25. infeksi intrauterine

8/17/2019 25. Infeksi Intrauterine

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• Infeksi intrauterin atau korioamnionitis merupakan infeksi pada cairanamnion, se aput korioamnion dan atauuterus !an" tim#u se"era se#e umatau padasaat persa inan !an" dise#a#kan o e$ #akteri

• Korioamnionitis di$u#un"kan den"an %&'

(&) kasus sepsis neonata dini danp


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• Infeksi ini#er$u#un"an den"anketu#an peca$ dini dan persa inan

ama*


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+am#ar %* Ko onisasi #akteri koriodesidua dapat men!e#a#kan persa inanpremaTUR


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ene itian terak$ir mem#uktikanadan!a $u#un"an

• Infeksi den"an ke ainan neuro o"is termasuksere#ra pa si

• Se ain itu -u"a dapat men!e#a#kan sepsis,respira

tor!distress, ke-an",perdara$an intra.entriku ar• #erat a$ir renda$*• ada i#u -u"a dapatmen!e#a#kan sepsis,

endometritis pasca persa inan dan infeksi uka•

Infeksi intrauterin dise#utkan se#a"ai sa a$ satu faktor pen!e#a# utama dari persa inanpreterm


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ETIOLOGI• Or"anisme pen!e#a# dari korioamnionitis serin"ka

imu tipe

• +i##s, dkk/012%3 men"identi4kasikanmikroor"anisme !an" ditemukan da am cairanamnionpasien den"an korioamnionitis !aitu5akteroides Sp /%6)3, +ardnere a .a"ina is/%()3,"rup 7 streptokokus /0%)3, streptokokus aero#

-enis ain /08)3, E*co i/0&)3,dan "ram ne"atif ain /0&)3*

•

9ampir semua #akteri da am pene itian terse#utmerupakan #akteri !an" ditemukan pada sediaanapus :anita den"an .a"inosis#akteria *

• 5an!ak pene itian men"$u#un"kan ke-adian korioa

mnionitis den"an .a"inosis #akteria


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• Korioamnionitis ter-adi pa in" serin" saat persa inan sesuda$ peca$n!ase aput ketu#an* ;a aupun san"at

-aran", korioamnionitis dapat -u"a ter-adipadakeadaan dimana se aput ketu#an masi$ intak

•

Se#an!ak 8) dari neonatus !an" a$ir dari i#u den"an korioamnionitisden"an peca$n!a se aput ketu#an <%( -am se#e um persa inan, akan menderita#akteremia* 5i a peca$n!a se aput ketu#an ter-adi=%( -am maka se#an!ak 0>)neonatusakan men"a ami #akteremia

• +e-a a pada i#u dapat asimtomatis atau$an!a #erupa demam rin"an dan -aran" men!e#a#kan sepsis pada i#u*

•

Streptokokus "rup A -u"a dapat men!e#akan infeksi -anin dan ron""a amnion pada se aput ketu#an !an"masi$ intak

• Or"anisme pen!e#a# infeksi men!e#ar pertama ka i

ke da am ruan" koriodesidua, dan pada #e#erapakasus dapat me intas me a ui mem#ran korioamnion


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• Setiap ke$ami an den"an korioamnionitismerupakan faktor risiko pen!e#a#prematuritas dan ketu#an peca$ dini* 5an!ak pene itian !an" men"$u#un"kanantara korioamnionitis den"an persa inan prematur*

• Teori !an" pa in" #an!akdiper"unakansaat ini ada a$ teori in.asi #akteri dariruan" koriodesidua, !an"memu ai ter-adin!a proses persa inan preterm* 9a ini dikarenakan pe

epasan endotoksin dan eksotoksin o e$ #akteriakan men"akiti.asi desidua dan mem#ranfetusuntuk memproduksi #e#erapa sitokin, !an"diantaran!a tumor nekrosis factor'?

• /TNF' ?3, inter eukin'0?, inter eukin'07,inter eukin'@, inter eukin'2, dan"ranu ositeco oni stimu atin" factor /+ sF3*


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Kemudian se uru$ sitokin, endotoksin daneksotoksin akan menstimu asi sintesis prosta" andin !an"akan terakumu asi den"ansintesis dan pe epasan meta oprotease dan komponen #ioaktif ainn!a*

rosta" andin akan menstimu asi kontraksi uterussementara meta oprotease akanmen!eran"mem#ran korioamnion !an" akan men!e#a#kanpeca$n!a mem#ran*Meta oprotease akanmem#entuk ko a"en di ser.iks !an"men!e#a#kan ter-adin!aper unakan ser.iks

ersa inan prematur dise#a#kan aki#at -anin itu sen

diri* ada -anin !an"terinfeksi ter-adi penin"katan kadar sekresi kortikotropin aki#at penin"katan dari corticotropin re easin" $ormone / R93 dari$ipota amus -anin dan -u"a produksi R9dari p asenta* 9a ini akan menin"katkan kadar produksi adrena -anin #erupa penin"katan kortiso


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DIAGNOSIS• Tanda dan "e-a a k inis korioamnionitis me iputi• Bemam /su$u intrapartum = 0&&*(C F atau = 8>,2C 3• Takikardia i#u /=0%&D menit3• Takikardia -anin /=0@&D menit3• airan ketu#an #er#au atau tampak

puru en6*uterus tera#a te"an"• eukositosis i#u / eukosit 06*&&&'02*&&& se mm835i a terdapat

dua dari enam "e-a a diatas ditemukan pada ke$ami an, maka

risikoter-adin!a neonatasepsis menin"kat*+i##s, dkk men"emukakan "e-a adan tanda infeksi intrapartum !aitu su$ui#u G 8>,2C dan % atau

e#i$ dari kondisi di#a:a$ iniH takikardia i#u /=0&&D menit3,takikardia -anin /=0@& D menit3, n!eri uterus, cairanamnion #er#au dan eukositosisi#u /=06*&&& se mm

• Korioamnionitis serin"ka i #ukan suatu "e-a a akut, namunmerupakan suatu proses kronis dan tidak menun-ukkan "e-a asampai persa inan dimu ai atau ter-adi ketu#an peca$ dini* 5a$kansampai sete a$ persa inan seka ipun pada :anita !an" ter#uktimemi iki korioamnionitis /me a ui pemeriksaan $isto o"is atau

ku tur3 dapat tidak ditemukan tanda k asik diatas se ain tanda'tanda prematuritas


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Terdapat #e#erapa metode a#oratorium ain !an" di$arapkan dapatmem#antu pene"akkan dia"nosis, #e#erapa diantaran!a sepertipemeriksaan serum R

• 'reati.e protein materna , pemeriksaan esterase eukosit cairanamnion, dan deteksi asam or"anik #akteria den"an kromato"ra4"as'cairan

• enin"katan kadar R memi iki spesi4sitas !an" tin""i untuk

dia"nosis korioamnionitis* Kadar R rata'rata pada ke$ami anada a$ &,>'&,1 m" d * Terdapat penin"katan sedikitse amapersa inan

• emeriksaan an"sun" dari cairan amnion dapat mem#erikan kriteria !an" e#i$ pasti dari korioamnionitis* Kom#inasi pe:arnaan+ram dan ku tur dari $asi amniosintesis merupakan metodedia"nostik ter#aik

• Bitemukann!a #akteri "rampositif memi iki ni ai prediktif positif/ positif predicti.e .a ue 3 18,8), sedan"kanditemukann!a"ram ne"atif memi iki ni ai prediktif ne"atif 26,() / ne"atifpredicti.e.a ue


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• N 3* Akurasi tes ter"antun" dari konsentrasi #akteri saat pen"am#i ansampe

• ada pasien den"an suspek korioamnionitis, kadar " ukosacairanamnion !an" renda$ merupakan prediktor !an" #aikdari $asi positif ku tur cairanamnion namun merupakanprediktor !an" #uruk untuk korioamnionitis secara k inis

• Bitemukann!a eukosit esterase anti"en pada cairanamnion memi iki sensiti.itas10) dan ni ai 16)*Beteksiasam or"anik #akteri den"an men""unakan kromato"ra4"as'cairancukup sensitif namun memer ukan a at !an"rumit dan tidak praktis

• 9asi pemeriksaan mikroskopik !an" menun-an" dia"nosis korioamnionitisada a$ ketika ter i$at set

eukosit mononuc ear dan po imonorfonuk earmen"in4 trasise aput korion* Se#e um %& min""u $ampir semua se eukosit po imorfonuk ear ada a$ se !an" #erasadari i#u, sedan"kan se an-utn!a merupakan responin amasidari -anin


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PENATALAKSANAAN


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PENATALAKSANAAN• Korioamnionitis diterapi antimikro#a dan -anin

di a$irkan tanpa memandan"usia "estasi*• Anti#iotika !an" di#erikan ada a$ anti#iotika intra

.ena #erspektrum uas* Untuk se#a"ian #esarkasus, cukup di"unakan anti#iotika tun""a *

Terdapatpene itian !an" mem#uktikan #a$:apem#erian anti#iotika

intrapartum di#andin"kanden"an postpartumakan menurunkan ke-adian sepsis L pneumonianeonata danmor#iditas postpartum i#u*

• Standar #aku -enis pem#erian anti#iotika untukko

rioamnionitis akut #e um ada, #an!ak studi me akukan e.a uasi ter$adappem#erian anti#iotika* Terdapat studi !an" merekomendasikanpem#erianampisi in/% " setiap @ -am3 ditam#a$ den"an "entamisin /0,&'0,6m" k" setiap 2 -am3


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• Re"imen intra.ena !an" direkomendasikan termasuk cefoDitin /( %"r3,cefotetan /%D%"r3, piperasi inatau me oci in /(D8'("r3, ampisi in su #aktam

/(D8"r3,tikarsi in k a.u anat /(D8"r3*• ada kasus !an" e#i$ #erat misa n!a pada sepsisdapat di#erikan terapi kom#inasi !an" terdiri daripenisi in atau ampisi in,

• Amino" ikosidadan a"en anaero# seperti k indamisin /8D1&&"r3* iteratur ain men"an-urkanpem#erian"entamisin 6m" k"55 $ari dosis tun""a

• ada korioamnionitis amapem#erian anti#iotika #e um ada standar #aku* em

#erian anti#iotika intra.enadapat di an-utkan$in""a (2'>% -am #e#as demam, kemudiandi an-utkan den"ananti#iotika ora * Kepustakaan

ain men!arankan pem#erian terapi parentera$in""a0'% $ari postpartum, tanpa tam#a$ananti#iotika ora sesuda$n!a


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• i i$an cara persa inan pada kasus korioamnionitis se#aikn!a per.a"inam*J

• Jika persa inan tidak tim#u spontan, maka di akukan induksi

persa inan, #aik den"anmedikamentosa atau mekanik• ersa inan pera#dominam menin"katkan risikodemampostpartum aki#at infeksi /endometritis3 pada i#u*Endometritis dapatter-adipada 8&) pasien den"an persa inan pera#dominam,

di#andin"kan risiko padapersa inan per.a"inam $an!a 0&)* Mor#iditas i#u menin"kat 6D ipat padapersa inanpera#dominam -ika di#andin"kanden"an persa inan per.a"inam

• Namunpersa inan pera#dominam dapat dipertim#an"kan

#i a persa inan diperkirakan #e umse esai da am inter.a 0% -am sete a$ dia"nosis dite"akkan* 9a ini didasarkandarisuatu pene itian !an" men"emukakan tidak terdapatn!a per#edaan penin"kataninfeksi neonatus -ika -arak antaradia"nosis korioamnionitis dan persa inan < 0% -am,namun

penin"katan ke-adian infeksi neonatus sete a$ inter.a 0%am #e um da at di astikan*


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MORBIDITAS DAN MORTALITASAKIBAT KORIOAMNIONITIS

• Korioamnionitis men"aki#atkan morta itas perinata !an"

si"ni4kan, terutamapada neonatus den"an #erat #adana$ir renda$, dimana ter-adi penin"katan 8'(D ipat kematian perinata diantara neonatusden"an #erat a$ir !an" renda$ !an"di a$irkan dari i#u!an" menderita korioamnionitis* Se ain itu ter-adi -u"a

ke-adian respirator! distress s!ndrome/RBS3, perdara$an intra.entriku ar, dan sepsisneonataatau menin"itis

• Janin memi iki risiko tin""i ter$adap ke-adianpneumonianeonata ataupun kon"enita aki#at aspirasi cairan amion !an" terinfeksi*Korioamnionitis di$u#un"kanden"an %&'(&) kasus sepsis neonata danpneumonia*Korioamnionitis merupakan pen!e#a# n!atater-adin!a mor#iditas materna ,namun -aran"men"aki#atkan morta itas materna * 5akteremia dapatter-adi pada %' 6) kasus*

• Infeksi intrapartum menin"katkan risiko infeksi puerpura is


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• TERIMA KASI9


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• reterm de i.er! is t$e c$ief pro# em in o#stetrics toda!,accountin" for >& percent of perinata morta it! and near !$a f of on"'term neuro o"ic mor#idit!* 0,% ApproDimate ! 0&percent of a #irt$s are preterm, #ut most of t$e seriousi ness and deat$ is concentrated in t$e 0 to % percent ofinfants :$o are #orn at ess t$an 8% :eeks of "estation and:$o :ei"$ ess t$an 06&& "* ApproDimate ! %& percent ofpreterm #irt$s are t$e resu t of a p$!sician s decision to#rin" a#out de i.er! for materna or feta indications, andt$e remainder fo o: t$e spontaneous onset of a#or orrupture of t$e mem#ranes* 8 T$e rate of preterm de i.er!$as not decreased in t$e past se.era decades, ( #ut t$esur.i.a rate of infants de i.ered premature ! $asincreased, so t$at 2& percent of infants :ei"$in" 6&& to0&&& " no: sur.i.e* T$e percenta"e of sur.i.ors :it$$andicaps, $o:e.er, $as c$an"ed itt e, so t$at t$ea#so ute num#er of sur.i.in" preterm infants :it$$andicaps $as increased* %,6

http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007


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• ORGANISMS


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• 5acteria ma! in.ade t$e uterus #! mi"ration from t$e a#domina ca.it! t$rou"$ t$e

fa opian tu#es, inad.ertent need e contamination at t$e time of amniocentesis or

c$orionic'.i us samp in", $emato"enous spread t$rou"$ t$e p acenta, or passa"e t$rou"$

t$e cer.iD from t$e .a"ina*• In :omen in spontaneous preterm a#or :it$ intact mem#ranes, t$e most common !

identi4ed #acteria are Ureaplasma urealyticum, Mycoplasma hominis, Gardnerella

vaginalis, peptostreptococci, and #acteroides species P a .a"ina or"anisms of re ati.e !

o: .iru ence* %&'%6 T$e or"anisms often associated :it$ "enita tract infection in

nonpre"nant :omen, Neisseria gonorrhoeae and Chlamydia trachomatis, are rare ! found

in t$e uterus #efore mem#rane rupture, :$ereas t$ose most often associated :it$

c$orioamnionitis and feta infection after mem#rane rupture, "roup 5 streptococci

and Escherichia coli, are found on ! occasiona !* Rare !, nonQ"enita tract or"anisms, suc$

as mout$ or"anisms of t$e "enus capnoc!top$a"a, are found in t$e uterus in association

:it$ preterm a#or and c$orioamnionitis %@ t$ese or"anisms ma! reac$ t$e uterus t$rou"$

t$e p acenta from t$e circu ation or per$aps #! ora Q"enita contact* Ne.ert$e ess, most

#acteria found in t$e uterus in association :it$ preterm a#or are of .a"ina ori"in*

A t$ou"$ it $as not #een studied eDtensi.e !, intrauterine .ira infection is pro#a# ! not a

common cause of spontaneous preterm de i.er!* %>

http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007


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• TIMING OF INFECTION


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TIMING OF INFECTION• ;$! .er! ear !, #ut not ater, preterm de i.eries are associated :it$

intrauterine infection $as ne.er #een satisfactori ! eDp ained* It is a so notc ear :$en t$e #acteria ascend from t$e .a"ina* 9o:e.er, recente.idence su""ests t$at intrauterine infection ma! occur uite ear ! in

pre"nanc! and remain undetected for mont$s* For eDamp e, U.urealyticum $as #een detected in some samp es of amniotic uid o#tainedfor routine c$romosoma ana !sis at 06 to 02 :eeks of "estation* Most oft$ese :omen $ad de i.er! at around %( :eeks* 8&'8% Furt$ermore, $i"$concentrations of inter eukin'@ in t$e amniotic uid at 06 to %& :eeks:ere associated :it$ spontaneous preterm de i.er! as ate as 8% to 8(

:eeks* 88,8(• In anot$er eDamp e su""estin" c$ronic infection, $i"$ 4#ronectin

concentrations in t$e cer.iD or .a"ina at %( :eeks /considered a markerof upper "enita tract infection3 :ere associated :it$ t$e de.e opment ofc$orioamnionitis an a.era"e of > :eeks ater* 86 Fina !, somenonpre"nant :omen :it$ #acteria .a"inosis $a.e intrauterineco oni ation associated :it$ c$ronic p asma'ce endometritis* 0(,8@ It ist$erefore possi# e t$at t$e intrauterine co oni ation associated :it$spontaneous preterm a#or is present at conception* It is important toemp$asi e t$at most of t$ese c$ronic upper "enita tract infections remainas!mptomatic and are not associated :it$ fe.er, a tender uterus, orperip$era '# ood eukoc!tosis*

http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007


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• If intrauterine or"anisms are not c eared :it$in four to ei"$t :eeksafter t$e eDpandin" mem#ranes sea t$e endometria ca.it! nearmid'pre"nanc!, t$e infection often #ecomes s!mptomatic andresu ts in spontaneous preterm a#or or rupture of t$e mem#ranes*Accordin" to t$is scenario, once t$e or"anisms a read! in t$e uterus

are destro!ed #! t$e mot$er s immune s!stem, fe: ne:intrauterine infections occur as on" as t$e mem#ranes remainintact, since or"anisms no on"er ascend from t$e .a"ina to t$euterus* A t$ou"$ unpro.ed, t$is $!pot$esis ma! eDp ain t$efre uent association #et:een infection and ear ! preterm de i.er!and t$e re ati.e rarit! of intrauterine infection as :omen approac$

term* An a ternati.e $!pot$esis to eDp ain t$is association is re atedto t$e timin" of t$e initiation of t$e feta immune response* It ma!#e t$at on ! :it$ a maturin" immune s!stem is t$e fetus a# e to"enerate t$e c!tokine or $ormona response necessar! to initiate

a#or*

• BACTERIAL VAGINOSIS


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BACTERIAL VAGINOSIS• ;omen :$o $a.e #acteria .a"inosis, de4ned as a decrease in

t$e norma ! occurrin" acto#aci us species and a massi.eincrease in ot$er or"anisms, inc udin" G. vaginalis, #acteroidesspecies, mo#i uncus species, U. urealyticum, and M.hominis, $a.e a dou# ed risk of spontaneous preterm de i.er!*8>'(0 It is unkno:n :$et$er #acteria .a"inosis can actua !cause preterm a#or and de i.er! if t$e or"anisms do notascend into t$e uterus* 5acteria .a"inosis is associated :it$increased concentrations of e astase, mucinase, and sia idase

in t$e .a"ina and cer.iD* (%,(8 9o:e.er, since t$e .ast ma-orit!of :omen :$o $a.e ear ! spontaneous preterm de i.er! $a.eor"anisms in t$e uterus, it ma! not #e necessar! to in.oke t$e

oca action of .a"ina infection as t$e cause of t$e pretermde i.er!* It is more ike ! t$at #acteria .a"inosis is a marker ofintrauterine co oni ation :it$ simi ar or"anisms* %6,((,(6 If.a"ina infection a one /in t$e a#sence of ascendin" infection3or infections suc$ as periodontitis (@ and urinar! tract infection(> actua ! cause spontaneous preterm de i.er!, t$emec$anisms are unkno:n* One possi# e eDp anation isacti.ation of a oca in ammator! response #! c!tokines or

endotoDins carried in t$e # ood from t$e .a"ina to t$e uterus*

• MECHANISMS OF PRETERM DELIVERY DUE TO INFECTION

http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007http://www.nejm.org/doi/full/10.1056/NEJM200005183422007


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• Bata from anima , in .itro, and $uman studies a pro.ide a consistent picture of$o: #acteria infection resu ts in spontaneous preterm de i.er! / Fi"ure 8 FIGURE3 otentia at$:a!s from $oriodecidua 5acteria o oni ation to retermBe i.er!*3*%2,%1,(2'62 5acteria in.asion of t$e c$oriodecidua space, actin" in partt$rou"$ re ease of endotoDins and eDotoDins, acti.ates t$e decidua and t$e fetamem#ranes to produce a num#er of c!tokines, inc udin" tumor necrosis factor ?,inter eukin'0?, inter eukin'07, inter eukin'@, inter eukin'2, and "ranu oc!te co on!'stimu atin" factor* %2,%1,(2'62 Furt$ermore, c!tokines, endotoDins, and eDotoDinsstimu ate prosta" andin s!nt$esis and re ease and a so initiate neutrop$ic$emotaDis, in4 tration, and acti.ation, cu minatin" in t$e s!nt$esis and re ease ofmeta oproteases and ot$er #ioacti.e su#stances* T$e prosta" andins stimu ateuterine contractions :$i e t$e meta oproteases attack t$e c$orioamnioticmem#ranes, eadin" to rupture* T$e meta oproteases a so remode t$e co a"en int$e cer.iD and soften it* 6>'61

• Ot$er pat$:a!s ma! $a.e a ro e as :e * For eDamp e, prosta" andinde$!dro"enases in c$orionic tissue inacti.ate prosta" andins produced in t$eamnion, pre.entin" t$em from reac$in" t$e m!ometrium and causin" contractions*@&'@% $orionic infection decreases t$e acti.it! of t$ese de$!dro"enases, a o:in"increasin" uantities of prosta" andins to reac$ t$e m!ometrium* Anot$er pat$:a!#! :$ic$ infection ma! cause preterm de i.er! in.o .es t$e fetus itse f* In fetuses:it$ infections, increases in #ot$ feta $!pot$a amic and p acenta production ofcorticotropin're easin" $ormone cause an increase in feta corticotropin secretion,:$ic$ in turn increases feta adrena production of cortiso * T$e increase in cortisosecretion resu ts in increased production of prosta" andins* @8 A so, :$en t$e fetusitse f is infected, t$e feta production of c!tokines is increased and t$e time tode i.er! is marked ! decreased* @( 9o:e.er, t$e re ati.e contri#utions of t$ematerna and t$e feta compartments to t$e o.era in ammator! response areunkno:n

• MARKERS OF INFECTION

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• Intrauterine infection is often c$ronic, and it is usua ! as!mptomatic unti a#or #e"ins ort$e mem#ranes rupture* E.en durin" a#or, most :omen :$o are ater demonstrated /#!$isto o"ic 4ndin"s or cu ture3 to $a.e c$orioamnionitis $a.e no s!mptoms ot$er t$anpreterm a#or P no fe.er, a#domina pain, or perip$era '# ood eukoc!tosis, and t$ere isusua ! no feta tac$!cardia* @6 T$erefore, identif!in" :omen :it$ intrauterine infections is

a ma-or c$a en"e* Su#stances found in a#norma uantities in amniotic uid and at ot$ersites in :omen :it$ intrauterine infection are isted in Ta# e 0 TABLE 1 Markers ofIntrauterine Infection in re"nant ;omen** @@

• T$e #est'studied site of infection is t$e amniotic uid* As :e as containin" #acteria,amniotic uid from :omen :it$ intrauterine infections $as o:er " ucose concentrations,$i"$er :$ite'ce counts, and $i"$er concentrations of comp ement 8 and .ariousc!tokines t$an uid from uninfected :omen* %1,@>,@2 9o:e.er, detectin" #acteria or

measurin" c!tokines and ot$er ana !tes in amniotic uid re uires amniocentesis, and it isnot c ear t$at amniocentesis impro.es t$e outcome of pre"nanc!, e.en in :omen :it$s!mptoms of preterm a#or* At present, it is not appropriate to o#tain amniotic uidroutine ! to test for intrauterine infection in :omen :$o are not in a#or*

• ositi.e resu ts on tests of .a"ina secretions for #acteria .a"inosis, :$et$er done #!+ram s stainin" @1 or #! t$e use of Amse s criteria /$omo"eneous .a"ina disc$ar"e,:$ite ce s rin"ed #! #acteria, an amine odor :$en .a"ina uid is com#ined :it$

potassium $!droDide, and p9 a#o.e (*63, >& are associated :it$ intrauterine infection andpredict preterm de i.er!* 8>'(0 In :omen :it$ preterm a#or and as!mptomatic :omen, apositi.e resu t on t$e test of .a"ina or cer.ica secretions for 4#ronectin, a protein of t$ep acenta mem#ranes, not on ! is t$e #est predictor of spontaneous preterm de i.er!, #uta so is stron" ! associated :it$ su#se uent c$orioamnionitis and neonata sepsis*86,>0'>8 It is #e ie.ed t$at intrauterine infection disrupts t$e eDtrace u ar c$oriodecidua#asement mem#rane, causin" eaka"e of t$is protein into t$e cer.iD and .a"ina* >%,>8

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• In :omen :it$ s!mptoms of preterm a#or, $i"$ concentrations of man!c!tokines in t$e .a"ina or cer.ica secretions, inc udin" tumor necrosisfactor ?, inter eukin'0, inter eukin'@, and inter eukin'2, are associated:it$ ear ! preterm de i.er!* >(,>6 In :omen recei.in" routine prenatacare, $i"$ cer.ica concentrations of inter eukin'@ a so predictsu#se uent preterm de i.er! and add to t$e predicti.e .a ue ofmeasurements of 4#ronectin* >@ 9o:e.er, ot$er t$an testin" for #acteria.a"inosis, no .a"ina or cer.ica test is common ! used to predictintrauterine infection*

• A s$ort cer.iD, as determined #! u trasono"rap$!, corre ates :it$ se.eramarkers of infection and c$orioamnionitis* >>,>2 A t$ou"$ a s$ort cer.iDmi"$t faci itate t$e ascension of #acteria into t$e uterus, it is a so ike !t$at in some :omen, t$e cer.iD s$ortens in response to an upper "enitatract infection t$at $as a read! occurred* 9o:e.er, since an ear !preterm de i.er! due to infection ma! #e indistin"uis$a# e from one dueto a structura ! inade uate cer.iD, it remains uncertain :$et$er t$e

en"t$ of t$e cer.iD s$ortens #efore or after a si ent uterine infection*

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• ;omen :it$ s!mptoms of preterm a#or :$o ater $a.e a preterm de i.er! $a.e$i"$ serum concentrations of inter eukin'@, inter eukin'2, and tumor necrosis factor?*>1 Amon" :omen :it$out s!mptoms of preterm a#or :$o are screened routine !,"ranu oc!te co on!'stimu atin" factor is t$e on ! c!tokine :$ose circu atin"concentrations in serum $a.e #een found to #e $i"$ #efore t$e onset of preterm

a#or*2& Nonc!tokine markers of infection inc ude $i"$ serum 'reacti.e protein andferritin concentrations* 20'28 In :omen recei.in" routine prenata care, o: serumferritin concentrations are indicati.e of o: iron stores, #ut $i"$ serum ferritinconcentrations appear to represent an acute'p$ase reaction and predict pretermde i.er!* Serum ferritin concentrations a so dou# e :it$in a :eek after mem#ranerupture, pro#a# ! indicatin" pro"ressi.e intrauterine infection* 2( 9i"$ cer.icaconcentrations of ferritin a so predict su#se uent spontaneous preterm de i.er!* 26

• Amon" t$e markers of intrauterine infection, #acteria .a"inosis and a $istor! ofear ! preterm de i.er! can #e determined #efore pre"nanc!* 5efore %& :eeks of"estation, #acteria .a"inosis, $i"$ concentrations of 4#ronectin in t$e .a"ina uid,2@ and a s$ort cer.iD $a.e a #een associated :it$ c$ronic infection* Soon aftermid'pre"nanc!, in :omen not in a#or, $i"$ cer.ica or .a"ina 4#ronectinconcentrations, a s$ort cer.iD, $i"$ concentrations of se.era c!tokines in t$e.a"ina or cer.ica uid, and $i"$ serum "ranu oc!te co on!'stimu atin" factor andferritin concentrations $a.e a #een associated :it$ an increased risk ofspontaneous preterm de i.er!* Fina !, preterm a#or #et:een %& and %2 :eeks of"estation is itse f $i"$ ! corre ated :it$ intrauterine infection, and t$is re ation ise.en stron"er amon" :omen :it$ a s$ort cer.iD, $i"$ cer.ica or .a"ina 4#ronectinconcentrations, or $i"$ concentrations of .arious c!tokines in t$e amniotic, cer.ica ,or .a"ina uids or in t$e serum*

• Bespite t$ese corre ations, none of t$ese markers $a.e #een found usefu in t$e

• TREATMENT OF INFECTION TO PREVENT PRETERM DELIVERY

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• In t$e ear ! 01>&s, a pro on"ed course of tetrac!c ine, #e"innin" in t$e midd e trimester, :as found to reducet$e fre uenc! of preterm de i.er! #ot$ in :omen :$o $ad as!mptomatic #acteriuria and in t$ose :$o did not*> T$is treatment fe into disuse, pro#a# ! #ecause of tetrac!c ine're ated toot$ and #one d!sp asias in t$einfants* T$e resu ts of treatment :it$ er!t$rom!cin, tar"etin" ureap asma or m!cop asma in t$e .a"ina orcer.iD, $a.e #een miDed* 2> It s$ou d #e noted t$at ureap asma is part of t$e .a"ina micro ora in man!:omen, and its presence in t$e o:er "enita tract, un ike its presence in t$e upper "enita tract, $as not #eenassociated :it$ an increased risk of spontaneous preterm de i.er!* 22

• In recent !ears, tria s of prenata treatment for t$e pre.ention of preterm de i.er! $a.e focused on #acteria.a"inosis, :it$ intri"uin" #ut miDed resu ts* 21'1( T$e o.era resu ts su""est t$at in :omen :it$ a pre.iouspreterm de i.er! and :it$ #acteria .a"inosis dia"nosed in t$e second trimester, treatment for one :eek ormore :it$ ora metronida o e, and per$aps :it$ er!t$rom!cin, resu ts in a si"ni4cant reduction in t$eincidence of preterm de i.er!* 21'10 T$ere :as no si"ni4cant reduction in preterm de i.er! :$en anti#iotics:ere administered .a"ina !, :$en s$orter courses of anti#iotics or anti#iotic re"imens not inc udin"metronida o e :ere used, or :$en t$e :omen treated :ere at o: risk /usua ! de4ned as not $a.in" $ad aprior preterm de i.er!3* 10'1(

• For :omen :it$ intact mem#ranes and :it$ s!mptoms of preterm a#or, anti#iotic treatment does not usua !de a! de i.er!, reduce t$e risk of preterm de i.er!, or impro.e t$e neonata outcome* 16 In t$ese tria s, t$e:omen :ere usua ! treated :it$ penici in and cep$a osporin deri.ati.es or er!t$rom!cin* 9o:e.er, in t:osma , randomi ed tria s, a pro on"ed course of metronida o e p us ampici in resu ted in a su#stantia de a!unti de i.er!, an increase of %&& to 8&& " in t$e mean #irt$ :ei"$t, a reduction in t$e incidence of pretermde i.er!, and in o:er neonata mor#idit!, as compared :it$ p ace#o* 1@,1> 5ecause of our concern a#out t$eeDcessi.e use of anti#iotics in pre"nanc! and t$e sma samp es in #ot$ studies, :e are re uctant torecommend c$an"es in practice at t$is time*

•

For :omen :$o present :it$ preterm rupture of t$e mem#ranes, pre.entin" preterm de i.er! is not areasona# e "oa * 9o:e.er, t$ere is su#stantia e.idence t$at anti#iotic treatment of t$ese :omen for a :eekor more si"ni4cant ! increases t$e time to de i.er! and reduces t$e incidence of c$orioamnionitis andimpro.es .arious measures of neonata mor#idit!* 12 Simi ar !, in :omen :$o test positi.e for "roup 5streptococcus in t$e .a"ina, t$ere is no: e.idence t$at penici in treatment durin" a#or reduces t$e rate ofneonata "roup 5 streptococca sepsis, #ut not t$at of spontaneous preterm de i.er!* 11

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• CONCLUSIONS• T$e recent increase in kno: ed"e a#out infection and preterm

de i.er! $as raised man! uestions and su""ested ne:strate"ies for pre.ention* It is not kno:n $o: and :$en #acteriain.ade t$e uterus and :$et$er additiona , as !etundocumented, infections :it$ .iruses, proto oa, or #acteriaot$er t$an t$ose a read! descri#ed are in.o .ed in pretermde i.er!* 0&& 9a.in" more information a#out t$e c$ronicit! ofuterine infections #ot$ #efore and durin" pre"nanc! and t$e

mec$anisms #! :$ic$ t$e mot$er and fetus respond to #acteriainfection is crucia to de.e opin" a #etter understandin" of t$eseinfections* 5ecause c$ronic upper "enita tract infections are

ar"e ! as!mptomatic, more discriminatin" markers to identif!:omen :it$ t$ese infections for stud! and inter.ention areneeded* Fina !, a deeper understandin" of t$e re ation #et:eenintrauterine infection and spontaneous preterm de i.er! :ipermit t$e c inica in.esti"ation of treatments to reducespontaneous preterm de i.er! and its associated on"'termmor#idit! and morta it!*
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25. infeksi intrauterine

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