BACTERIAL VAGINOSIS AND ITS IMPLICATION IN PRETERM

LABOR AND PREMATURE RUPTURE OF MEMBRANES

A Review of the Literature

HeatherDam Reynolds, CNM, MSN

ARSTfW.CT

Preterm delivery continues to occur in 5% to 10% of all births. with a perinatal mortality
rate between 50% and 80%. In recent years. the role of infection with lower genitaltract
organisms in precipitating prefers labor/delivery and premature rupture of membranes
has come under considerable study. This article reviews the mechanwns by w&h
Infection rnq p!q a iole in theseproblems. with a specificfacw on Sactenalvagnosti.
Clinical management issuesare addressed. including screeningof prenatal patients.
diagnotic criteria. and treatment poss,b,l,ties

Preterm delivery (PTD) accounts for
approximately 5% to 10% of all
births. It causes between 50% and
80% of all pain&l deaths and con-
etitutes the major problem m contrtb-
uting IO worldwide petinatal mortality
rates (l-10). As of 1985, the overall
p&natal mtx?ality rate in the United
States stood at 9 0 neonatal deaths
per 1,OtH live births (19.1 per 1.000
for black infants). with PTD respon-
stble for two-thirds of al: deaths (7).
Though the perinatal death rate has
decreased. prtmartly because of im-
proved technology in caring for very
preterm infants, the incidence of mD
remains high
The epidemiology of pretenn labor
(PTL)/PTD is multifaceted. Impor-
tant risk factors include socioeco-
nomic conditions, life-style, environ-
mental factors, and current and past
medical, surgical, and obstebic histo-
ries. as well as other valiables ihat are
unknown (11-22). Prevention of
PTLIPTD and preterm premature
rupture of membranes (PROM) de-
pends on the identification and miti-
&ion of these contributing risk fac-
tors.
MtCROBlOLOGtC FACTORS
ASSOCtATED WIT
PRETERM DELRlERY
Strong evidence implica:es intmuter-
ine infection as a salient agent in
some cases of PTLVlD and PROM
(23301. Researchers have post-
la!nd that such intrauterine infection
may precipitate as much as 17% to
25% of all PTDs W-361. Although
untreated bacterfurfa has long been
implicated in the occurrence of FTU
PTD and PROM (37431: the real-
ization that lower genital tract organ-
isms may alea play a role in initiating
uterine activity !ading to PTL and
PROM is more recent (29.4649).
Interestingly enough, when Ben-
irxhke l50) suggested as long ago as
1960 the route by which bacterial in-
fection occurred in the fetus prior to
birth. ie. via maternal circulation
through the placenta or through the
membranes from the cewtx, he was
likewise identifying the route by
which PTL/PROM might be MUIT-
ling. In 1988, Romero and Mazor
(24) identified several mechanisms
by which microorganisms may be-
come elaborated in the intmutefine
environment These mechanisms in-
clude microorganisms
ascending from the ve@inaand cer-
ViY
-hematogenour dissemination
through the placenta (tinsplacen-
tal infecttan)
-rekcgmde seedingfrom the @to-
nal catity through the iatlopian
blbeq o*
 -accidental lricl introducbonduring
tnwsive procedures,suches am-
niocentesis,percutaneousblood
sanlplig,chorionicvi8vlmpling
or shundng124).
Of these pathways, the ascending
route through the cewtcal canal is
p=Obably the Iost pr&&t 0e.
Preterm uterine activity k believed
to be mediated by the high phospho-
Itpaw A2 activity I selected organ-
krm in the vaginal flora, which pro-
motes release of arachidonic acid
from cell membranes. The placental
membranes then utilize the arechi-
donlc acid to synthesize prostaglan-
din E2 (51-541. The role of pros-
taglandins in facilitating cetical of-
facement and dilatation is well
documented (55-60). In the case of
PROM, it is theorized that these
lower genital tract organisms Qener-
ate the production of immunoglobu-
lin A, protease, neuraminidase, and
mudnase enzymes, which may pro-
vide them accessto the lower uterine
segment past the cervical plug/
banien and weaken the integrity of
the membranes, thus leading to their
ruphtre (531.
In an effort to determine categod-
tally the impact of infection on PTL/
PTD/PROM, the National Institutes
of Health (NIH) has been funding a
multicentered nationwide project in
the last few years whose aim k to
identify the specific microorgankms
Heether Reynolds, cmi. MSN. ,s m
asWant pmjesor In the nwae-
mldt&y pmgmm at Yale Uniunsity
School of Nursingand the Dimxor oj
the Nurse-Midwijey Serviceet
Vole-New Hauen Hapftool. She received
her M.S.N in matem&ncubom
nursing/nurse-midwiferylrom Yele in
1980. She previouslyaught i the
gmduatenurse-midsijey pmgmm at
U!wnity of Colomdojmm
1983-1986. aJ& which time she joined
the Yale Universityjocuity. in addltfon
to her jaw/y responsibilities,she
providesjUn-scopenurse-midur$q,
290
implicated in PTUPTD and PROM,
and to test modes of treatment.
There is hope that some understand-
ing of the role of infection in prectp-
itattng PTL/PTD and PROM may
sco be forthcominq.
several lower genital tract organ-
isms have been imolicated in PTU
PTD and PROM. most notably group
a beta-hemolytic streptococcus,
chlamydia, mycoplasmas (Urea-
plasma urealyticum, Mycoplasmo
hominis), and btchomonads. as well
as those ongankms responsible for
the clinical syndrome of bacteria!
vagtnosis(BV). The remainder of this
atide will focus on the role of BV.
because there k controversy as to
whether or not it k a condition wer-
renting Ireatlent.
BACTERIAL VAGINOSIS
The cause of BV was first identified
by Gardner and Dukes (61) in 1955
as Haemophilur wginalis, based on
ik mtcroscopicappearance es seem-
ingly from the Haemophllus genus.
Up until that time, the condition that
H. unginoliscaused had been &erred
to as nonspecific vagtnitis (61).
Over the years, it has been called
various names as lore infamation
unfolded as to the paticulars of the
condition and the criteria for ik dkg-
ask. When it was felt that the mi-
crobe resembled the genus Coyw-
bactertum rather than Haemophilus,
the name was changed to Cotyne-
bacterium uoginolis. It has also been
known as Geninereb vagtnalk in
honor oi one of ik discoveren, Gerd-
ner. Cunently the condition it cares
Is known as BV. Along with deter-
mining ik taxcm~ny, there has long
bee mxh contmversy as to the mi-
crobiology. sexual transmksiblltty,
and pathweic cause 01 BV 162-
64). the t& incidence of BV is dif-
ficult to ascertain because it is Qt a
reportable disease. Nevertheless. BV
k estimated b exist in 21% to 64% of
women, tith a h&her prevalence in
sexually transmitted disease (STD)
clinia and/or sexually acttw women
w-69). Other arglmlenk that sup-
port ik sexual trensmksibility include
Joemel of Nurse~hlidwtfmy l Vol. 36, Na. 5. SeptemberlOc&er 1991
a higher recovery rate in prepubes-
cent girls with a history of sexual
abuse when compared with those
without such hktoy (701; a high re-
covery rate of H. wgtnab from UK-
thrds of male partners of infected
women (61); a high recnece rate
in women whose partnem are un-
treated (61); lower prevalence in
women whose partners utilize con-
doms (71); increased occurrece in
prtiouely culture-negative hxarcer-
ated women after a weekend release
(with a assumption/presumption
that thev were sexuallv active on
their rel&el 172); and-its frequent
as5odatto with other STDs 173. 74)
and in women with multiple s&i
palIners (75). In COiles?,some other
&dies we found a low recurrence
rate in women whose partners re
main untie&d (76); no difference in
successfuleradication of the organ-
ism In women whose partners re-
ceived treatme,t or those who re-
ceived pkxebo (77); and no differ-
ence in BV cauece in virginal and
sexually active adoleuen: Pm&s
(781. Thouah ik STD statushas been
debated without unanimiiy of agree-
ment ik parlicular epidemiologic dis-
bibutfon suppmts sexual kansmk-
ston in some situations
DlAGNOSfS
Although other dtagnc&c methods
are utilized to identify BV (eg. Gram
stetnl, the clinical c&da ta which
other methods are compared (and
thus may be considered the gald
standard1 include evidence of vag-
nal secretions that have a pH > 4.5
bmrral va!#ial pH k between 3.0
and 4.0 in women of repmduciive
age), that are homogenous with low
vkcosily. that contain clue cells (vag-
inal epitheliel cells with peppering of
bacteria on cell surface that creates a
ra&?etirregukr border to cells), and
that release amine fishy odor
when mixed with 10% potassium hy-
droxide (KOH) (79-81). More so-
phisticated micrcbi&g% techniques
for conftfg the diagnods are avafl-
able and may be utilii at the dk-
cretio of the clinician. One such
confirmatoty test is done with gas-
liquid chromatography (GLC). As
microorganislnsp, short chain or-
ganic acids are produced as a
byproduct The microorganisms may
b+z identified by the patterns that
these organic acids produce .with
GLC. Generally the diagnosis of BV
by GLC is based on succinawlactate
ratio ~0.4 or more than trace
amounts of volatile organic acids
(68). Krohn et al (82) compared
GLC, Gram stain, and G. uoginaiis
cuuure fortheksesitivi~, specificity,birth iveight >255w g). Additionally,
a:! predict&lily in diagnosing BV in
a cohort of 593 pregnant women
(see Table 11 with the aforemen-
tioned gold &ndard. The authors
concluded that Gram stain was pref-
erableoverCLC endvaginalcultures
because it was lesscostly. had higher
frequency of interpretable results,
and is easier to store and txmsport
When comparing Gram stain to the
clinical gold standard criteria, Martiw
et al (46) found that Gram stein di-
agnosis had 89% sensitivity, 95%
specificity, a pl+v* predicxJ~ v&e
of 81%, and a negative predictive
value of 98%.
There seems to be a developing
consensus that several organisms
(aerobes and anaerobes) are assw-
ated with and/or constitute what is
under the category oi 6V. These in-
clude G. wxginalis, Bocteroides spe-
des, Pept-us species, Mobilun-
cus, and hf. hominis (46, 63, 64).
!Ni!h a belter undemtanding of its mi-
crobldogy, the role of 6V, w-ticu-
lady in the perinataf period, is being
more clearly elucidated. BV has oi
only been tbought to play a role in
TABLE1
Specificity, Sensitivity, and Predictive Value of Gas-Liquid
Chromatography, GordnerelIo oagfnaIfs Culture, and Gram Stain
Mei%& in Magno+~..U ------
~-*a&! !k&+e
Labomtay Method speafiatv
Gas-liquidchromatography 81%
69%
pdn~; W~llallscullwe
95%
PTL and PROM, but also in p&pw
htm endometritis (79, 831.
THEROLEofBA-
VAGINOSIS IN
PRETERM DELIVERY
Eschenbach et al (83) compared the
prevalence of BV in ve$nal fluid as
identified by GLC among gravid
women admined in PTL kwtation
~37 weeks. birth weight -&OO si
with a wmpadson group delivering
at term (gestational a* >3i weeks,
awfiatd
GLC was used in a third group of
women with early-owl postpartum
endomebitis to assessthe prevaiencr
of BV. of the 740 women enrolled in
the prospective study, 121 had PTD,
of which 57 were eligible for GLC
analysis. The remaining 64 preterm
patients were excluded as cases if
they had a noninfectious etiology for
PTL (eg, placenta abruptio/previa,
vagmal bleeding of unknown eiiol-
ogy, or severe medical problem ne-
cessitatinginduction) or if a sample of
their amniotic fluid (Af) was not ob-
tained by the hospital staff (n = 40).
The GLC results of these 57 cases
were then compared with CLC re-
suits of the 114 unmatched controls
derived from the 740 women en-
rolled in the study. These controls
were consecutively selected as the
first two Patients who were eligible
once a case had been identified.
When basic demographics of age,
race. marital status, parity, and
whetber or not patients were on pub-
UC assistancewere compared, there
were no significant differences In the
two groups. BV was found in 28
%
__ 59.3 ?reg!!srrt W@E%?a*
Sensitivity Predict&eValue
78%
92% $2
62% 76%
(49%) of the 57 cases versus 27
124%) of the 314 controls IF =
:OOOil. Additioally, PROM OC-
w-red sig.~iticanUymore in casesva-
suscontrols, 26 (46%) of 57 and four
(4%) of 114, respectively (P =
.OLJS).Unforhmately, the presence of
other organisms, which unilatemily
or syrzrgkti&~ with BV tight pre-
cipitate PTL, was not asw5e.d in this
study. hi the third group of -en
who developed evidence of early
postpartum endometritis, BV-
organisms were more fre
quentiy (61 of 101) recowred from
their endometrium then other xgan-
tsms.Additionally, in this w
STOUD.those with E. IJo&& and
kaembes remained feb& sign&
cantly longer after begInning antibi-
otic therapy than those without these
organisms (57.1 hours versu~i36.3
hours, P = .02).
Mlnkoff et al (48) examined sew
eral omanisms. inch&m those that
ce& norl.sp&fic (using
v-dgini& cn-
agnosticcriteria for BV of pH > 4.5.
fishy odor with KOH, and due c&)
and their possible irnpliution in pre-
mNti!y and FROM. Two hundred
fifty g&d women were cultured at
their first prenatal visit (gestational
age, 13.8 * 3.6 weeks); 188 were
available for study analysis. Of the
250 X+*-C
,11, @,
_ *vere excluded horn
final analysis, including individuals
whoaborted (n = 8), hadtwins (n =
7). had elecfive indudions (n = 10)
or elected cesareansection (n = ZO),
who delivered elsewhere fn = 4). or
whose charts were unavailable for re-
view In = 13). Althouah nonswcific
vaginks (BV) was found more fre-
quently in patients who develowd
FlI_ (n = 14 of 35) and PROM (n =
16 of 40) and dellvered low birth
weight infants (LJ3W) (n = 9 of 18),
sig-
the difference was not statistically
nificant. Of interest is Boctwoida
species (which was sfgnificaatly asso-
ciated with PTD delivery L41.78 wr-
sus 23.6%; P < ,031, infants weigh-
ing less than 2503 g [44% versus
24.596; P < ,051 and pretenn PROM
[P i ,011) is believed to be one of
the organismsunder the constellation
of BV, though it may exist indepen-
dently in the lower genital @act. BP-
cause the cuhures were done in the
early second trimester of pregnancy
(average gestational age around 14
weeks), they may not accurately *em
flat the vagMal flora at time of deliv-
cay. Whether or not BV may have
developed kter in gestation and thus
play e more significant role in PTL
and PROM can only be conjectured.
PTL associatedwith intmamniotk
infection and BV was studied by
Gravett et al (44). Sixty consecutive
afebrile women who presented in
PTL (gestational age <35 weeks)
were examined for subclinical AF in-
fetion vie abdominal amniocentesis.
Of these 60 women, six were ex-
eluded for mmplicetions. which in-
cluded placenta abraptiolprevie. or if
hospital staff was unable to retrieve a
sample of AF. Thus the date on 54
women were available for AF analy-
sis. Controls matched on age, race.
paiti, tioeconomic stetus, marital
status. and gestational age were pro-
spectively obtained for 44 of the 54
cases. The 10 for whom they were
unable to find matched contlols were
similar to atber cases. Both cases
and controls undenvent a speculum
exam where cewicallvaginal cultures
were obtained for gonoahea, herpes
simplex, cytomegalovirus ICMVI.
Chlomydie tmchomotls. G. uoginolis,
U. urealyticum, and M. hominis, and
a CLC analysis for BV was per-
formed. Microorganisms including
bacteria, Candida olbicans, and my-
coplasmas were isolated from 13
(24%) of the 54 cases.These women
were then placed into three catego-
ries based on their AF findings: 1) AF
positive for bateda or C. olblcans, n
= 6 (11%); 2) AF positive for mycc-
plasmas, n = 7 (13%); and 3) AF
sterile. n = 41 (76%). Each group
that was positive for microorganisms
was then compared to the group that
had sterile AF. The interval behveen
the onset of PTL and PTD was sig-
nificantly shorter (0.6 versus 34.3
days; P c ,011 for those women who
had bacteria/C. albians-positive tn.
lx-amniotic cultures than for those
292
with sterile cultures. Additionally,
women with bacteria/C. albicans-
positive amniotic cultures had de-
creasedresponsivenessto tocolysisin
compxison with tbe culture-sterile
women (0 versus 81x; P < .005k
when compared with their 44
matched controls, positive BV (by
GLC an&Xs on vagjnal secretions)
was found more often in PTL cases
(43% vel+us 14% of control, P = .02
McNemar test).
Gmvett et al (45). in another study
of the association of BV and C. ho-
chomotis infection with adverse preg-
nancy outcome, found that women
with BV delivered infants with a
lower mean birth weight than women
without BV (2960 + 847 g versus
3184 t 748 gj. They studied 582
women seen consecutively in a uni-
versity hospital clinic in thefr second
and third trimesters. For&eight of
these women were excluded from
the final analysis because of multiple
gestation. conwnital anomalies, da-
centa previa/abruptio. havingre-
ceived antibiotic treatment within 30
days, or because of the unavailability
of follow-up information. The
women had lower genital tract cul-
tore5 via sterile speculum exam for
gonorrhea. chkmydia. herpes, and
BV. BV diagnosed by GLC was
found in 102 119%) of the 534 pe-
Gents.When basic demwreohicsand
socioeconomic factors-v&e corn-
oared between those with BV and
ihose without BV, there was no sig-
nificant difference except with tbe ex-
pellence of plioiorfirst-trimester spon-
teneous abortion. Those women with
BV were more likely to have had a
history of first-himester spontaneous
e.bortion. BV independent of an in-
fection with chkmydia was signifi-
cantly more associated with preterm
PROM (P < .Ol; odds ratio 2.4).
PTL (P < .Ol; odds ratio 2.2). and
AF infection (P i .05: odds ratio
2.1 I. Although the presence of go-
orrhea. chlamvdia. and hem-es was
assessedin thy* &dy, othe; organ-
.. .
isms that mev dav a role in PROM
and PTL lsuch as Trichomones UQ-
ginofis, mycopksmas. and beta strep-
tococci), were not. If any of these lat-
ter organisms were also present, it
could have confounded the findtngs.
Matins et al (46) looked at the in-
cidence of oeniti infection in three
groups of &men: those who deliv-
.
ered meterm. those with PTL but de-
likered et term, and controls who de-
livered at term. Women presenting to
labor and delivery with PTL, with or
without PROM. with aestational ewe
between 20 anh 36 &eks were ei-
rollea in the stodv In = 971. Controls
were obtained at a womens clinic
during their prenatal visitswhen they
v~erebehveen 20 and 36 weeks ges-
tabion. Both groups undenvent spec-
ulum exam where vaginaUcewical
cultures were obtained for g~nor-
rhea, group B etreptoaxci Candtda
specks, Urealyticum, hf. hominis,
Mobiluncus specks, and Bademides
species. Dkgnosis of BV ws deter-
mined by Gmm stein in casesand in
controls and also by the presence in
the vaginal discharge of tvm of there
three criteria: pH > 4.7, amine odor
with the addition of KOH solution, or
presence of clue cells (to compare
the specificfty. sensitivity, and predic-
tive value of Gram stain to the clinical
criteria in diagnosing BV). They
found a significant relationship be-
tween BV and prematutify after ad-
justing for the cxcull~nce of chk-
mydia (odds ratio 2.5; P = .03).
In summary, five studies (three
case-control and two cohort) exem-
ining the essodation between BV
and PTL and PROM were twiewed.
The preponderance of the evidence
in these studies supports en assock-
tion between BV and PnmROM
(seeTabk2). Tbeonesh~dyindiceling
no association assessed outcome
based on vaginal cultures obtained
from gravidwomen In early secondki-
m&a, which may not refkct the ste-
tus of thesewomen kter in pregnawy.
MANAGEMENT DECISIONS IN
GRAUID WOMEN WtTH
6ACTERW YAGlNOSlS
BV may play a causative role in the
occurrence of PTL&TD and PROM.
TABLE 2
Studies of Bactertal Vaginosis Association wtth Preterm Labor and Premature Rutiure of Membranes
Given the information we have,
these questions arise:
1) Should gravid women be rou-
tinely screened for BV? If so.
which of the methods is diagnos-
tically more accurate and cost-
effective.
2) Should treatment be instituted in
pregnant women who are positive
for BV and. if so, which antibiotic
should be used?
3) Should the partners of these
women also be treated?
To address the first westion, it
would seem premature to begin
screening all gravid women for BV
until the evidence is clearer as to the
o~limum time ~renataltv that such
testing should o&r. Fro& a preven-
tion standpoint, late second trimester
to early third trimester may be the
logical time for this to be done. Se-
lective screening may be more prof-
itable; we may wish specifically to
meen those women with known risk
factors for FTL and PROM, such as
previous or current STDs, other gen-
itourinaty tract infections, or history
of PTL.
The previously discussed gold
standard clinical diagnostic criteria
are readily available in most prenatal
care settings and should be the first
method used in diagnosis. Other di-
agnostic measures, such as GLC,
Gram stain, and culhxes, have rea-
sonable specificity, sensitivity, and
predictive value for BV. are lessavail-
able in most clinical settings,ar,d may
be more costly. Any of these latter
labor&y methods may be utiliied
by the clinician to confirm the gold
standard findinos. thouoh doinu this
would appear t;, be red&d&-
Siiould heabnent be instituted in
pregnant women who are positive for
BV and. if so, which antibiotic should
be used? Clearly. more clinical trials
are needed to determine whether
treating BV in pregnancy will im-
prove patnatal outcomes. To date.
several studies have indicated that in
idiopathic FTL, lreeatmentwith anti-
biotics may effectively reduce the oc-
currence of PI73 153, 8+871: one
other study has suggested,however,
that treating makes no difference in
the outcome (88). It is hoped that the
NIH project findings will enlighten us
as to the efficacy of treatment. Even if
the decision is made to treat the preg-
nant woman. many clinicians are re-
Want to use metronidarole (the
drug of choice) because of its poss-
ble mutagentc and/or carcinogenic
efficts (89). On the o:he: h&
ampicillin, although not contraindi-
cated in pregnancy, is only 50% to
60% effective (90). In the pregnant
woman, the Centers for Disease
Control recommends alternative
treatment with dindamycin 3Ctl mg
b.i.d. for seven days (91). However,
use of clindamycin may precipitate
gastrointestinal problems including
pseudomembranous colitis foecur-
&ce rate 2% to 10%). which may
be fatal (921. Use of clindamvcin
intravaginall~ for treatment of_BV
was noted to produce a cure in 93%
lat one week) and 90% (at one
month) of patients treated with ciin-
damycin phosphate cream in com-
parison to 25% of those treated with
a placebo (92). Thus, an alternative
to systemic treatment with oral ciin-
damycin might exist with in@waginal
treatment (92); whether or not it is
safer than the oral route remains un-
Cle.?X.
Should partners be treatedas well?
Given the evidence that in certain cir-
cumztances BV may be sexually
kansmitted, it would seem r-n-
able that if one is planning to treat the
woman, treatment of her male part-
ner should also be considered (93,
94). Trealment of the womans part-
ner, if not done concurrently with
treatment of the woman. may well be
indicated If she continues to test pas-
itive for BV after her treatment.
Some clinicians may prefer not to
treat a clients partner with whom
they have had limited contact or for
whom wescribing medication is
based & histay obtained wand-
hand. Referral of the nartner to a
clinic or dinician for evaluation may
be an alternative. Another alternative
to treatment of sexual partner(s)
might include the recommendation
of condom usage by partnerls) of the
gravid woman who is either diag-
nosed wiul BV and/or has risk factors
forPTL.
In summary. although the data are
ay SlQgestiW of a causal relation-
ship between BV and FTLPTD and
PROM, wldqread screening of the
gmvtd woman may not be indicated
at &ii time. Howeuq wreening tn a
select group of women at risk fcr sex-
uaUy transmitted diseases may pro-
vide a more profitable exercise. Ad-
ditionally, treatment of the woman
with signs of BV infection, as well as
treatment of her partner, may be ap-
propriate in certain situationsto emd-
icate thz organism effectively and to
improve the chances for a healthy
pzdnatal outcome.
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2. Fuchs F. Prevention of prematw
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126:809-20.
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low birth weight Washington. DC: Na-
kmal Academy &, 1985.
4. Kelly HJ. Infant mortality in Mln-
nesota la birth cohort shtdyl. Minneapa-
lis: Minnesota Department of Health.
1974.
5. Kitchen WH. Yu WA. Or@!l AA,
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89:887-91.
6. Mcllwaine GM, GilUan M. Hcwar
RCL. Dunn F. MacNaughton MC, The
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Ow Future
College of Nurse-Midwives
37th Annual Meeting
May l&21.1992
Phoenix, Ationa
For Further Information Co&a:
ACNM Eeadoualters
Journal of Nurse-Miduriky
preterm labor. Am J Obstet Gynecol
1989; 745626.
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ICDCl89-02xX.
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l Vol. 36, No. 5. Se#temb-er/Odober 1991