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The Effectiveness of Screening for Hepatitis C in Pregnancy
OBSTETRICS OBSTETRICS
The Effectiveness of Screening for Hepatitis C in Pregnancy Colleen D. McDermott, MD, MSc, Catherine C. Moravac, BSc, Mark H. Yudin, MD, MSc University of Toronto, St. Michael’s Hospital, Department of Obstetrics and Gynaecology, Toronto ON
Abstract Objective: To determine the effectiveness of universal versus targeted screening for hepatitis C (HCV) during pregnancy at an urban health care centre. Methods: We conducted a cross-sectional study of 653 pregnant women. Patients completed a demographic and standardized questionnaire identifying known risk factors for HCV. Patients then underwent blood testing for HCV antibodies. The effectiveness of screening based on risk factors was determined by comparing the number of women who screened positive for HCV risk factors with those who tested seropositive. Results: Of those who entered the study, 0.5% (3/645) tested positive for HCV. HCV risk factor screening showed that 72% answered Yes to one or more risk factors and 28% answered No to all risk factors. Answering Yes to any risk factor was not associated with testing positive for HCV antibodies (P > 0.05). Screening positive for a high severity risk factor (exposure to intravenous drug use or to the blood of an HCV-positive individual) was associated with testing positive for HCV antibodies (P = 0.002), but screening positive for a moderate or low severity risk factor was not (P > 0.05). Conclusion: During pregnancy, universal testing for HCV and testing based on the presence of any risk factors for HCV is not recommended. HCV testing based on the presence of high severity risk factors, however, may be warranted.
Résumé Objectif : Déterminer l’efficacité du dépistage universel de l’hépatite C (VHC), par comparaison avec le dépistage ciblé, pendant la grossesse au sein d’un centre de soins urbain. Méthodes : Nous avons mené une étude transversale auprès de 653 femmes enceintes. Les patientes ont rempli un questionnaire démographique et standardisé identifiant les facteurs de risque connus en ce qui concerne le VHC. Les patientes ont par la suite subi une analyse sanguine visant les anticorps du VHC. L’efficacité du dépistage en fonction des facteurs de risque a été déterminée en comparant le nombre de femmes qui ont obtenu des résultats positifs dans le cadre du dépistage des facteurs de risque du VHC au nombre de celles qui se sont avérées séropositives. Résultats : Parmi les femmes qui ont participé à l’étude, 0,5 % (3/645) ont obtenu un résultat positif pour ce qui est du VHC. Le dépistage des facteurs de risque du VHC a indiqué que 72 % des participantes
Key Words: Hepatitis C, pregnancy, prevalence, screening Competing Interests: None declared. Received on May 27, 2010 Accepted on July 27, 2010
ont répondu « Oui » pour ce qui est d’un ou de plusieurs facteurs de risque et que 28 % ont répondu « Non » pour ce qui est de tous les facteurs de risque. Le fait de répondre « Oui » pour ce qui est de quelque facteur de risque que ce soit n’a pas été associé à l’obtention de résultats positifs au dépistage des anticorps du VHC (P > 0,05). Le fait d’obtenir des résultats positifs au dépistage d’un facteur de risque de gravité élevée (exposition à des drogues intraveineuses ou au sang d’une personne séropositive pour le VHC) a été associé à l’obtention de résultats positifs au dépistage des anticorps du VHC (P = 0,002); cependant, le fait d’obtenir des résultats positifs au dépistage d’un facteur de risque de gravité modérée ou faible ne présentait pas une telle association (P > 0,05). Conclusion : Pendant la grossesse, le dépistage universel du VHC et le dépistage en fonction de la présence de quelque facteur de risque du VHC que ce soit ne sont pas recommandés. Toutefois, le recours au dépistage du VHC en fonction de la présence de facteurs de risque de gravité élevée pourrait être justifié. J Obstet Gynaecol Can 2010;32(11):1035–1041
INTRODUCTION
he hepatitis C virus is a single-stranded enveloped RNA virus that is transmitted by exposure to contaminated blood and blood products. HCV is the most common cause of chronic viral hepatitis and is closely ranked behind alcohol use as a major etiologic agent in cirrhosis, end-stage liver disease, and hepatocellular carcinoma.1 In 1999, the World Health Organization estimated that 170 million people were infected with HCV worldwide, representing 3% of the global population.2
T
There are no apparent deleterious effects of pregnancy on the course of HCV infection and there does not appear to be an increase in adverse pregnancy outcomes in HCV-infected women. Mother-to-infant transmission of HCV has a reported range of 0% to 35%, with an average crude rate of 5.6%.3 Vertical transmission rates are significantly higher for HIV-positive patients and intravenous drug users.3 Universal blood testing for HCV in pregnancy has not been recommended by the Public Health Agency of Canada or the Centers for Disease Control and Prevention in the United States because of the relatively low prevalence in the general population and the absence of documented NOVEMBER JOGC NOVEMBRE 2010 l 1035
OBSTETRICS
measures capable of influencing maternal-fetal transmission. Pregnancy, however, may be an important time to screen for HCV infection. Many women will already have reached their peak likelihood of becoming infected by the time they become pregnant, making the yield of testing near its maximum.4 Screening at this point in a woman’s life can also provide early diagnosis and treatment that may offset the future burden of HCV on the health care system.4 Further, testing for HCV during pregnancy may help to identify infected newborns, allowing for appropriate follow-up. Alternatively, targeted screening for specific HCV risk factors has been recommended by the Public Health Agency of Canada and the Centers for Disease Control and Prevention. It is currently recommended that individuals with one or more of these identified risk factors should be offered HCV serum screening.5 In HCV seroprevalence studies among inner city antenatal populations, however, targeted screening using HCV risk factors did not identify approximately half of the anti-HCV positive women.6,7 It has therefore been suggested that targeted screening for HCV among pregnant patients in higher risk populations may not be appropriate and that universal HCV blood testing, particularly in urban centres, may be warranted. The primary objective of the present study was to identify the clinical utility of targeted screening compared to universal blood testing for HCV among pregnant women attending a women’s health care centre in Toronto. Secondary objectives included determining HCV seroprevalence in this urban population and identifying risk factors that were most predictive of testing positive for HCV antibodies. METHODS
This was a cross-sectional study of pregnant women who presented to the Women’s Health Care Centre at St Michael’s Hospital in Toronto between September 1, 2005, and April 30, 2007. St Michael’s is a university hospital and the Women’s Health Care Centre is part of the hospital’s Inner City Health Program. As such, the centre’s patient population is very ethnically and socially diverse. All obstetric patients 15 years of age or older and presenting to this centre for antenatal care were eligible for the study. Patients who were under the age of 15 years, who could not read or understand English, or who had no access to an interpreter were excluded from the study.
ABBREVIATIONS HCV
hepatitis C virus
IVDU
intravenous drug user
1036 l NOVEMBER JOGC NOVEMBRE 2010
A study nurse approached eligible patients presenting for their first antenatal visit at the Women’s Health Care Centre. This nurse described the study, distributed an information pamphlet on HCV, and reviewed the study consent form with the patient. Those consenting to the study were asked to complete a demographic questionnaire and an HCV screening questionnaire on which they answered “Yes” or “No” to the presence of specific risk factors for HCV. Risk factors listed included IVDU, intercourse with an IVDU, receipt of a blood transfusion or solid organ transplant prior to 1992, receipt of blood components or solid organs from HCV-positive donors, significant exposure to the blood of an HCV-positive individual, receipt of clotting factors prior to 1988, hemodialysis treatment, persistently elevated liver enzymes, time spent in a correctional facility, children of HCV-infected mothers, HIV-positive individuals, and tattoo history.5 These were all listed because, according to the Public Health Agency of Canada, pregnant women with one or more of these risk factors should be considered for HCV blood testing. Patients were also asked to indicate the number of body piercings present, if they had ever inhaled illicit drugs, and if they would agree or disagree to universal blood testing for HCV during pregnancy. After completing the two questionnaires, participants were sent to the laboratory for blood testing. Each patient recruited to the study was screened for antibodies to HCV by means of an enzyme-linked immunosorbent assay (third generation ELISA, Abbott Diagnostics, Saint-Laurent, QC). For those who tested positive, a second screening test was performed for confirmation (third generation ELISA, Bio Rad Laboratories Ltd, Montréal, QC). If both of these tests were non-confirmatory, a confirmation recombinant immunoblot assay was done (RIBA, Innogenetics NV, Gent, Belgium). All of the above tests were ordered through a standardized provincial request form for antenatal tests including HCV, and testing was carried out at the Provincial Reference Laboratory. Questionnaires were collected and responses from the demographic and HCV screening questions were entered into a numeric database by one of the study investigators. Results from each participant’s HCV blood test were also entered into the database. Responses to the 14 HCV screening questions were combined to create a variable that indicated the number of positive risk factors. The number of positive risk factors was categorized into none or at least one, and sensitivity, specificity, and negative and positive predictive values for HCV antibodies were estimated. The association between answering “Yes” to at least one screening question and testing positive for HCV antibodies was evaluated using Fisher exact tests, with P < 0.05 considered statistically significant.
The Effectiveness of Screening for Hepatitis C in Pregnancy
The associations between answering “No” to all risk factors and demographic variables were analyzed using the two-sample t test for continuous variables and chi-square test for categorical variables, with P < 0.05 considered statistically significant. Risk factor analysis was then stratified according to the number of positive responses: positive for no risk factors, positive for one risk factor, and positive for two or more risk factors. The associations between these groupings of the number of positive risk factors and testing positive for HCV antibodies were determined using Fisher exact tests, with P < 0.05 considered statistically significant. Risk factors were also stratified according to severity. The index of severity was created by the study investigators and was based on clinical knowledge and judgment. The “high severity risk factor” category included IVDU, intercourse with an IVDU, and receipt of or significant exposure to the blood of an HCV-positive individual. The “moderate severity risk factor” category included being HIV positive, having spent time in a correctional facility, having an HCV-positive mother, receipt of a blood transfusion or solid organ transplant prior to 1992, receipt of clotting factors prior to 1988, and hemodialysis treatment. The “low severity risk factor” category included persistently elevated liver enzymes, history of tattoo, body piercings, and inhalation of illicit drugs. Once again, the associations between these groupings of risk factor severity and testing positive for HCV antibodies were determined using Fisher exact tests, with P < 0.05 considered statistically significant.
Table 1. Demographic details Variable
n (%)*
Age, years 25 (4) 277 (43) 332 (51) 16 (2)
15 to 20 21 to 30 31 to 40 ³ 41 Marital Status Single Married Separated/divorced Common law
106 (16) 498 (77) 9 (2) 32 (5)
Pregnancy 367 (60) 178 (29) 56 (9) 13 (2)
1 2 3 ³4 Income £ $20 000 $21 000 to $40 000 $41 000 to $60 000 ³ $61 000
99 (16.4) 119 (19.7) 70 (11.6) 315 (52.3)
Housing type 298 (47) 83 (13) 249 (39) 7 (1)
House Condominium Apartment Shelter People in household
10 (2) 323 (51) 181 (28) 77 (12) 45 (7)
1 2 3 4 ³5 Origin
This study was approved by the St Michael’s Hospital Research Ethics Board.
Immigrant Non-immigrant
361 (56) 283 (44)
Race
RESULTS
During the recruitment period 653 women consented to participate in the study. Of these women, eight refused HCV blood testing and three of the remaining 645 women tested positive for HCV antibodies on screening, indicating a sample prevalence of 0.5% (95% confidence interval 0.1% to 1.4%). Study participant demographics are presented in Table 1. Participants ranged in age from 15 to 43 years (mean 30.7 ± 5.1 years). The majority (77%) were married, in their first pregnancy (60%), or had an annual income ³ $61 000 (52%); 47% lived in a house. The mean number of people living per household was 2.8 ± 1.1. Among those surveyed, 56% were immigrants and the most self-identified races were Caucasian (36%), Asian (20%), and Hispanic (15%). Most were non-smokers (95%), although 23% of participants smoked prior to the current pregnancy.
227 (36) 127 (20) 94 (15) 62 (10) 28 (5) 28 (5) 26 (4) 2 (2) 18 (3)
Caucasian Asian Hispanic European West Indian East Indian African Native Other Smoking Current: yes no
35 (5) 618 (95)
Past:
147 (23) 506 (77)
yes no
Alcohol/week pre-pregnancy 0 1 2 3 ³4
350 (58) 74 (12) 69 (11) 39 (6) 78 (13)
*Denominator changes due to missing data from questionnaires.
NOVEMBER JOGC NOVEMBRE 2010 l 1037
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Table 2. HCV screening risk factors Risk factor
HCV seropositive n (%)*
HCV seronegative n (%)*
P
2/3 (67)
3/637 (< 1)
< 0. 001
1/2 (50)
12/640 (2)
0.04
0/2 (0)
6/639 (1)
> 0.99
0/2 (0)
0/640 (0)
Test not applicable
1/2 (50)
1/640 (< 1)
0.006
0/2 (0)
0/640 (0)
Test not applicable
0/2 (0)
0/640 (0)
Test not applicable
1/2 (50)
9/640 (1)
0.03
0/2 (0)
4/638 (1)
> 0.99
0/2 (2)
1/639 (1)
> 0.99
0/3 (0)
2/639 (1)
> 0.99
2/3 (67)
101/642 (16)
0.07
2/3 (67)
424/642 (66)
> 0.99
1/2 (50)
79/639 (12)
0.2
IVDU Yes Intercourse with IVDU Yes Transfusion/transplant before 1992 Yes Blood/organs from HCV-positive donor Yes Exposure to HCV-positive blood Yes Clotting factors before 1988 Yes Hemodialysis treatment Yes Elevated liver enzymes Yes Time in correctional facility Yes HCV-positive mother Yes HIV positive Yes Tattoos Yes Body piercings Yes Inhaled illicit drugs Yes
*Denominator changes due to missing data from questionnaires.
Three patients were found to be HCV seropositive. The first patient to be detected positive for HCV antibodies was 29 years of age, single, gravida 1, para 0, had immigrated to Canada in 1998 from Rwanda, earned £ $20 000 per annum, lived alone in an apartment, did not consume any alcohol prior to pregnancy, had always been a non-smoker, and was unaware of her HCV status prior to this testing. The second patient detected was 19 years of age, single, gravida 2, para 0, Canadian-born and Caucasian, earned £ $20 000 per annum, lived with one other person in an apartment, continued to smoke during her pregnancy, and was aware of her HCV status prior to this testing. The third patient detected positive on blood testing was 22 years of age, in a common1038 l NOVEMBER JOGC NOVEMBRE 2010
law relationship, gravida 1, para 0, had immigrated to Canada in 1998 from an undocumented country, earned £ 20 000 per annum, lived with one other person in an apartment, did not consume any alcohol prior to pregnancy, had always been a non-smoker, and was also aware of her HCV status prior to this testing. Statistical comparison between HCV-positive and HCV-negative patients was not feasible given the low HCV seroprevalence rate. The results for positive HCV screening based on each risk factor assessment are summarized in Table 2. Results are shown separately for HCV seropositive and seronegative study participants. In total, 469 women (72%) answered “Yes” to at least one HCV screening risk factor and 181
The Effectiveness of Screening for Hepatitis C in Pregnancy
Table 3. Risk factor stratification based on number of positive risk factors HCV seropositive n (%)*
HCV seronegative n (%)*
P
0
1/3 (33)
178/640 (28)
> 0.99
1
0/3 (0)
326/640 (51)
0.4
³2
2/3 (67)
136/640 (21)
0.6
Number of positive risk factor response(s)
*Denominator changes due to missing data from questionnaires.
Table 4. Risk factor stratification based on severity HCV seronegative n (%)*
P
2/3 (67)
14/640 (2)
0.002
1/3 (33)
626/640 (98)
Moderate‡
0/3 (0)
13/640 (2)
Yes
3/3 (100)
627/640 (98)
2/3 (67)
459/640 (72)
1/3 (33)
181/640 (28)
Risk factor severity High† Yes
HCV seropositive n (%)*
No > 0.99
No Low§ Yes
> 0.99
No *Denominator changes due to missing data from questionnaires. †High risk factors: IVDU, intercourse with an IVDU, and receipt of or exposure to blood of an HCV-positive individual. ‡Moderate risk factors: HIV positive, time in a correctional facility, HCV-positive mother, blood transfusion or solid organ transplant before 1992, clotting factors before 1988, and hemodialysis treatment. §Low risk factors: elevated liver enzymes, history of tattoo, body piercings, and inhalation of illicit drugs.
women (28%) responded “No” to all HCV risk factors. There was a statistically significant association between being positive for HCV antibodies on blood testing and a positive response to IVDU (P < 0. 001), ever having intercourse with an IVDU (P = 0.04), having elevated liver enzymes (P = 0.03), or having a history of exposure to HCV-positive blood (P = 0.006). Overall, a positive response to at least one risk factor had a sensitivity of 67%, a specificity of 28%, a positive predictive value of 0.4%, and a negative predictive value of 99% for identifying patients with HCV. Women who responded “No” to all risk factors were more likely to be older (mean age 32 vs. 30, P < 0.001), to be non-smokers (88% vs. 73%, P < 0.001), and to drink significantly less prior to pregnancy (5% vs. 11% consuming ³ four drinks per week, P = 0.002).
Risk factor stratification according to the number of positive screening responses for both HCV seropositive and seronegative women is presented in Table 3. There was no correlation between the number of positive risk factors (positive for no risk factor, one risk factor, or two or more risk factors) and the likelihood of being HCV positive (P > 0.05). Risk factor assessment according to the level of severity for HCV seropositive and seronegative women is summarized in Table 4. There was a statistically significant association between testing positive for HCV antibodies and having a positive response to a high severity risk factor (P = 0.002). However, responding “Yes” to a moderate or low severity risk factor was not significantly associated with testing positive for HCV (P > 0.99 for both risk groups). A positive response to a high severity risk factor conferred a sensitivity of 67%, a specificity of 98%, a positive predictive value of 13%, and a negative predictive value of > 99% for identifying patients with HCV. At the end of the HCV screening questionnaire, participants were asked if they would agree or disagree with a policy of universal blood testing for HCV during pregnancy. A total of 582 women (92%) stated that they would agree to this type of testing during pregnancy, indicating a high degree of acceptance. DISCUSSION
This study showed that universal blood testing for HCV in pregnancy was not an appropriate use of health care resources in this urban population. In addition, pregnant women who were positive for any HCV risk factor were not at significant risk of being HCV seropositive. Stratifying risk factors by number of positive responses to screening questions was also not predictive of HCV positivity. These findings suggest that performing antenatal HCV blood testing in pregnant women who simply have a positive response to any of the screening questions may not be a useful strategy. When screening questions were stratified by severity, however, there was a significant association between having a “high severity risk factor” and being HCV positive. When risk factors were assessed individually, these high severity risk factors, as well as having elevated liver enzymes, were also independently associated with being HCV positive. Current recommendations for HCV testing during pregnancy in Canada state that individuals with one or more identified risk factors should be tested for HCV antibodies.5 Previous studies have indicated that this method of screening will fail to identify a significant proportion of infected women, particularly in inner city populations. In an anonymous serosurvey of 599 pregnant women recruited NOVEMBER JOGC NOVEMBRE 2010 l 1039
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from an inner city clinic as well as from a private practice in Philadelphia, Silverman et al. reported that significantly more women in the clinic service (5.2%) were seropositive for HCV than in the private practice (1.5%).6 In this study, substance abuse was the most commonly identified risk factor for HCV, and targeted risk factor screening would have failed to detect half of the HCV-positive women. Ward et al. completed another study at an inner city London obstetric hospital that examined the seroprevalence of HCV in 4825 pregnant women over two years.7 The prevalence of HCV among this multiethnic antenatal population was 0.8%, and no risk factors were identified by a thorough screening history in 50% of these seropositive patients. The results of these studies suggest that targeted screening for HCV in pregnancy may not be an adequate strategy in an inner city population, and that universal blood testing may be more appropriate. The findings of the present study are not consistent with these results. We have demonstrated that targeted HCV blood testing during pregnancy based on any positive responses to documented HCV risk factors is not a useful strategy, but there is an association between testing positive for a high severity risk factor and being HCV seropositive. Therefore, HCV blood testing based on the presence of a high severity risk factor may be a more useful method of identifying women who are truly HCV seropositive. The prevalence of HCV in this population was found to be 0.5%. Although this finding was significantly lower than expected, this is the first study to document the prevalence of HCV in a pregnant population based in Toronto. The global seroprevalence of HCV is estimated to be 3% with significant geographic variation, ranging from 0.01% to 0.1% in the United Kingdom to from 17% to 26% in Egypt.8 The prevalence rates of HCV in pregnancy around the world also vary and are reported at 0.2% to 2.4% in Europe,9–14 1.1% in Australia,15 1.3% in Taiwan,16 2.6% in Japan,17–19 3.2% to 4.5% in the United States,20,21 and 13.7% in Egypt.22 The largest study to date was performed in Italy and found a seroprevalence of 2.4% after following a cohort of 15 250 pregnant women over four years.14 To date there are no published data on the prevalence and incidence of HCV in pregnant women in Canada. The low prevalence of HCV found in this study appears to support the concept that universal blood testing for HCV during pregnancy is not a worthwhile strategy and further justifies testing based on HCV risk factor severity for this pregnant population in Toronto. Despite this low prevalence, 92% of participants in this study noted they would agree to universal HCV blood screening during pregnancy, indicating a high acceptance rate. 1040 l NOVEMBER JOGC NOVEMBRE 2010
The primary limitation of this study was the small sample size of HCV seropositive women. Since only three patients were found to be HCV positive, we were unable to compare the demographic features of HCV-positive women to those of HCV-negative women. The small number of HCVpositive patients also limited the accuracy of sensitivity and specificity calculations for HCV risk factor assessment in relation to HCV seropositivity. It should be noted, however, that our study population was large (n = 653), and identifying only three HCV seropositive patients simply indicated a low prevalence rate in this population. In addition, participants were recruited from a centre that is part of an inner city health program, and, as such, we anticipated a study population of lower socioeconomic status. Instead, demographic data revealed that the majority of women had an annual income of $61 000 or more, almost half lived in a house, and most were either married or in a common-law relationship. This may explain the low prevalence of HCV identified in this setting. Therefore, the results of this study appear to reflect those of a population with a mixed socioeconomic background and may be more applicable to the average urban obstetrical patient population in Canada. Interestingly, of the patients who were found to be HCV positive, all three had annual incomes £ $20 000 and lived in apartments, and two of the three patients were single and immigrants to Canada. Future research efforts in this field should include a costeffectiveness analysis of HCV blood testing in pregnancy based on screening by risk factor severity. A recent study by Plunkett et al.23 investigated the cost-effectiveness of universal HCV blood screening compared to no screening in asymptomatic pregnant women. Using a decision tree with Markov analysis, they found that no screening is a less costly and more effective strategy than the alternate strategy of screening and subsequent treatment of progressive disease. This type of analysis examining HCV screening in pregnancy based on risk factor severity would be of the utmost importance in guiding future clinical practice. In addition, more studies identifying HCV prevalence during pregnancy in other geographic areas throughout Canada would add further insight into the overall disease burden, and would help to establish the true need for national screening and testing for this virus during pregnancy. CONCLUSION
The findings of this study do not support universal blood testing for HCV during pregnancy, nor do they support testing for HCV in women who are positive for any known HCV risk factor in such an urban population. Instead, we have demonstrated and recommend that pregnant women who have an identified risk factor of high severity (IVDU,
The Effectiveness of Screening for Hepatitis C in Pregnancy
intercourse with an IVDU, and receipt of or exposure to HCV-positive blood) should be considered for HCV antibody testing. We have also identified a relatively low seroprevalence of HCV in pregnancy in this urban Canadian population.
11. Hillemanns P, Langenegger P, Langer PC, Knitza R, Hasbargen U, Hepp H. Prevalence and follow-up of hepatitis C virus infection in pregnancy [article in German]. Z Geburtshilfe Neonatol 1998;202:127–30. 12. Ades AE, Parker S, Walker J, Cubitt WD, Jones R. HCV prevalence in pregnant women in the UK. Epidemiol Infect 2000;125:399–405.
ACKNOWLEDGMENTS
13. Balogun MA, Ramsay ME, Parry JV, Donovan L, Andres NJ, Newham JA, et al. The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England. Epidemiol Infect 2000;125:705–12.
The authors wish to thank The Physicians’ Services Incorporated Foundation for funding.
14. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant woman. Hepatology 2000;31:751–5.
REFERENCES
15. Garner JJ, Gaughwin M, Dodding J, Wilson K. Prevalence of hepatitis C infection in pregnant women in South Australia. Med J Aust 1997;166:470–2.
1. Seeff LB. Natural history of hepatitis C. Hepatology 1997;26(3 Suppl 1):21S–28S. 2. World Health Organization and Viral Hepatitis Prevention Board. Global surveillance and control of hepatitis C. J Viral Hepat 1999;6:35–47. 3. Yeung LTF, King SM, Roberts EA. Mother-to-infant transmission of hepatitis C virus. Hepatology 2001;34:223–9. 4. Burns DN, Minkoff H. Hepatitis C: screening in pregnancy. Obstet Gynecol 1999;94:1044–8. 5. Health Canada. Hepatitis C prevention and control: a public health consensus. Can Commun Dis Rep 1999; 25S2:1–22. 6. Silverman NS, Jenkin BK, Wu C, McGillen P, Knee G. Hepatitis C virus in pregnancy: seroprevalence and risk factors for infection. Am J Obstet Gynecol 1993;169:583–7. 7. Ward C, Tudor-Williams G, Cotzias T, Hargreaves S, Regan L, Foster GR. Prevalence of hepatitis C among pregnant women attending an inner London obstetric department: uptake and acceptability of named antenatal testing. Gut 2000;47:277–80. 8. Wasley A, Alter MJ. Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Dis 2000;20:1–16. 9. Salleras L, Bruguera M, Vidal J, Plans P, Dominguez A, Navas E, et al. The seroepidemiology of hepatitis C virus infection in pregnant women in Catalonia. Med Clin (Barc) 1994;103:721–4. 10. Roudot-Thoraval F, Deforges L, Girollet PP, Maria B, Milliez J, Pathier D, et al. Prevalence of hepatitis C virus antibodies (tests ELISA 2 and RIBA 2) in a population of pregnant women in France [article in French]. Gastroenterol Clin Biol 1992;16:255–9.
16. Chang M-H. Mother to infant transmission of hepatitis C virus. Clin Invest Med 1996;19:368–72. 17. Ohto H, Terazawa S, Sasaki N, Sasaki N, Hino K, Ishiwata C, et al.; The Vertical Transmission of Hepatitis C Virus Collaborative Study Group. Transmission of hepatitis C from mothers to infants. New Engl J Med 1994;330:744–50. 18. Moriya T, Sasaki F, Mizui M, Ohno N, Mohri H, Mishiro S, et al. Transmission of hepatitis C virus from mothers to infants: its frequency and risk factors revisited. Biomed Pharmacother 1995;49:59–64. 19. Aizaki H, Saito A, Kusakawa I, Ashiwara Y, Nagamori S, Toda G, et al. Mother-to-child transmission of a hepatitis C virus variant with an insertional mutation in its hypervariable region. J Hepatol 1996;25:608–13. 20. Silverman NS, Snyder M, Hodinka RL, McGillen P, Knee G. Detection of hepatitis C virus antibodies and specific hepatitis C virus ribonucleic acid sequences in cord bloods from a heterogeneous prenatal population. Am J Obstet Gynecol 1995;173:1396–400. 21. Reinus JF, Leikin EL, Alter HJ, Cheung L, Shindo M, Jett B, et al. Failure to detect vertical transmission of hepatitis C virus. Ann Intern Med 1992;117:881–6. 22. Agha S, Sherif LS, Allam MA, Fawzy M. Transplacental transmission of hepatitis C virus in HIV-negative mothers. Res Virol 1998;149:229–34. 23. Plunkett BA, Grobman WA. Routine hepatitis C virus screening in pregnancy: a cost-effectiveness analysis. Am J Obstet Gynecol 2005;192:1153–6.
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The Effectiveness of Screening for Hepatitis C in Pregnancy Colleen D. McDermott, MD, MSc, Catherine C. Moravac, BSc, Mark H. Yudin, MD, MSc University of Toronto, St. Michael’s Hospital, Department of Obstetrics and Gynaecology, Toronto ON
Abstract Objective: To determine the effectiveness of universal versus targeted screening for hepatitis C (HCV) during pregnancy at an urban health care centre. Methods: We conducted a cross-sectional study of 653 pregnant women. Patients completed a demographic and standardized questionnaire identifying known risk factors for HCV. Patients then underwent blood testing for HCV antibodies. The effectiveness of screening based on risk factors was determined by comparing the number of women who screened positive for HCV risk factors with those who tested seropositive. Results: Of those who entered the study, 0.5% (3/645) tested positive for HCV. HCV risk factor screening showed that 72% answered Yes to one or more risk factors and 28% answered No to all risk factors. Answering Yes to any risk factor was not associated with testing positive for HCV antibodies (P > 0.05). Screening positive for a high severity risk factor (exposure to intravenous drug use or to the blood of an HCV-positive individual) was associated with testing positive for HCV antibodies (P = 0.002), but screening positive for a moderate or low severity risk factor was not (P > 0.05). Conclusion: During pregnancy, universal testing for HCV and testing based on the presence of any risk factors for HCV is not recommended. HCV testing based on the presence of high severity risk factors, however, may be warranted.
Résumé Objectif : Déterminer l’efficacité du dépistage universel de l’hépatite C (VHC), par comparaison avec le dépistage ciblé, pendant la grossesse au sein d’un centre de soins urbain. Méthodes : Nous avons mené une étude transversale auprès de 653 femmes enceintes. Les patientes ont rempli un questionnaire démographique et standardisé identifiant les facteurs de risque connus en ce qui concerne le VHC. Les patientes ont par la suite subi une analyse sanguine visant les anticorps du VHC. L’efficacité du dépistage en fonction des facteurs de risque a été déterminée en comparant le nombre de femmes qui ont obtenu des résultats positifs dans le cadre du dépistage des facteurs de risque du VHC au nombre de celles qui se sont avérées séropositives. Résultats : Parmi les femmes qui ont participé à l’étude, 0,5 % (3/645) ont obtenu un résultat positif pour ce qui est du VHC. Le dépistage des facteurs de risque du VHC a indiqué que 72 % des participantes
Key Words: Hepatitis C, pregnancy, prevalence, screening Competing Interests: None declared. Received on May 27, 2010 Accepted on July 27, 2010
ont répondu « Oui » pour ce qui est d’un ou de plusieurs facteurs de risque et que 28 % ont répondu « Non » pour ce qui est de tous les facteurs de risque. Le fait de répondre « Oui » pour ce qui est de quelque facteur de risque que ce soit n’a pas été associé à l’obtention de résultats positifs au dépistage des anticorps du VHC (P > 0,05). Le fait d’obtenir des résultats positifs au dépistage d’un facteur de risque de gravité élevée (exposition à des drogues intraveineuses ou au sang d’une personne séropositive pour le VHC) a été associé à l’obtention de résultats positifs au dépistage des anticorps du VHC (P = 0,002); cependant, le fait d’obtenir des résultats positifs au dépistage d’un facteur de risque de gravité modérée ou faible ne présentait pas une telle association (P > 0,05). Conclusion : Pendant la grossesse, le dépistage universel du VHC et le dépistage en fonction de la présence de quelque facteur de risque du VHC que ce soit ne sont pas recommandés. Toutefois, le recours au dépistage du VHC en fonction de la présence de facteurs de risque de gravité élevée pourrait être justifié. J Obstet Gynaecol Can 2010;32(11):1035–1041
INTRODUCTION
he hepatitis C virus is a single-stranded enveloped RNA virus that is transmitted by exposure to contaminated blood and blood products. HCV is the most common cause of chronic viral hepatitis and is closely ranked behind alcohol use as a major etiologic agent in cirrhosis, end-stage liver disease, and hepatocellular carcinoma.1 In 1999, the World Health Organization estimated that 170 million people were infected with HCV worldwide, representing 3% of the global population.2
T
There are no apparent deleterious effects of pregnancy on the course of HCV infection and there does not appear to be an increase in adverse pregnancy outcomes in HCV-infected women. Mother-to-infant transmission of HCV has a reported range of 0% to 35%, with an average crude rate of 5.6%.3 Vertical transmission rates are significantly higher for HIV-positive patients and intravenous drug users.3 Universal blood testing for HCV in pregnancy has not been recommended by the Public Health Agency of Canada or the Centers for Disease Control and Prevention in the United States because of the relatively low prevalence in the general population and the absence of documented NOVEMBER JOGC NOVEMBRE 2010 l 1035
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measures capable of influencing maternal-fetal transmission. Pregnancy, however, may be an important time to screen for HCV infection. Many women will already have reached their peak likelihood of becoming infected by the time they become pregnant, making the yield of testing near its maximum.4 Screening at this point in a woman’s life can also provide early diagnosis and treatment that may offset the future burden of HCV on the health care system.4 Further, testing for HCV during pregnancy may help to identify infected newborns, allowing for appropriate follow-up. Alternatively, targeted screening for specific HCV risk factors has been recommended by the Public Health Agency of Canada and the Centers for Disease Control and Prevention. It is currently recommended that individuals with one or more of these identified risk factors should be offered HCV serum screening.5 In HCV seroprevalence studies among inner city antenatal populations, however, targeted screening using HCV risk factors did not identify approximately half of the anti-HCV positive women.6,7 It has therefore been suggested that targeted screening for HCV among pregnant patients in higher risk populations may not be appropriate and that universal HCV blood testing, particularly in urban centres, may be warranted. The primary objective of the present study was to identify the clinical utility of targeted screening compared to universal blood testing for HCV among pregnant women attending a women’s health care centre in Toronto. Secondary objectives included determining HCV seroprevalence in this urban population and identifying risk factors that were most predictive of testing positive for HCV antibodies. METHODS
This was a cross-sectional study of pregnant women who presented to the Women’s Health Care Centre at St Michael’s Hospital in Toronto between September 1, 2005, and April 30, 2007. St Michael’s is a university hospital and the Women’s Health Care Centre is part of the hospital’s Inner City Health Program. As such, the centre’s patient population is very ethnically and socially diverse. All obstetric patients 15 years of age or older and presenting to this centre for antenatal care were eligible for the study. Patients who were under the age of 15 years, who could not read or understand English, or who had no access to an interpreter were excluded from the study.
ABBREVIATIONS HCV
hepatitis C virus
IVDU
intravenous drug user
1036 l NOVEMBER JOGC NOVEMBRE 2010
A study nurse approached eligible patients presenting for their first antenatal visit at the Women’s Health Care Centre. This nurse described the study, distributed an information pamphlet on HCV, and reviewed the study consent form with the patient. Those consenting to the study were asked to complete a demographic questionnaire and an HCV screening questionnaire on which they answered “Yes” or “No” to the presence of specific risk factors for HCV. Risk factors listed included IVDU, intercourse with an IVDU, receipt of a blood transfusion or solid organ transplant prior to 1992, receipt of blood components or solid organs from HCV-positive donors, significant exposure to the blood of an HCV-positive individual, receipt of clotting factors prior to 1988, hemodialysis treatment, persistently elevated liver enzymes, time spent in a correctional facility, children of HCV-infected mothers, HIV-positive individuals, and tattoo history.5 These were all listed because, according to the Public Health Agency of Canada, pregnant women with one or more of these risk factors should be considered for HCV blood testing. Patients were also asked to indicate the number of body piercings present, if they had ever inhaled illicit drugs, and if they would agree or disagree to universal blood testing for HCV during pregnancy. After completing the two questionnaires, participants were sent to the laboratory for blood testing. Each patient recruited to the study was screened for antibodies to HCV by means of an enzyme-linked immunosorbent assay (third generation ELISA, Abbott Diagnostics, Saint-Laurent, QC). For those who tested positive, a second screening test was performed for confirmation (third generation ELISA, Bio Rad Laboratories Ltd, Montréal, QC). If both of these tests were non-confirmatory, a confirmation recombinant immunoblot assay was done (RIBA, Innogenetics NV, Gent, Belgium). All of the above tests were ordered through a standardized provincial request form for antenatal tests including HCV, and testing was carried out at the Provincial Reference Laboratory. Questionnaires were collected and responses from the demographic and HCV screening questions were entered into a numeric database by one of the study investigators. Results from each participant’s HCV blood test were also entered into the database. Responses to the 14 HCV screening questions were combined to create a variable that indicated the number of positive risk factors. The number of positive risk factors was categorized into none or at least one, and sensitivity, specificity, and negative and positive predictive values for HCV antibodies were estimated. The association between answering “Yes” to at least one screening question and testing positive for HCV antibodies was evaluated using Fisher exact tests, with P < 0.05 considered statistically significant.
The Effectiveness of Screening for Hepatitis C in Pregnancy
The associations between answering “No” to all risk factors and demographic variables were analyzed using the two-sample t test for continuous variables and chi-square test for categorical variables, with P < 0.05 considered statistically significant. Risk factor analysis was then stratified according to the number of positive responses: positive for no risk factors, positive for one risk factor, and positive for two or more risk factors. The associations between these groupings of the number of positive risk factors and testing positive for HCV antibodies were determined using Fisher exact tests, with P < 0.05 considered statistically significant. Risk factors were also stratified according to severity. The index of severity was created by the study investigators and was based on clinical knowledge and judgment. The “high severity risk factor” category included IVDU, intercourse with an IVDU, and receipt of or significant exposure to the blood of an HCV-positive individual. The “moderate severity risk factor” category included being HIV positive, having spent time in a correctional facility, having an HCV-positive mother, receipt of a blood transfusion or solid organ transplant prior to 1992, receipt of clotting factors prior to 1988, and hemodialysis treatment. The “low severity risk factor” category included persistently elevated liver enzymes, history of tattoo, body piercings, and inhalation of illicit drugs. Once again, the associations between these groupings of risk factor severity and testing positive for HCV antibodies were determined using Fisher exact tests, with P < 0.05 considered statistically significant.
Table 1. Demographic details Variable
n (%)*
Age, years 25 (4) 277 (43) 332 (51) 16 (2)
15 to 20 21 to 30 31 to 40 ³ 41 Marital Status Single Married Separated/divorced Common law
106 (16) 498 (77) 9 (2) 32 (5)
Pregnancy 367 (60) 178 (29) 56 (9) 13 (2)
1 2 3 ³4 Income £ $20 000 $21 000 to $40 000 $41 000 to $60 000 ³ $61 000
99 (16.4) 119 (19.7) 70 (11.6) 315 (52.3)
Housing type 298 (47) 83 (13) 249 (39) 7 (1)
House Condominium Apartment Shelter People in household
10 (2) 323 (51) 181 (28) 77 (12) 45 (7)
1 2 3 4 ³5 Origin
This study was approved by the St Michael’s Hospital Research Ethics Board.
Immigrant Non-immigrant
361 (56) 283 (44)
Race
RESULTS
During the recruitment period 653 women consented to participate in the study. Of these women, eight refused HCV blood testing and three of the remaining 645 women tested positive for HCV antibodies on screening, indicating a sample prevalence of 0.5% (95% confidence interval 0.1% to 1.4%). Study participant demographics are presented in Table 1. Participants ranged in age from 15 to 43 years (mean 30.7 ± 5.1 years). The majority (77%) were married, in their first pregnancy (60%), or had an annual income ³ $61 000 (52%); 47% lived in a house. The mean number of people living per household was 2.8 ± 1.1. Among those surveyed, 56% were immigrants and the most self-identified races were Caucasian (36%), Asian (20%), and Hispanic (15%). Most were non-smokers (95%), although 23% of participants smoked prior to the current pregnancy.
227 (36) 127 (20) 94 (15) 62 (10) 28 (5) 28 (5) 26 (4) 2 (2) 18 (3)
Caucasian Asian Hispanic European West Indian East Indian African Native Other Smoking Current: yes no
35 (5) 618 (95)
Past:
147 (23) 506 (77)
yes no
Alcohol/week pre-pregnancy 0 1 2 3 ³4
350 (58) 74 (12) 69 (11) 39 (6) 78 (13)
*Denominator changes due to missing data from questionnaires.
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Table 2. HCV screening risk factors Risk factor
HCV seropositive n (%)*
HCV seronegative n (%)*
P
2/3 (67)
3/637 (< 1)
< 0. 001
1/2 (50)
12/640 (2)
0.04
0/2 (0)
6/639 (1)
> 0.99
0/2 (0)
0/640 (0)
Test not applicable
1/2 (50)
1/640 (< 1)
0.006
0/2 (0)
0/640 (0)
Test not applicable
0/2 (0)
0/640 (0)
Test not applicable
1/2 (50)
9/640 (1)
0.03
0/2 (0)
4/638 (1)
> 0.99
0/2 (2)
1/639 (1)
> 0.99
0/3 (0)
2/639 (1)
> 0.99
2/3 (67)
101/642 (16)
0.07
2/3 (67)
424/642 (66)
> 0.99
1/2 (50)
79/639 (12)
0.2
IVDU Yes Intercourse with IVDU Yes Transfusion/transplant before 1992 Yes Blood/organs from HCV-positive donor Yes Exposure to HCV-positive blood Yes Clotting factors before 1988 Yes Hemodialysis treatment Yes Elevated liver enzymes Yes Time in correctional facility Yes HCV-positive mother Yes HIV positive Yes Tattoos Yes Body piercings Yes Inhaled illicit drugs Yes
*Denominator changes due to missing data from questionnaires.
Three patients were found to be HCV seropositive. The first patient to be detected positive for HCV antibodies was 29 years of age, single, gravida 1, para 0, had immigrated to Canada in 1998 from Rwanda, earned £ $20 000 per annum, lived alone in an apartment, did not consume any alcohol prior to pregnancy, had always been a non-smoker, and was unaware of her HCV status prior to this testing. The second patient detected was 19 years of age, single, gravida 2, para 0, Canadian-born and Caucasian, earned £ $20 000 per annum, lived with one other person in an apartment, continued to smoke during her pregnancy, and was aware of her HCV status prior to this testing. The third patient detected positive on blood testing was 22 years of age, in a common1038 l NOVEMBER JOGC NOVEMBRE 2010
law relationship, gravida 1, para 0, had immigrated to Canada in 1998 from an undocumented country, earned £ 20 000 per annum, lived with one other person in an apartment, did not consume any alcohol prior to pregnancy, had always been a non-smoker, and was also aware of her HCV status prior to this testing. Statistical comparison between HCV-positive and HCV-negative patients was not feasible given the low HCV seroprevalence rate. The results for positive HCV screening based on each risk factor assessment are summarized in Table 2. Results are shown separately for HCV seropositive and seronegative study participants. In total, 469 women (72%) answered “Yes” to at least one HCV screening risk factor and 181
The Effectiveness of Screening for Hepatitis C in Pregnancy
Table 3. Risk factor stratification based on number of positive risk factors HCV seropositive n (%)*
HCV seronegative n (%)*
P
0
1/3 (33)
178/640 (28)
> 0.99
1
0/3 (0)
326/640 (51)
0.4
³2
2/3 (67)
136/640 (21)
0.6
Number of positive risk factor response(s)
*Denominator changes due to missing data from questionnaires.
Table 4. Risk factor stratification based on severity HCV seronegative n (%)*
P
2/3 (67)
14/640 (2)
0.002
1/3 (33)
626/640 (98)
Moderate‡
0/3 (0)
13/640 (2)
Yes
3/3 (100)
627/640 (98)
2/3 (67)
459/640 (72)
1/3 (33)
181/640 (28)
Risk factor severity High† Yes
HCV seropositive n (%)*
No > 0.99
No Low§ Yes
> 0.99
No *Denominator changes due to missing data from questionnaires. †High risk factors: IVDU, intercourse with an IVDU, and receipt of or exposure to blood of an HCV-positive individual. ‡Moderate risk factors: HIV positive, time in a correctional facility, HCV-positive mother, blood transfusion or solid organ transplant before 1992, clotting factors before 1988, and hemodialysis treatment. §Low risk factors: elevated liver enzymes, history of tattoo, body piercings, and inhalation of illicit drugs.
women (28%) responded “No” to all HCV risk factors. There was a statistically significant association between being positive for HCV antibodies on blood testing and a positive response to IVDU (P < 0. 001), ever having intercourse with an IVDU (P = 0.04), having elevated liver enzymes (P = 0.03), or having a history of exposure to HCV-positive blood (P = 0.006). Overall, a positive response to at least one risk factor had a sensitivity of 67%, a specificity of 28%, a positive predictive value of 0.4%, and a negative predictive value of 99% for identifying patients with HCV. Women who responded “No” to all risk factors were more likely to be older (mean age 32 vs. 30, P < 0.001), to be non-smokers (88% vs. 73%, P < 0.001), and to drink significantly less prior to pregnancy (5% vs. 11% consuming ³ four drinks per week, P = 0.002).
Risk factor stratification according to the number of positive screening responses for both HCV seropositive and seronegative women is presented in Table 3. There was no correlation between the number of positive risk factors (positive for no risk factor, one risk factor, or two or more risk factors) and the likelihood of being HCV positive (P > 0.05). Risk factor assessment according to the level of severity for HCV seropositive and seronegative women is summarized in Table 4. There was a statistically significant association between testing positive for HCV antibodies and having a positive response to a high severity risk factor (P = 0.002). However, responding “Yes” to a moderate or low severity risk factor was not significantly associated with testing positive for HCV (P > 0.99 for both risk groups). A positive response to a high severity risk factor conferred a sensitivity of 67%, a specificity of 98%, a positive predictive value of 13%, and a negative predictive value of > 99% for identifying patients with HCV. At the end of the HCV screening questionnaire, participants were asked if they would agree or disagree with a policy of universal blood testing for HCV during pregnancy. A total of 582 women (92%) stated that they would agree to this type of testing during pregnancy, indicating a high degree of acceptance. DISCUSSION
This study showed that universal blood testing for HCV in pregnancy was not an appropriate use of health care resources in this urban population. In addition, pregnant women who were positive for any HCV risk factor were not at significant risk of being HCV seropositive. Stratifying risk factors by number of positive responses to screening questions was also not predictive of HCV positivity. These findings suggest that performing antenatal HCV blood testing in pregnant women who simply have a positive response to any of the screening questions may not be a useful strategy. When screening questions were stratified by severity, however, there was a significant association between having a “high severity risk factor” and being HCV positive. When risk factors were assessed individually, these high severity risk factors, as well as having elevated liver enzymes, were also independently associated with being HCV positive. Current recommendations for HCV testing during pregnancy in Canada state that individuals with one or more identified risk factors should be tested for HCV antibodies.5 Previous studies have indicated that this method of screening will fail to identify a significant proportion of infected women, particularly in inner city populations. In an anonymous serosurvey of 599 pregnant women recruited NOVEMBER JOGC NOVEMBRE 2010 l 1039
OBSTETRICS
from an inner city clinic as well as from a private practice in Philadelphia, Silverman et al. reported that significantly more women in the clinic service (5.2%) were seropositive for HCV than in the private practice (1.5%).6 In this study, substance abuse was the most commonly identified risk factor for HCV, and targeted risk factor screening would have failed to detect half of the HCV-positive women. Ward et al. completed another study at an inner city London obstetric hospital that examined the seroprevalence of HCV in 4825 pregnant women over two years.7 The prevalence of HCV among this multiethnic antenatal population was 0.8%, and no risk factors were identified by a thorough screening history in 50% of these seropositive patients. The results of these studies suggest that targeted screening for HCV in pregnancy may not be an adequate strategy in an inner city population, and that universal blood testing may be more appropriate. The findings of the present study are not consistent with these results. We have demonstrated that targeted HCV blood testing during pregnancy based on any positive responses to documented HCV risk factors is not a useful strategy, but there is an association between testing positive for a high severity risk factor and being HCV seropositive. Therefore, HCV blood testing based on the presence of a high severity risk factor may be a more useful method of identifying women who are truly HCV seropositive. The prevalence of HCV in this population was found to be 0.5%. Although this finding was significantly lower than expected, this is the first study to document the prevalence of HCV in a pregnant population based in Toronto. The global seroprevalence of HCV is estimated to be 3% with significant geographic variation, ranging from 0.01% to 0.1% in the United Kingdom to from 17% to 26% in Egypt.8 The prevalence rates of HCV in pregnancy around the world also vary and are reported at 0.2% to 2.4% in Europe,9–14 1.1% in Australia,15 1.3% in Taiwan,16 2.6% in Japan,17–19 3.2% to 4.5% in the United States,20,21 and 13.7% in Egypt.22 The largest study to date was performed in Italy and found a seroprevalence of 2.4% after following a cohort of 15 250 pregnant women over four years.14 To date there are no published data on the prevalence and incidence of HCV in pregnant women in Canada. The low prevalence of HCV found in this study appears to support the concept that universal blood testing for HCV during pregnancy is not a worthwhile strategy and further justifies testing based on HCV risk factor severity for this pregnant population in Toronto. Despite this low prevalence, 92% of participants in this study noted they would agree to universal HCV blood screening during pregnancy, indicating a high acceptance rate. 1040 l NOVEMBER JOGC NOVEMBRE 2010
The primary limitation of this study was the small sample size of HCV seropositive women. Since only three patients were found to be HCV positive, we were unable to compare the demographic features of HCV-positive women to those of HCV-negative women. The small number of HCVpositive patients also limited the accuracy of sensitivity and specificity calculations for HCV risk factor assessment in relation to HCV seropositivity. It should be noted, however, that our study population was large (n = 653), and identifying only three HCV seropositive patients simply indicated a low prevalence rate in this population. In addition, participants were recruited from a centre that is part of an inner city health program, and, as such, we anticipated a study population of lower socioeconomic status. Instead, demographic data revealed that the majority of women had an annual income of $61 000 or more, almost half lived in a house, and most were either married or in a common-law relationship. This may explain the low prevalence of HCV identified in this setting. Therefore, the results of this study appear to reflect those of a population with a mixed socioeconomic background and may be more applicable to the average urban obstetrical patient population in Canada. Interestingly, of the patients who were found to be HCV positive, all three had annual incomes £ $20 000 and lived in apartments, and two of the three patients were single and immigrants to Canada. Future research efforts in this field should include a costeffectiveness analysis of HCV blood testing in pregnancy based on screening by risk factor severity. A recent study by Plunkett et al.23 investigated the cost-effectiveness of universal HCV blood screening compared to no screening in asymptomatic pregnant women. Using a decision tree with Markov analysis, they found that no screening is a less costly and more effective strategy than the alternate strategy of screening and subsequent treatment of progressive disease. This type of analysis examining HCV screening in pregnancy based on risk factor severity would be of the utmost importance in guiding future clinical practice. In addition, more studies identifying HCV prevalence during pregnancy in other geographic areas throughout Canada would add further insight into the overall disease burden, and would help to establish the true need for national screening and testing for this virus during pregnancy. CONCLUSION
The findings of this study do not support universal blood testing for HCV during pregnancy, nor do they support testing for HCV in women who are positive for any known HCV risk factor in such an urban population. Instead, we have demonstrated and recommend that pregnant women who have an identified risk factor of high severity (IVDU,
The Effectiveness of Screening for Hepatitis C in Pregnancy
intercourse with an IVDU, and receipt of or exposure to HCV-positive blood) should be considered for HCV antibody testing. We have also identified a relatively low seroprevalence of HCV in pregnancy in this urban Canadian population.
11. Hillemanns P, Langenegger P, Langer PC, Knitza R, Hasbargen U, Hepp H. Prevalence and follow-up of hepatitis C virus infection in pregnancy [article in German]. Z Geburtshilfe Neonatol 1998;202:127–30. 12. Ades AE, Parker S, Walker J, Cubitt WD, Jones R. HCV prevalence in pregnant women in the UK. Epidemiol Infect 2000;125:399–405.
ACKNOWLEDGMENTS
13. Balogun MA, Ramsay ME, Parry JV, Donovan L, Andres NJ, Newham JA, et al. The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England. Epidemiol Infect 2000;125:705–12.
The authors wish to thank The Physicians’ Services Incorporated Foundation for funding.
14. Conte D, Fraquelli M, Prati D, Colucci A, Minola E. Prevalence and clinical course of chronic hepatitis C virus infection and rate of HCV vertical transmission in a cohort of 15,250 pregnant woman. Hepatology 2000;31:751–5.
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