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BACKGROUND: Given the high cost of neonatal intensive care and the serious sequelae associated with preterm delivery, an inexpensive safe treatment that would reduce the risk of preterm delivery is appealing. One previous study demonstrated a small decrease in the rate of preterm delivery using oral erythromycin plus metronidazole in a population of women at high risk of preterm delivery (mostly women with a previous preterm delivery)1; a small study of women at low risk of preterm delivery, however, found no benefit.2
POPULATION STUDIED: Women presenting for prenatal care were considered for randomization. Exclusions were reasonable and included women with: symptoms of vaginitis, contraindications to metronidazole, recent or anticipated antibiotic use, preterm labor, planned or current cervical cerclage, multifetal gestation, failure to have a postscreening visit before 24-weeks’ gestation, and unanticipated use of antibiotics between the screening and the postscreening visit. This was a group of fairly low-risk and adherent patients.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study. Women were considered to have BV if they had a vaginal hydrogen ion concentration higher than 4.4 and a positive Gram’s stain using reasonable criteria well described by the authors. Women with BV who were seen before 24 weeks’ gestation, had given consent, and had not used antibiotics since the screening were randomized to receive either 2 doses of 2 g of oral metronidazole 48 hours apart or a matching placebo. They were scheduled for a follow-up visit at least 2 weeks later and were given 2 more doses of the same active medication or placebo given previously. Randomization was well described, and concealment of allocation was adequate. One significant weakness of this study is the large number of women who screened positive for BV but were excluded from randomization (4604 out of 6540, including 2126 who had difficulty arranging follow-up).
OUTCOMES MEASURED: The primary outcome measures were the length of gestation and the rate of preterm labor.
RESULTS: No significant differences in the length of gestation or in birth weight were observed between the treatment and placebo groups. The number of preterm deliveries - 116 of 953 (12.2%) in the metronidazole group and 121 of 956 (12.5%) in the placebo group-make the likelihood of any clinically significant difference extremely small. Extreme prematurity, low birth weight, and very low birth weight were also equal between the 2 groups. Subgroup analyses for women with significant risk factors for premature delivery, such as previous preterm delivery and prepregnancy weight less than 50 kg (110 pounds), also failed to show any benefit of treatment.
There is no benefit to screening for BV in asymptomatic pregnant women in the second trimester who are at low risk for preterm delivery. For those women at highest risk for preterm labor (ie, those with a previous preterm delivery or a prepregnancy weight <50 kg), the results of a previous study1 suggest a benefit from treatment with metronidazole plus erythromycin. It is also still reasonable to treat symptomatic BV with metronidazole on the basis of its ability to improve symptoms, its established safety in midgestation, and the theoretical possibility that some small subgroup (excluded from this study) might have a lowered incidence of preterm labor.
BACKGROUND: Given the high cost of neonatal intensive care and the serious sequelae associated with preterm delivery, an inexpensive safe treatment that would reduce the risk of preterm delivery is appealing. One previous study demonstrated a small decrease in the rate of preterm delivery using oral erythromycin plus metronidazole in a population of women at high risk of preterm delivery (mostly women with a previous preterm delivery)1; a small study of women at low risk of preterm delivery, however, found no benefit.2
POPULATION STUDIED: Women presenting for prenatal care were considered for randomization. Exclusions were reasonable and included women with: symptoms of vaginitis, contraindications to metronidazole, recent or anticipated antibiotic use, preterm labor, planned or current cervical cerclage, multifetal gestation, failure to have a postscreening visit before 24-weeks’ gestation, and unanticipated use of antibiotics between the screening and the postscreening visit. This was a group of fairly low-risk and adherent patients.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study. Women were considered to have BV if they had a vaginal hydrogen ion concentration higher than 4.4 and a positive Gram’s stain using reasonable criteria well described by the authors. Women with BV who were seen before 24 weeks’ gestation, had given consent, and had not used antibiotics since the screening were randomized to receive either 2 doses of 2 g of oral metronidazole 48 hours apart or a matching placebo. They were scheduled for a follow-up visit at least 2 weeks later and were given 2 more doses of the same active medication or placebo given previously. Randomization was well described, and concealment of allocation was adequate. One significant weakness of this study is the large number of women who screened positive for BV but were excluded from randomization (4604 out of 6540, including 2126 who had difficulty arranging follow-up).
OUTCOMES MEASURED: The primary outcome measures were the length of gestation and the rate of preterm labor.
RESULTS: No significant differences in the length of gestation or in birth weight were observed between the treatment and placebo groups. The number of preterm deliveries - 116 of 953 (12.2%) in the metronidazole group and 121 of 956 (12.5%) in the placebo group-make the likelihood of any clinically significant difference extremely small. Extreme prematurity, low birth weight, and very low birth weight were also equal between the 2 groups. Subgroup analyses for women with significant risk factors for premature delivery, such as previous preterm delivery and prepregnancy weight less than 50 kg (110 pounds), also failed to show any benefit of treatment.
There is no benefit to screening for BV in asymptomatic pregnant women in the second trimester who are at low risk for preterm delivery. For those women at highest risk for preterm labor (ie, those with a previous preterm delivery or a prepregnancy weight <50 kg), the results of a previous study1 suggest a benefit from treatment with metronidazole plus erythromycin. It is also still reasonable to treat symptomatic BV with metronidazole on the basis of its ability to improve symptoms, its established safety in midgestation, and the theoretical possibility that some small subgroup (excluded from this study) might have a lowered incidence of preterm labor.
BACKGROUND: Given the high cost of neonatal intensive care and the serious sequelae associated with preterm delivery, an inexpensive safe treatment that would reduce the risk of preterm delivery is appealing. One previous study demonstrated a small decrease in the rate of preterm delivery using oral erythromycin plus metronidazole in a population of women at high risk of preterm delivery (mostly women with a previous preterm delivery)1; a small study of women at low risk of preterm delivery, however, found no benefit.2
POPULATION STUDIED: Women presenting for prenatal care were considered for randomization. Exclusions were reasonable and included women with: symptoms of vaginitis, contraindications to metronidazole, recent or anticipated antibiotic use, preterm labor, planned or current cervical cerclage, multifetal gestation, failure to have a postscreening visit before 24-weeks’ gestation, and unanticipated use of antibiotics between the screening and the postscreening visit. This was a group of fairly low-risk and adherent patients.
STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study. Women were considered to have BV if they had a vaginal hydrogen ion concentration higher than 4.4 and a positive Gram’s stain using reasonable criteria well described by the authors. Women with BV who were seen before 24 weeks’ gestation, had given consent, and had not used antibiotics since the screening were randomized to receive either 2 doses of 2 g of oral metronidazole 48 hours apart or a matching placebo. They were scheduled for a follow-up visit at least 2 weeks later and were given 2 more doses of the same active medication or placebo given previously. Randomization was well described, and concealment of allocation was adequate. One significant weakness of this study is the large number of women who screened positive for BV but were excluded from randomization (4604 out of 6540, including 2126 who had difficulty arranging follow-up).
OUTCOMES MEASURED: The primary outcome measures were the length of gestation and the rate of preterm labor.
RESULTS: No significant differences in the length of gestation or in birth weight were observed between the treatment and placebo groups. The number of preterm deliveries - 116 of 953 (12.2%) in the metronidazole group and 121 of 956 (12.5%) in the placebo group-make the likelihood of any clinically significant difference extremely small. Extreme prematurity, low birth weight, and very low birth weight were also equal between the 2 groups. Subgroup analyses for women with significant risk factors for premature delivery, such as previous preterm delivery and prepregnancy weight less than 50 kg (110 pounds), also failed to show any benefit of treatment.
There is no benefit to screening for BV in asymptomatic pregnant women in the second trimester who are at low risk for preterm delivery. For those women at highest risk for preterm labor (ie, those with a previous preterm delivery or a prepregnancy weight <50 kg), the results of a previous study1 suggest a benefit from treatment with metronidazole plus erythromycin. It is also still reasonable to treat symptomatic BV with metronidazole on the basis of its ability to improve symptoms, its established safety in midgestation, and the theoretical possibility that some small subgroup (excluded from this study) might have a lowered incidence of preterm labor.