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Do complementary agents lower HbA1c when used with standard type 2 diabetes therapy?
No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
No, there is no high-quality evidence that supports using complementary or alternative agents to lower hemoglobin A1c (HbA1c) in patients with noninsulin-dependent type 2 diabetes. Oral chromium in widely varying doses reduces HbA1c a small amount (strength of recommendation [SOR]: C, meta-analysis of low-quality randomized, controlled trials [RCTs] of disease-oriented outcomes, with inconsistent results).
Oral cinnamon 1 to 3 g/d causes a small (<0.1%) drop in HbA1c (SOR: C, meta-analysis of low-quality RCTs of disease-oriented outcomes).
Fenugreek, milk thistle, safflower oil, and sweet potato extract may also reduce HbA1c (SOR: C, small, low-quality RCTs of disease-oriented outcomes).
EVIDENCE SUMMARY
Almost all complementary and alternative agents reviewed here were tested against placebo, and most were used in combination with standard therapy, usually identified as diet with or without oral hypoglycemic agents (TABLE).1-8
Meta-analyses evaluate effects of chromium and cinnamon
A meta-analysis of 13 RCTs evaluating the effect of oral chromium in patients with type 2 diabetes (age range not given) found a small improvement in HbA1c.1 Limitations of the meta-analysis included a wide range of chromium dosages and preparations. Ten studies showed no benefit, and of the 3 showing improvement, the researchers rated 2 as poor-quality.
A meta-analysis of 5 RCTs assessing the effect of oral cinnamon in patients with type 2 diabetes, 42 to 71 years of age, found that cinnamon produced a clinically irrelevant but statistically significant decrease in mean HbA1c.2 After analyzing the 2 RCTs with the largest effects, the researchers concluded that cinnamon might have a greater effect in patients with poorly controlled diabetes (baseline HbA1c>8.2%).
When they evaluated these RCTs for study homogeneity, they found significant differences among the studies in subject age, gender, ethnicity, body mass index, disease duration, concurrent medications, and baseline HbA1c levels, as well as variations in cinnamon dose, preparation, and therapy duration. Furthermore, only one of the studies reported randomization methods and whether allocation was concealed.
What about caiapo, fenugreek, milk thistle, and safflower oil?
Two small, moderate-quality RCTs of caiapo (sweet potato skin extract) in diet-controlled patients with diabetes demonstrated small but possibly clinically significant reductions in HbA1c between the intervention and control groups.3,4
TABLE
Effect of complementary or alternative agents on HbA1c in type 2 diabetes
CAA* | Dose/day | Concurrent diabetes therapy | Study type | Study size | Study duration | Difference in HbA1c (in HbA1c units) | 95% CI or P value |
Chromium1 | 1.28-1000 mcg | Not given | Meta-analysis of 13 RCTs | 381 | 3 wk-8 mo | -0.6† | -0.9 to -0.2 |
Cinnamon2 | 1-3 g | Various oral hypoglycemic agents‡ | Meta-analysis of 5 RCTs | 315 | 1.5-4 mo | -0.09 (WMD)† | -0.14 to -0.04 |
Caiapo3 | 4 g | Diet only | RCT | 61 | 5 mo | -0.21 (caiapo)§ +0.25 (placebo)§ | P=.08
P=.0001 |
Caiapo4 | 4 g | Diet only | RCT | 61 | 3 mo | -0.53 (caiapo)§ +0.06 (placebo)§ | P<.001
P=.23 |
Trigonella foenum-graecum (fenugreek)5 | 6.84 g | Sulfonylurea | RCT | 69 | 3 mo | -1.46 (fenugreek)§ -0.41 (placebo)§ | P<.05
P<.05 |
Silybum marianum (milk thistle)6 | 200 mg | Metformin and sulfonylurea | RCT | 51 | 4 mo | -1.0 (milk thistle)§ +1.2 (placebo)§ | P<.001
P<.0001 |
Silybum marianum (milk thistle)7 | 200 mg | Sulfonylurea | RCT | 38 | 4 mo | -1.5 (milk thistle)§ -0.5 (placebo)§ | P<.05
P=NS |
Safflower oil vs conjugated linoleic acid8 | 8 g | Various oral hypoglycemic agents‡ | DBRCD | 35 | 4 mo | -0.6 (safflower oil)§ +0.1 (conjugated linoleic acid)§ | P=.0007
P=NS |
CAA, complementary or alternative agents; CI, confidence interval; DBRCD, double-blind, randomized, crossover design; HbA1c, glycosylated hemoglobin A1c; NS, not significant; RCT, randomized controlled trial; WMD, weighted mean difference.
*All CAAs were compared against placebo, with the exception of safflower oil, which was compared against conjugated linoleic acid supplementation.
† Change in HbA1c means at study endpoint; the difference in HbA1c in intervention vs placebo groups.
‡ Oral hypoglycemic agents included a-glucosidase inhibitors, biguanides, glinides, glitazones, sulfonylureas, and thiazolidinediones.
§ Change in HbA1c means at study endpoint; the change in HbA1c from baseline.
Four small, placebo-controlled RCTs of fenugreek, milk thistle, and safflower oil found statistically and clinically significant reductions in HbA1c, but all these studies were of poor quality with unclear methods of randomization, threats to blinding, and a lack of baseline demographics.5-8
RECOMMENDATIONS
Both the American Diabetes Association (ADA) and the Diabetes UK Nutrition Working Group state that, “there is no clear evidence of benefit from vitamin or mineral supplementation in people with diabetes (compared with the general population), who do not have underlying deficiencies.”9,10 The ADA specifically states that chromium cannot be recommended because it lacks any clear benefit.9
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
1. Balk ME, Tatsioni A, Lichtenstein AH, et al. Effect of chromium supplementation on glucose metabolism and lipids: a systematic review of randomized controlled trials. Diabetes Care. 2007;30:2154-2163.
2. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: Systematic review and meta analysis. Clin Nutr. 2012;31:609-615.
3. Ludvik B, Hanefeld M, Pacini G. Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects. Diabetes Obes Metab. 2008;10:586-592.
4. Ludvik, B, Neuffer, B, Pacini G. Efficacy of Ipomoea batatas (Caiapo) on diabetes control in type 2 diabetic subjects treated with diet. Diabetes Care. 2004;27:436-440.
5. Lu FR, Shen L, Qin Y, et al. Clinical observation on trigonella foenum-graecum L. total saponins in combination with sulfonylureas in the treatment of type 2 diabetes mellitus. Chin J Integr Med. 2008;14:56-60.
6. Huseini HF, Larijani B, Heshmat R, et al. The efficacy of Silybummarianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res. 2006;20:1036-1039.
7. Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long-term and postprandial glycemic control and body mass index in type 2 diabetes. J Med Food. 2007;10:543-547.
8. Asp ML, Collene AL, Norris LE, et al. Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized,double-masked, crossover study. Clin Nutr. 2011;30:443-449.
9. American Diabetes Association; Bantle JP, Wylie-Rosett J, Albright AL, et al. Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care. 2008;31 suppl 1:S61-S78.
10. Diabetes UK Nutrition Working Group, Dyson PA, Kelly T, Deakin T, et al. Evidence-Based Nutrition Guidelines for the Prevention and Management of Diabetes. Diabetes UK Web site. Available at: www.diabetes.org.uk/Documents/Reports/nutritional-guidelines-2013-amendment-0413.pdf. Accessed October 2, 2013.
Evidence-based answers from the Family Physicians Inquiries Network
Is it safe to vaccinate children against varicella while they’re in close contact with a pregnant woman?
YES. All healthy children without evidence of immunity to varicella who are living in a household with a susceptible pregnant woman should be vaccinated (strength of recommendation [SOR]: C, expert opinion).
The risk of transmission of vaccine virus to household contacts is very low (SOR: B, observational studies). Transmission is higher, but still rare, among contacts of immunocompromised vaccinees (SOR: B, observational studies).
Varicella infection has not been reported in unborn babies of women who had contact with a recently vaccinated person.
Evidence summary
Pregnant women without immunity to varicella are at risk of developing chickenpox, which can cause congenital varicella syndrome. An estimated 44 cases of congenital varicella occurred each year in the prevaccine era.1
Varicella vaccine contains live attenuated virus. Approximately 2% to 3% of vaccinees develop either a localized rash around the injection site or a generalized rash.1 The vaccine virus can, theoretically, spread from vaccinees who develop a rash to other people. Nevertheless, the probability of contracting varicella after contact with a healthy vaccinee is very low.
Minimal transmission, no infection from contact with healthy vaccinees
A prospective vaccine efficacy study found that 3 of 446 (0.67%) contacts of healthy vaccinees seroconverted, but had no clinical evidence of varicella.2 In a smaller study, 30 immunocompromised siblings of 37 healthy children who received varicella vaccine showed no clinical or serological evidence of the virus.3
Five case reports document varicella infection in people who had contact with healthy vaccinees.1 One of these was a pregnant woman who chose to terminate the pregnancy, but subsequent tests showed no virus in the fetus.4 We couldn’t find any reports of congenital varicella attributable to infection of the mother from a recent vaccinee.
Transmission by immunocompromised vaccinees is slightly higher
The risk of contracting vaccine-associated varicella from contact with an immunocompromised vaccinee is slightly higher than for a healthy vaccinee. The National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study evaluated transmission and infectivity of the varicella vaccine virus in the close contacts of 482 vaccinated children with leukemia.5 One hundred fifty-six vaccinees developed a rash approximately one month after vaccination. Among 88 healthy susceptible siblings in close contact with the 156 vaccinees, 15 (17%) showed evidence of virus transmission. Of the 15, 4 had subclinical infection and the other 11 had a mild rash.
Recommendations
The American Academy of Pediatrics, Advisory Committee on Immunization Practices, and Centers for Disease Control and Prevention say that no precautions are necessary after varicella vaccination of family members in households with pregnant women. If a vaccinee develops a rash, precautions such as separating the vaccinee and the pregnant woman until the rash resolves are advisable. Giving Varicella zoster immune globulin to pregnant women without immunity who are exposed to varicella should be considered. Varicella vaccines are contraindicated in people with malignancies, immunodeficiencies (congenital or acquired), and immunosuppression caused by medications.1,3,6,7
1. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40.
2. Weibel R, Neff B, Kuter B, et al. Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med. 1984;310:1409-1415.
3. Diaz PS, Au D, Smith S, et al. Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. Pediatrics. 1991;87:166-170.
4. Salzman MB, Sharrar RG, Steinberg S, et al. Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother. J Pediatr. 1997;131:151-154.
5. Tsolia M, Gershon AA, Steinberg SP, et al. Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group. J Pediatr. 1990;116:184-189.
6. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007;120:221-231.
7. Centers for Disease Control and Prevention. Varicella vaccine—Q&As about pregnancy. Available at: http://cdc.gov/vaccines/VPD-VAC/varicella/vac-faqs-clinic-preg.htm. Accessed October 11, 2010.
YES. All healthy children without evidence of immunity to varicella who are living in a household with a susceptible pregnant woman should be vaccinated (strength of recommendation [SOR]: C, expert opinion).
The risk of transmission of vaccine virus to household contacts is very low (SOR: B, observational studies). Transmission is higher, but still rare, among contacts of immunocompromised vaccinees (SOR: B, observational studies).
Varicella infection has not been reported in unborn babies of women who had contact with a recently vaccinated person.
Evidence summary
Pregnant women without immunity to varicella are at risk of developing chickenpox, which can cause congenital varicella syndrome. An estimated 44 cases of congenital varicella occurred each year in the prevaccine era.1
Varicella vaccine contains live attenuated virus. Approximately 2% to 3% of vaccinees develop either a localized rash around the injection site or a generalized rash.1 The vaccine virus can, theoretically, spread from vaccinees who develop a rash to other people. Nevertheless, the probability of contracting varicella after contact with a healthy vaccinee is very low.
Minimal transmission, no infection from contact with healthy vaccinees
A prospective vaccine efficacy study found that 3 of 446 (0.67%) contacts of healthy vaccinees seroconverted, but had no clinical evidence of varicella.2 In a smaller study, 30 immunocompromised siblings of 37 healthy children who received varicella vaccine showed no clinical or serological evidence of the virus.3
Five case reports document varicella infection in people who had contact with healthy vaccinees.1 One of these was a pregnant woman who chose to terminate the pregnancy, but subsequent tests showed no virus in the fetus.4 We couldn’t find any reports of congenital varicella attributable to infection of the mother from a recent vaccinee.
Transmission by immunocompromised vaccinees is slightly higher
The risk of contracting vaccine-associated varicella from contact with an immunocompromised vaccinee is slightly higher than for a healthy vaccinee. The National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study evaluated transmission and infectivity of the varicella vaccine virus in the close contacts of 482 vaccinated children with leukemia.5 One hundred fifty-six vaccinees developed a rash approximately one month after vaccination. Among 88 healthy susceptible siblings in close contact with the 156 vaccinees, 15 (17%) showed evidence of virus transmission. Of the 15, 4 had subclinical infection and the other 11 had a mild rash.
Recommendations
The American Academy of Pediatrics, Advisory Committee on Immunization Practices, and Centers for Disease Control and Prevention say that no precautions are necessary after varicella vaccination of family members in households with pregnant women. If a vaccinee develops a rash, precautions such as separating the vaccinee and the pregnant woman until the rash resolves are advisable. Giving Varicella zoster immune globulin to pregnant women without immunity who are exposed to varicella should be considered. Varicella vaccines are contraindicated in people with malignancies, immunodeficiencies (congenital or acquired), and immunosuppression caused by medications.1,3,6,7
YES. All healthy children without evidence of immunity to varicella who are living in a household with a susceptible pregnant woman should be vaccinated (strength of recommendation [SOR]: C, expert opinion).
The risk of transmission of vaccine virus to household contacts is very low (SOR: B, observational studies). Transmission is higher, but still rare, among contacts of immunocompromised vaccinees (SOR: B, observational studies).
Varicella infection has not been reported in unborn babies of women who had contact with a recently vaccinated person.
Evidence summary
Pregnant women without immunity to varicella are at risk of developing chickenpox, which can cause congenital varicella syndrome. An estimated 44 cases of congenital varicella occurred each year in the prevaccine era.1
Varicella vaccine contains live attenuated virus. Approximately 2% to 3% of vaccinees develop either a localized rash around the injection site or a generalized rash.1 The vaccine virus can, theoretically, spread from vaccinees who develop a rash to other people. Nevertheless, the probability of contracting varicella after contact with a healthy vaccinee is very low.
Minimal transmission, no infection from contact with healthy vaccinees
A prospective vaccine efficacy study found that 3 of 446 (0.67%) contacts of healthy vaccinees seroconverted, but had no clinical evidence of varicella.2 In a smaller study, 30 immunocompromised siblings of 37 healthy children who received varicella vaccine showed no clinical or serological evidence of the virus.3
Five case reports document varicella infection in people who had contact with healthy vaccinees.1 One of these was a pregnant woman who chose to terminate the pregnancy, but subsequent tests showed no virus in the fetus.4 We couldn’t find any reports of congenital varicella attributable to infection of the mother from a recent vaccinee.
Transmission by immunocompromised vaccinees is slightly higher
The risk of contracting vaccine-associated varicella from contact with an immunocompromised vaccinee is slightly higher than for a healthy vaccinee. The National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study evaluated transmission and infectivity of the varicella vaccine virus in the close contacts of 482 vaccinated children with leukemia.5 One hundred fifty-six vaccinees developed a rash approximately one month after vaccination. Among 88 healthy susceptible siblings in close contact with the 156 vaccinees, 15 (17%) showed evidence of virus transmission. Of the 15, 4 had subclinical infection and the other 11 had a mild rash.
Recommendations
The American Academy of Pediatrics, Advisory Committee on Immunization Practices, and Centers for Disease Control and Prevention say that no precautions are necessary after varicella vaccination of family members in households with pregnant women. If a vaccinee develops a rash, precautions such as separating the vaccinee and the pregnant woman until the rash resolves are advisable. Giving Varicella zoster immune globulin to pregnant women without immunity who are exposed to varicella should be considered. Varicella vaccines are contraindicated in people with malignancies, immunodeficiencies (congenital or acquired), and immunosuppression caused by medications.1,3,6,7
1. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40.
2. Weibel R, Neff B, Kuter B, et al. Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med. 1984;310:1409-1415.
3. Diaz PS, Au D, Smith S, et al. Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. Pediatrics. 1991;87:166-170.
4. Salzman MB, Sharrar RG, Steinberg S, et al. Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother. J Pediatr. 1997;131:151-154.
5. Tsolia M, Gershon AA, Steinberg SP, et al. Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group. J Pediatr. 1990;116:184-189.
6. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007;120:221-231.
7. Centers for Disease Control and Prevention. Varicella vaccine—Q&As about pregnancy. Available at: http://cdc.gov/vaccines/VPD-VAC/varicella/vac-faqs-clinic-preg.htm. Accessed October 11, 2010.
1. Centers for Disease Control and Prevention. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40.
2. Weibel R, Neff B, Kuter B, et al. Live attenuated varicella virus vaccine: efficacy trial in healthy children. N Engl J Med. 1984;310:1409-1415.
3. Diaz PS, Au D, Smith S, et al. Lack of transmission of the live attenuated varicella vaccine virus to immunocompromised children after immunization of their siblings. Pediatrics. 1991;87:166-170.
4. Salzman MB, Sharrar RG, Steinberg S, et al. Transmission of varicella-vaccine virus from a healthy 12-month-old child to his pregnant mother. J Pediatr. 1997;131:151-154.
5. Tsolia M, Gershon AA, Steinberg SP, et al. Live attenuated varicella vaccine: evidence that the virus is attenuated and the importance of skin lesions in transmission of varicella-zoster virus. National Institute of Allergy and Infectious Diseases Varicella Vaccine Collaborative Study Group. J Pediatr. 1990;116:184-189.
6. American Academy of Pediatrics Committee on Infectious Diseases. Prevention of varicella: recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule. Pediatrics. 2007;120:221-231.
7. Centers for Disease Control and Prevention. Varicella vaccine—Q&As about pregnancy. Available at: http://cdc.gov/vaccines/VPD-VAC/varicella/vac-faqs-clinic-preg.htm. Accessed October 11, 2010.
Evidence-based answers from the Family Physicians Inquiries Network
Prophylactic oxytocin: Before or after placental delivery?
Either is fine.
Timing alone doesn’t influence the drug’s efficacy in preventing postpartum bleeding (strength of recommendation: B, randomized controlled trial [RCT] and prospective cohort studies).
Evidence summary
The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.1 A number of studies have evaluated the timing of oxytocin after delivery (TABLE).
TABLE
What studies say about the timing of oxytocin and PPH risk
| STUDY TYPE (YEAR) | OXYTOCIN GIVEN AFTER | OUTCOMES (RISK OF PPH) | |
|---|---|---|---|
| DELIVERY OF ANTERIOR SHOULDER (N) | DELIVERY OF PLACENTA (N) | ||
| DBRCT (2001)2 | 745 | 741 | No difference (OR=0.92; 95% CI, 0.59-1.43) |
| DBRCT (2004)3 | 27 | 24 | Incidence lower when given after delivery of placenta (P=.049) |
| Cohort (2006)4 | 82 | 52 | Incidence lower when given after delivery of anterior shoulder (OR=0.33; 95% CI, 0.11-0.98) |
| RCT (1997)5 | 827 | 821 | Incidence lower when given after delivery of anterior shoulder (OR=0.50; 95% CI, 0.34-0.73) |
| Cohort (1996)6 | 524 (given after delivery of head) | 478 | Incidence lower when given after delivery of head (OR=0.60; 95% CI, 0.41-0.87) |
| CI, confidence interval; DBRCT, double-blinded randomized controlled trial; OR, odds ratio; PPH, postpartum hemorrhage; RCT, randomized controlled trial. | |||
Which timing is best? It depends on the study
A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.2 The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).
A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.3 The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.
A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.4 In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.
Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.
Recommendations
The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.7 ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.
The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.8 The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.
The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.9 WHO advocates administration within 1 minute of delivery of the baby.
1. Prendiville W, Elbourne D, Chalmers I. The effects of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials. Br J Obstet Gynaecol. 1988;95:3-16.
2. Jackson KW, Jr, Allbert JR, Schemmer GK, et al. A randomized, controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage. Am J Obstet Gynecol. 2001;185:873-877.
3. Huh WK, Chelmow D, Malone F. A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage. Gynecol Obstet Invest. 2004;58:72-76.
4. Fujimoto M, Takeuchi K, Sugimoto M, et al. Prevention of postpartum hemorrhage by uterotonic agents: comparison of oxytocin and methylergometrine in the management of the third stage of labor. Acta Obstet Gynecol Scand. 2006;85:1310-1314.
5. Khan GQ, John IS, Wani S, et al. Controlled cord traction versus minimal intervention techniques in delivery of the placenta: a randomized controlled trial. Am J Obstet Gynecol. 1997;177:770-774.
6. Soriano D, Dulitzki M, Schiff E, et al. A prospective cohort study of oxytocin plus ergometrine compared with oxytocin alone for prevention of postpartum haemorrhage. Br J Obstet Gynaecol. 1996;103:1068-1073.
7. American College of Obstetricians and Gynecologists. Practice Bulletin Number 76, June 2006. Postpartum hemorrhage. Obstet Gynecol. 2006;76:1-9.
8. Quinlan J, Bailey E, Dresang L, et al. for the Advanced Life Support in Obstetrics Advisory Board. 2007-2008 Advanced Life Support in Obstetrics Course Syllabus. Leawood, Kan: American Academy of Family Physicians; 2006.
9. Managing Complications in Pregnancy and Child-birth: A Guide for Midwives and Doctors. Geneva, Switzerland: World Health Organization, 2003. Available at: www.who.int/reproductivehealth/impac/clinical_principles/normal_lobour_C57_C76.html. Accessed May 12, 2008.
Either is fine.
Timing alone doesn’t influence the drug’s efficacy in preventing postpartum bleeding (strength of recommendation: B, randomized controlled trial [RCT] and prospective cohort studies).
Evidence summary
The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.1 A number of studies have evaluated the timing of oxytocin after delivery (TABLE).
TABLE
What studies say about the timing of oxytocin and PPH risk
| STUDY TYPE (YEAR) | OXYTOCIN GIVEN AFTER | OUTCOMES (RISK OF PPH) | |
|---|---|---|---|
| DELIVERY OF ANTERIOR SHOULDER (N) | DELIVERY OF PLACENTA (N) | ||
| DBRCT (2001)2 | 745 | 741 | No difference (OR=0.92; 95% CI, 0.59-1.43) |
| DBRCT (2004)3 | 27 | 24 | Incidence lower when given after delivery of placenta (P=.049) |
| Cohort (2006)4 | 82 | 52 | Incidence lower when given after delivery of anterior shoulder (OR=0.33; 95% CI, 0.11-0.98) |
| RCT (1997)5 | 827 | 821 | Incidence lower when given after delivery of anterior shoulder (OR=0.50; 95% CI, 0.34-0.73) |
| Cohort (1996)6 | 524 (given after delivery of head) | 478 | Incidence lower when given after delivery of head (OR=0.60; 95% CI, 0.41-0.87) |
| CI, confidence interval; DBRCT, double-blinded randomized controlled trial; OR, odds ratio; PPH, postpartum hemorrhage; RCT, randomized controlled trial. | |||
Which timing is best? It depends on the study
A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.2 The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).
A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.3 The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.
A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.4 In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.
Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.
Recommendations
The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.7 ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.
The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.8 The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.
The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.9 WHO advocates administration within 1 minute of delivery of the baby.
Either is fine.
Timing alone doesn’t influence the drug’s efficacy in preventing postpartum bleeding (strength of recommendation: B, randomized controlled trial [RCT] and prospective cohort studies).
Evidence summary
The prophylactic use of oxytocic drugs reduces the risk of postpartum hemorrhage (PPH) by about 40% and has been widely adopted as a routine policy in the active management of the third stage of labor.1 A number of studies have evaluated the timing of oxytocin after delivery (TABLE).
TABLE
What studies say about the timing of oxytocin and PPH risk
| STUDY TYPE (YEAR) | OXYTOCIN GIVEN AFTER | OUTCOMES (RISK OF PPH) | |
|---|---|---|---|
| DELIVERY OF ANTERIOR SHOULDER (N) | DELIVERY OF PLACENTA (N) | ||
| DBRCT (2001)2 | 745 | 741 | No difference (OR=0.92; 95% CI, 0.59-1.43) |
| DBRCT (2004)3 | 27 | 24 | Incidence lower when given after delivery of placenta (P=.049) |
| Cohort (2006)4 | 82 | 52 | Incidence lower when given after delivery of anterior shoulder (OR=0.33; 95% CI, 0.11-0.98) |
| RCT (1997)5 | 827 | 821 | Incidence lower when given after delivery of anterior shoulder (OR=0.50; 95% CI, 0.34-0.73) |
| Cohort (1996)6 | 524 (given after delivery of head) | 478 | Incidence lower when given after delivery of head (OR=0.60; 95% CI, 0.41-0.87) |
| CI, confidence interval; DBRCT, double-blinded randomized controlled trial; OR, odds ratio; PPH, postpartum hemorrhage; RCT, randomized controlled trial. | |||
Which timing is best? It depends on the study
A well-constructed double-blinded RCT found no significant difference in the incidence of PPH when oxytocin was given after delivery of the anterior shoulder or the placenta.2 The study included 1486 patients; 745 received 20 units of oxytocin on delivery of the anterior shoulder, and 741 received an identical dose of oxytocin on delivery of the placenta. The incidence of PPH was 5.4% for the anterior shoulder group and 5.8% for the placenta group (P=.72). Likewise, no significant difference between the groups was noted in the proportion of women with estimated blood loss (EBL) ≥500 mL (7.5% vs 9.7%; P=.15).
A much smaller double-blinded RCT found that PPH occurred significantly less often when oxytocin was delayed until after delivery of the placenta.3 The study comprised 51 patients; 27 received 10 units of oxytocin on delivery of the anterior shoulder and 24 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 0% when oxytocin was given after delivery of the placenta vs 14.8% when it was given on delivery of the anterior shoulder (P=.049). However, the study was limited by its size and potential inaccuracies in estimating blood loss.
A prospective cohort study noted a significant reduction in the risk of PPH when oxytocin was given after delivery of the anterior shoulder, compared with the placenta.4 In this study, 82 patients received 5 units of oxytocin on delivery of the anterior shoulder, and 52 received an identical dose after delivery of the placenta. The incidence of PPH ≥500 mL was 7.3% in the anterior shoulder group and 19.2% in the placenta group. However, the study was not blinded and was limited by its small sample size.
Two earlier studies, an RCT and a prospective cohort study, concluded that oxytocin is more effective in reducing PPH when given before placental delivery (after delivery of the anterior shoulder and head, respectively).5,6 Neither of these studies was blinded nor controlled for nonpharmacologic interventions, however.
Recommendations
The American College of Obstetricians and Gynecologists (ACOG) states that ongoing blood loss accompanied by decreased uterine tone requires uterotonic agents as first-line treatment for PPH.7 ACOG doesn’t make specific recommendations regarding the timing of oxytocin administration.
The American Academy of Family Physicians (AAFP) recommends oxytocin as the uterotonic agent of choice for preventing PPH.8 The AAFP further advocates active management of the third stage of labor to decrease PPH by administering oxytocin as soon as possible after delivery of the anterior shoulder and before delivery of the placenta.
The World Health Organization (WHO) also recommends oxytocin as the uterotonic of choice.9 WHO advocates administration within 1 minute of delivery of the baby.
1. Prendiville W, Elbourne D, Chalmers I. The effects of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials. Br J Obstet Gynaecol. 1988;95:3-16.
2. Jackson KW, Jr, Allbert JR, Schemmer GK, et al. A randomized, controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage. Am J Obstet Gynecol. 2001;185:873-877.
3. Huh WK, Chelmow D, Malone F. A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage. Gynecol Obstet Invest. 2004;58:72-76.
4. Fujimoto M, Takeuchi K, Sugimoto M, et al. Prevention of postpartum hemorrhage by uterotonic agents: comparison of oxytocin and methylergometrine in the management of the third stage of labor. Acta Obstet Gynecol Scand. 2006;85:1310-1314.
5. Khan GQ, John IS, Wani S, et al. Controlled cord traction versus minimal intervention techniques in delivery of the placenta: a randomized controlled trial. Am J Obstet Gynecol. 1997;177:770-774.
6. Soriano D, Dulitzki M, Schiff E, et al. A prospective cohort study of oxytocin plus ergometrine compared with oxytocin alone for prevention of postpartum haemorrhage. Br J Obstet Gynaecol. 1996;103:1068-1073.
7. American College of Obstetricians and Gynecologists. Practice Bulletin Number 76, June 2006. Postpartum hemorrhage. Obstet Gynecol. 2006;76:1-9.
8. Quinlan J, Bailey E, Dresang L, et al. for the Advanced Life Support in Obstetrics Advisory Board. 2007-2008 Advanced Life Support in Obstetrics Course Syllabus. Leawood, Kan: American Academy of Family Physicians; 2006.
9. Managing Complications in Pregnancy and Child-birth: A Guide for Midwives and Doctors. Geneva, Switzerland: World Health Organization, 2003. Available at: www.who.int/reproductivehealth/impac/clinical_principles/normal_lobour_C57_C76.html. Accessed May 12, 2008.
1. Prendiville W, Elbourne D, Chalmers I. The effects of routine oxytocic administration in the management of the third stage of labour: an overview of the evidence from controlled trials. Br J Obstet Gynaecol. 1988;95:3-16.
2. Jackson KW, Jr, Allbert JR, Schemmer GK, et al. A randomized, controlled trial comparing oxytocin administration before and after placental delivery in the prevention of postpartum hemorrhage. Am J Obstet Gynecol. 2001;185:873-877.
3. Huh WK, Chelmow D, Malone F. A double-blinded, randomized controlled trial of oxytocin at the beginning versus the end of the third stage of labor for prevention of postpartum hemorrhage. Gynecol Obstet Invest. 2004;58:72-76.
4. Fujimoto M, Takeuchi K, Sugimoto M, et al. Prevention of postpartum hemorrhage by uterotonic agents: comparison of oxytocin and methylergometrine in the management of the third stage of labor. Acta Obstet Gynecol Scand. 2006;85:1310-1314.
5. Khan GQ, John IS, Wani S, et al. Controlled cord traction versus minimal intervention techniques in delivery of the placenta: a randomized controlled trial. Am J Obstet Gynecol. 1997;177:770-774.
6. Soriano D, Dulitzki M, Schiff E, et al. A prospective cohort study of oxytocin plus ergometrine compared with oxytocin alone for prevention of postpartum haemorrhage. Br J Obstet Gynaecol. 1996;103:1068-1073.
7. American College of Obstetricians and Gynecologists. Practice Bulletin Number 76, June 2006. Postpartum hemorrhage. Obstet Gynecol. 2006;76:1-9.
8. Quinlan J, Bailey E, Dresang L, et al. for the Advanced Life Support in Obstetrics Advisory Board. 2007-2008 Advanced Life Support in Obstetrics Course Syllabus. Leawood, Kan: American Academy of Family Physicians; 2006.
9. Managing Complications in Pregnancy and Child-birth: A Guide for Midwives and Doctors. Geneva, Switzerland: World Health Organization, 2003. Available at: www.who.int/reproductivehealth/impac/clinical_principles/normal_lobour_C57_C76.html. Accessed May 12, 2008.
Evidence-based answers from the Family Physicians Inquiries Network
What are the risks and benefits of elective induction for uncomplicated term pregnancies?
Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant (strength of recommendation [SOR]: B). The benefit of elective induction for nonmedical reasons is unclear (SOR: B).
Elective inductions can add costs and legal risks
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Family physicians cherish having long, collaborative relationships with patients. But when they practice obstetrics, this desire can result in feeling pressured to grant requests by pregnant patients for elective inductions. As indicated in this Clinical Inquiry, elective inductions may be relatively safe in some situations, but they always incur added costs. The cost of cervical ripening, extra monitoring, and medications to promote uterine contractions fall to the medical system. There also may be added legal risk to the provider. Eventually, some elective induction will have a bad outcome and there will be no way to defend the decision to induce as medically necessary.
Evidence summary
Induction of labor is a viable therapeutic option when the benefits of timely delivery outweigh the risks of unnecessary cesarean section or prematurity. Two large retrospective studies support the concept that cesarean section rates and admissions to neonatal intensive care units are higher with elective induction as opposed to expectant management (TABLE).1,2 A large population-based study suggests that the higher cesarean section rates in elective induction is present only among nulliparous women; in multiparous women, the rate is the same as expectant management.3 Contrasting these results are those of a large systematic review, which found lower cesarean section rates in electively induced women. Two more recent studies, a retrospective cohort study4 and a randomized controlled trial,5 found a much lower incidence of cesarean section and operative vaginal deliveries among induced vs expectantly managed women at term.
TABLE
Summary of evidence regarding induction of labor
| STUDY | METHODS | CESAREAN DELIVERY RATE | OPERATIVE VAGINAL DELIVERY | PERINATAL COMPLICATIONS |
|---|---|---|---|---|
| Cammu, 20021 | Matched cohort study. 7683 women in IND group, 7683 women in EM group. 38–410/7 weeks gestation. | 9.9% vs 6.5% (P=.001); NNH=30. | 31.67% vs 29.1% (P=.001); NNH=39. | NICU admission 10.7% vs 9.4% (RR=1.03<1.14<1.25; P=.001). |
| Boulvain, 20012 | Retrospective cohort study.7430 women between 38 and 40 6/7weeks.531women in induced group vs 3353 women in spontaneous labor group. | Induction of labor was found to be associated with higher risk of cesarean delivery (7.7% to 3.6%) (RR=2.4; 95% CI, 1.1–3.4). | IND vs spontaneous labor 28.1% vs 30.1% (RR=1.0; 95% CI, 0.9–1.2); not statistically significant. | NICU admission 4.1% vs 2.8% (RR=1.6; 95% CI, 1.0–2.4). |
| Dublin, 20003 | Population-based cohort study.2886 induced vs 9648 spontaneous labor. 37–41weeks gestation. | In nulliparous women 19% of IND group had cesarean delivery vs 10% nulliparous of women in spontaneous labor group (NNH=11). No association was seen in multiparous women. | 18.6% vs 15.5% (RR=1.2; 95% CI, 1.02–1.32). | Shoulder dystocia 3.0% vs 1.7% (RR=1.32; 95% CI, 1.02–1.69); NNH=77. |
| Nicholson, 20044 | Retrospective cohort study.100 women in active management (AM) group, 300 selected subjects in standard management (SM) group. 38 to to 410/7 weeks gestation. | AM group vs SM group had higher rates of induction (63% vs 23.7%; risk ratio=2.66 [95% CI, 2.07–3.43]). AM group vs SM group had a lower cesarean delivery rate (4% vs 16.7%; risk ratio=0.24; 95% CI, 0.09–0.65; NNT=7). | AM group vs SM group 16% vs 15.3%. Not statically significant. | No significant differences. |
| Nielson, 20055 | 116 women (45 nulliparous) randomized at ≥39 wks to expectant management or induction with oxytocin and/or amniotomy. | 6.9% (8/116) IND group. vs 7.3% (8/110) in EM group. Not statistically significant. | 6.9% (8/116) IND group vs 8.2% (9/116) EM group. Not statistically significant. | No mention. |
| Sanchez-Ramos, 20036 | Systematic review of 16 randomized controlled trials (6588 women). Included women at 41 weeks gestation. | 20.1% in IND group vs 22.0% in EM group. NNT=52; odds reduction of 12% (95% CI, 0.78–0.99). Statistically significant. | No mention. | Perinatal mortality rate: 0.09% IND group vs 0.33% EM group. Not statistically significant. |
| IND, induction; EM, expectant management; AM, active management; SM, standard management; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; NNT, number needed to treat; NNH, number needed to harm. | ||||
Recommendations from others
A 1999 American College of Obstetricians and Gynecologists (ACOG) practice bulletin states that labor may be induced for logistic reasons such as psychosocial factors and distance from hospital, as long as 1 of these 4 criteria is met: (1) fetal heart tones have been documented for 20 weeks by nonelectronic fetoscope or for 30 weeks by Doppler; (2) it has been 36 weeks since a positive serum or urine human chorionic gonadotropin pregnancy test was performed; (3) ultrasound measurement of crown-rump length, obtained at 6 to 12 weeks, supports a gestational age of at least 39 weeks; (4) ultrasound obtained at 13 to 20 weeks confirms the gestational age of at least 39 weeks determined by clinical history and physical examination. The ACOG recommendation (which dates back to 1989) is for induction of low-risk pregnancy at the 43rd week of gestation.7
The Royal College of Obstetricians and Gynaecologists recommends that women with uncomplicated pregnancies be offered induction of labor beyond 41 weeks.8 The Department of Obstetrics and Gynecology and Reproductive Biology at Harvard Medical School recommends routine induction of labor be recommended at 41 weeks’ gestation.9
1. Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective labor induction in nulliparous women: A matched cohort study. Am J Obstet Gynecol 2002;186:240-244.
2. Boulvain M, Marcoux S, Bureau M, Fortier M, Fraser W. Risks of induction of labour in uncomplicated term pregnancies. Paediatric Perinatal Epidemiology 2001;15:131-139.
3. Dublin S, Lydon-Rochelle M, Kaplan RC, Watts DH, Critchlow CW. Maternal and neonatal outcomes after induction of labor without an identified indication. Am J Obstet Gynecol 2000;183:986-994.
4. Nicholson JM, Kellar LC, Cronholm PF, Macones GA. Active management of risk in pregnancy at term in an urban population: An association between a higher induction of labor rate and a lower cesarean delivery rate. Am J Obstet Gynecol 2004;191:1516-1528.
5. Nielsen PE, Howard BC, Hill CC, Larson PL, Holland RHB, Smith PN. Comparison of elective induction of labor with favorable Bishop scores versus expectant management: A randomized clinical trial. J Maternal Fetal Neonatal Med 2005;18:59-64.
6. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz A. Labor induction versus expectant management for postterm pregnancies: A systematic review with meta-analysis. Obstet Gynecol 2003;101:1312-1318.
7. ACOG Practice Bulletin. Induction of labor. Int J Gynecol Obstet 2000;69:283-292.
8. Royal College of Obstetricians and Gynaecologists. Induction of Labour London: RCOG Press; 2001.
9. Rand L, Robinson JN, Economy KE, Norwitz ER. Post-term induction of labor revisited. Obstet Gynecol 2000;96:779-783.
Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant (strength of recommendation [SOR]: B). The benefit of elective induction for nonmedical reasons is unclear (SOR: B).
Elective inductions can add costs and legal risks
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Family physicians cherish having long, collaborative relationships with patients. But when they practice obstetrics, this desire can result in feeling pressured to grant requests by pregnant patients for elective inductions. As indicated in this Clinical Inquiry, elective inductions may be relatively safe in some situations, but they always incur added costs. The cost of cervical ripening, extra monitoring, and medications to promote uterine contractions fall to the medical system. There also may be added legal risk to the provider. Eventually, some elective induction will have a bad outcome and there will be no way to defend the decision to induce as medically necessary.
Evidence summary
Induction of labor is a viable therapeutic option when the benefits of timely delivery outweigh the risks of unnecessary cesarean section or prematurity. Two large retrospective studies support the concept that cesarean section rates and admissions to neonatal intensive care units are higher with elective induction as opposed to expectant management (TABLE).1,2 A large population-based study suggests that the higher cesarean section rates in elective induction is present only among nulliparous women; in multiparous women, the rate is the same as expectant management.3 Contrasting these results are those of a large systematic review, which found lower cesarean section rates in electively induced women. Two more recent studies, a retrospective cohort study4 and a randomized controlled trial,5 found a much lower incidence of cesarean section and operative vaginal deliveries among induced vs expectantly managed women at term.
TABLE
Summary of evidence regarding induction of labor
| STUDY | METHODS | CESAREAN DELIVERY RATE | OPERATIVE VAGINAL DELIVERY | PERINATAL COMPLICATIONS |
|---|---|---|---|---|
| Cammu, 20021 | Matched cohort study. 7683 women in IND group, 7683 women in EM group. 38–410/7 weeks gestation. | 9.9% vs 6.5% (P=.001); NNH=30. | 31.67% vs 29.1% (P=.001); NNH=39. | NICU admission 10.7% vs 9.4% (RR=1.03<1.14<1.25; P=.001). |
| Boulvain, 20012 | Retrospective cohort study.7430 women between 38 and 40 6/7weeks.531women in induced group vs 3353 women in spontaneous labor group. | Induction of labor was found to be associated with higher risk of cesarean delivery (7.7% to 3.6%) (RR=2.4; 95% CI, 1.1–3.4). | IND vs spontaneous labor 28.1% vs 30.1% (RR=1.0; 95% CI, 0.9–1.2); not statistically significant. | NICU admission 4.1% vs 2.8% (RR=1.6; 95% CI, 1.0–2.4). |
| Dublin, 20003 | Population-based cohort study.2886 induced vs 9648 spontaneous labor. 37–41weeks gestation. | In nulliparous women 19% of IND group had cesarean delivery vs 10% nulliparous of women in spontaneous labor group (NNH=11). No association was seen in multiparous women. | 18.6% vs 15.5% (RR=1.2; 95% CI, 1.02–1.32). | Shoulder dystocia 3.0% vs 1.7% (RR=1.32; 95% CI, 1.02–1.69); NNH=77. |
| Nicholson, 20044 | Retrospective cohort study.100 women in active management (AM) group, 300 selected subjects in standard management (SM) group. 38 to to 410/7 weeks gestation. | AM group vs SM group had higher rates of induction (63% vs 23.7%; risk ratio=2.66 [95% CI, 2.07–3.43]). AM group vs SM group had a lower cesarean delivery rate (4% vs 16.7%; risk ratio=0.24; 95% CI, 0.09–0.65; NNT=7). | AM group vs SM group 16% vs 15.3%. Not statically significant. | No significant differences. |
| Nielson, 20055 | 116 women (45 nulliparous) randomized at ≥39 wks to expectant management or induction with oxytocin and/or amniotomy. | 6.9% (8/116) IND group. vs 7.3% (8/110) in EM group. Not statistically significant. | 6.9% (8/116) IND group vs 8.2% (9/116) EM group. Not statistically significant. | No mention. |
| Sanchez-Ramos, 20036 | Systematic review of 16 randomized controlled trials (6588 women). Included women at 41 weeks gestation. | 20.1% in IND group vs 22.0% in EM group. NNT=52; odds reduction of 12% (95% CI, 0.78–0.99). Statistically significant. | No mention. | Perinatal mortality rate: 0.09% IND group vs 0.33% EM group. Not statistically significant. |
| IND, induction; EM, expectant management; AM, active management; SM, standard management; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; NNT, number needed to treat; NNH, number needed to harm. | ||||
Recommendations from others
A 1999 American College of Obstetricians and Gynecologists (ACOG) practice bulletin states that labor may be induced for logistic reasons such as psychosocial factors and distance from hospital, as long as 1 of these 4 criteria is met: (1) fetal heart tones have been documented for 20 weeks by nonelectronic fetoscope or for 30 weeks by Doppler; (2) it has been 36 weeks since a positive serum or urine human chorionic gonadotropin pregnancy test was performed; (3) ultrasound measurement of crown-rump length, obtained at 6 to 12 weeks, supports a gestational age of at least 39 weeks; (4) ultrasound obtained at 13 to 20 weeks confirms the gestational age of at least 39 weeks determined by clinical history and physical examination. The ACOG recommendation (which dates back to 1989) is for induction of low-risk pregnancy at the 43rd week of gestation.7
The Royal College of Obstetricians and Gynaecologists recommends that women with uncomplicated pregnancies be offered induction of labor beyond 41 weeks.8 The Department of Obstetrics and Gynecology and Reproductive Biology at Harvard Medical School recommends routine induction of labor be recommended at 41 weeks’ gestation.9
Elective induction of labor for term, singleton, uncomplicated pregnancies appears safe for both the mother and infant (strength of recommendation [SOR]: B). The benefit of elective induction for nonmedical reasons is unclear (SOR: B).
Elective inductions can add costs and legal risks
Jon O. Neher, MD
Valley Medical Center, Renton, Wash
Family physicians cherish having long, collaborative relationships with patients. But when they practice obstetrics, this desire can result in feeling pressured to grant requests by pregnant patients for elective inductions. As indicated in this Clinical Inquiry, elective inductions may be relatively safe in some situations, but they always incur added costs. The cost of cervical ripening, extra monitoring, and medications to promote uterine contractions fall to the medical system. There also may be added legal risk to the provider. Eventually, some elective induction will have a bad outcome and there will be no way to defend the decision to induce as medically necessary.
Evidence summary
Induction of labor is a viable therapeutic option when the benefits of timely delivery outweigh the risks of unnecessary cesarean section or prematurity. Two large retrospective studies support the concept that cesarean section rates and admissions to neonatal intensive care units are higher with elective induction as opposed to expectant management (TABLE).1,2 A large population-based study suggests that the higher cesarean section rates in elective induction is present only among nulliparous women; in multiparous women, the rate is the same as expectant management.3 Contrasting these results are those of a large systematic review, which found lower cesarean section rates in electively induced women. Two more recent studies, a retrospective cohort study4 and a randomized controlled trial,5 found a much lower incidence of cesarean section and operative vaginal deliveries among induced vs expectantly managed women at term.
TABLE
Summary of evidence regarding induction of labor
| STUDY | METHODS | CESAREAN DELIVERY RATE | OPERATIVE VAGINAL DELIVERY | PERINATAL COMPLICATIONS |
|---|---|---|---|---|
| Cammu, 20021 | Matched cohort study. 7683 women in IND group, 7683 women in EM group. 38–410/7 weeks gestation. | 9.9% vs 6.5% (P=.001); NNH=30. | 31.67% vs 29.1% (P=.001); NNH=39. | NICU admission 10.7% vs 9.4% (RR=1.03<1.14<1.25; P=.001). |
| Boulvain, 20012 | Retrospective cohort study.7430 women between 38 and 40 6/7weeks.531women in induced group vs 3353 women in spontaneous labor group. | Induction of labor was found to be associated with higher risk of cesarean delivery (7.7% to 3.6%) (RR=2.4; 95% CI, 1.1–3.4). | IND vs spontaneous labor 28.1% vs 30.1% (RR=1.0; 95% CI, 0.9–1.2); not statistically significant. | NICU admission 4.1% vs 2.8% (RR=1.6; 95% CI, 1.0–2.4). |
| Dublin, 20003 | Population-based cohort study.2886 induced vs 9648 spontaneous labor. 37–41weeks gestation. | In nulliparous women 19% of IND group had cesarean delivery vs 10% nulliparous of women in spontaneous labor group (NNH=11). No association was seen in multiparous women. | 18.6% vs 15.5% (RR=1.2; 95% CI, 1.02–1.32). | Shoulder dystocia 3.0% vs 1.7% (RR=1.32; 95% CI, 1.02–1.69); NNH=77. |
| Nicholson, 20044 | Retrospective cohort study.100 women in active management (AM) group, 300 selected subjects in standard management (SM) group. 38 to to 410/7 weeks gestation. | AM group vs SM group had higher rates of induction (63% vs 23.7%; risk ratio=2.66 [95% CI, 2.07–3.43]). AM group vs SM group had a lower cesarean delivery rate (4% vs 16.7%; risk ratio=0.24; 95% CI, 0.09–0.65; NNT=7). | AM group vs SM group 16% vs 15.3%. Not statically significant. | No significant differences. |
| Nielson, 20055 | 116 women (45 nulliparous) randomized at ≥39 wks to expectant management or induction with oxytocin and/or amniotomy. | 6.9% (8/116) IND group. vs 7.3% (8/110) in EM group. Not statistically significant. | 6.9% (8/116) IND group vs 8.2% (9/116) EM group. Not statistically significant. | No mention. |
| Sanchez-Ramos, 20036 | Systematic review of 16 randomized controlled trials (6588 women). Included women at 41 weeks gestation. | 20.1% in IND group vs 22.0% in EM group. NNT=52; odds reduction of 12% (95% CI, 0.78–0.99). Statistically significant. | No mention. | Perinatal mortality rate: 0.09% IND group vs 0.33% EM group. Not statistically significant. |
| IND, induction; EM, expectant management; AM, active management; SM, standard management; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; NNT, number needed to treat; NNH, number needed to harm. | ||||
Recommendations from others
A 1999 American College of Obstetricians and Gynecologists (ACOG) practice bulletin states that labor may be induced for logistic reasons such as psychosocial factors and distance from hospital, as long as 1 of these 4 criteria is met: (1) fetal heart tones have been documented for 20 weeks by nonelectronic fetoscope or for 30 weeks by Doppler; (2) it has been 36 weeks since a positive serum or urine human chorionic gonadotropin pregnancy test was performed; (3) ultrasound measurement of crown-rump length, obtained at 6 to 12 weeks, supports a gestational age of at least 39 weeks; (4) ultrasound obtained at 13 to 20 weeks confirms the gestational age of at least 39 weeks determined by clinical history and physical examination. The ACOG recommendation (which dates back to 1989) is for induction of low-risk pregnancy at the 43rd week of gestation.7
The Royal College of Obstetricians and Gynaecologists recommends that women with uncomplicated pregnancies be offered induction of labor beyond 41 weeks.8 The Department of Obstetrics and Gynecology and Reproductive Biology at Harvard Medical School recommends routine induction of labor be recommended at 41 weeks’ gestation.9
1. Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective labor induction in nulliparous women: A matched cohort study. Am J Obstet Gynecol 2002;186:240-244.
2. Boulvain M, Marcoux S, Bureau M, Fortier M, Fraser W. Risks of induction of labour in uncomplicated term pregnancies. Paediatric Perinatal Epidemiology 2001;15:131-139.
3. Dublin S, Lydon-Rochelle M, Kaplan RC, Watts DH, Critchlow CW. Maternal and neonatal outcomes after induction of labor without an identified indication. Am J Obstet Gynecol 2000;183:986-994.
4. Nicholson JM, Kellar LC, Cronholm PF, Macones GA. Active management of risk in pregnancy at term in an urban population: An association between a higher induction of labor rate and a lower cesarean delivery rate. Am J Obstet Gynecol 2004;191:1516-1528.
5. Nielsen PE, Howard BC, Hill CC, Larson PL, Holland RHB, Smith PN. Comparison of elective induction of labor with favorable Bishop scores versus expectant management: A randomized clinical trial. J Maternal Fetal Neonatal Med 2005;18:59-64.
6. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz A. Labor induction versus expectant management for postterm pregnancies: A systematic review with meta-analysis. Obstet Gynecol 2003;101:1312-1318.
7. ACOG Practice Bulletin. Induction of labor. Int J Gynecol Obstet 2000;69:283-292.
8. Royal College of Obstetricians and Gynaecologists. Induction of Labour London: RCOG Press; 2001.
9. Rand L, Robinson JN, Economy KE, Norwitz ER. Post-term induction of labor revisited. Obstet Gynecol 2000;96:779-783.
1. Cammu H, Martens G, Ruyssinck G, Amy JJ. Outcome after elective labor induction in nulliparous women: A matched cohort study. Am J Obstet Gynecol 2002;186:240-244.
2. Boulvain M, Marcoux S, Bureau M, Fortier M, Fraser W. Risks of induction of labour in uncomplicated term pregnancies. Paediatric Perinatal Epidemiology 2001;15:131-139.
3. Dublin S, Lydon-Rochelle M, Kaplan RC, Watts DH, Critchlow CW. Maternal and neonatal outcomes after induction of labor without an identified indication. Am J Obstet Gynecol 2000;183:986-994.
4. Nicholson JM, Kellar LC, Cronholm PF, Macones GA. Active management of risk in pregnancy at term in an urban population: An association between a higher induction of labor rate and a lower cesarean delivery rate. Am J Obstet Gynecol 2004;191:1516-1528.
5. Nielsen PE, Howard BC, Hill CC, Larson PL, Holland RHB, Smith PN. Comparison of elective induction of labor with favorable Bishop scores versus expectant management: A randomized clinical trial. J Maternal Fetal Neonatal Med 2005;18:59-64.
6. Sanchez-Ramos L, Olivier F, Delke I, Kaunitz A. Labor induction versus expectant management for postterm pregnancies: A systematic review with meta-analysis. Obstet Gynecol 2003;101:1312-1318.
7. ACOG Practice Bulletin. Induction of labor. Int J Gynecol Obstet 2000;69:283-292.
8. Royal College of Obstetricians and Gynaecologists. Induction of Labour London: RCOG Press; 2001.
9. Rand L, Robinson JN, Economy KE, Norwitz ER. Post-term induction of labor revisited. Obstet Gynecol 2000;96:779-783.
Evidence-based answers from the Family Physicians Inquiries Network
Is exercise treadmill testing useful for detecting heart disease in women?
Exercise treadmill testing has a sensitivity of 70% and specificity of 61% for the detection of coronary artery disease (CAD) in women (strength of recommendation [SOR]: A, based on a meta-analysis). It is useful for detecting CAD in symptomatic women who have an intermediate risk as determined by age and symptoms (SOR: C, based on expert opinion). Exercise treadmill testing may also have an application in determining exercise capacity and potential as a tool to predict cardiovascular death in women (SOR: A, cohort study).
Evidence-based summary
Few studies of exercise treadmill testing include a significant number of women, which makes it difficult to ascertain its value for detecting CAD in women. A large meta-analysis of 19 studies looked specifically at women (n=3721) and found that noninvasive exercise tests only “moderately useful” for the detection of CAD. Exercise treadmill testing in women had a specificity of 0.70 (95% confidence interval [CI], 0.64–0.75), a sensitivity of 0.61 (95% CI, 0.54–0.68), a positive likelihood ratio of 2.25 (95% CI, 1.84–2.66) and a negative likelihood ratio of 0.55 (95% CI, 0.47–0.62). In comparison, exercise treadmill testing in men had a sensitivity of 0.70 and a specificity of 0.77.1 The Table demonstrates how exercise treadmill testing performs for different levels of pretest probability.
Among the theoretical reasons for the diminished accuracy of the exercise treadmill testing in women are the varying catecholamine response to exercise, a higher incidence of mitral valve prolapse, and chest wall anatomy different than that in men.1 Also, the methods used in performing exercise treadmill testing, as well as the thresholds for an abnormal test result, were established for men. Accuracy may also be affected by the subjectivity inherent in the performance and interpretation of the exercise treadmill testing, in particular, the reading of the ST segment.2
A large cohort study of 2994 asymptomatic women found that those women with a below-average peak exercise capacity and heart-rate recovery rate were 3.5 times more likely to die of cardiovascular causes than women who were above average (95% CI, 1.57–7.86).3 Another cohort study of 5721 women found that an exercise capacity of <5 metabolic equivalents (METS) tripled the risk of death as compared with those with an exercise capacity of >8 METS.4 These studies support the role of exercise treadmill testing for risk stratification for CAD disease in women.
TABLE
Post-test probabilities of coronary artery disease using exercise echocardiogram
| Post-test probability of CAD | ||
|---|---|---|
| Pretest symptoms/probability of CAD | Positive test ( %) | Negative test (%) |
| Definite angina—71% probability | 85 | 57 |
| Probable angina—31% probability | 50 | 20 |
| Nonspecific chest pain—6% probability | 13 | 3 |
| CAD, coronary artery disease. | ||
| Table adapted from Kwok et al 1999.1 | ||
Recommendations from others
The Institute for Clinical Systems Improvement states that exercise treadmill testing has application for the detection of coronary artery disease in those women with an intermediate (10%–90%) pretest probability of coronary artery disease as determined by age, gender, and symptoms. The intermediate category includes women aged 30 to 49 years with typical symptoms of angina, women aged 50 to 59 years with typical or atypical symptoms of angina, and women aged 60 to 69 years with atypical or nonanginal chest pain. All other women fall into groups with pretest probability either high enough or low enough that the exercise treadmill testing is less useful.5
The American College of Cardiology (ACC) and the American Heart Association concluded that the diagnosis of CAD in women presents difficulties not experienced with men, due primarily to the lower sensitivity and specificity of exercise treadmill testing. The ACC recommends exercise treadmill testing for the diagnosis of CAD in patients with an intermediate pretest probability of coronary disease based on age, gender, and symptoms. (This recommendation is described as one for which there is evidence or general agreement that a given procedure or treatment is useful and effective.)6
False-positive rate and costs may argue for stress radionuclide or echocardiogram
Lynda Montgomery, MD, MEd
Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio
The relative lack of evidence regarding the diagnostic accuracy of exercise treadmill testing in women is frustrating given the prevalence of both CAD and symptoms of chest pain in women. Nevertheless, it seems clear that the false-positive rate and costs argue that unless a woman meets specific criteria (eg, International Sensitivity Index recommendations), stress radionuclide or stress echocardiogram are better initial tests. I will use exercise treadmill testing when evaluating exercise capacity in my women patients.
1. Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-666.
2. Sketch MH, Mohiuddin SM, Lynch JD, Zencka AE, Runco V. Significant sex differences in the correlation of electrocardiographic exercise testing and coronary arteriograms. Am J Cardiol 1975;36:69-173.
3. Mora S, Redberg RF, Cui Y, et al. Ability of exercise testing to predict cardiovascular and all cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study. JAMA 2003;290:1600-1607.
4. Gulati M, Pandey DK, Arnsdorf MF, et al. Exercise capacity and the risk of death in women: the St. James Women Take Heart Project. Circulation 2003;108:1554-1559.
5. Institute for Clinical Systems Improvement. Health Care Guidelines Supplement: Cardiac Stress Test Supplement. October 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=155. Accessed on March 9, 2004.
6. American College of Cardiology/American Heart Association 2002 Guideline. Update for the Management of Patients with Chronic Stable Angina. Available at: www.acc.org/clinical/guidelines/stable/stable_clean.pdf. Accessed on March 9, 2004.
Exercise treadmill testing has a sensitivity of 70% and specificity of 61% for the detection of coronary artery disease (CAD) in women (strength of recommendation [SOR]: A, based on a meta-analysis). It is useful for detecting CAD in symptomatic women who have an intermediate risk as determined by age and symptoms (SOR: C, based on expert opinion). Exercise treadmill testing may also have an application in determining exercise capacity and potential as a tool to predict cardiovascular death in women (SOR: A, cohort study).
Evidence-based summary
Few studies of exercise treadmill testing include a significant number of women, which makes it difficult to ascertain its value for detecting CAD in women. A large meta-analysis of 19 studies looked specifically at women (n=3721) and found that noninvasive exercise tests only “moderately useful” for the detection of CAD. Exercise treadmill testing in women had a specificity of 0.70 (95% confidence interval [CI], 0.64–0.75), a sensitivity of 0.61 (95% CI, 0.54–0.68), a positive likelihood ratio of 2.25 (95% CI, 1.84–2.66) and a negative likelihood ratio of 0.55 (95% CI, 0.47–0.62). In comparison, exercise treadmill testing in men had a sensitivity of 0.70 and a specificity of 0.77.1 The Table demonstrates how exercise treadmill testing performs for different levels of pretest probability.
Among the theoretical reasons for the diminished accuracy of the exercise treadmill testing in women are the varying catecholamine response to exercise, a higher incidence of mitral valve prolapse, and chest wall anatomy different than that in men.1 Also, the methods used in performing exercise treadmill testing, as well as the thresholds for an abnormal test result, were established for men. Accuracy may also be affected by the subjectivity inherent in the performance and interpretation of the exercise treadmill testing, in particular, the reading of the ST segment.2
A large cohort study of 2994 asymptomatic women found that those women with a below-average peak exercise capacity and heart-rate recovery rate were 3.5 times more likely to die of cardiovascular causes than women who were above average (95% CI, 1.57–7.86).3 Another cohort study of 5721 women found that an exercise capacity of <5 metabolic equivalents (METS) tripled the risk of death as compared with those with an exercise capacity of >8 METS.4 These studies support the role of exercise treadmill testing for risk stratification for CAD disease in women.
TABLE
Post-test probabilities of coronary artery disease using exercise echocardiogram
| Post-test probability of CAD | ||
|---|---|---|
| Pretest symptoms/probability of CAD | Positive test ( %) | Negative test (%) |
| Definite angina—71% probability | 85 | 57 |
| Probable angina—31% probability | 50 | 20 |
| Nonspecific chest pain—6% probability | 13 | 3 |
| CAD, coronary artery disease. | ||
| Table adapted from Kwok et al 1999.1 | ||
Recommendations from others
The Institute for Clinical Systems Improvement states that exercise treadmill testing has application for the detection of coronary artery disease in those women with an intermediate (10%–90%) pretest probability of coronary artery disease as determined by age, gender, and symptoms. The intermediate category includes women aged 30 to 49 years with typical symptoms of angina, women aged 50 to 59 years with typical or atypical symptoms of angina, and women aged 60 to 69 years with atypical or nonanginal chest pain. All other women fall into groups with pretest probability either high enough or low enough that the exercise treadmill testing is less useful.5
The American College of Cardiology (ACC) and the American Heart Association concluded that the diagnosis of CAD in women presents difficulties not experienced with men, due primarily to the lower sensitivity and specificity of exercise treadmill testing. The ACC recommends exercise treadmill testing for the diagnosis of CAD in patients with an intermediate pretest probability of coronary disease based on age, gender, and symptoms. (This recommendation is described as one for which there is evidence or general agreement that a given procedure or treatment is useful and effective.)6
False-positive rate and costs may argue for stress radionuclide or echocardiogram
Lynda Montgomery, MD, MEd
Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio
The relative lack of evidence regarding the diagnostic accuracy of exercise treadmill testing in women is frustrating given the prevalence of both CAD and symptoms of chest pain in women. Nevertheless, it seems clear that the false-positive rate and costs argue that unless a woman meets specific criteria (eg, International Sensitivity Index recommendations), stress radionuclide or stress echocardiogram are better initial tests. I will use exercise treadmill testing when evaluating exercise capacity in my women patients.
Exercise treadmill testing has a sensitivity of 70% and specificity of 61% for the detection of coronary artery disease (CAD) in women (strength of recommendation [SOR]: A, based on a meta-analysis). It is useful for detecting CAD in symptomatic women who have an intermediate risk as determined by age and symptoms (SOR: C, based on expert opinion). Exercise treadmill testing may also have an application in determining exercise capacity and potential as a tool to predict cardiovascular death in women (SOR: A, cohort study).
Evidence-based summary
Few studies of exercise treadmill testing include a significant number of women, which makes it difficult to ascertain its value for detecting CAD in women. A large meta-analysis of 19 studies looked specifically at women (n=3721) and found that noninvasive exercise tests only “moderately useful” for the detection of CAD. Exercise treadmill testing in women had a specificity of 0.70 (95% confidence interval [CI], 0.64–0.75), a sensitivity of 0.61 (95% CI, 0.54–0.68), a positive likelihood ratio of 2.25 (95% CI, 1.84–2.66) and a negative likelihood ratio of 0.55 (95% CI, 0.47–0.62). In comparison, exercise treadmill testing in men had a sensitivity of 0.70 and a specificity of 0.77.1 The Table demonstrates how exercise treadmill testing performs for different levels of pretest probability.
Among the theoretical reasons for the diminished accuracy of the exercise treadmill testing in women are the varying catecholamine response to exercise, a higher incidence of mitral valve prolapse, and chest wall anatomy different than that in men.1 Also, the methods used in performing exercise treadmill testing, as well as the thresholds for an abnormal test result, were established for men. Accuracy may also be affected by the subjectivity inherent in the performance and interpretation of the exercise treadmill testing, in particular, the reading of the ST segment.2
A large cohort study of 2994 asymptomatic women found that those women with a below-average peak exercise capacity and heart-rate recovery rate were 3.5 times more likely to die of cardiovascular causes than women who were above average (95% CI, 1.57–7.86).3 Another cohort study of 5721 women found that an exercise capacity of <5 metabolic equivalents (METS) tripled the risk of death as compared with those with an exercise capacity of >8 METS.4 These studies support the role of exercise treadmill testing for risk stratification for CAD disease in women.
TABLE
Post-test probabilities of coronary artery disease using exercise echocardiogram
| Post-test probability of CAD | ||
|---|---|---|
| Pretest symptoms/probability of CAD | Positive test ( %) | Negative test (%) |
| Definite angina—71% probability | 85 | 57 |
| Probable angina—31% probability | 50 | 20 |
| Nonspecific chest pain—6% probability | 13 | 3 |
| CAD, coronary artery disease. | ||
| Table adapted from Kwok et al 1999.1 | ||
Recommendations from others
The Institute for Clinical Systems Improvement states that exercise treadmill testing has application for the detection of coronary artery disease in those women with an intermediate (10%–90%) pretest probability of coronary artery disease as determined by age, gender, and symptoms. The intermediate category includes women aged 30 to 49 years with typical symptoms of angina, women aged 50 to 59 years with typical or atypical symptoms of angina, and women aged 60 to 69 years with atypical or nonanginal chest pain. All other women fall into groups with pretest probability either high enough or low enough that the exercise treadmill testing is less useful.5
The American College of Cardiology (ACC) and the American Heart Association concluded that the diagnosis of CAD in women presents difficulties not experienced with men, due primarily to the lower sensitivity and specificity of exercise treadmill testing. The ACC recommends exercise treadmill testing for the diagnosis of CAD in patients with an intermediate pretest probability of coronary disease based on age, gender, and symptoms. (This recommendation is described as one for which there is evidence or general agreement that a given procedure or treatment is useful and effective.)6
False-positive rate and costs may argue for stress radionuclide or echocardiogram
Lynda Montgomery, MD, MEd
Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Ohio
The relative lack of evidence regarding the diagnostic accuracy of exercise treadmill testing in women is frustrating given the prevalence of both CAD and symptoms of chest pain in women. Nevertheless, it seems clear that the false-positive rate and costs argue that unless a woman meets specific criteria (eg, International Sensitivity Index recommendations), stress radionuclide or stress echocardiogram are better initial tests. I will use exercise treadmill testing when evaluating exercise capacity in my women patients.
1. Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise testing to detect coronary artery disease in women. Am J Cardiol 1999;83:660-666.
2. Sketch MH, Mohiuddin SM, Lynch JD, Zencka AE, Runco V. Significant sex differences in the correlation of electrocardiographic exercise testing and coronary arteriograms. Am J Cardiol 1975;36:69-173.
3. Mora S, Redberg RF, Cui Y, et al. Ability of exercise testing to predict cardiovascular and all cause death in asymptomatic women: a 20-year follow-up of the lipid research clinics prevalence study. JAMA 2003;290:1600-1607.
4. Gulati M, Pandey DK, Arnsdorf MF, et al. Exercise capacity and the risk of death in women: the St. James Women Take Heart Project. Circulation 2003;108:1554-1559.
5. Institute for Clinical Systems Improvement. Health Care Guidelines Supplement: Cardiac Stress Test Supplement. October 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=155. Accessed on March 9, 2004.
6. American College of Cardiology/American Heart Association 2002 Guideline. Update for the Management of Patients with Chronic Stable Angina. Available at: www.acc.org/clinical/guidelines/stable/stable_clean.pdf. Accessed on March 9, 2004.
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5. Institute for Clinical Systems Improvement. Health Care Guidelines Supplement: Cardiac Stress Test Supplement. October 2002. Available at: www.icsi.org/knowledge/detail.asp?catID=29&itemID=155. Accessed on March 9, 2004.
6. American College of Cardiology/American Heart Association 2002 Guideline. Update for the Management of Patients with Chronic Stable Angina. Available at: www.acc.org/clinical/guidelines/stable/stable_clean.pdf. Accessed on March 9, 2004.
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