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How should we follow up a positive screen for anemia in a 1-year old?
Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3–6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency (strength of recommendation [SOR]: B; evidence from randomized controlled trials with some conflicting results; lack of evidence for long-term benefits/harms of screening strategies).
In these cases, further testing with a complete blood count, mean corpuscular volume, red cell distribution width (RDW), serum ferritin concentration, as well as hemoglobinopathy screening when appropriate, may be effective in determining the cause of anemia (SOR: C, expert opinion).
Evidence summary
A prospective study of 1128 children identified as anemic with a screening hemoglobin level showed that subsequent testing—which included mean corpuscular volume, protoporphyrin, transferrin, and ferritin measurements—did not reliably distinguish potential responders from nonresponders to a 3-month trial of empiric iron therapy.1 In fact, more than half of the responders would have been missed if treatment had been restricted to infants with abnormal mean corpuscular volume or iron studies.
Because of the simplicity, low cost, and relative safety of iron therapy for infants, this trial suggests that a therapeutic trial of iron be given first, reserving further work-up for the small number of infants that still have unexplained hemoglobin concentrations of <11.0 g/dL after a therapeutic trial. Similar results were found in a prospective controlled treatment trial among Alaskan Native children2 as well as a trial of empiric iron therapy among infants with anemia.3
Another prospective study of 970 healthy infants identified 62 infants with a heel-stick capillary hematocrit of <33%. Of these, 31 had repeat hematocrit values of <33% as confirmed by subsequent heel-stick complete blood count measurement. Twenty of these anemic infants (65%) completed the study protocol, which included a 1-month trial of iron, a follow-up complete blood count, and hemoglobin electrophoresis for those infants with persistent microcytosis or positive sickle preparation (performed at initial screening for all African American infants). Six infants (30%) had an increase in hemoglobin concentration of 1.0 g/dL or more and were presumed to be iron-deficient; they went on to receive an additional 2 months of iron therapy. Two of these were found to have co-existing alpha-thalassemia. Of the remainder, 11 (55%) were determined to have a low-normal hematocrit (mean=31.5 ± 0.9), 1 had alpha thalassemia alone, 1 had coexisting alpha-thalassemia and hemoglobin AS, and 1 had hemoglobin SC. Review of data showed that abnormal diagnoses (iron deficiency, thalassemia, and sickle cell trait or disease) were found in 9 of 11 infants with high RDW and in none of the 9 with normal RDW. The authors concluded that RDW alone appears to be predictive of identifiable causes of anemia when used to screen healthy 12-month-old babies.4
A recent Cochrane review suggests there is a clinically significant benefit for the treatment of iron-deficiency anemia; however, there is a need for further randomized controlled trials with long-term follow-up.5 A randomized controlled trial of iron supplementation vs placebo in 278 infants testing positive for iron-deficiency anemia demonstrated that once daily, moderate-dose ferrous sulfate (FeSO4) therapy (3 mg/kg/d of elemental iron) given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy.6 Another study demonstrated that iron sulfate drops (40 mg elemental iron divided 3 times a day) or a single daily dose of microencapsulated ferrous fumarate sprinkles (80 mg elemental iron) plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects.7
In a retrospective cohort study8 of 1358 innercity children aged 9 to 36 months who underwent screening, 343 (25%) had anemia (Hgb <11 g/dL); of these, 239 (72%) were prescribed iron and 95 (28%) were not. Responders were defined as those with a hemoglobin value of greater than 11 g/dL or an increase of 1 g/dL documented within 6 months of the initial screening visit. Follow-up rates for both groups were low (~50%), but of those prescribed iron, 107 of 150 (71%) responded to treatment compared with 27 of 48 (68%) of those who did not receive iron. Since similar response rates were seen among infants who did and infants who did not receive iron therapy, proving the benefit of routine screening followed by a trial of iron may be problematic in populations with higher rates of anemia, low follow-up rates, and high spontaneous resolution rates.
Recommendations from others
The United States Preventive Services Task Force,9 American Academy of Family Physicians,10 and American Academy of Pediatrics11 recommend screening infants for iron-deficiency anemia but do not address appropriate follow-up for positive screens.
The Centers for Disease Control and Prevention (CDC) guidelines recommend performing a confirmatory hemoglobin and hematocrit after a positive anemia screening. If anemia is confirmed and the child is not ill, then treat with iron replacement (3 mg elemental iron/kg/daily) for 4 weeks followed by a repeat test. An increase in hemoglobin concentration ≥1 g/dL or in hematocrit ≥3% confirms the diagnosis of iron-deficiency anemia. If iron-deficiency anemia is confirmed, they recommend continuing iron therapy for 2 more months (3 months total treatment), and rechecking hemoglobin or hematocrit 6 months after successful treatment is completed. Nonresponders, despite compliance with the iron supplementation regimen and the absence of acute illness, should undergo further evaluation including mean corpuscular volume, RDW, and serum ferritin concentration.12
Treating anemia without testing for the cause is the approach of most FPs
Quadri Yasmeen, MD
Baylor College of Medicine, Houston, Tex
For infants 9 months to 1 year of age, there is no consensus regarding appropriate follow-up of positive screens for anemia. It is known that most of them have iron deficiency anemia and empiric treatment with iron supplements have been studied in several prospective trials.
It is also unclear which red cell indices should be tested for diagnosing the different types of anemia. One study found RDW testing alone could predict the cause of anemia. Based on my clinical experience with innercity Hispanic babies, CDC guidelines seem to include appropriate follow-up. A Cochrane review suggests the need for further randomized controlled trials with long-term follow-up. There is evidence that treating anemia without initial testing for the cause is the approach of choice of most physicians, and there is some evidence that further testing may delay or result in nontreatment of infants who would have benefited from iron therapy.
1. Dallman PR, Reeves JD, Driggers DA, Lo EY. Diagnosis of iron deficiency: the limitations of laboratory tests in predicting response to iron treatment in 1-year-old infants. J Pediatr 1981;99:376-381.
2. Margolis HS, Hardison HH, Bender TR, Dallman PR. Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy. Am J Clin Nutr 1981;34:2158-2168.
3. Driggers DA, Reeves JP, Lo EY, Dallman PR. Iron deficiency in one-year-old infants: comparison of results of a therapeutic trial in infants with anemia or low-normal hemoglobin values. J Pediatr 1981;98:753-758.
4. Choi YS, Reid T. Anemia and red cell distribution width at the 12-month well-baby examination. South Med J 1998;91:372-374.
5. Logan S, Martins S, Gilbert R. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia (Cochrane review). Cochrane Database Syst Rev Library, Issue 2, 2004;2001(2):CD001444.-
6. Reeves JD, Yip R. Lack of adverse side effects of oral ferrous sulfate therapy in 1-year-old infants. Pediatrics 1985;75:352-355.
7. Zlotkin S, Arthur P, Antwi KY, Yeung G. Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods. Am J Clin Nutr 2001;74:791-795.
8. Bogen DL, Krause JP, Serwint JR. Outcome of children identified as anemic by routine screening in an innercity clinic. Arch Pediatr Adolesc Med 2001;155:366-371.
9. US Preventive Services Task Force (USPSTF). Screening: Iron deficiency anemia. Guide to Clinical Preventive Services. Rockville, Md: USPSTF; 1996. Available at: www.ahrq.gov/clinic/uspstf/uspsiron.htm. Accessed on February 7, 2005.
10. American Academy of Family Physicians. Summary of Policy Recommendations for Periodic Health Examinations, revision 5.6, August 2004. Available at: www.aafp.org/x24975.xml. Accessed on February 7, 2005.
11. Kohli-Kumar M. Screening for anemia in children: AAP recommendations—a critique. Pediatrics 2001;108:E56.-
12. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47(RR-3):1-29.Available at: www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm. Accessed on February 7, 2005.
Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3–6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency (strength of recommendation [SOR]: B; evidence from randomized controlled trials with some conflicting results; lack of evidence for long-term benefits/harms of screening strategies).
In these cases, further testing with a complete blood count, mean corpuscular volume, red cell distribution width (RDW), serum ferritin concentration, as well as hemoglobinopathy screening when appropriate, may be effective in determining the cause of anemia (SOR: C, expert opinion).
Evidence summary
A prospective study of 1128 children identified as anemic with a screening hemoglobin level showed that subsequent testing—which included mean corpuscular volume, protoporphyrin, transferrin, and ferritin measurements—did not reliably distinguish potential responders from nonresponders to a 3-month trial of empiric iron therapy.1 In fact, more than half of the responders would have been missed if treatment had been restricted to infants with abnormal mean corpuscular volume or iron studies.
Because of the simplicity, low cost, and relative safety of iron therapy for infants, this trial suggests that a therapeutic trial of iron be given first, reserving further work-up for the small number of infants that still have unexplained hemoglobin concentrations of <11.0 g/dL after a therapeutic trial. Similar results were found in a prospective controlled treatment trial among Alaskan Native children2 as well as a trial of empiric iron therapy among infants with anemia.3
Another prospective study of 970 healthy infants identified 62 infants with a heel-stick capillary hematocrit of <33%. Of these, 31 had repeat hematocrit values of <33% as confirmed by subsequent heel-stick complete blood count measurement. Twenty of these anemic infants (65%) completed the study protocol, which included a 1-month trial of iron, a follow-up complete blood count, and hemoglobin electrophoresis for those infants with persistent microcytosis or positive sickle preparation (performed at initial screening for all African American infants). Six infants (30%) had an increase in hemoglobin concentration of 1.0 g/dL or more and were presumed to be iron-deficient; they went on to receive an additional 2 months of iron therapy. Two of these were found to have co-existing alpha-thalassemia. Of the remainder, 11 (55%) were determined to have a low-normal hematocrit (mean=31.5 ± 0.9), 1 had alpha thalassemia alone, 1 had coexisting alpha-thalassemia and hemoglobin AS, and 1 had hemoglobin SC. Review of data showed that abnormal diagnoses (iron deficiency, thalassemia, and sickle cell trait or disease) were found in 9 of 11 infants with high RDW and in none of the 9 with normal RDW. The authors concluded that RDW alone appears to be predictive of identifiable causes of anemia when used to screen healthy 12-month-old babies.4
A recent Cochrane review suggests there is a clinically significant benefit for the treatment of iron-deficiency anemia; however, there is a need for further randomized controlled trials with long-term follow-up.5 A randomized controlled trial of iron supplementation vs placebo in 278 infants testing positive for iron-deficiency anemia demonstrated that once daily, moderate-dose ferrous sulfate (FeSO4) therapy (3 mg/kg/d of elemental iron) given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy.6 Another study demonstrated that iron sulfate drops (40 mg elemental iron divided 3 times a day) or a single daily dose of microencapsulated ferrous fumarate sprinkles (80 mg elemental iron) plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects.7
In a retrospective cohort study8 of 1358 innercity children aged 9 to 36 months who underwent screening, 343 (25%) had anemia (Hgb <11 g/dL); of these, 239 (72%) were prescribed iron and 95 (28%) were not. Responders were defined as those with a hemoglobin value of greater than 11 g/dL or an increase of 1 g/dL documented within 6 months of the initial screening visit. Follow-up rates for both groups were low (~50%), but of those prescribed iron, 107 of 150 (71%) responded to treatment compared with 27 of 48 (68%) of those who did not receive iron. Since similar response rates were seen among infants who did and infants who did not receive iron therapy, proving the benefit of routine screening followed by a trial of iron may be problematic in populations with higher rates of anemia, low follow-up rates, and high spontaneous resolution rates.
Recommendations from others
The United States Preventive Services Task Force,9 American Academy of Family Physicians,10 and American Academy of Pediatrics11 recommend screening infants for iron-deficiency anemia but do not address appropriate follow-up for positive screens.
The Centers for Disease Control and Prevention (CDC) guidelines recommend performing a confirmatory hemoglobin and hematocrit after a positive anemia screening. If anemia is confirmed and the child is not ill, then treat with iron replacement (3 mg elemental iron/kg/daily) for 4 weeks followed by a repeat test. An increase in hemoglobin concentration ≥1 g/dL or in hematocrit ≥3% confirms the diagnosis of iron-deficiency anemia. If iron-deficiency anemia is confirmed, they recommend continuing iron therapy for 2 more months (3 months total treatment), and rechecking hemoglobin or hematocrit 6 months after successful treatment is completed. Nonresponders, despite compliance with the iron supplementation regimen and the absence of acute illness, should undergo further evaluation including mean corpuscular volume, RDW, and serum ferritin concentration.12
Treating anemia without testing for the cause is the approach of most FPs
Quadri Yasmeen, MD
Baylor College of Medicine, Houston, Tex
For infants 9 months to 1 year of age, there is no consensus regarding appropriate follow-up of positive screens for anemia. It is known that most of them have iron deficiency anemia and empiric treatment with iron supplements have been studied in several prospective trials.
It is also unclear which red cell indices should be tested for diagnosing the different types of anemia. One study found RDW testing alone could predict the cause of anemia. Based on my clinical experience with innercity Hispanic babies, CDC guidelines seem to include appropriate follow-up. A Cochrane review suggests the need for further randomized controlled trials with long-term follow-up. There is evidence that treating anemia without initial testing for the cause is the approach of choice of most physicians, and there is some evidence that further testing may delay or result in nontreatment of infants who would have benefited from iron therapy.
Healthy infants who test positive for anemia on routine screening at 1 year of age are most likely iron-deficient and may be treated empirically with a trial of iron therapy (3–6 mg of elemental iron/kg/d). Documentation of response to iron confirms the diagnosis of iron-deficiency (strength of recommendation [SOR]: B; evidence from randomized controlled trials with some conflicting results; lack of evidence for long-term benefits/harms of screening strategies).
In these cases, further testing with a complete blood count, mean corpuscular volume, red cell distribution width (RDW), serum ferritin concentration, as well as hemoglobinopathy screening when appropriate, may be effective in determining the cause of anemia (SOR: C, expert opinion).
Evidence summary
A prospective study of 1128 children identified as anemic with a screening hemoglobin level showed that subsequent testing—which included mean corpuscular volume, protoporphyrin, transferrin, and ferritin measurements—did not reliably distinguish potential responders from nonresponders to a 3-month trial of empiric iron therapy.1 In fact, more than half of the responders would have been missed if treatment had been restricted to infants with abnormal mean corpuscular volume or iron studies.
Because of the simplicity, low cost, and relative safety of iron therapy for infants, this trial suggests that a therapeutic trial of iron be given first, reserving further work-up for the small number of infants that still have unexplained hemoglobin concentrations of <11.0 g/dL after a therapeutic trial. Similar results were found in a prospective controlled treatment trial among Alaskan Native children2 as well as a trial of empiric iron therapy among infants with anemia.3
Another prospective study of 970 healthy infants identified 62 infants with a heel-stick capillary hematocrit of <33%. Of these, 31 had repeat hematocrit values of <33% as confirmed by subsequent heel-stick complete blood count measurement. Twenty of these anemic infants (65%) completed the study protocol, which included a 1-month trial of iron, a follow-up complete blood count, and hemoglobin electrophoresis for those infants with persistent microcytosis or positive sickle preparation (performed at initial screening for all African American infants). Six infants (30%) had an increase in hemoglobin concentration of 1.0 g/dL or more and were presumed to be iron-deficient; they went on to receive an additional 2 months of iron therapy. Two of these were found to have co-existing alpha-thalassemia. Of the remainder, 11 (55%) were determined to have a low-normal hematocrit (mean=31.5 ± 0.9), 1 had alpha thalassemia alone, 1 had coexisting alpha-thalassemia and hemoglobin AS, and 1 had hemoglobin SC. Review of data showed that abnormal diagnoses (iron deficiency, thalassemia, and sickle cell trait or disease) were found in 9 of 11 infants with high RDW and in none of the 9 with normal RDW. The authors concluded that RDW alone appears to be predictive of identifiable causes of anemia when used to screen healthy 12-month-old babies.4
A recent Cochrane review suggests there is a clinically significant benefit for the treatment of iron-deficiency anemia; however, there is a need for further randomized controlled trials with long-term follow-up.5 A randomized controlled trial of iron supplementation vs placebo in 278 infants testing positive for iron-deficiency anemia demonstrated that once daily, moderate-dose ferrous sulfate (FeSO4) therapy (3 mg/kg/d of elemental iron) given to fasting 1-year-old infants results in no more gastrointestinal side effects than placebo therapy.6 Another study demonstrated that iron sulfate drops (40 mg elemental iron divided 3 times a day) or a single daily dose of microencapsulated ferrous fumarate sprinkles (80 mg elemental iron) plus ascorbic acid resulted in a similar rate of successful treatment of anemia without side effects.7
In a retrospective cohort study8 of 1358 innercity children aged 9 to 36 months who underwent screening, 343 (25%) had anemia (Hgb <11 g/dL); of these, 239 (72%) were prescribed iron and 95 (28%) were not. Responders were defined as those with a hemoglobin value of greater than 11 g/dL or an increase of 1 g/dL documented within 6 months of the initial screening visit. Follow-up rates for both groups were low (~50%), but of those prescribed iron, 107 of 150 (71%) responded to treatment compared with 27 of 48 (68%) of those who did not receive iron. Since similar response rates were seen among infants who did and infants who did not receive iron therapy, proving the benefit of routine screening followed by a trial of iron may be problematic in populations with higher rates of anemia, low follow-up rates, and high spontaneous resolution rates.
Recommendations from others
The United States Preventive Services Task Force,9 American Academy of Family Physicians,10 and American Academy of Pediatrics11 recommend screening infants for iron-deficiency anemia but do not address appropriate follow-up for positive screens.
The Centers for Disease Control and Prevention (CDC) guidelines recommend performing a confirmatory hemoglobin and hematocrit after a positive anemia screening. If anemia is confirmed and the child is not ill, then treat with iron replacement (3 mg elemental iron/kg/daily) for 4 weeks followed by a repeat test. An increase in hemoglobin concentration ≥1 g/dL or in hematocrit ≥3% confirms the diagnosis of iron-deficiency anemia. If iron-deficiency anemia is confirmed, they recommend continuing iron therapy for 2 more months (3 months total treatment), and rechecking hemoglobin or hematocrit 6 months after successful treatment is completed. Nonresponders, despite compliance with the iron supplementation regimen and the absence of acute illness, should undergo further evaluation including mean corpuscular volume, RDW, and serum ferritin concentration.12
Treating anemia without testing for the cause is the approach of most FPs
Quadri Yasmeen, MD
Baylor College of Medicine, Houston, Tex
For infants 9 months to 1 year of age, there is no consensus regarding appropriate follow-up of positive screens for anemia. It is known that most of them have iron deficiency anemia and empiric treatment with iron supplements have been studied in several prospective trials.
It is also unclear which red cell indices should be tested for diagnosing the different types of anemia. One study found RDW testing alone could predict the cause of anemia. Based on my clinical experience with innercity Hispanic babies, CDC guidelines seem to include appropriate follow-up. A Cochrane review suggests the need for further randomized controlled trials with long-term follow-up. There is evidence that treating anemia without initial testing for the cause is the approach of choice of most physicians, and there is some evidence that further testing may delay or result in nontreatment of infants who would have benefited from iron therapy.
1. Dallman PR, Reeves JD, Driggers DA, Lo EY. Diagnosis of iron deficiency: the limitations of laboratory tests in predicting response to iron treatment in 1-year-old infants. J Pediatr 1981;99:376-381.
2. Margolis HS, Hardison HH, Bender TR, Dallman PR. Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy. Am J Clin Nutr 1981;34:2158-2168.
3. Driggers DA, Reeves JP, Lo EY, Dallman PR. Iron deficiency in one-year-old infants: comparison of results of a therapeutic trial in infants with anemia or low-normal hemoglobin values. J Pediatr 1981;98:753-758.
4. Choi YS, Reid T. Anemia and red cell distribution width at the 12-month well-baby examination. South Med J 1998;91:372-374.
5. Logan S, Martins S, Gilbert R. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia (Cochrane review). Cochrane Database Syst Rev Library, Issue 2, 2004;2001(2):CD001444.-
6. Reeves JD, Yip R. Lack of adverse side effects of oral ferrous sulfate therapy in 1-year-old infants. Pediatrics 1985;75:352-355.
7. Zlotkin S, Arthur P, Antwi KY, Yeung G. Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods. Am J Clin Nutr 2001;74:791-795.
8. Bogen DL, Krause JP, Serwint JR. Outcome of children identified as anemic by routine screening in an innercity clinic. Arch Pediatr Adolesc Med 2001;155:366-371.
9. US Preventive Services Task Force (USPSTF). Screening: Iron deficiency anemia. Guide to Clinical Preventive Services. Rockville, Md: USPSTF; 1996. Available at: www.ahrq.gov/clinic/uspstf/uspsiron.htm. Accessed on February 7, 2005.
10. American Academy of Family Physicians. Summary of Policy Recommendations for Periodic Health Examinations, revision 5.6, August 2004. Available at: www.aafp.org/x24975.xml. Accessed on February 7, 2005.
11. Kohli-Kumar M. Screening for anemia in children: AAP recommendations—a critique. Pediatrics 2001;108:E56.-
12. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47(RR-3):1-29.Available at: www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm. Accessed on February 7, 2005.
1. Dallman PR, Reeves JD, Driggers DA, Lo EY. Diagnosis of iron deficiency: the limitations of laboratory tests in predicting response to iron treatment in 1-year-old infants. J Pediatr 1981;99:376-381.
2. Margolis HS, Hardison HH, Bender TR, Dallman PR. Iron deficiency in children: the relationship between pretreatment laboratory tests and subsequent hemoglobin response to iron therapy. Am J Clin Nutr 1981;34:2158-2168.
3. Driggers DA, Reeves JP, Lo EY, Dallman PR. Iron deficiency in one-year-old infants: comparison of results of a therapeutic trial in infants with anemia or low-normal hemoglobin values. J Pediatr 1981;98:753-758.
4. Choi YS, Reid T. Anemia and red cell distribution width at the 12-month well-baby examination. South Med J 1998;91:372-374.
5. Logan S, Martins S, Gilbert R. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia (Cochrane review). Cochrane Database Syst Rev Library, Issue 2, 2004;2001(2):CD001444.-
6. Reeves JD, Yip R. Lack of adverse side effects of oral ferrous sulfate therapy in 1-year-old infants. Pediatrics 1985;75:352-355.
7. Zlotkin S, Arthur P, Antwi KY, Yeung G. Treatment of anemia with microencapsulated ferrous fumarate plus ascorbic acid supplied as sprinkles to complementary (weaning) foods. Am J Clin Nutr 2001;74:791-795.
8. Bogen DL, Krause JP, Serwint JR. Outcome of children identified as anemic by routine screening in an innercity clinic. Arch Pediatr Adolesc Med 2001;155:366-371.
9. US Preventive Services Task Force (USPSTF). Screening: Iron deficiency anemia. Guide to Clinical Preventive Services. Rockville, Md: USPSTF; 1996. Available at: www.ahrq.gov/clinic/uspstf/uspsiron.htm. Accessed on February 7, 2005.
10. American Academy of Family Physicians. Summary of Policy Recommendations for Periodic Health Examinations, revision 5.6, August 2004. Available at: www.aafp.org/x24975.xml. Accessed on February 7, 2005.
11. Kohli-Kumar M. Screening for anemia in children: AAP recommendations—a critique. Pediatrics 2001;108:E56.-
12. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. MMWR Recomm Rep 1998;47(RR-3):1-29.Available at: www.cdc.gov/mmwr/preview/mmwrhtml/00051880.htm. Accessed on February 7, 2005.
Evidence-based answers from the Family Physicians Inquiries Network
Should we screen for bacterial vaginosis in those at risk for preterm labor?
Bacterial vaginosis (BV) is associated with preterm delivery (strength of recommendation [SOR]: A, meta-analysis). However, treating asymptomatic, low-risk women with BV does not always prevent preterm delivery (SOR: A, randomized controlled trials [RCTs]). There is some benefit to early screening by Gram stain using Nugent’s criteria1 (Table ) and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants (SOR: B, conflicting RCTs).
Empirically treating high-risk women without documented infection has been associated with an increase in preterm deliveries and neonatal infections (SOR: B, single RCT).
TABLE
Nugent’s Criteria
| Score | Lactobacillus morphotypes | Gardnerella and Bacteroides spp. morphotypes | Curved gram-variable rods |
|---|---|---|---|
| 0 | 4+ | 0 | 0 |
| 1 | 3+ | 1+ | 1+ or 2+ |
| 2 | 2+ | 2+ | 3+ or 4+ |
| 3 | 1+ | 3+ | |
| 4 | 0 | 4+ | |
| 1+, <1 morphotype present; 2+, 1 to 4 morphotypes present; 3+, 5 to 30 morphotypes present; 4+, >30 morphotypes present. The diagnosis of bacterial vaginosis is present with a score of 7 or greater. From Nugent 1991.1 | |||
Evidence summary
Bacterial vaginosis in early pregnancy is a risk factor for preterm delivery.2 The role of BV in preterm labor is not well understood, but it has been consistently associated with preterm labor and delivery. The detection of BV in early pregnancy seems to be a stronger risk factor for preterm delivery than BV in later pregnancy.
Studies evaluating the screening and treatment of BV in women at risk for preterm delivery have demonstrated varying results. Most treatment studies have excluded women who are in the first trimester. A meta-analysis of 7 RCTs reviewed the evidence of screening for BV in pregnancy.3 In this meta-analysis, 5 of the trials specified that women were asymptomatic, and the other 2 did not comment on whether the women were symptomatic or not. In general, there was no benefit to routine screening and treatment of BV.
However, a subgroup of high-risk women seems to benefit from screening and treatment. They defined high-risk women as those have had a preterm delivery, premature rupture of membranes, birth weight <2500 g, or spontaneous abortion. Treating BV in women with a high-risk pregnancy decreased preterm delivery (absolute risk reduction [ARR]=0.22; 90% confidence interval [CI], 0.13–0.31; number needed to treat [NNT]=4.5) regardless of antibiotic choice. However, 2 trials of high-risk women who were empirically treated for BV, but did not have BV, showed an increase in preterm delivery less than 34 weeks (number needed to harm [NNH]=11).
A new study evaluating screening for vaginal infections in pregnancy has demonstrated a reduction in preterm delivery.4 In this study, looking at a general obstetrical population in Austria, 4429 asymptomatic pregnant women between 15 and 19.6 weeks gestation had a vaginal screen for bacterial vaginosis, candidiasis and trichomoniasis. The 2048 women in the intervention group were given the results of the screen from their maternity care provider. The 2097 women in the control group and their providers did not receive the results of the vaginal screen. There were 447 women in the intervention group and 441 women in the control group with positive screens. Using the Nugent criteria, women who were diagnosed with BV received a 6-day course of intravaginal clindamycin 2% cream. Those with positive test results for Candida were treated with intravaginal clotrimazole 0.1 g; those with positive results for trichomonas received intravaginal metronidazole 500 mg for 7 days. After treatment, women with a positive test result in the intervention group had a second vaginal smear between 24 and 28 weeks. Persistent BV was treated with oral clindamycin 300 mg twice daily for 7 days. If Candida or trichomonas were noted, women were treated with the intravaginal clotrimazole or metronidazole. A statistically significant reduction was seen in preterm births in the intervention group(3.0% vs 5.3%, 95% CI, 1.2–3.6; P=.0001; number needed to screen=44).
A large study in 2000 that looked at the use of metronidazole in the treatment of asymptomatic women for BV did not demonstrate any reduction in preterm birth.5 In this study, 21,965 asymptomatic women between 8 and 22 weeks gestation were screened for BV with Gram stain using Nugent’s criteria. Then, 1953 women with BV were randomized to receive either 1 g of metronidazole orally for 2 days or placebo. Between 24 and 29 weeks, all of the women were then rescreened for BV by Gram stain. Even if the results were negative, women received another course of the metronidazole or placebo. In this study, preterm delivery rates did not improve for either low- or high-risk women. Specifically, a subgroup analysis of 213 women with previous preterm delivery did not show any benefit to treatment with metronidazole.
In 2003, a Cochrane meta-analysis of 5 studies involving 622 women with previous preterm birth showed a decrease in the risk of low birth weight infants born to women receiving antibiotics vs placebo for the treatment of BV (odds ratio [OR]=0.31; 95% CI, 0.13–0.75).6 Treatment also decreased the risk of preterm-prelabor rupture of membranes (OR=0.14; 95% CI, 0.05–0.38) compared with placebo. Unfortunately, these studies did not always specify whether women were asymptomatic for BV infection. In many of the trials, symptomatic women were excluded as they were automatically treated with antibiotics.
In 2003, 2 RCTs evaluating the early treatment of asymptomatic BV in low- and high-risk patients showed a decrease in preterm labor. The first RCT included 494 asymptomatic pregnant women who presented for prenatal care between 12 and 22 weeks gestation. If women had BV detected by Gram stain using Nugent’s criteria, they were randomized to receive either 300 mg oral clindamycin twice daily for 5 days or placebo. In the general population, treatment with clindamycin reduced the rate of late miscarriage and spontaneous preterm delivery by 10.4% (95% CI, 5.0–15.8). In women with a previous preterm delivery or a late miscarriage the proportion of preterm delivery or late miscarriage was reduced (16.6% vs 42%).7
The second RCT included 409 asymptomatic women between 13 and 20 weeks gestation with BV by Gram stain using Nugent’s criteria. Investigators randomized women to intravaginal clindamycin each night for 3 days. At a second visit, 20 to 24 days after treatment, women were retested for BV and if they were positive, they received a 7-day course of intravaginal clindamycin or placebo based on the previous randomization. In this study, the incidence of preterm birth was reduced from 10% to 4% (relative risk [RR]=0.38; 95% CI, 0.16–0.90; NNT=17). This study only included 21 women with previous preterm delivery and a subgroup analysis was not performed.8
Intravaginal clindamycin has been associated with worse pregnancy outcomes for patients who do not have bacterial vaginosis. A randomized trial of the prophylactic intravaginal clindamycin 2% cream to prevent preterm birth in high-risk women showed an increase in spontaneous preterm delivery in women who actually used all of the medication and did not have BV (NNH=12.3; P<.05).9
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routinely screening for BV for high-risk pregnant women. Furthermore, they recommend against screening for average risk women.10
The Centers for Disease Control and Prevention recommends that high-risk pregnant women (eg, those women who have had a previous preterm delivery) with asymptomatic BV may be evaluated for treatment. The recommended treatment regimens are metronidazole 500 mg orally twice a day for 5 days, metronidazole gel intravaginally for 5 days, or clindamycin cream intravaginally for 7 days.11
The Cochrane Pregnancy and Childbirth Group finds no evidence supporting routine screening and treatment for asymptomatic bacterial vaginosis in pregnancy, except possibly for women with a history of preterm birth.6
The American College of Obstetrics and Gynecology summarizes no data supports screening for BV to prevent preterm birth. Their bulletin references a subgroup of women with previous preterm birth who did show benefit from treatment for BV, but the authors speculated that reanalysis with the inclusion of the largest trial to date, which did not show a benefit for this subgroup, might nullify these results.12
Until there’s more research, only screen women who are high-risk or symptomatic
Grace Alfonsi, MD
Denver Health, Denver, Colo
Although the association of BV and chorioamnionitis and preterm labor is strong, the RCTs do not show any change in outcomes by screening and treating asymptomatic BV in pregnancy except in women who already have a history of preterm labor or premature rupture of membranes. Our practice was screening and treating all pregnant women at the first prenatal visit until about 3 years ago when the RCTs failed to show an impact. The studies that brought BV to the forefront of this discussion show that the inflammatory response caused by BV start in the first trimester or before and treatment is most effective when done early. Perhaps these RCTs are not treating enough women early in pregnancy to see a difference in outcome.
The study we need to have (and which may never be done) would test the treatment of women with BV, either just before conception or early in the first trimester. I am awaiting the next round of information, but for now, I only screen women who are high risk or women who are symptomatic.
1. Nugent RP, Krohn M, Hillier S. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Mic 1991;29:297-301.
2. Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003;189:139-147.
3. Guise JM, Mahon SM, Aickin M, Helfand M, Peipert JF, Westhoff C. Screening for bacterial vaginosis in pregnancy. Am J Prev Med 2001;20(3 Suppl):62-72.
4. Kiss H, Petricevic L, Husslein P. Prospective randomized controlled trial of an infection screening programme to reduce the rate of preterm delivery. BMJ 2004;329:371-374.
5. Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000;342:534-540.
6. McDonald H, Brocklehurst P, Parsons J, Vigneswaran R. Antibiotics for treating bacterial vaginosis in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
7. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised trial. Lancet 2003;361:983-988.
8. Lamont RF, Duncan SL, Mandal D, Basset P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003;101:516-522.
9. Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double blind trial. Br J Obstet Gynaecol 1999;106:652-657.
10. US Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy: recommendations and rationale. Am J Prev Med 2001;20(3 Suppl):59-61.
11. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. Diseases characterized by vaginal discharge. MMWR Recomm Rep 2002;51(RR-6):43.-
12. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. Obstet Gynecol 2001;98:709-716.
Bacterial vaginosis (BV) is associated with preterm delivery (strength of recommendation [SOR]: A, meta-analysis). However, treating asymptomatic, low-risk women with BV does not always prevent preterm delivery (SOR: A, randomized controlled trials [RCTs]). There is some benefit to early screening by Gram stain using Nugent’s criteria1 (Table ) and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants (SOR: B, conflicting RCTs).
Empirically treating high-risk women without documented infection has been associated with an increase in preterm deliveries and neonatal infections (SOR: B, single RCT).
TABLE
Nugent’s Criteria
| Score | Lactobacillus morphotypes | Gardnerella and Bacteroides spp. morphotypes | Curved gram-variable rods |
|---|---|---|---|
| 0 | 4+ | 0 | 0 |
| 1 | 3+ | 1+ | 1+ or 2+ |
| 2 | 2+ | 2+ | 3+ or 4+ |
| 3 | 1+ | 3+ | |
| 4 | 0 | 4+ | |
| 1+, <1 morphotype present; 2+, 1 to 4 morphotypes present; 3+, 5 to 30 morphotypes present; 4+, >30 morphotypes present. The diagnosis of bacterial vaginosis is present with a score of 7 or greater. From Nugent 1991.1 | |||
Evidence summary
Bacterial vaginosis in early pregnancy is a risk factor for preterm delivery.2 The role of BV in preterm labor is not well understood, but it has been consistently associated with preterm labor and delivery. The detection of BV in early pregnancy seems to be a stronger risk factor for preterm delivery than BV in later pregnancy.
Studies evaluating the screening and treatment of BV in women at risk for preterm delivery have demonstrated varying results. Most treatment studies have excluded women who are in the first trimester. A meta-analysis of 7 RCTs reviewed the evidence of screening for BV in pregnancy.3 In this meta-analysis, 5 of the trials specified that women were asymptomatic, and the other 2 did not comment on whether the women were symptomatic or not. In general, there was no benefit to routine screening and treatment of BV.
However, a subgroup of high-risk women seems to benefit from screening and treatment. They defined high-risk women as those have had a preterm delivery, premature rupture of membranes, birth weight <2500 g, or spontaneous abortion. Treating BV in women with a high-risk pregnancy decreased preterm delivery (absolute risk reduction [ARR]=0.22; 90% confidence interval [CI], 0.13–0.31; number needed to treat [NNT]=4.5) regardless of antibiotic choice. However, 2 trials of high-risk women who were empirically treated for BV, but did not have BV, showed an increase in preterm delivery less than 34 weeks (number needed to harm [NNH]=11).
A new study evaluating screening for vaginal infections in pregnancy has demonstrated a reduction in preterm delivery.4 In this study, looking at a general obstetrical population in Austria, 4429 asymptomatic pregnant women between 15 and 19.6 weeks gestation had a vaginal screen for bacterial vaginosis, candidiasis and trichomoniasis. The 2048 women in the intervention group were given the results of the screen from their maternity care provider. The 2097 women in the control group and their providers did not receive the results of the vaginal screen. There were 447 women in the intervention group and 441 women in the control group with positive screens. Using the Nugent criteria, women who were diagnosed with BV received a 6-day course of intravaginal clindamycin 2% cream. Those with positive test results for Candida were treated with intravaginal clotrimazole 0.1 g; those with positive results for trichomonas received intravaginal metronidazole 500 mg for 7 days. After treatment, women with a positive test result in the intervention group had a second vaginal smear between 24 and 28 weeks. Persistent BV was treated with oral clindamycin 300 mg twice daily for 7 days. If Candida or trichomonas were noted, women were treated with the intravaginal clotrimazole or metronidazole. A statistically significant reduction was seen in preterm births in the intervention group(3.0% vs 5.3%, 95% CI, 1.2–3.6; P=.0001; number needed to screen=44).
A large study in 2000 that looked at the use of metronidazole in the treatment of asymptomatic women for BV did not demonstrate any reduction in preterm birth.5 In this study, 21,965 asymptomatic women between 8 and 22 weeks gestation were screened for BV with Gram stain using Nugent’s criteria. Then, 1953 women with BV were randomized to receive either 1 g of metronidazole orally for 2 days or placebo. Between 24 and 29 weeks, all of the women were then rescreened for BV by Gram stain. Even if the results were negative, women received another course of the metronidazole or placebo. In this study, preterm delivery rates did not improve for either low- or high-risk women. Specifically, a subgroup analysis of 213 women with previous preterm delivery did not show any benefit to treatment with metronidazole.
In 2003, a Cochrane meta-analysis of 5 studies involving 622 women with previous preterm birth showed a decrease in the risk of low birth weight infants born to women receiving antibiotics vs placebo for the treatment of BV (odds ratio [OR]=0.31; 95% CI, 0.13–0.75).6 Treatment also decreased the risk of preterm-prelabor rupture of membranes (OR=0.14; 95% CI, 0.05–0.38) compared with placebo. Unfortunately, these studies did not always specify whether women were asymptomatic for BV infection. In many of the trials, symptomatic women were excluded as they were automatically treated with antibiotics.
In 2003, 2 RCTs evaluating the early treatment of asymptomatic BV in low- and high-risk patients showed a decrease in preterm labor. The first RCT included 494 asymptomatic pregnant women who presented for prenatal care between 12 and 22 weeks gestation. If women had BV detected by Gram stain using Nugent’s criteria, they were randomized to receive either 300 mg oral clindamycin twice daily for 5 days or placebo. In the general population, treatment with clindamycin reduced the rate of late miscarriage and spontaneous preterm delivery by 10.4% (95% CI, 5.0–15.8). In women with a previous preterm delivery or a late miscarriage the proportion of preterm delivery or late miscarriage was reduced (16.6% vs 42%).7
The second RCT included 409 asymptomatic women between 13 and 20 weeks gestation with BV by Gram stain using Nugent’s criteria. Investigators randomized women to intravaginal clindamycin each night for 3 days. At a second visit, 20 to 24 days after treatment, women were retested for BV and if they were positive, they received a 7-day course of intravaginal clindamycin or placebo based on the previous randomization. In this study, the incidence of preterm birth was reduced from 10% to 4% (relative risk [RR]=0.38; 95% CI, 0.16–0.90; NNT=17). This study only included 21 women with previous preterm delivery and a subgroup analysis was not performed.8
Intravaginal clindamycin has been associated with worse pregnancy outcomes for patients who do not have bacterial vaginosis. A randomized trial of the prophylactic intravaginal clindamycin 2% cream to prevent preterm birth in high-risk women showed an increase in spontaneous preterm delivery in women who actually used all of the medication and did not have BV (NNH=12.3; P<.05).9
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routinely screening for BV for high-risk pregnant women. Furthermore, they recommend against screening for average risk women.10
The Centers for Disease Control and Prevention recommends that high-risk pregnant women (eg, those women who have had a previous preterm delivery) with asymptomatic BV may be evaluated for treatment. The recommended treatment regimens are metronidazole 500 mg orally twice a day for 5 days, metronidazole gel intravaginally for 5 days, or clindamycin cream intravaginally for 7 days.11
The Cochrane Pregnancy and Childbirth Group finds no evidence supporting routine screening and treatment for asymptomatic bacterial vaginosis in pregnancy, except possibly for women with a history of preterm birth.6
The American College of Obstetrics and Gynecology summarizes no data supports screening for BV to prevent preterm birth. Their bulletin references a subgroup of women with previous preterm birth who did show benefit from treatment for BV, but the authors speculated that reanalysis with the inclusion of the largest trial to date, which did not show a benefit for this subgroup, might nullify these results.12
Until there’s more research, only screen women who are high-risk or symptomatic
Grace Alfonsi, MD
Denver Health, Denver, Colo
Although the association of BV and chorioamnionitis and preterm labor is strong, the RCTs do not show any change in outcomes by screening and treating asymptomatic BV in pregnancy except in women who already have a history of preterm labor or premature rupture of membranes. Our practice was screening and treating all pregnant women at the first prenatal visit until about 3 years ago when the RCTs failed to show an impact. The studies that brought BV to the forefront of this discussion show that the inflammatory response caused by BV start in the first trimester or before and treatment is most effective when done early. Perhaps these RCTs are not treating enough women early in pregnancy to see a difference in outcome.
The study we need to have (and which may never be done) would test the treatment of women with BV, either just before conception or early in the first trimester. I am awaiting the next round of information, but for now, I only screen women who are high risk or women who are symptomatic.
Bacterial vaginosis (BV) is associated with preterm delivery (strength of recommendation [SOR]: A, meta-analysis). However, treating asymptomatic, low-risk women with BV does not always prevent preterm delivery (SOR: A, randomized controlled trials [RCTs]). There is some benefit to early screening by Gram stain using Nugent’s criteria1 (Table ) and treating BV-positive women with a history of preterm delivery, premature rupture of membranes, low birth weight infants, or spontaneous abortion. In this group, treatment has been associated with decreased rates of preterm labor, preterm prelabor rupture of membranes, and low birth weight infants (SOR: B, conflicting RCTs).
Empirically treating high-risk women without documented infection has been associated with an increase in preterm deliveries and neonatal infections (SOR: B, single RCT).
TABLE
Nugent’s Criteria
| Score | Lactobacillus morphotypes | Gardnerella and Bacteroides spp. morphotypes | Curved gram-variable rods |
|---|---|---|---|
| 0 | 4+ | 0 | 0 |
| 1 | 3+ | 1+ | 1+ or 2+ |
| 2 | 2+ | 2+ | 3+ or 4+ |
| 3 | 1+ | 3+ | |
| 4 | 0 | 4+ | |
| 1+, <1 morphotype present; 2+, 1 to 4 morphotypes present; 3+, 5 to 30 morphotypes present; 4+, >30 morphotypes present. The diagnosis of bacterial vaginosis is present with a score of 7 or greater. From Nugent 1991.1 | |||
Evidence summary
Bacterial vaginosis in early pregnancy is a risk factor for preterm delivery.2 The role of BV in preterm labor is not well understood, but it has been consistently associated with preterm labor and delivery. The detection of BV in early pregnancy seems to be a stronger risk factor for preterm delivery than BV in later pregnancy.
Studies evaluating the screening and treatment of BV in women at risk for preterm delivery have demonstrated varying results. Most treatment studies have excluded women who are in the first trimester. A meta-analysis of 7 RCTs reviewed the evidence of screening for BV in pregnancy.3 In this meta-analysis, 5 of the trials specified that women were asymptomatic, and the other 2 did not comment on whether the women were symptomatic or not. In general, there was no benefit to routine screening and treatment of BV.
However, a subgroup of high-risk women seems to benefit from screening and treatment. They defined high-risk women as those have had a preterm delivery, premature rupture of membranes, birth weight <2500 g, or spontaneous abortion. Treating BV in women with a high-risk pregnancy decreased preterm delivery (absolute risk reduction [ARR]=0.22; 90% confidence interval [CI], 0.13–0.31; number needed to treat [NNT]=4.5) regardless of antibiotic choice. However, 2 trials of high-risk women who were empirically treated for BV, but did not have BV, showed an increase in preterm delivery less than 34 weeks (number needed to harm [NNH]=11).
A new study evaluating screening for vaginal infections in pregnancy has demonstrated a reduction in preterm delivery.4 In this study, looking at a general obstetrical population in Austria, 4429 asymptomatic pregnant women between 15 and 19.6 weeks gestation had a vaginal screen for bacterial vaginosis, candidiasis and trichomoniasis. The 2048 women in the intervention group were given the results of the screen from their maternity care provider. The 2097 women in the control group and their providers did not receive the results of the vaginal screen. There were 447 women in the intervention group and 441 women in the control group with positive screens. Using the Nugent criteria, women who were diagnosed with BV received a 6-day course of intravaginal clindamycin 2% cream. Those with positive test results for Candida were treated with intravaginal clotrimazole 0.1 g; those with positive results for trichomonas received intravaginal metronidazole 500 mg for 7 days. After treatment, women with a positive test result in the intervention group had a second vaginal smear between 24 and 28 weeks. Persistent BV was treated with oral clindamycin 300 mg twice daily for 7 days. If Candida or trichomonas were noted, women were treated with the intravaginal clotrimazole or metronidazole. A statistically significant reduction was seen in preterm births in the intervention group(3.0% vs 5.3%, 95% CI, 1.2–3.6; P=.0001; number needed to screen=44).
A large study in 2000 that looked at the use of metronidazole in the treatment of asymptomatic women for BV did not demonstrate any reduction in preterm birth.5 In this study, 21,965 asymptomatic women between 8 and 22 weeks gestation were screened for BV with Gram stain using Nugent’s criteria. Then, 1953 women with BV were randomized to receive either 1 g of metronidazole orally for 2 days or placebo. Between 24 and 29 weeks, all of the women were then rescreened for BV by Gram stain. Even if the results were negative, women received another course of the metronidazole or placebo. In this study, preterm delivery rates did not improve for either low- or high-risk women. Specifically, a subgroup analysis of 213 women with previous preterm delivery did not show any benefit to treatment with metronidazole.
In 2003, a Cochrane meta-analysis of 5 studies involving 622 women with previous preterm birth showed a decrease in the risk of low birth weight infants born to women receiving antibiotics vs placebo for the treatment of BV (odds ratio [OR]=0.31; 95% CI, 0.13–0.75).6 Treatment also decreased the risk of preterm-prelabor rupture of membranes (OR=0.14; 95% CI, 0.05–0.38) compared with placebo. Unfortunately, these studies did not always specify whether women were asymptomatic for BV infection. In many of the trials, symptomatic women were excluded as they were automatically treated with antibiotics.
In 2003, 2 RCTs evaluating the early treatment of asymptomatic BV in low- and high-risk patients showed a decrease in preterm labor. The first RCT included 494 asymptomatic pregnant women who presented for prenatal care between 12 and 22 weeks gestation. If women had BV detected by Gram stain using Nugent’s criteria, they were randomized to receive either 300 mg oral clindamycin twice daily for 5 days or placebo. In the general population, treatment with clindamycin reduced the rate of late miscarriage and spontaneous preterm delivery by 10.4% (95% CI, 5.0–15.8). In women with a previous preterm delivery or a late miscarriage the proportion of preterm delivery or late miscarriage was reduced (16.6% vs 42%).7
The second RCT included 409 asymptomatic women between 13 and 20 weeks gestation with BV by Gram stain using Nugent’s criteria. Investigators randomized women to intravaginal clindamycin each night for 3 days. At a second visit, 20 to 24 days after treatment, women were retested for BV and if they were positive, they received a 7-day course of intravaginal clindamycin or placebo based on the previous randomization. In this study, the incidence of preterm birth was reduced from 10% to 4% (relative risk [RR]=0.38; 95% CI, 0.16–0.90; NNT=17). This study only included 21 women with previous preterm delivery and a subgroup analysis was not performed.8
Intravaginal clindamycin has been associated with worse pregnancy outcomes for patients who do not have bacterial vaginosis. A randomized trial of the prophylactic intravaginal clindamycin 2% cream to prevent preterm birth in high-risk women showed an increase in spontaneous preterm delivery in women who actually used all of the medication and did not have BV (NNH=12.3; P<.05).9
Recommendations from others
The US Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routinely screening for BV for high-risk pregnant women. Furthermore, they recommend against screening for average risk women.10
The Centers for Disease Control and Prevention recommends that high-risk pregnant women (eg, those women who have had a previous preterm delivery) with asymptomatic BV may be evaluated for treatment. The recommended treatment regimens are metronidazole 500 mg orally twice a day for 5 days, metronidazole gel intravaginally for 5 days, or clindamycin cream intravaginally for 7 days.11
The Cochrane Pregnancy and Childbirth Group finds no evidence supporting routine screening and treatment for asymptomatic bacterial vaginosis in pregnancy, except possibly for women with a history of preterm birth.6
The American College of Obstetrics and Gynecology summarizes no data supports screening for BV to prevent preterm birth. Their bulletin references a subgroup of women with previous preterm birth who did show benefit from treatment for BV, but the authors speculated that reanalysis with the inclusion of the largest trial to date, which did not show a benefit for this subgroup, might nullify these results.12
Until there’s more research, only screen women who are high-risk or symptomatic
Grace Alfonsi, MD
Denver Health, Denver, Colo
Although the association of BV and chorioamnionitis and preterm labor is strong, the RCTs do not show any change in outcomes by screening and treating asymptomatic BV in pregnancy except in women who already have a history of preterm labor or premature rupture of membranes. Our practice was screening and treating all pregnant women at the first prenatal visit until about 3 years ago when the RCTs failed to show an impact. The studies that brought BV to the forefront of this discussion show that the inflammatory response caused by BV start in the first trimester or before and treatment is most effective when done early. Perhaps these RCTs are not treating enough women early in pregnancy to see a difference in outcome.
The study we need to have (and which may never be done) would test the treatment of women with BV, either just before conception or early in the first trimester. I am awaiting the next round of information, but for now, I only screen women who are high risk or women who are symptomatic.
1. Nugent RP, Krohn M, Hillier S. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Mic 1991;29:297-301.
2. Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003;189:139-147.
3. Guise JM, Mahon SM, Aickin M, Helfand M, Peipert JF, Westhoff C. Screening for bacterial vaginosis in pregnancy. Am J Prev Med 2001;20(3 Suppl):62-72.
4. Kiss H, Petricevic L, Husslein P. Prospective randomized controlled trial of an infection screening programme to reduce the rate of preterm delivery. BMJ 2004;329:371-374.
5. Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000;342:534-540.
6. McDonald H, Brocklehurst P, Parsons J, Vigneswaran R. Antibiotics for treating bacterial vaginosis in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
7. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised trial. Lancet 2003;361:983-988.
8. Lamont RF, Duncan SL, Mandal D, Basset P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003;101:516-522.
9. Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double blind trial. Br J Obstet Gynaecol 1999;106:652-657.
10. US Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy: recommendations and rationale. Am J Prev Med 2001;20(3 Suppl):59-61.
11. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. Diseases characterized by vaginal discharge. MMWR Recomm Rep 2002;51(RR-6):43.-
12. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. Obstet Gynecol 2001;98:709-716.
1. Nugent RP, Krohn M, Hillier S. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Mic 1991;29:297-301.
2. Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C, Husslein P. Bacterial vaginosis as a risk factor for preterm delivery: a meta-analysis. Am J Obstet Gynecol 2003;189:139-147.
3. Guise JM, Mahon SM, Aickin M, Helfand M, Peipert JF, Westhoff C. Screening for bacterial vaginosis in pregnancy. Am J Prev Med 2001;20(3 Suppl):62-72.
4. Kiss H, Petricevic L, Husslein P. Prospective randomized controlled trial of an infection screening programme to reduce the rate of preterm delivery. BMJ 2004;329:371-374.
5. Carey JC, Klebanoff MA, Hauth JC, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000;342:534-540.
6. McDonald H, Brocklehurst P, Parsons J, Vigneswaran R. Antibiotics for treating bacterial vaginosis in pregnancy (Cochrane Review). In: The Cochrane Library, Issue 3, 2004. Chichester, UK: John Wiley & Sons, Ltd.
7. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised trial. Lancet 2003;361:983-988.
8. Lamont RF, Duncan SL, Mandal D, Basset P. Intravaginal clindamycin to reduce preterm birth in women with abnormal genital tract flora. Obstet Gynecol 2003;101:516-522.
9. Vermeulen GM, Bruinse HW. Prophylactic administration of clindamycin 2% vaginal cream to reduce the incidence of spontaneous preterm birth in women with an increased recurrence risk: a randomised placebo-controlled double blind trial. Br J Obstet Gynaecol 1999;106:652-657.
10. US Preventive Services Task Force. Screening for bacterial vaginosis in pregnancy: recommendations and rationale. Am J Prev Med 2001;20(3 Suppl):59-61.
11. Sexually transmitted diseases treatment guidelines 2002. Centers for Disease Control and Prevention. Diseases characterized by vaginal discharge. MMWR Recomm Rep 2002;51(RR-6):43.-
12. ACOG Practice Bulletin. Assessment of risk factors for preterm birth. Clinical management guidelines for obstetrician-gynecologists. Number 31, October 2001. Obstet Gynecol 2001;98:709-716.