Amniotic Infection Syndrome: Nosologyand Reproducibility of Placental ReactionPatterns

RAYMOND W. REDLINE,1* ONA FAYE-PETERSEN,2 DEBRA HELLER,3

FAISAL QURESHI,4 VAN SAVELL,5 CAROLE VOGLER,6 AND THE SOCIETY FOR PEDIATRICPATHOLOGY, PERINATAL SECTION, AMNIOTIC FLUID INFECTION NOSOLOGY COMMITTEE1Department of Pathology, University Hospitals of Cleveland and Case Western Reserve University, 11100 EuclidAvenue, Cleveland, OH 44106, USA2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA3Department of Pathology, University of Medicine and Dentistry of New JerseyNew Jersey Medical School,Newark, NJ, USA4Pathology Department, DMC University Laboratories, Hutzel Site and Wayne State University, Detroit, MI, USA5Department of Pathology, Driscoll Childrens Hospital, Corpus Christie, TX, USA6Department of Pathology, St. Louis University School of Medicine, St. Louis, MO, USA

Received July 1, 2002; accepted May 12, 2003; published online September 11, 2003.

ABSTRACTClinically responsive placental examination seeks to pro-vide useful information regarding the etiology, progno-sis, and recurrence risk of pregnancy disorders. Thepurpose of this study was to assemble and validate acomplete set of the placental reaction patterns seen withamniotic fluid infection in the hope that this might pro-vide a standardized diagnostic framework useful forpracticing pathologists. Study cases (14 with amnioticfluid infection, 6 controls) were reviewed blindly by sixpathologists after agreement on a standard set of diag-nostic criteria. After analysis of initial results, criteriawere refined and a second, overlapping set of cases werereviewed. Majority vote served as the gold standard.Grading and staging of maternal and fetal inflammatoryresponses was found to be more reproducible using atwo- versus three-tiered grading system than a three-versus five-tiered staging system (overall agreement81% vs. 71%). Sensitivity, specificity, and efficiency forindividual observations ranged from 67100% (24/30 90%). Reproducibility was measured by unweightedkappa values and interpreted as follows: 0.2, poor;

0.20.6, fair/moderate; 0.6, substantial. Kappa valuesfor the 12 lesions evaluated in 20 cases by the six pathol-ogists were: acute chorioamnionitis/maternal inflamma-tory response (any, 0.93; severe 0.76; advanced stage,0.49); chronic (subacute) chorioamnionitis (0.25); acutechorioamnionitis/fetal inflammatory response (any,0.90; severe, 0.55; advanced stage, 0.52); chorionic vesselthrombi (0.37); peripheral funisitis (0.84); acute villitis(0.90); acute intervillositis/intervillous abscesses (0.65),and decidual plasma cells (0.30). Adoption of this clearlydefined, clinically relevant, and pathologically reproduc-ible terminology could enhance clinicopathologic corre-lation and provide a framework for future clinical re-search.

Key words: amniotic infection syndrome, chorioamnio-nitis, nomenclature, placenta, reproducibility

INTRODUCTIONThe general sequence of pathologic changes ac-companying amniotic fluid infection has been rec-ognized for some time [1, 2]. Other clinically rele-vant histologic patterns have been added to thisbasic framework [39]. Despite a fairly extensive*Corresponding author, e-mail: raymond.redline@uhhs.com

Pediatric and Developmental Pathology 6, 435448, 2003

DOI: 10.1007/s10024-003-7070-y

2003 Society for Pediatric Pathology

literature on this topic, there has been little changein the prevailing diagnostic terminology which hasbasically been acute chorioamnionitis with orwithout funisitis. Recent data has suggested a re-lationship between placental inflammation andimportant clinical outcomes such as neurologicimpairment and chronic lung disease [1012]. Thishas coincided with a more active clinical approachto the management of chorioamnionitis and pre-term labor [13]. These changes have led to the needfor more detailed description, more specific diag-nostic criteria, and greater standardization of di-agnostic terminology in this area.

As in other organ systems, questions havebeen raised regarding the reliability of placentaldiagnosis, i.e., the ability of expert placental pa-thologists to agree with each other and with theirgeneral pathology colleagues [1416]. With re-newed interest in the clinical significance of pla-cental pathology, the time seems appropriate tointroduce more precision and uniformity in pla-cental diagnosis. With this in mind, the PerinatalSection of the Society for Pediatric Pathology hasundertaken an initiative to review, define, and val-idate diagnostic criteria for a number of differentplacental reaction patterns. The current report pre-sents the results of the Amniotic Fluid InfectionNosology Committee.

METHODSA study set of 20 cases was assembled from the filesof University Hospitals of Cleveland. Three slidesfrom each case (umbilical cord, placental mem-brances, and one full-thickness section of placentalparenchyma) were selected. Gestational age andplacental weight were provided for each case.Fourteen placentas were originally diagnosed byone of the pathologists (R.W.R.) with one or morefindings consistent with amniotic fluid infection.The remaining six placentas had other pathologicdiagnoses, but lacked signs of amniotic fluid infec-tion. Placental reaction patterns relevant to amni-otic fluid infection were chosen for evaluation.These patterns are described below, summarizedin Table 1, and illustrated in Figures 13. All caseswere examined in a blinded fashion by the sixmembers of the study group using a previouslyagreed upon set of diagnostic criteria (round 1).Terminology was chosen to correspond as closely

as possible to that proposed by the College ofAmerican Pathologists consensus group on placen-tal diagnosis [17]. Tabulated results from the pre-liminary round (round 1) were circulated and dis-cussed. Representative photomicrographs of eachlesion were reviewed at a meeting of the Society forPediatric PathologyPerinatal Section. After theinitial review a second revised set of diagnosticcriteria were proposed and agreed upon. Twelve ofthe original cases were retained, eight new caseswere added (five new cases and three new con-trols), and the numerical order was changed. Thissecond overlapping set of 20 cases was then circu-lated for reexamination followed by an analysis ofindividual performance and reproducibility (round2).

The revised diagnostic criteria as agreed uponby the study participants before the final evalua-tion (round 2) were as follows:

Maternal inflammatory responsesStage/progression of disease

Stage 1 (acute subchorionitis/early acute chorion-itis) patchy-diffuse accumulations of neutro-phils in the subchorionic plate fibrin (Fig. 1a)and/or membranous chorionic trophoblast layer (afew scattered neutrophils in the lower half of cho-rionic plate and/or the membranous chorionicconnective tissue are allowed) (Fig. 1b). Stage 2(acute chorioamnionitis) more than a few scat-tered neutrophils in the chorionic plate or mem-branous chorionic connective tissue and/or theamnion (Fig. 1c). Stage 3 (necrotizing chorioam-nionitis) degenerating neutrophils (karyorrhe-xis), thickened eosinophilic amniotic basementmembrane, and at least focal amnionic epithelialdegeneration/sloughage (Fig. 1d).

Grade/intensity

Grade 1 (mildmoderate) individual or smallclusters of maternal neutrophils diffusely infiltrat-ing amnion, chorionic plate, chorion laevae, and/orsubchorionic fibrin (Fig. 1c). Grade 2 (severe) three or more chorionic microabscesses (microab-scess confluent neutrophils measuring at least10 20 cells in extent) between chorion anddecidua in the membranes and/or under the cho-rionic plate (Fig. 1e) or a continuous band ofconfluent chorionic polymorphonuclear leuko-

436 R.W. REDLINE ET AL.

Tab

le1.

Pla

cen

tare

acti

on

pat

tern

sre

late

dto

amn

ioti

cfl

uid

infe

ctio

n:

no

men

clat

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and

defi

nit

ion

s

Dia

gno

stic

cate

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ugg

este

dd

iagn

ost

icte

rmin

olo

gyD

efin

itio

ns

Mat

ern

alin

flam

mat

ory

resp

onse

Sta

ge 1

Ear

lyA

cute

sub

chor

ion

itis

orch

orio

nit

isP

MN

insu

bch

orio

nic

fib

rin

and

/or

mem

bra

ne

trop

hob

last

(Fig

.1a

,b)

2In

term

edia

teA

cute

chor

ioam

nio

nit

isD

iffu

se-p

atch

yP

MN

infi

bro

us

chor

ion

and

/or

amn

ion

(Fig

.1c

)

3A

dva

nce

dN

ecro

tizi

ng

chor

ioam

nio

nit

isP

MN

kary

orrh

exis

,am

nio

cyte

nec

rosi

s,an

d/o

ram

nio

nb

asem

ent

mem

bra

ne

thic

ken

ing/

hyp

ereo

sin

oph

ilia

(Fig

.1d

)

Gra

de 1

Mil

dm

oder

ate

No

spec

ial

term

inol

ogy

requ

ired

Not

seve

reas

defi

ned

bel

ow

2S

ever

eS

ever

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ute

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nit

isor

wit

hsu

bch

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nic

mic

roab

sces

ses

Con

flu

ent

PM

N(

10