatal carepoor prenatal care

poor maternal nutritionpoor maternal nutrition

urinary tract infectionurinary tract infection

smoking andsmoking and

low socioeconomic statuslow socioeconomic status

Recently periodontal infection has beenRecently periodontal infection has beenidentified as a risk factor for PLBWidentified as a risk factor for PLBW

Risk factorsRisk factors


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MechanismMechanism

Bacterial vaginosisBacterial vaginosis-- it is a gramit is a gramnegative, predominantly anaerobicnegative, predominantly anaerobicinfection of the vagina, usually diagnosedinfection of the vagina, usually diagnosed

from clinical signs and symptoms.from clinical signs and symptoms. It is a relatively common condition thatIt is a relatively common condition that

occursin about 10 % of all pregnancies.occursin about 10 % of all pregnancies.

It may ascend from vagina to the cervixIt may ascend from vagina to the cervix

and even result in inflammation of theand even result in inflammation of thematernalmaternal-- fetal membranesfetal membranes(chorioamnionitis)(chorioamnionitis)


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Extending beyond the membranes,Extending beyond the membranes,the organisms may appear in thethe organisms may appear in the

amniotic fluid compartment that isamniotic fluid compartment that isshared with the fetal lungs and orshared with the fetal lungs and ormay involve placental tissues andmay involve placental tissues andresult in exposure to the fetusviaresult in exposure to the fetusvia

the blood stream.the blood stream. It appears that inflammation of theIt appears that inflammation of the

uterus and membranes represent auterus and membranes represent acommon effector mechanism thatcommon effector mechanism thatresultsin preterm birth, and thus,resultsin preterm birth, and thus,either clinical or subclinical infectioneither clinical or subclinical infectionis a likely stimulus for increasedis a likely stimulus for increasedinflammation.inflammation.


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How periodontal infection leads toHow periodontal infection leads to

PLBWPLBW11Microorganisms along with theirMicroorganisms along with theirvirulence factors have the capabilityvirulence factors have the capability

to disseminate:to disseminate: DirectlyDirectly

IndirectlyIndirectly

Posing a threat to the fetoPosing a threat to the feto--placentalplacentalunit.unit.


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A periodontal infection may influenceA periodontal infection may influencethe pregnancy outcomes bythe pregnancy outcomes byproviding a source of gramproviding a source of gram--negativenegativeanaerobic organisms and bacterialanaerobic organisms and bacterial

componentssuch ascomponentssuch aslipopolysaccharides .lipopolysaccharides .

These can trigger the release ofThese can trigger the release ofimmune modulatorssuch as PGEimmune modulatorssuch as PGE22

and TNFand TNF--, which are normally, which are normallyinvolved in normal parturition, and ininvolved in normal parturition, and inturn, may influence the course ofturn, may influence the course ofpregnancypregnancy

Indirect mechanismIndirect mechanism


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Entry of inflammatory products (PgE2, Il-6, TNF- ),

endotoxin, and/or periodontal bacteria into thebloodstream and their translocation to the fetus anddecidual tissues


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Periodontal disease is a lowPeriodontal disease is a low--gradegradeinfection dominated by Graminfection dominated by Gram--

negative anaerobic andnegative anaerobic andmicroaerophilic bacteria resulting inmicroaerophilic bacteria resulting inlocal and systemicinflammatory andlocal and systemicinflammatory andimmune responses.immune responses.

Inflamed periodontal tissuesserve asInflamed periodontal tissuesserve asreservoirs for periodontal pathogens,reservoirs for periodontal pathogens,endotoxins, and inflammatoryendotoxins, and inflammatory

mediators.mediators.


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Hence, maternal periodontal diseaseHence, maternal periodontal diseasemay be connected with pretermmay be connected with preterm

delivery through mechanisms involvingdelivery through mechanisms involvinginflammatory mediators or a directinflammatory mediators or a direct

bacterial assault on the amnion.bacterial assault on the amnion.

Upregulation of proinflammatoryUpregulation of proinflammatory

cytokines resulting from the normalcytokines resulting from the normalhost response to an infectious agenthost response to an infectious agent

may represent the key mechanismmay represent the key mechanism

linking periodontal disease to PLBW.linking periodontal disease to PLBW.


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Microbiological products such asMicrobiological products such asendotoxin will trigger a host immuneendotoxin will trigger a host immune

response, causing both localresponse, causing both localinflammation and activation of solubleinflammation and activation of soluble

proinflammatory mediators such as ILproinflammatory mediators such as IL--

1, TNF1, TNF--alpha, and MMPs.alpha, and MMPs.

These inflammatory markers haveThese inflammatory markers havebeen shown to cross the placentalbeen shown to cross the placental

barrier and to cause fetal toxicity,barrier and to cause fetal toxicity,

resulting in preterm delivery and lowresulting in preterm delivery and low--birthbirth--weight babiesweight babies..


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Therefore, fetal exposure to oralTherefore, fetal exposure to oralpathogens, as evidenced by an IgMpathogens, as evidenced by an IgM

response, is associated with pretermresponse, is associated with pretermbirth, and the risk for preterm birth isbirth, and the risk for preterm birth isgreatest among fetuses thatgreatest among fetuses thatdemonstrate an inflammatorydemonstrate an inflammatory

response.response.Other studies have also providedOther studies have also provided

evidence that distant, lowevidence that distant, low--grade oralgrade oralinfection might trigger inflammation ofinfection might trigger inflammation of

the human maternalthe human maternal--fetal unit in afetal unit in amanner analogous to that seen withmanner analogous to that seen withbacterial vaginosisbacterial vaginosis


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microorganismsmicroorganisms

Triggering factorsTriggering factors

TNFTNF , cytokines etc., cytokines etc.

Premature labourPremature labour

Indirect mechanismIndirect mechanism


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Bacterial invasion of the choriodecidualBacterial invasion of the choriodecidual

space can activate the fetal membranes orspace can activate the fetal membranes ortrigger the maternal immune system totrigger the maternal immune system toproduce a variety of cytokines and growthproduce a variety of cytokines and growthfactors.factors.

The combination of increased fetal adrenalThe combination of increased fetal adrenalcortisol production, increased prostaglandincortisol production, increased prostaglandinproduction, the release of MMPs, andproduction, the release of MMPs, and

increased cytokines and chemokines mayincreased cytokines and chemokines maylead to myometrial contractions, membranelead to myometrial contractions, membranerupture, cervical ripening, and pretermrupture, cervical ripening, and pretermdelivery.delivery.

Direct mechanismDirect mechanism


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Furthermore, the inflammatory burdenFurthermore, the inflammatory burden

results in distress and fetal growthresults in distress and fetal growth

restriction.restriction.

Madianos et al. extended the work ofMadianos et al. extended the work ofSocransky et al.,shifting the focus toSocransky et al.,shifting the focus to

examine the potential role of maternalexamine the potential role of maternalinfection with specific organisms withininfection with specific organisms withinboth the orange and redboth the orange and red

complexes, because these are thecomplexes, because these are thecomplexes most strongly correlated tocomplexes most strongly correlated to

severe periodontal diseasesevere periodontal disease


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The highest rate of prematurity (66.7%)The highest rate of prematurity (66.7%)was observed among those motherswas observed among those mothers

without a protective red complexwithout a protective red complexIgG response coupled with a fetalIgG response coupled with a fetalimmunoglobulinM (IgM) response toimmunoglobulinM (IgM) response toorange complex microbes.orange complex microbes.

These data support the concept thatThese data support the concept thatmaternal periodontal infection in thematernal periodontal infection in theabsence of a protective maternalabsence of a protective maternalantibody response is associated withantibody response is associated with

the systemic distribution of oralthe systemic distribution of oralorganisms to the fetus, resulting inorganisms to the fetus, resulting inpreterm birth.preterm birth.


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The high prevalence of elevated fetalThe high prevalence of elevated fetalIgM to C. rectus among prematureIgM to C. rectus among premature

infants raises the possibility that thisinfants raises the possibility that thisspecific maternal oral pathogen mayspecific maternal oral pathogen may

serve as a primary fetal infectiousserve as a primary fetal infectious

agent eliciting preterm birth. Moreagent eliciting preterm birth. Morerecent findings support this claim:recent findings support this claim:

when subgingival bacteria werewhen subgingival bacteria wereevaluated together, P. micros and C.evaluated together, P. micros and C.

rectus were found to play a significantrectus were found to play a significantrole in increasing the risk for PLBW.role in increasing the risk for PLBW.


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Recently, F. nucleatum, a gramRecently, F. nucleatum, a gram--negative anaerobe ubiquitous to thenegative anaerobe ubiquitous to the

oral cavity, was isolated from theoral cavity, was isolated from theamniotic fluid, placenta, andamniotic fluid, placenta, and

chorioamnionic membranes of womenchorioamnionic membranes of women

delivering prematurely.delivering prematurely.22

To test theTo test thestrength of this finding, pregnant micestrength of this finding, pregnant mice

were infected with F. nucleatum,were infected with F. nucleatum,resulting in premature delivery,resulting in premature delivery,

stillbirths, and non sustained livestillbirths, and non sustained livebirthsbirths.(2).(2)


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The bacterial infection was restrictedThe bacterial infection was restrictedinside the uterus, without spreadinginside the uterus, without spreading

systemically, although invasion of thesystemically, although invasion of theendothelial cells lining the bloodendothelial cells lining the blood

vessels was also observed. Thevessels was also observed. The

bacteria then crossed thebacteria then crossed the

endothelium, proliferated inendothelium, proliferated insurrounding tissues, and finally spreadsurrounding tissues, and finally spreadto the amniotic fluid. This pattern ofto the amniotic fluid. This pattern of

infection paralleled that observed ininfection paralleled that observed inhumanshumans


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microorganismsmicroorganisms

Hematogenous spreadHematogenous spread

Fetoplacental unitFetoplacental unitinfectioninfection

chorioamnionitischorioamnionitis

Premature rupturePremature rupture

of membraneof membrane

Direct mechanismDirect mechanism


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Proposed biological model of periodontal disease and

preterm low birth weight8.


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Offenbacher etOffenbacher et al.al.(3)(3)were the first to report awere the first to report a

link between poor maternal periodontallink between poor maternal periodontalhealth and adverse pregnancy outcomes,health and adverse pregnancy outcomes,including preterm birth, in humans. Theyincluding preterm birth, in humans. Theycompared the periodontal conditions ofcompared the periodontal conditions of

women who had delivered a lowwomen who had delivered a low--birthbirth--weight infant with women who had givenweight infant with women who had givenbirth to a fullbirth to a full--term, normalterm, normal--weight infant.weight infant.

Women with 60 or more sites with clinicalWomen with 60 or more sites with clinical

attachment loss of 3attachment loss of 3 mm were muchmm were muchmore likely than periodontally healthymore likely than periodontally healthywomen to experience an adversewomen to experience an adversepregnancy outcomepregnancy outcome

Review of literatureReview of literature


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CaseCase controlcontrol

studystudy

NoNo. of. of

sbjsbj

No.No.ofof

cntrcntrll

findingsfindings ObstetrcalObstetrcal

Def ofDef of

casecaseOffenbaOffenba--cher etcher et

Al 1996Al 1996(3)(3)

JeffcoatJeffcoatetet al. 2001al. 2001(1,313(1,313patients)patients)(4)(4)

9393

NSNS

3131

NSNS

Cases had significantlyCases had significantlymore (3.1more (3.1 mm vs.mm vs.2.82.8 mm) and extensivemm) and extensiveCAL than controlsCAL than controls

Significant odds ratiosSignificant odds ratios(comparing severe(comparing severeperiodontitis (90+ sitesperiodontitis (90+ siteswith CAL 3with CAL 3 mm) tomm) tohealth (3 mm)) for PTBmm)) for PTB


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CohortCohort

studiesstudies

No.No.

ExpoExpo--sedsed

No.No.

unexunexposdposd

findingsfindings PeriodontitisPeriodontitisexposure definitionexposure definition

OffenbacherO

ffenbacheretet al. 2006al. 2006

(3)(3)

DrtbudakDrtbudak

etet al.al.20052005(5)(5)

735735(mild to(mild tosevereseveredisease)disease)

1111

285

285

2525

PTB (


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SignificanceSignificance Expectant mothers should beExpectant mothers should be

counseled in the importance of oralcounseled in the importance of oralhealth.health.

Regular dental examinations for allRegular dental examinations for all

pregnant patientspregnant patients Aggressive periodontal therapy forAggressive periodontal therapy forinfectionsinfections

Frequent reinforcement of oral hygieneFrequent reinforcement of oral hygiene

and dental care by medical providersand dental care by medical providers Preventive oral care servicesshould bePreventive oral care servicesshould be

provided as early in pregnancy asprovided as early in pregnancy aspossible.possible.


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If examination indicates a need forIf examination indicates a need forperiodontal therapy, theseperiodontal therapy, these

proceduresshould be scheduledproceduresshould be scheduledearly in the 2nd trimester.early in the 2nd trimester.

The presence of acute infection,The presence of acute infection,abscess, or other potentiallyabscess, or other potentiallydisseminating sources ofsepsis maydisseminating sources ofsepsis maywarrant prompt intervention,warrant prompt intervention,irrespective of the stage ofirrespective of the stage of

pregnancy.pregnancy.


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MitchellMitchell--Lewis etLewis et al.al. (6)(6) found that womenfound that womenwho received dental cleanings duringwho received dental cleanings during

pregnancy were less likely than untreatedpregnancy were less likely than untreatedwomen to give birth to a preterm, lowwomen to give birth to a preterm, low--birthbirth--weight infant (13.5% vs. 18.9%,weight infant (13.5% vs. 18.9%,PP == 0.36). Lopez et0.36). Lopez et al.al. (7)(7) reported that areported that a

regimen ofscaling, chlorhexidineregimen ofscaling, chlorhexidinemouthrinses, and frequent maintenancemouthrinses, and frequent maintenancecare in women with gingivitis reduced thecare in women with gingivitis reduced the

rate of preterm birth/low birth weightrate of preterm birth/low birth weightwhen compared to women with untreatedwhen compared to women with untreatedperiodontitis (2.5% vs. 8.6%,periodontitis (2.5% vs. 8.6%,PP


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ReferrencesReferrences1.1. Gibbs RS. The relationship betweenGibbs RS. The relationship between

infections and adverse pregnancyinfections and adverse pregnancyoutcomes: an overview. Ann Periodontoloutcomes: an overview. Ann Periodontol

2001: 6: 1532001: 6: 153163.163.

2.2. Hill GB: investigating the source of amnioticHill GB: investigating the source of amnioticfluid isolates of fusobacteria ,fluid isolates of fusobacteria , clin infect disclin infect dis16(suppl 4):423, 199316(suppl 4):423, 1993

3.3. Offenbacher S, Katz V, Fertik G, Collins J,Offenbacher S, Katz V, Fertik G, Collins J,Boyd D, Maynor G, McKaig R, Beck J.Boyd D, Maynor G, McKaig R, Beck J.

Periodontal infection as a possible riskPeriodontal infection as a possible riskfactor for preterm low birth weight. Jfactor for preterm low birth weight. JPeriodontol 1996: 67: 1103Periodontol 1996: 67: 11031113.1113.


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4.4. Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP,Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP,Goldenberg RL, Hauth JC. Periodontal infectionGoldenberg RL, Hauth JC. Periodontal infection

and preterm birth: results of a prospective study.and preterm birth: results of a prospective study.J Am Dent Assoc 2001: 132: 875J Am Dent Assoc 2001: 132: 875880.880.

5.5. Dortbudak O, Eberhardt R, Ulm M, Persson GR.Dortbudak O, Eberhardt R, Ulm M, Persson GR.Periodontitis, a marker of risk in pregnancy forPeriodontitis, a marker of risk in pregnancy for

preterm birth. J Clin Periodontol 2005: 32: 45preterm birth. J Clin Periodontol 2005: 32: 4552.52.6.6. MitchellMitchell--Lewis D, Engebretson SP, Chen J,Lewis D, Engebretson SP, Chen J,

Lamster IB, Papapanou PN. PeriodontalLamster IB, Papapanou PN. Periodontalinfections and preinfections and pre--term birth: early findings fromterm birth: early findings from

a cohort of young minority women in New York.a cohort of young minority women in New York.Eur J Oral Sci 2001: 109: 34Eur J Oral Sci 2001: 109: 3439.39.


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7.7. Lopez NJ, Da Silva I, Ipinza J, Gutierrez J.Lopez NJ, Da Silva I, Ipinza J, Gutierrez J.Periodontal therapy reduces the rate ofPeriodontal therapy reduces the rate of

preterm low birth weight in women withpreterm low birth weight in women withpregnancypregnancy--associated gingivitis. Jassociated gingivitis. J

Periodontol 2005: 76: 2144Periodontol 2005: 76: 21442153.2153.

8. Douglass C. Does periodontal diseaserelate to preterm low birth weight babies?

The Colgate Oral Care Report 2002;11:1-3.

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