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Predictive value for preterm birth of abnormalvaginal flora, bacterial vaginosis and aerobic

vaginitis during the first trimester of pregnancyGG Donders,a,b,c K Van Calsteren,a,b,c G Bellen,a R Reybrouck,d T Van den Bosch,a,c I Riphagen,aS Van Lierdee

a Femicare vzw, Clinical Research for Women, Tienen, Belgium b Department of Obstetrics and Gynaecology, Heilig Hart Ziekenhuis, Tienen,

Belgium c Departments of Obstetrics and Gynecology, Gasthuisberg University Hospital, Leuven, Belgium d Departments of Microbiology ande Pediatrics, Heilig Hart Ziekenhuis, Tienen, Belgium

Correspondence:GG Donders, Department of Obstetrics and Gynaecology, Heilig Hart Hospital, Kliniekstraat 45, 3300 Tienen, Belgium. Email

[email protected]

Accepted 1 November 2008. Published Online 17 June 2009.

Introduction Abnormal vaginal flora (AVF) before 14 gestational

weeks is a risk factor for preterm birth (PTB). The presence of

aerobic microorganisms and an inflammatory response in the

vagina may also be important risk factors.

AimThe primary aim of the study was to investigate the

differential influences of AVF, full and partial bacterial vaginosis,

and aerobic vaginitis in the first trimester on PTB rate. The

secondary aim was to elucidate why treatment with metronidazole

has not been found to be beneficial in previous studies.

Setting Unselected women with low-risk pregnancies attending

the prenatal unit of the Heilig Hart General Hospital in Tienen,Belgium, were included in the study.

Materials and methods At the first prenatal visit, 1026 women

were invited to undergo sampling of the vaginal fluid for wet

mount microscopy and culture, of whom 759 were fully evaluable.

Abnormal vaginal flora (AVF; disappearance of lactobacilli),

bacterial vaginosis (BV), aerobic vaginitis (AV), increased

inflammation (more than ten leucocytes per epithelial cell) and

vaginal colonisation with Candida (CV) were scored according to

standardised definitions. Partial BV was defined as patchy streaks

of BV flora or sporadic clue cells mixed with other flora, and full

BV as a granular anaerobic-type flora or more than 20% clue

cells. Vaginal fluid was cultured for aerobic bacteria,Mycoplasmahominisand Ureaplasma urealyticum. Outcome was recorded as

miscarriage 13 weeks + 6 days [early miscarriage (EM), n = 8

(1.1%)], between 14 + 0 and 24 weeks + 6 days [late miscarriage

(LM),n = 7 (0.9%)], delivery or miscarriage 34 weeks + 6 days

n = 29 (3.8%)], 36 weeks + 6 days n = 70 (9.2%)]. PTB between

25 + 0 and 36 weeks + 6 days was further divided in severe PTB

(SPTB, 25 + 0 to 34 weeks + 6 days) and mild PTB (MPTB,

35 + 0 to 36 weeks + 6 days).

Results Women without abnormalities of the vaginal flora in the

first trimester had a 75% lower risk of delivery before 35 weeks

compared with women with AVF [odds ratio (OR) 0.26; 95%

confidence interval (CI) 0.120.56]. The absence of lactobacilli

(AVF) was associated with increased risks of PTB (OR 2.4; 95%

CI 1.24.8), EPTB (OR 6.2; 95% CI 2.714) and miscarriage (OR

4.9; 95% CI 1.417). BV was associated with increased risks of

PTB (OR 2.4; 95% CI 1.14.7), EPTB (OR 5.3; 95% CI 2.112.9)

and miscarriage (OR 6.6; 95% CI 2.120.9) and coccoid AV was

associated with increased risks of EPTB (OR 3.2; 95% CI 1.29.1)and miscarriage (OR 5.2; 95% CI 1.517). In women with BV,

partial BV had a detrimental effect on the risk of PTB for all

gestational ages, but full BV did not. Preterm deliveries later than

24 weeks+ 6 days were more frequent when M. hominis was

present (EPTB OR 13.3; 95% CI 3.255).

DiscussionBacterial vaginosis, AV and AVF are associated with

PTB, especially LM and severe PTB between 25 and 35 weeks. The

absence of lactobacilli (AVF), partial BV and M. hominis, but not

full BV, were associated with an increased risk of preterm delivery

after 24 weeks+ 6 days. As metronidazole effectively treats full BV,

but is ineffective against other forms of AVF, the present data

may help to explain why its use to prevent PTB has not been

successful in most studies.

Keywords Aerobic vaginitis, bacterial vaginosis, lactobacillary

grades, M. hominis, pregnancy outcome, prematurity, wet mount

microscopy.

Please cite this paper as: Donders G, Van Calsteren K, Bellen G, Reybrouck R, Van den Bosch T, Riphagen I, Van Lierde S. Predictive value for preterm birth

of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG 2009;116:13151324.

2009 The Authors Journal compilation RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 1315

DOI: 10.1111/j.1471-0528.2009.02237.x

www.bjog.orgGeneral obstetrics


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ntroduction

or decades, the important objective of reducing the pre-

erm birth (PTB) rate has presented a challenge. Socio-

conomic variables, maternal smoking, genital infections

nd short cervix are among the recognised risk factors for

TB that can be addressed, at least theoretically.1

Many studies suggest that the presence of AVF early in

regnancy increases the risk of PTB, premature rupture ofhe membranes and low birth weight, as does the presence of

naerobic overgrowth, for example in bacterial vaginosis

BV), and aerobic overgrowth, for example in aerobic vagini-

is (AV) or trichomoniasis.2,3 BV can be treated, with similar

linical cure rates, with either metronidazole or clindamycin,

which are both efficient antibiotics for anaerobic infections.

However, clindamycin has a broader spectrum than metroni-

azole and has in vitro activity against anaerobes as well as

erobic organisms such as streptococci and Staphylococcus

ureus. During pregnancy, treatment of BV/AVF with metro-

idazole has been found to be unsuccessful, but some rando-mised studies have shown a clear benefit of treatment with

lindamycin over placebo in reducing the rates of PTB and

reterm rupture of membranes.

The Preterm Risk Early in Pregnancy (PREP) study was

esigned to detect risk factors for preterm delivery at pre-

atal visits before the 16th week of pregnancy. In this

eport, we describe the influences of different subtypes of

AVF on pregnancy outcome.

Materials and methods

Participants and proceduresDuring the period June 2000 to December 2001, 1026

nselected pregnant women presenting for their first prena-

al visit at the Heilig Hart General Hospital in Tienen, Bel-

ium, were asked to participate in a surveillance study to

ssess the importance of first trimester screening in the pre-

ention of preterm delivery. The study was reviewed and

pproved by the ethical committee of the Heilig Hart Gen-

ral Hospital and prior written informed consent was

btained from all patients.

All women underwent a vaginal ultrasound examinationt the first prenatal consultation to confirm the gestational

ge of the pregnancy, and this was corrected, if the men-

trual and the ultrasound dates differed by more than

week. A vaginal smear was taken to assess vaginal micro-

ora by phase contrast microscopy. Two or three electronic

mages for each slide were stored for later review, if neces-

ary. Vaginal swabs were taken for detection of aerobic bac-

erial overgrowth, Candida colonisation and significant

Mycoplasma hominis and Ureaplasma urealyticum colonisa-

ion. Urinary cultures were performed for the detection of

ignificant bacterial colonisation.

For this study, we selected only women who were having

a singleton pregnancy, who attended the hospital for their

first antenatal visit at between 9 and 16 weeks of preg-

nancy, for whom the gestational age of the foetus was con-

firmed by ultrasound before 16 weeks, who had complete

data available regarding intake wet mount microscopy and

M. hominis cultures and who had confirmed outcome data

available. Obstetric data on 801 women (84%) were thus

collected. One box of 42 fresh slides of vaginal fluid was

accidentally discarded in the laboratory before the slides

could be read. The final number of fully evaluable women

was therefore 759.

The obstetric outcome was assessed using the mean birth

weight (low birth weight was defined as


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partial BV, as described elsewhere.6 These BV streaks are

characterised by small, uncountable bacteria that overlie one

another so that they cannot be distinguished or counted

individually, and appear to be identical to the streaks seen in

full BV. In partial BV, however, these streaks occur on thesame slides as AV flora or normal flora.

Aerobic vaginitis

Aerobic vaginitis corresponds to another type of disturbed

microflora, in which the lactobacilli are replaced by aero-

bic facultative pathogens (intestinal microorganisms, such

as Escherichia coli, enterococci, Staphylococcus spp. and

group B streptococci), vaginal leucocytosis and parabasal

cells. Sexually transmitted infections with organisms, such

as Chlamydia trachomatis, Neisseria gonorrhoeae and

Trichomonas vaginalis have to be excluded.

7

The clinicalpicture of severe AV often includes a red, inflamed vagi-

nal mucosa, a yellowish sticky discharge, a high pH above

6 and an odour that is unpleasant but not like fishy

odour.8 Such a severe form of AV is thought to occur

only rarely in pregnancy, but less severe forms may be

more frequent. Because of the infrequent occurrence of

severe AV during pregnancy, coccoid microflora was used

as a substitute criterion for AV. Coccoid microflora is

defined as microflora containing easily recognisable cocci

on microscopic examination: separate cocci, or cocci

bunched together in little collections, or cocci regularly

arranged in chains. Coccoid flora can consist of round

cocci, ovaloid cocci or cocci-bacillary morphotypes,

but aerobic cocci are always thicker and more

pronounced than anaerobic bacteria, and, unlike anaero-

bic, BV-associated flora, can be distinguished and countedindividually.

Lactobacillary grades (LBGs)

Lactobacillary grades are modifications of Schroders classifi-

cation.9 LBG I corresponds to normal microflora with a

predominant presence ofLactobacillus morphotypes. LBG II

corresponds to intermediate, mixed flora, LBG IIa being

near-normal with lactobacilli outnumbering other microor-

ganisms, and LBG IIb having other microorganisms outnum-

bering lactobacillary morphotypes. LBG III corresponds to

completely disrupted flora in which only bacteria other thanLactobacillusmorphotypes are present.

Leucocytes

The lowest leucocyte score of 0 corresponds to fewer than

ten leucocytes per high-power field (HPF; 400 magnifica-

tion). For more than ten leucocytes per HPF, a score of 1

corresponds to fewer than ten leucocytes per epithelial

cell and a score of 2 to more than ten leucocytes per

epithelial cell. This system corresponds well with severity

of symptoms in nonpregnant patients8 and pregnant

patients.10

A B

C D

Figure 1. (A) Partial bacterial vaginosis (BV), defined as streaks of BV flora in a smear that also shows areas of normal or different flora. (B) Full BV,

defined as a complete absence of lactobacilli, typical granular microflora with uncountable numbers of bacteria, and clue cells. (C) Coccoid AV flora.

(D) Mainly staphoid aerobic vaginitis (AV) flora (a Candida blastospore is also visible). Similarities between the flora in the upper left corner of (A)

(showing partial BV) and the flora in (C) and (D) are striking.

Predictive value of abnormal vaginal flora for preterm birth

2009 The Authors Journal compilation RCOG 2009 BJOG An International Journal of Obstetrics and Gynaecology 1317


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Table2.

Pregnancyoutcomeforallwomenwithsingletonpregnancies,completeinformationregardingintakemicroscop

y,sonographicconfirmationofgestationalage,andcomplete

informationregardingpregnancyoutco

medata

n

36wk+

6days

(term)

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