Introduction
Substantial reductions in mother-to-child transmission of HIV have been achieved since the adoption of prenatal zidovudine therapy [1] and elective Cesarean delivery (C-section) [2] as prevention strategies. Using both these interventions together is a cost-effective strategy to prevent mother-to-child HIV transmission [3-6]. Because vertical transmission of HIV occurs predominantly in women with detectable HIV RNA during pregnancy [7,8], combination antiretroviral therapy is an effective and safe alternative prevention strategy [9]. Currently, in the United States, it is recommended that only HIV-infected pregnant women with HIV RNA levels > 1000 copies/ml should be counseled about the reduced risk of HIV transmission with a scheduled C-section (although European guidelines suggest an offer to all HIV-infected pregnant women) [10,11].
Mother-to-child transmission of hepatitis C virus (HCV) is less common than that of HIV and is associated with the presence of HCV RNA in the mother [12-14]. Recent guidelines do not recommend elective C-section for prevention of mother-to-child transmission in women with chronic HCV infection, because of a lack of evidence of efficacy [14,15]. However, HIV/HCV coinfection increases the likelihood of mother-to-child HCV transmission four- to five-fold [14,16], and recent data from a large European prospective study found a significant protective effect of C-section on HCV transmission by HIV/HCV-coinfected mothers [17]. Antiviral therapy to prevent maternal HCV transmission is not an option because ribavirin and pegylated alfa-interferon, the current standard of care for treatment of chronic HCV [15], cannot be used during pregnancy [14]. Breast feeding is generally not considered a risk factor for mother-to-child transmission of HCV [18].
Between 6000 and 7000 deliveries to HIV-infected mothers occurred annually in the United States between 1988 and 1994 [19]. Individuals whose route of HIV infection was through injection drug use have an extremely high likelihood of being coinfected with HCV, because HCV is more easily transmitted through this route than HIV [20]. Assuming that 28% of HIV-infected women in the United States were infected through injection drug use [21], and that their pregnancy rate is comparable to that of women infected with HIV by other means [22], an estimated 1700-2000 HIV/HCV-coinfected women give birth in the United States each year. The current standard of care in the United States does not routinely offer HIV/HCV-coinfected women who have achieved effective suppression of HIV RNA with antiretroviral therapy the option to consider elective C-section to prevent transmission of HCV to their children. Consideration of this option requires a trade-off between the immediate risks of C-section complications, which are higher in HIV-infected women [23-25], and the benefits of avoiding the sequelae of chronic HCV infection in their offspring, which will generally occur in adulthood if at all [26].
The objective of this analysis was to determine the net health consequences, costs, and cost-effectiveness of elective C-section to prevent perinatal transmission of HCV in coinfected women with suppressed HIV RNA but detectable HCV RNA. Two strategies were compared: (i) recommending C-section to all coinfected women meeting the criteria, and (ii) recommending C-section only when indicated based on fetal status (standard care). Health outcomes and costs for both the mother and child were considered and the sensitivity of results was examined for varying C-section acceptance rates by the mothers and for variability in our estimates of C-section benefits and risks.
Methods
Decision analytic model
A decision analytic model was developed using the software program DATA Pro (TreeAge Software Inc., Williamstown, Massachusetts, USA) to compare the recommendation for an elective C-section with standard care. The possible pathways for different perinatal care options are outlined in Figure 1. If C-section is recommended, mothers may accept or reject the recommendation, and most who accept will deliver by elective C-section. However, some will require urgent (non-scheduled) C-section or deliver vaginally if, for instance, they deliver before the recommended time of elective C-section of 38 weeks. Women who do not accept the recommendation will deliver vaginally, by elective C-section, and by urgent C-section at the same rates as for the current standard of care. Women may survive delivery with or without complications or may die. HCV infection can occur regardless of maternal outcome.
Each delivery mode is associated with a unique maternal death rate, complication rate, and HCV vertical transmission rate. Women are assumed to have been identified as HCV-infected as part of their HIV clinical care [27]. Because the analysis is limited to women who do not have detectable HIV RNA, it is conservatively assumed that vertical transmission of HIV does not occur with or without C-section. The potential impact of antiretroviral treatment (prescribed for HIV disease) on maternal HCV transmission is unclear, because studies of the effects of antiretroviral drugs on HCV RNA levels give conflicting results; with the initiation of HIV treatment, there may be an initial increase in HCV RNA levels followed by a gradual decrease [28]. In the model, it was assumed that antiretroviral therapy had no impact on outcomes.
Maternal quality-adjusted life year (QALY) decrements and hospital and physician costs were also recorded and depended on mode of delivery and the presence of complications. QALY decrements and future costs of HCV treatment were recorded for those children infected with HCV who are expected to progress to chronic HCV infection. The recommendation for C-section strategy was compared with standard care in terms of the incremental number of HCV transmissions avoided, the incremental number of maternal deaths, and the incremental cost-effectiveness ratio. This ratio was defined as the total incremental costs for mother and child associated with the recommendation for C-section divided by the total incremental QALYs. A technical appendix giving the model structure in detail is available from the authors upon request.
Clinical data sources
Estimates of the rates of vaginal delivery, elective C-section, and urgent C-section with and without a recommendation for C-section were taken from a randomized trial of elective Cesarean section in HIV-infected women published by the European Mode of Delivery Collaboration (Table 1) [29]. The probability of acceptance of the recommendation for C-section was derived from the acceptance rate for enrollment in the pilot phase of this study [30]. The maternal morbidity rates for vaginal delivery, elective C-section, and urgent C-section were from the Women and Infants Transmission Study conducted in 1186 HIV-infected pregnant women in the United States [23], which recorded higher morbidity rates than have been reported for HIV-uninfected women [37,38]; the corresponding maternal mortality rates were derived from a published decision analysis of C-section in HIV-infected women in the United States [6].
The rates of vertical HCV transmission for vaginal and C-section deliveries in HIV-infected women were taken from the European Paediatric Hepatitis C Virus Network pooled retrospective analysis of prospectively collected data from 1474 HCV-infected women, of whom 503 were coinfected with HIV and HCV [17]. HCV transmission was considered to have occurred if the child was HCV antibody positive beyond 18 months and/or had at least two positive qualitative polymerase chain reaction tests on two separate occasions. This study found a significant benefit of C-section on HCV transmission, with an adjusted odds ratio of 0.36. Because this study did not distinguish between elective and urgent C-section, a single transmission rate of 8.2% for both types of C-section was used (versus a 17.3% transmission rate for vaginal delivery). This is a conservative assumption because of the lower risk of maternal blood exposure with elective C-section versus urgent C-section [29].
Cost-effectiveness parameters
The costs of vaginal delivery, elective C-section, and urgent C-section in the United States were estimates of the costs of providing these services (rather than charges for the services) as recommended by the Panel on Cost-Effectiveness in Health and Medicine (Table 1) [39]. Non-obstetric costs for the mother, including costs of HIV and HCV treatment, were excluded from the analysis because they were assumed to be unaffected by the C-section recommendation. Hospital costs were from the University HealthSystem Consortium and physician costs were from the Medicare physician fee schedule for 2003 [31,32].
The quality-of-life decrement to the mother from undergoing a C-section or experiencing delivery complications was assumed to be the equivalent of the loss of 1 week of life [6]. These assumptions were varied in sensitivity analyses from no decrement to 3 months. The quality-adjusted life expectancy (QALE) for women with HIV/HCV coinfection was from a previously published study and was varied in sensitivity analysis by 50% [33]. The quality-of-life decrement for HCV-infected versus HCV-uninfected infants was determined by comparing their QALE values. The QALE and HCV treatment costs for HCV-infected infants were derived from estimates for a 40-year-old adult chronically infected with type 1 HCV (19.4 discounted QALYs and $22 000 discounted lifetime treatment costs, assuming treatment with pegylated alfa-interferon and weight-based ribavirin dosing) [34]. Because symptomatic liver disease is rare in chronically HCV-infected children [26], a conservative assumption was made that the health effects of HCV infection would not become evident and treatment would not be initiated until age 40. For uninfected infants, QALE was determined using an estimate of life expectancy for newborns [35] and age- and sex-adjusted quality-of-life estimates from the Beaver Dam Health Outcomes Study [36].
To reflect the fact that HCV patients may be located in higher- or lower-cost practice settings, sensitivity analyses were conducted in which all costs were simultaneously increased or decreased by 50%. All costs are reported in 2003 US dollars. Costs and QALYs were discounted at 3% per year and a societal perspective was adopted [39]. Maternal and child QALYs were combined in the calculation of the cost-effectiveness ratio, taking the viewpoint that from a societal perspective the value of a life year is not dependent on age [39].
Sensitivity analyses
Probability distributions were derived from published confidence intervals or estimated ranges, or calculated using reported sample sizes (Table 1). In univariate cohort analyses, each of the parameters was varied from the highest to the lowest 95% confidence interval values of the distributions. For the difference in HCV transmission rates between C-section and vaginal delivery, this resulted in a parameter range of a reduction of 5 to 14 percentage points (versus 9 points in the base case). In addition, the maternal acceptance of the recommendation for C-section was varied between 5 and 100%, because the acceptability of the recommendation may be different for preventing HCV transmission than for preventing HIV transmission. The impact of using C-section rates recently reported for a sample of HIV-infected women in the United States that included women with both detectable and undetectable HIV RNA was also examined [2]. Because these C-section rates are higher than those used in the base-case analysis, the incremental benefit of a recommendation for C-section to prevent perinatal HCV transmission would be expected to be smaller than in the base case. When the probability of mode of delivery was varied for one type of delivery, the probabilities for the remaining two modes of delivery were assumed to be in proportion to their occurrence in the base case. To account for multivariate effects, a probabilistic sensitivity analysis was conducted using 1000 second-order Monte Carlo cohort simulations in which the variable values were drawn from each of the probability distributions.
Results
Hepatitis C perinatal transmission and maternal mortality
In the base-case analysis, elective C-section for coinfected women with suppressed HIV RNA but detectable HCV RNA avoided 45 vertical HCV transmissions per 1000 deliveries and increased maternal mortality by one death per 100 000 deliveries (Table 2). In univariate sensitivity analyses, the results were sensitive to the efficacy of C-section in preventing transmission, the probability of C-section occurring in the absence of a recommendation, and the rates of maternal acceptance of the recommendation. The number of vertical transmissions avoided per 1000 deliveries varied from 23 to 67, depending on the rates of HCV transmission tested in the sensitivity analysis using the confidence intervals in the original study. Results were not sensitive to the probability of elective C-sections occurring in the absence of a recommendation, based on the confidence intervals that were estimated from the European Mode of Delivery Collaboration data [29]. Using the probability of C-section of 48% recently reported in the United States for HIV-infected pregnant women [2] and assuming that 14.5% of these procedures are urgent C-sections, as occurred in the European study, the number of transmissions avoided declined to 30 per 1000 deliveries. As maternal acceptance of the recommendation for C-section increased from 5 to 100%, the number of vertical transmissions avoided per 1000 deliveries increased from 3 to 56, and the maternal mortality increased from 0 to 2 per 100 000 deliveries. None of the other univariate analyses indicated that results were sensitive to the parameter ranges that were tested.
In probabilistic sensitivity analysis, the trade-offs between number of HCV transmissions avoided and maternal mortality per 100 000 deliveries that resulted from the Monte Carlo simulations were examined (Fig. 2). In the base case, the ratio of additional maternal deaths per 1000 HCV transmissions avoided was 1/45, or 0.02. Of the 1000 Monte Carlo simulations, 65% resulted in ≤ 1 additional maternal death per 1000 HCV transmissions avoided and 80% resulted in ≤ 2 additional maternal deaths per 1000 HCV transmissions avoided.
Cost-effectiveness analysis
In the cost-effectiveness analysis, two scenarios regarding the outcomes of maternal-child HCV transmission were examined (Table 3). The probability of developing chronic HCV infection after mother-to-child HCV transmission was assumed to be 50% in the first scenario and 75% in the second scenario, reflecting the current uncertainty about HCV infection outcomes in these children [26]. In the first scenario, a recommendation for C-section resulted in an increase in 0.24 QALY per child and a loss of 0.02 QALY per mother, for a net gain of 0.22 QALY (Table 3). At an incremental cost of $1300, the incremental cost- effectiveness ratio was $6100/QALY. In the second scenario, a recommendation for C-section resulted in an increase in 0.36 QALY per child and a loss of 0.02 QALY per mother (the same for the mother as in the first scenario); incremental costs were $1300, and the incremental cost-effectiveness ratio was $3900/QALY. Using the probability of elective Cesarean delivery derived from United States data on HIV-infected pregnant women, the cost-effectiveness ratios in the two scenarios were $5800/QALY and $3800/QALY, respectively. In the high-cost practice setting, the cost-effectiveness ratios in the two scenarios were $9100/QALY and $5900/QALY, and in the low-cost practice setting they were $3100/QALY and $2000/QALY. Sensitivity analyses that varied maternal QALE and the maternal quality-of-life decrement associated with C-section did not have an impact on these ratios.
Discussion
Our results indicate that elective C-section would provide substantial clinical benefits at a reasonable cost for coinfected pregnant women with suppressed HIV RNA but detectable HCV RNA. Assuming 2000 pregnancies per year among HIV/HCV-coinfected women in the United States, a recommendation for elective C-section could avoid up to 90 perinatal HCV transmissions per year and incur a risk of one additional maternal death in 50 years. The incremental cost-effectiveness ratio associated with this recommendation would be $3900-6100/QALY compared with standard care. This is well below the median reported in a review of cost-effectiveness ratios for clinical preventive services from studies published in 1976-1997, which was $14 000/QALY (in 1998 US dollars) [40]. A study recently presented at a national meeting concluded that, if elective C-section reduced the risk of perinatal HCV transmission by 40% in all HCV-infected women, the cost-effectiveness ratio of this intervention would be less than $50 000/QALY [41].
Previous analyses that included elective C-section as a strategy to prevent perinatal transmission of other infectious diseases have described similar trade-offs. In an analysis of the costs and benefits of elective C-section to prevent perinatal HIV transmission in women with detectable HIV RNA, Mrus and colleagues [6] projected that 58 HIV transmissions would be avoided per year with a risk of one additional maternal death in 20 years Subsequently, a recommendation for C-section in these HIV-detectable women became the standard of care in the United States [9]. Randolph and colleagues [42] described a similar trade-off for elective C-section to prevent neonatal herpes simplex virus (HSV) transmission in women with genital HSV lesions at delivery without a history of genital HSV. They projected that C-section would prevent 18 perinatal HSV infections per year and incur a risk of one additional maternal death in 100 years. The HIV and HSV trade-off results are not directly comparable with the results of the analysis of C-section to prevent HCV transmission, however, because the health consequences for HCV-infected children are different from the consequences for HIV-infected children or HSV-infected children.
While our study is intended to provide insight into a strategy that could potentially prevent HCV transmission, several limitations of our analysis deserve emphasis. First, the probabilities of acceptance of the recommendation for elective C-section and the resulting modes of delivery are derived from a study of elective C-section to prevent HIV transmission that was conducted in Europe [29] and may differ from those in the United States. Second, the data source for the effectiveness of C-section in preventing HCV transmission did not distinguish between elective and urgent C-section results [17]. Third, our analysis did not incorporate the potential impact of antiretroviral treatment (prescribed for HIV disease) in lowering the risk of HCV transmission, because this effect is unknown for HIV/HCV-coinfected mothers with detectable HCV RNA. Future studies may show an HCV transmission benefit, particularly for mothers who have been receiving effective antiretroviral therapy for a long period of time. This would reduce the estimated number of perinatal transmissions avoided by C-section. Fourth, the estimate of HIV/HCV-coinfected pregnant women in the United States is imprecise, because we used infection with HIV through injection drug use as a proxy for HCV infection. Not all of these pregnancies could actually benefit from a recommendation for C-section, because our results are only relevant for mothers receiving adequate prenatal care, who have been documented to have achieved HIV RNA suppression, and who have the opportunity to schedule an elective C-section. Fifth, while the cost-effectiveness ratio allows a direct comparison with other preventive interventions, it assumes equivalence between QALY values for pregnant women and their offspring. Societal preferences may be inconsistent with this assumption [43]. We stress the importance of considering a wide range of factors in addition to the results of our analysis in developing clinical recommendations for HIV/HCV-coinfected women.
Elective C-section is already recommended for pregnant women whose HIV RNA is detectable. A recommendation for elective C-section among HIV/HCV-coinfected women could avoid an additional 90 perinatal HCV transmissions per year in the United States with a risk of one maternal death in 50 years, and this policy has a cost-effectiveness ratio lower than for most clinical preventive services. Our results indicate that elective C-section should be offered to HIV/HCV-coinfected pregnant women with undetectable HIV RNA but detectable HCV RNA.
Sponsorship: Dr Schackmann was supported in part by KO1 DA017179 from the National Institute on Drug Abuse/NIH, and Dr Goldie was supported in part by R01-A142006-08 from National Institutes of Health, USA.
References
1. Lindegren ML, Byers RH, Jr, Thomas P, Davis SF, Caldwell B, Rogers M, et al. Trends in perinatal transmission of HIV/AIDS in the United States. JAMA 1999, 282:531-538.
2. Dominguez KL, Lindegren ML, D'Almada PJ, Peters VB, Frederick T, Rakusan TA, et al. Increasing trend of Cesarean deliveries in HIV-infected women in the United States from 1994 to 2000. J Acquir Immune Defic Syndr 2003, 33:232-238.
3. Ratcliffe J, Ades AE, Gibb D, Sculpher MJ, Briggs AH. Prevention of mother-to-child transmission of HIV-1 infection: alternative strategies and their cost-effectiveness. AIDS 1998, 12: 1381-1388.
4. Halpern MT, Read JS, Ganoczy DA, Harris DR. Cost-effectiveness of cesarean section delivery to prevent mother-to-child transmission of HIV-1. AIDS 2000, 14:691-700.
5. Chen KT, Sell RL, Tuomala RE. Cost-effectiveness of elective cesarean delivery in human immunodeficiency virus-infected women(1). Obstet Gynecol 2001, 97:161-168.
6. Mrus JM, Goldie SJ, Weinstein MC, Tsevat J. The cost-effectiveness of elective Cesarean delivery for HIV-infected women with detectable HIV RNA during pregnancy. AIDS 2000, 14: 2543-2552.
7. Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA, 3rd, Whitehouse J, et al. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med 1999, 341:385-393.
8. Garcia PM, Kalish LA, Pitt J, Minkoff H, Quinn TC, Burchett SK, et al. Maternal levels of plasma human immunodeficiency virus type 1 RNA and the risk of perinatal transmission. Women and Infants Transmission Study Group. N Engl J Med 1999, 341: 394-402.
9. American College of Obstricians and Gynecologists Committee Opinion. Scheduled Cesarean delivery and the prevention of vertical transmission of HIV infection. Int J Gynaecol Obstet 2001, 73:279-281. [Committee Opinion No. 234, May 2000, which replaces No. 219, August 1999.]
10. Public Health Service Task Force.
Recommendations for Use of Antiretroviral Drugs In Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States. Washington, DC: Public Health Service Task Force; 2003. Available at
www.AIDSinfo.nih.gov. 11. Coll O, Fiore S, Floridia M, Giaquinto C, Grosch-Worner I, Guiliano M, et al. Pregnancy and HIV infection: a European consensus on management. AIDS 2002, 16(Suppl 2):S1-S18.
12. Thomas SL, Newell ML, Peckham CS, Ades AE, Hall AJ. A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection. Int J Epidemiol 1998, 27:108-117.
13. Yeung LT, King SM, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001, 34:223-229.
14. Roberts EA, Yeung L. Maternal-infant transmission of hepatitis C virus infection. Hepatology 2002, 36:S106-S113.
15. National Institutes of Health. National Institutes of Health Consensus Development Conference Statement: management of hepatitis C, 2002. Hepatology 2002, 36:S3-S21.
16. Gibb DM, Goodall RL, Dunn DT, Healy M, Neave P, Cafferkey M, et al. Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission. Lancet 2000, 356:904-907.
17. European Paediatric Hepatitis C Virus Network. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. Br J Obstet Gynaecol 2001, 108:371-377.
18. American Academy of Pediatrics. Committee on Infectious Diseases. Hepatitis C virus infection. Pediatrics 1998, 101:481-485.
19. Byers RH, Jr, Caldwell MB, Davis S, Gwinn M, Lindegren ML. Projection of AIDS and HIV incidence among children born infected with HIV. Stat Med 1998, 17:169-181.
20. Sulkowski MS, Mast EE, Seeff LB, Thomas DL. Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000, 30: S77-S84.
21. Bozzette SA, Berry SH, Duan N, Frankel MR, Leibowitz AA, Lefkowitz D, et al. The care of HIV-infected adults in the United States. HIV Cost and Services Utilization Study Consortium. N Engl J Med 1998, 339:1897-1904.
22. Chu SY, Hanson DL, Jones JL. Pregnancy rates among women infected with human immunodeficiency virus. Adult/Adolescent HIV Spectrum of Disease Project Group. Obstet Gynecol 1996, 87:195-198.
23. Read JS, Tuomala R, Kpamegan E, Zorrilla C, Landesman S, Brown G, et al. Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study. J Acquir Immune Defic Syndr 2001, 26:236-245.
24. Grubert TA, Reindell D, Kastner R, Belohradsky BH, Gurtler L, Stauber M, et al. Rates of postoperative complications among human immunodeficiency virus-infected women who have undergone obstetric and gynecologic surgical procedures. Clin Infect Dis 2002, 34:822-830.
25. Fiore S, Thorne C, for the European Collaborative Study. Complications after delivery in HIV infected and uninfected women in Europe. XIV International Conference on AIDS. Barcelona, July 2002 [abstract TuPeC4762].
26. Jonas MM. Children with hepatitis C. Hepatology 2002, 36:S173-S178.
27. Yeargin P, Donnelly R, Weyer D (eds). Clinical Management of the HIV-Infected Adult, A Manual for Clinicians. Atlanta, GA: Southeast and Midwest AIDS Training and Education Centers; 2003.
28. Cooper CL, Cameron DW. Review of the effect of highly active antiretroviral therapy on hepatitis C virus (HCV) RNA levels in human immunodeficiency virus and HCV coinfection. Clin Infect Dis 2002, 35:873-879.
29. The European Mode of Delivery Collaboration. Elective Caesarean-section versus vaginal delivery in prevention of vertical HIV-1 transmission: a randomised clinical trial. Lancet 1999, 353:1035-1039.
30. Newell ML, Parazzini F, Mandelbrot L, Peckham C, Semprini A, Bazin B, et al. A randomised trial of mode of delivery in women infected with the human immunodeficiency virus. Br J Obstet Gynaecol 1998, 105:281-285.
31. University HealthSystem Consortium.
CDP Online Report: University HealthSystem Consortium 2003. Available at
www.uhc.edu (accessed 4 April 2003).
33. Kuehne FC, Bethe U, Freedberg K, Goldie SJ. Treatment for hepatitis C virus in human immunodeficiency virus- infected patients: clinical benefits and cost-effectiveness. Arch Intern Med 2002, 162:2545-2556.
34. Salomon JA, Weinstein MC, Hammitt JK, Goldie SJ. Cost-effectiveness of treatment for chronic hepatitis C infection in an evolving patient population. JAMA 2003, 290:228-237.
35. Arias E. United States life tables, 2000. Natl Vital Stat Rep 2002, 51:1-38.
36. Fryback DG, Dasbach EJ, Klein R, Klein BE, Dorn N, Peterson K, et al. The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making 1993, 13: 89-102.
37. Grubert TA, Reindell D, Kastner R, Lutz-Friedrich R, Belohradsky BH, Dathe O. Complications after caesarean section in HIV-1-infected women not taking antiretroviral treatment. Lancet 1999, 354:1612-1613.
38. Hebert PR, Reed G, Entman SS, Mitchel EF, Jr, Berg C, Griffin MR. Serious maternal morbidity after childbirth: prolonged hospital stays and readmissions. Obstet Gynecol 1999, 94: 942-947.
39. Gold MR, Siegel JE, Russell LB, Weinstein MC (eds). Cost Effectiveness in Health and Medicine. New York: Oxford University Press; 1996.
40. Stone PW, Teutsch S, Chapman RH, Bell C, Goldie SJ, Neumann PJ. Cost-utility analyses of clinical preventive services: published ratios, 1976-1997. Am J Prev Med 2000, 19:15-23.
41. Plunkett B, Grobman W. Elective cesarean delivery to prevent perinatal transmission of hepatitis c virus: a cost-effectivenenss analysis. Am J Obstet Gynecol 2003, 189:S97.
42. Randolph AG, Washington AE, Prober CG. Cesarean delivery for women presenting with genital herpes lesions. Efficacy, risks, and costs. JAMA 1993, 270:77-82.
43. Ubel PA, Nord E, Gold M, Menzel P, Prades JL, Richardson J. Improving value measurement in cost-effectiveness analysis. Med Care 2000, 38:892-901.
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