Correspondence
Bacterial Vaginosis and Preterm Birth
N Engl J Med 1996; 334:1337-1339May 16, 1996
- Article
To the Editor:
The report by Hillier et al. on vaginal infections and preterm birth (Dec. 28 issue)1 adds conclusive weight to over a dozen descriptive studies linking bacterial vaginosis and prematurity. The comparatively modest 40 percent increase in the risk of preterm birth and low birth weight may have been due to the relatively late second-trimester enrollment. In contrast, Kurki et al. found that the risk of preterm birth was seven times higher among women in Helsinki, Finland, with bacterial vaginosis evaluated early in pregnancy.2 The relative absence of other risk factors for prematurity among these Finnish women highlights the importance of bacterial vaginosis even in women deemed to be at low risk for preterm birth.
Hillier et al. note the elimination of prematurity attributable to bacterial vaginosis in women receiving antibiotics “effective against bacterial vaginosis” but give scant information about this key point. Other investigators have performed controlled trials with the use of oral metronidazole, clindamycin, or erythromycin to reduce the risk of preterm birth associated with bacterial vaginosis in selected and unselected populations.3-5
In the same issue of the Journal, Hauth et al. report on a trial in which metronidazole and erythromycin reduced the risk of prematurity in two groups of women (with low maternal weight or a prior preterm delivery), the majority of whom were black.6 Other women can benefit as well. We conducted a controlled trial of treatment of lower reproductive tract infections during early pregnancy (with oral clindamycin for bacterial vaginosis), which reduced the number of preterm births by half in an unselected population of women in Denver.4
We share the concern of Hauth et al. about the possible adverse effects of unnecessarily broad or unindicated antimicrobial treatment. Studies evaluating topical treatment for bacterial vaginosis demonstrate a similar nonsignificant excess risk of prematurity, possibly because of the overgrowth of Enterobacteriaceae.7 We believe systemic treatment is required for adequate management of bacterial-vaginosis–associated microbes within uterine tissues.
These and other studies strongly suggest, if not mandate, that women be screened and treated for bacterial vaginosis and other common genitourinary infections (bacteriuria, trichomoniasis, chlamydia infection, and so forth) during pregnancy. Treatment of these conditions during pregnancy — or possibly in preparation for pregnancy — can incrementally reduce the risk of preterm birth in the general population.
7 ReferencesJames A. McGregor, M.D., C.M.
Janice I. French, C.N.M.
University of Colorado Health Sciences Center, Denver, CO 802621
Hillier SL ,Nugent RP ,Eschenbach DA , et al. Association between bacterial vaginosis and preterm delivery of a low-birth-weight infant. N Engl J Med 1995;333:1737-1742
Full Text | Web of Science | Medline2
Kurki T ,Sivonen A ,Renkonen OV ,Savia E ,Ylikorkala O . Bacterial vaginosis in early pregnancy and pregnancy outcome. Obstet Gynecol 1992;80:173-177
Web of Science | Medline3
Morales WJ ,Schorr S ,Albritton J . Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol 1994;171:345-349
Web of Science | Medline4
McGregor JA ,French JI ,Parker R , et al. Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. Am J Obstet Gynecol 1995;173:157-167
CrossRef | Web of Science | Medline5
McGregor JA ,French JI ,Richter R , et al. Cervicovaginal microflora and pregnancy outcome: results of a double-blind, placebo-controlled trial of erythromycin treatment. Am J Obstet Gynecol 1990;163:1580-1591
Web of Science | Medline6
Hauth JC ,Goldenberg RL ,Andrews WW ,DuBard MB ,Copper RL . Reduced incidence of preterm delivery with metronidazole and erythromycin in women with bacterial vaginosis. N Engl J Med 1995;333:1732-1736
Full Text | Web of Science | Medline7
Joesoef MR ,Hillier SL ,Wiknjosastro G , et al. Intravaginal clindamycin treatment for bacterial vaginosis: effects on preterm delivery and low birth weight. Am J Obstet Gynecol 1995;173:1527-1531
CrossRef | Web of Science | Medline
To the Editor:
The studies by Hauth et al. and Hillier et al. showed that bacterial vaginosis can have dramatic consequences in terms of low birth weight and preterm delivery. We estimated, on the basis of published data, the benefits (reduced numbers of low-birth-weight infants and preterm deliveries) and cost (net expenditures or savings) of universal screening and treatment of pregnant women who are positive for bacterial vaginosis.
A 1995 report from the Center for the Future of Children estimated that in 1988 first-year medical costs for low-birth-weight infants (<2500 g) were $15,000 higher than for full-term infants.1 The report also noted that low-birth-weight infants require more health care services as they mature and that some do not entirely outgrow their health problems. The emotional and financial consequences for their families are obvious.
About 7.2 percent of 4 million infants born in 1993 had a low birth weight.2 Adjusting 1988 cost estimates to 1993 dollars and multiplying by the estimated number of low-birth-weight babies in 1993 (288,000), we calculated that the direct medical expense for the first year of life was $6.3 billion, or $21,800 per affected infant.
In 1993, 78.9 percent of pregnant women began prenatal care in the first trimester.2 Assuming that none of these women were screened or treated for bacterial vaginosis, the additional cost of screening each woman would have been about $20, for a total cost of $62 million. On the basis of the findings of Hillier et al., about 16 percent, or 500,000, of those screened would have had positive tests. If all these women had been treated with metronidazole (250 mg three times a day for seven days), the total cost of treatment would have been approximately $13.3 million. Thus, the cost of screening and treatment in 1993 would have totaled $75.3 million.
Hillier et al. indicate that the rate of low-birth-weight babies was 9.7 percent among the women who were positive for bacterial vaginosis and 6.6 percent among those who were negative. Universal screening and treatment would have reduced the overall rate of low-birth-weight babies from 7.2 percent to 6.8 percent, a difference of 15,600 babies. The total amount saved would have been $340 million (or $21,800 per low-birth-weight delivery prevented).
Rarely do we achieve a better outcome at a lower cost, as this analysis suggests. Most of the time, an improved outcome costs more. Cost effectiveness could be increased by targeting pregnant women considered to be at high risk according to the risk factors identified by both Hauth et al. and Hillier et al. Each dollar spent on screening and treatment for bacterial vaginosis in the high-risk groups would save about $25 of the cost for low-birth-weight babies. A universal screening strategy is better for both the patient and the payer — a combination that is hard to beat.
2 ReferencesBernard S. Bloom, Ph.D.
University of Pennsylvania, Philadelphia, PA 19104David W. Lee, Ph.D.
Searle, Skokie, IL 600771
Lewit EM ,Baker LS ,Corman H ,Shiono PH . The direct cost of low birth weight. Future Child 1995;5:35-56
CrossRef | Web of Science | Medline2
Ventura SJ, Martin JA, Taffel SM, et al. Advance report of final natality statistics, 1993. Vol. 3. Atlanta: Centers for Disease Control and Prevention, 1995.
Author/Editor Response
The authors reply:
To the Editor: We share McGregor and French's optimism regarding the potential for preemptive intervention based on our findings to reduce the incidence of preterm birth among women with bacterial vaginosis. However, we believe that only prospective, randomized, and ideally, blinded clinical trials should be used to establish practice guidelines for the treatment of bacterial vaginosis in all pregnant women. The study by Hauth et al. and that reported by Morales et al.1 focused on relatively small numbers of asymptomatic women (624 and 80, respectively) who were considered to be at increased risk for preterm delivery.
Many questions remain to be addressed, especially the benefit of screening and treatment in low-risk asymptomatic women with bacterial vaginosis and the ideal antimicrobial treatment. Hauth et al. used the combination of metronidazole and erythromycin to eradicate upper genital tract colonization and infection and not simply to treat bacterial vaginosis. The Maternal–Fetal Medicine Units Network of the National Institute of Child Health and Human Development has begun a multicenter trial of screening and treatment in a group of nearly 2000 unselected asymptomatic women with either bacterial vaginosis or Trichomonas vaginalis infection, in order to determine whether treatment with oral metronidazole alone will reduce preterm births.
We are aware of and commend the work of McGregor and French and their colleagues,2 but we believe that, at this time, they are too enthusiastic about requiring universal screening for bacterial vaginosis in all pregnant women (more than 4 million each year in the United States). We believe it is essential to document that the benefits associated with treatment of bacterial vaginosis will outweigh the potential risks.
Finally, in regard to the comments of Bloom and Lee, we again submit that sufficient data from randomized trials must be available to determine the benefits before performing cost–benefit analyses. According to another analysis of costs associated with bacterial vaginosis, the excess costs for preterm, low-birth-weight deliveries attributable to bacterial vaginosis amounted to $252 million annually, and screening and treatment of all pregnant women with bacterial vaginosis would cost $50 million to $74 million annually.3 The cost effectiveness of universal screening and treatment for bacterial vaginosis cannot be evaluated until the effect of antibiotic therapy on the reduction of preterm births has been assessed in double-blind, randomized, placebo-controlled trials.
3 ReferencesJohn C. Hauth, M.D.
University of Alabama at Birmingham, Birmingham, AL 35233Sharon L. Hillier, Ph.D.
University of Pittsburgh, Pittsburgh, PA 152131
Morales WJ ,Schorr S ,Albritton J . Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Am J Obstet Gynecol 1994;171:345-349
Web of Science | Medline2
McGregor JA ,French JI ,Parker R , et al. Prevention of premature birth by screening and treatment for common genital tract infections: results of a prospective controlled evaluation. Am J Obstet Gynecol 1995;173:157-167
CrossRef | Web of Science | Medline3
Oleen-Burkey MA ,Hillier SL . Pregnancy complications associated with bacterial vaginosis and their estimated costs. Infect Dis Obstet Gynecol 1995;3:149-157
CrossRef | Medline
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1
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