Regarding to prevalence of preterm labor and its consequences, there are different reports on relationship between bacterial vaginosis and preterm labor. This study was performed to evaluate the effect of metronidazole therapy on preterm labor in women with bacterial vaginosis. This randomized clinical trial was performed on 120 women suffering from bacterial vaginosis at 20-34 weeks of pregnancy, to evaluate the therapeutic effect of metronidazole to delay preterm labor in Shabih Khani maternity hospital in Kashan, Iran in 2002. Bacterial vaginosis was diagnosed based on clinical and laboratory findings. The patients were randomly divided into two groups. The patients in the case group received 500 mg metronidazole BID for 7 consecutive days, but the control group did not receive it. The demographic characteristics of the patients such as, pregnancy age, educational level and job of the spouse were similar at both case and control groups. Double-blind follow up of the patients at the whole stages of parturition and after delivery with respect to the delivery method, infection, and fever was done by other practitioner besides the main researcher. The results were analyzed statistically by chi-square, and Fischer's exact tests. 420 patients entered the study, of whom 120 (28.6) had bacterial vaginosis. The antibiotic and control groups were not significantly different for maternal age, job of the spouse, and education. No difference was observed in spontaneous preterm birth before 37 weeks of gestation in antibiotic-treated compared with control group. Treatment with metronidazole in symptomatic women with a bacterial vaginosis in the late second trimester does not decrease the incidence of preterm delivery. Â© 2009 Tehran University of Medical Sciences. All rights reserved

Behrashi, M.

Moniri, R.

kashan university of medical sciences

 ORIGINAL REPORT  
 
*Corresponding Author: Mitra Behrashi 
Department of Obstetrics and Cynecology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran 
Tel: +98 361 5310306, Fax: +98 361 5551112, E-mail: Dr_behrahi2006@yahoo.com 
 
Effects of Metronidazole Therapy on Preterm Labor in Women 
with Bacterial Vaginosis 
Rezvan Moniri1*and Mitra Behrashi2 
1
 Department of Microbiology and Immunology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran 
2
 Department of Obstetrics and Gynecology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran 
 
Received:  12 May 2007; Received in revised form:  29 Feb. 2008; Accepted:  2 Jun. 2008 
 
Abstract- Regarding to prevalence of preterm labor and its consequences, there are different reports on rela-
tionship between bacterial vaginosis and preterm labor. This study was performed to evaluate the effect of 
metronidazole therapy on preterm labor in women with bacterial vaginosis. This randomized clinical trial was 
performed on 120 women suffering from bacterial vaginosis at 20-34 weeks of pregnancy, to evaluate the the-
rapeutic effect of metronidazole to delay preterm labor in Shabih Khani maternity hospital in Kashan, Iran in 
2002. Bacterial vaginosis was diagnosed based on clinical and laboratory findings. The patients were ran-
domly divided into two groups. The patients in the case group received 500 mg metronidazole BID for 7 con-
secutive days, but the control group did not receive it. The demographic characteristics of the patients such 
as, pregnancy age, educational level and job of the spouse were similar at both case and control groups. 
Double-blind follow up of the patients at the whole stages of parturition and after delivery with respect to the 
delivery method, infection, and fever was done by other practitioner besides the main researcher. The results 
were analyzed statistically by chi-square, and Fischer’s exact tests. 420 patients entered the study, of whom 
120 (28.6%) had bacterial vaginosis. The antibiotic and control groups were not significantly different for 
maternal age, job of the spouse, and education. No difference was observed in spontaneous preterm birth be-
fore 37 weeks of gestation in antibiotic-treated compared with control group. Treatment with metronidazole 
in symptomatic women with a bacterial vaginosis in the late second trimester does not decrease the incidence 
of preterm delivery. 
© 2009 Tehran University of Medical Sciences. All rights reserved. 
Acta Medica Iranica 2009; 47(3): 181-184. 
 
Key words: Bacterial vaginosis, preterm labor, metronidazole 
 
Introduction 
 
Bacterial vaginosis (BV) is the most common cause of 
vaginitis in women of child bearing age, with prevalence 
of 5-60% across the globe (1, 2). The rate of occurrence 
depends upon the population studied: 17-19% in family-
planning or student health clinics; 24-37% in sexually 
transmitted disease clinics; and 10-35% among pregnant 
women in the United States (3). BV is not outcome of a 
single organism. It represents a complex change in vagi-
nal flora characterized by a reduction in the prevalence 
and concentration of hydrogen peroxide-producing lac-
tobacilli and an increase in the prevalence and concen-
tration of the Gardnerella vaginalis, Mobiluncus spe-
cies, Mycoplasma hominis, anaerobic gram-negative 
rods belonging to the genera Prevotella, Porphyromonas, 
Atopobium vaginae and Bacteroides; and Peptostrepto-
coccus species(4). Approximately 50-75% of women 
with BV are asymptomatic (5, 6). Those with symptoms 
present with an unpleasant "fishy smelling" discharge 
that is more noticeable after unprotected intercourse (7). 
Pregnant women with BV appear to be at higher risk of 
preterm delivery (3, 8). The diagnosis of BV is clinical 
based on criteria that are simple and useful in office 
practice (9). BV resolves spontaneously in up to one-
third of non-pregnant and pregnant women (10, 11). 
Treatment is indicated in women with symptomatic in-
fection and those with asymptomatic infection prior to 
abortion or hysterectomy; asymptomatic pregnant wom-
en with previous preterm births may also benefit, but 
screening and treatment of these women is controversial. 
Metronidazole or clindamycin administered either orally 
or intra-vaginally will result in a high rate of clinical 
cure with 70-80% at four weeks of follow-up (12). 
Treatment is appropriate for pregnant women with 
symptomatic bacterial vaginosis (13).  
Effects of metronidazole therapy on preterm labor in women with bacterial vaginosis 
182  Acta Medica Iranica, Vol. 47, No. 3 (2009) 
Table 1. Socio-demographic characteristics of the women referred to Shabih-Khani maternity hospital 
 Control group Treatment group 
No. of pregnancies 60 60 
Maternal age (year) 
Mean (SD) 
 
27.6 ± 5.6 
 
25.7 ± 6.4 
Height (centimeter) 
Mean (SD) 
 
159 ±  0.1 
 
160 ± 0.3 
Weight (kilogram) 
Mean (SD) 
 
72 ±  0.4 
 
73 ± 0.1 
Measures of social status 
Good 
Intermediate 
Weak 
 
32(53.3) 
11(18.3) 
17(28.3) 
 
30(50) 
8(13.2) 
22(36.7) 
Educational qualifications 
Uneducated 
High school 
 
29(48.3) 
31(51.7) 
 
26(43.3) 
34(56.7) 
 
 
 
Screening and treatment of asymptomatic BV is contro-
versial. Most studies have reported an increased risk of 
preterm birth in these women; the pooled odds ratios for 
prematurity from two meta-analyses were 1.8 and 2.2 
(14).  
Despite the association between BV and preterm birth, 
most studies in general obstetric populations have not 
found that treatment of asymptomatic infection reduced 
the incidence of preterm labor or delivery (15-17). A 
Cochrane review of ten trials involving 4249 pregnant 
women reported that antibiotic therapy was highly effec-
tive in eradicating infection, but did not significantly 
reduce the odds of preterm birth at < 37 weeks (OR 
0.95, 95% CI 0.82-1.01), < 34 weeks (OR 1.20, 95% CI 
0.69-2.07), or < 32 weeks (OR 1.08, 95% CI 0.70-1.68) 
(15). Other systematic reviews have come to similar 
conclusions (18-20). Based upon these data, screening 
and treating all pregnant women with asymptomatic BV 
to prevent preterm birth and its consequences is not rec-
ommended. However, when the Cochrane reviewers 
separately analyzed the subgroup of women with a his-
tory of one or more prior preterm births, they found that 
detection and treatment of asymptomatic BV in this 
population appeared to markedly reduce the rate of pre-
term pre-labor rupture of membranes (OR 0.14, 95% CI 
0.05-0.38) and low birth weight (LBW) (OR 0.31, 95% 
CI 0.13-0.75), but did not significantly affect the risk of 
subsequent preterm birth (OR 0.83, 95% CI 0.59-1.17) 
(15). The objective of our study was screening of BV 
and treat symptomatic women with metronidazole and 
observation of the effect on delivery prior to 37 com-
pleted weeks (primary outcome). 
Patients and Methods 
 
The study was conducted in the Shabih-Khani maternity 
hospital in Kashan, Iran. The randomized consent design 
of clinical trial was approved by the Ethics Committee 
in Kashan University of Medical Sciences with the mod-
ification that all women were informed about the study 
procedure during the initial visit to Shabih-Khani mater-
nity hospital. Participants recruited were between 20 and 
34 weeks of gestational age at their initial visit to the 
clinic.  
If the woman agreed to participate in the study, a speci-
men of vaginal fluid was collected by the physician or 
the midwife from the posterior or the lateral vaginal wall 
and placed on a microscopic slide. The slides were air 
dried and observed at the department of microbiology, 
using Gram staining. BV was confirmed with homoge-
neous, grayish-white discharge, gram staining of vaginal 
secretions, Vaginal pH greater than 4.5, Clue cells on 
saline wet mount, and Positive whiff-amine test, defined 
as the presence of a fishy odor when KOH (10%) is 
added to vaginal discharge samples. Enrolment of par-
ticipants to the study began in March 2002 and contin-
ued until October 2002. During this period, approxi-
mately 420 women were registered in the Shabih-Khani 
clinic, 120 had bacterial vaginosis and all of these 120 
consented to participate in the study. All women with 
BV were randomized to either an intervention group 
with a 7-day regimen of treatment with metronidazole 
(500 mg orally BID) or a control group to remain un-
treated and uninformed of their BV status as stipulated 
in the pre-randomized consent design for clinical trials. 
R. Moniri and M. Behrashi 
  Acta Medica Iranica, Vol. 47, No. 3 (2009)    183 
Only women who were diagnosed with BV and random-
ized to the intervention group were told the result of 
their vaginal smear. Metronidazole treatment usually 
started within a week of diagnosis. Clinicians caring for 
the BV-positive group randomized to non-treatment 
were not told of the diagnosis. In the Kashan, where this 
study was conducted, all pregnant women attended to 
the Shabih-Khani maternity hospital which belongs to 
the public healthcare system. There is no private clinic 
care alternative. Therefore, all women studied had simi-
lar healthcare management throughout pregnancy. Preg-
nancy data were collected through the Medical Birth 
Register. Survival analysis was done with chi-square test 
and Fischer’s exact tests. The level of statistical signifi-
cance was set to P < 0.05. 
 
Results 
 
A total of 420 women were screened for BV. 120 
(28.6%) women had BV, 60 women were classified as 
treated and 60 as non-treated. Socio-demographic char-
acteristics of studied women are shown in Table 1. The 
mean age of the women in the intervention group was 
25.7 ± 6.4 years (mean ± SD), and the mean age of the 
women in the control group was 27.6 ± 5.6 years (mean 
± SD).  
There were 4 cases of delivery prior to 37 completed 
gestational weeks, 2 (3.3%) in the intervention group 
and 2 (3.3%) in the control group. No statistical differ-
ence was observed in spontaneous preterm birth before 
37 weeks gestation in antibiotic treated compared with 
control group. 
 
Discussion 
 
This study did not show any significant reduction in the 
incidence of preterm birth prior to 37 completed weeks 
associated with the treatment of BV with administration 
of metronidazole. Treatment of BV among women at 
high risk for preterm birth decreases the risk for preterm 
delivery (21-22). However, treatment of BV among 
women at moderate or low risk has no major effect on 
the risk for preterm birth or prepartum infections (16-17, 
23-24).  
On the basis of this study and others in the literature, it 
seems that metronidazole alone has no benefit in the 
prevention of preterm delivery in high risk women. We 
therefore do not recommend continued use of metroni-
dazole in the clinical setting for the prevention of pre-
term delivery. 
 
Acknowledgments 
 
This work was financially supported by a research grant 
from Deputy for Researches, Kashan University of Med-
ical Sciences and Health Services, Kashan, Iran. 
We thank Dr. Fereshteh Kazemeini for her assistance 
and Gholam Abbas Mossavi for his statistical advice. 
 
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Effects of metronidazole therapy on preterm labor in women with bacterial vaginosis

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Effects of metronidazole therapy on preterm labor in women with bacterial vaginosis

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