Skip Navigation

Impact of Maternal HIV Coinfection on the Vertical Transmission of Hepatitis C Virus: A Meta-analysis

  1. Chelsea B. Polis1,
  2. Snehal N. Shah2,
  3. Kristine E. Johnson3, and
  4. Amita Gupta3
  1. 1Department of Population, Family and Reproductive Health, Baltimore, Maryland
  2. 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  3. 3Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland
  1. Reprints or correspondence: Chelsea Polis, Dept. of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Rm. W4510, Baltimore, MD 21205 (cpolis{at}jhsph.edu).
 
Next Section

Abstract

Background. Observational studies suggest that maternal human immunodeficiency virus (HIV)-hepatitis C virus (HCV) coinfection is associated with increased odds of vertical HCV transmission. We performed a meta-analysis to summarize current evidence.

Methods. We systematically searched for relevant articles published during the period from January 1992 through July 2006 and independently abstracted articles that met our inclusion criteria. Under a random effects model, we calculated the pooled odds ratio for vertical HCV transmission according to maternal HIV-HCV coinfection status and performed sensitivity analyses.

Results. Ten articles met our inclusion criteria. Study quality varied widely, and study estimates displayed high statistical heterogeneity. Restriction of the analysis to studies that included>50 HIV-HCV—coinfected women provided our most reliable estimate: maternal HIV-HCV coinfection increases the odds of vertical HCV transmission by ∼90% (odds ratio, 1.9; 95% confidence interval, 1.36–2.67), compared with maternal HCV infection alone. When we restricted analyses to HIV-infected mothers with HCV viremia, the odds of vertical HCV transmission were 2.82-fold (95% confidence interval, 1.17-fold to 6.81-fold) greater than the odds for HIV-infected mothers without HCV viremia.

Conclusions. HIV-HCV—coinfected women have significantly higher odds of transmitting HCV to their infants than do women who are infected with HCV alone.

Globally, an estimated 170 million people (or 3.1% of the world's population) are infected with hepatitis C virus (HCV), and 40 million individuals are infected with HIV [1, 2]. Because these infections share transmission routes, HIV-HCV coinfection is not uncommon; it affects ∼4–5 million people [3, 4]. Both infections can be transmitted vertically from mother to child. Precise quantification of the number of HIV-HCV—coinfected women of childbearing age is difficult, but the shared risk groups and overlapping geographical distribution of the 2 infections suggests that HIV-HCV coinfection is an important public health issue. Efforts to prevent vertical HCV transmission will become increasingly important as the epidemic of HIV-HCV coinfection evolves.

The rate of risk of vertical HCV transmission ranges from 4% to 10%, and viremic women appear more likely to transmit HCV [5, 6]. Unlike HIV, the contributions of other potential risk factors for vertical transmission of HCV, such as breast-feeding and mode of infant delivery, remain poorly characterized. Understanding the epidemiology and risk factors for vertical transmission of HCV is essential in guiding future public health efforts. Although evidence suggests that, for the HCV-infected infant, disease progression is slow during the first 10–15 years of life, little is known about disease progression beyond adolescence [6]. In the United States, the prevalence of HCV infection in children ranges from 0.05% to 0.4% [7].

Observational studies suggest that maternal HIV-HCV coinfection is associated with increased vertical HCV transmission. The potential biological mechanisms responsible for this association are not clearly understood, although virologic and host factors likely play a role. HIV infection has been associated with an elevated HCV load [8], which may facilitate HCV vertical transmission. Other factors believed to influence HCV transmission rates include HCV genotype, severity of HCV-induced liver disease, hepatic inflammation (i.e., elevated alanine aminotransferase level), stage of HIV infection, HIV antiretroviral experience, active injection drug use (IDU), infant sex, and infant prematurity.

Pappalardo's [9] 2003 meta-analysis of 10 observational studies reported an OR of HCV vertical transmission of 2.82 (95% CI, 1.78–4.45) for HIV-HCV—coinfected mothers, compared with HCV-monoinfected mothers. Since the time of Pappalardo's publication [9], 2 additional studies have contributed to the knowledge base, including the largest cohort study to date, which was designed specifically to evaluate vertical HCV transmission in HIV-HCV—coinfected mothers [10, 11]. Because of the availability of these new data, we conducted a meta-analysis of published studies to investigate the impact of maternal HIV coinfection on the vertical transmission of HCV.

Previous SectionNext Section

Methods

Article identification. Using variations on the terms related to HCV, HIV, and vertical transmission, we searched Embase, Medline, Central, and Web of Science databases for English articles with the following keywords. For the Embase database, `hiv'/exp AND `hepatitis c'/exp AND vertical AND transmission AND [english]/lim AND [humans]/lim AND [embase]/lim. For the Medline database (via PubMed): “Hepatitis C/transmission”[MeSH] AND (“HIV Seropositivity”[MeSH] OR “HIV infections”[MeSH] OR “HIV”[MeSH] OR “HIV Seronegativity”[MeSH]) AND “Disease Transmission, vertical”[MeSH]. For the Central database, (HIV OR “human immunodeficiency virus”) AND (HCV OR “hepatitis C”) AND “vertical transmission.” And for the Web of Science database, document type=article TS= (((hiv OR HUMAN-IMMUNODEFICIENCY-VIRUS) AND (infection* OR seronegativ* OR seropositiv*)) AND (hepatitis C OR hcv) AND vertical transmission). We also hand-searched reference lists of relevant articles.

We excluded conference abstracts. Our search was restricted to 1992 (when the HCV EIA became available) through July 2006. All identified articles were screened, and we excluded articles that were determined to be irrelevant on the basis of a review of the title and/or abstract. Full texts of all remaining articles were retrieved and reviewed.

Exclusion of studies. Articles were excluded if they were not in the English language, did not present original data, did not provide complete data, did not compare HIV-HCV—coinfected women with HCV-monoinfected women, did not clearly identify the HCV testing strategy, or included <20 HIV-HCV—coinfected women.

The first HCV EIAs became available in 1992. Each subsequent generation of HCV ELISA tests increased the sensitivity and specificity and shortened the period between infection and detection. Standard HCV testing procedures usually include EIA followed by recombinant immunoblot assay (RIBA) and/or quantitative PCR [12]. We included studies in which maternal HCV infection was diagnosed using either EIA antibody testing (with or without confirmatory RIBA) or HCV RNA PCR. A woman was considered to be infected if she had at least 1 positive EIA result or detectable HCV viremia.

Diagnosis of HCV infection in infants is complicated by persistent maternal antibodies and transient HCV viremia. Although uninfected infants generally clear maternal HCV antibodies within 6–12 months, antibodies may persist longer in infants born to HIV-HCV—coinfected mothers [13]. The timing and duration of transient HCV viremia in infants is poorly understood, but for some infants, the infection will be cleared by the host's immune response. To minimize misclassification introduced by transient viremia and the presence of maternal antibodies, we included only studies in which infants underwent confirmatory testing (HCV EIA, with results confirmed by RIBA or HCV PCR) at ≥18 months of age and/or had 2 positive, independent HCV PCR test results that were separated by a minimum of 3 months. Children with an initial positive HCV antibody test result followed by a negative antibody test result during the interval visits were considered to be HCV infected only if they had a positive HCV PCR result at ≥6 months of age or if they had a detectable HCV antibody at ≥18 months of age. To minimize the potential for misclassification, we included studies in which HCV-infected infants received blood transfusions only if data were available to recalculate the ORs with these subjects excluded.

Quality assessment. Two independent reviewers abstracted each article separately. Where discrepancies arose, a third investigator arbitrated. Study quality was examined using 6 main characteristics: study design, information on differential loss to follow-up, risk of selection bias, provision of data on comparability between HIV-infected women and HIV-uninfected women, handling of risk for misclassification bias, and control for confounding factors. Risk of selection bias was “more” if no attempt was made to make groups comparable and “less” if some attempt, such as matching, was made. Comparability between HIV-infected and HIV-uninfected women was based on how many of the 6 potential characteristics for comparison (Cesarean delivery, breast-feeding, elevated maternal serum alanine aminotransferase level, HIV antiretroviral experience, IDU status, and infant prematurity) were reported; 1–2 reported characteristics were coded as “few,” 3–4 were coded as “some,” and 5–6 were coded as “many.” Handling risk of misclassification bias was “good” if the study included only infants who unequivocally contracted HCV through vertical transmission and if the diagnostic criteria for exposure and outcome exceeded our minimum diagnostic inclusion criteria; this category was coded as “fair” if there was less clarity regarding the means of HCV transmission (e.g., one study included HCV-infected infants who had HCV-infected mothers, but the infants had also received blood transfusions) or if the diagnostic methods met only minimum inclusion criteria.

Statistical methods. Quantitative analysis was performed using Stata software, version 9.1 (Stata). ORs and 95% CIs were calculated with maternal HIV status as the predictor and vertical HCV transmission as the outcome. We excluded data with potentially misclassified instances of vertical transmission from HIV-HCV—coinfected mothers that resulted from infant blood transfusions. Given the variability inherent in comparing observational studies, we pooled the data under a Dersimonian and Laird random effects model, which provides a more conservative estimate of significance [14].

We calculated the I2 statistic to evaluate the percentage of variability in effect estimates due to heterogeneity, as opposed to random error [15]. An I2 of ≥50% was considered to be evidence of substantial statistical heterogeneity.

Sensitivity analyses. We conducted 4 sensitivity analyses to determine how our results may have differed on the basis of different inclusion criteria. Studies that failed to measure maternal HCV viremia may have estimated ORs that failed to separate the effect of HCV viremia from the effect of HIV infection. Therefore, we conducted a sensitivity analysis that excluded studies that did not collect information on HCV viremia and that excluded data on mothers without HCV viremia. We also explored the effect of excluding retrospective studies. To examine the effect of sample size, we conducted a sensitivity analysis that included only studies that contained ≥50 HIV-HCV—coinfected women. Finally, we generated a L'abbé plot to identify extreme outliers and excluded studies thereby indicated [16].

Previous SectionNext Section

Results

Our literature search identified 243 articles. We retrieved 36 full-text articles for review, 26 of which did not meet our inclusion criteria (figure 1). Four included only women with HIV-HCV coinfection, and 14 included data for <20 HIV-HCV—coinfected women. Three articles did not meet our diagnostic criteria, 3 had unclear or missing data, and 2 did not use original data. The funnel plot provided no evidence of publication bias (figure 2) [10, 11, 17–24].

Figure 1
View larger version:
Figure 1

Flowchart of selection of articles for the meta-analysis

Figure 2
View larger version:
Figure 2

Funnel plot for publication bias

Qualitative analysis. Publication dates ranged from 1993 to 2005 (table 1). Nine studies were conducted in Europe [10, 11, 18–24], and of those, 7 were based in Italy [10, 19–24]. Only 1 study was based in the United States [17]. None of the studies were conducted in developing countries. Nine were prospective cohort studies [10, 11, 17, 19–24], and 1 was retrospective [18]. Studies generally recruited pregnant HCV-infected women, and many participants had a history of IDU. The sample sizes and proportion of HIV-HCV—coinfected mothers were highly variable.

Figure 3
View larger version:
Figure 3

Graphical displays of the 2 most reliable sensitivity analyses. A, Odds of vertical transmission of hepatitis C virus (HCV) from HIV-HCV—coinfected mothers to children, compared with HCV-monoinfected mothers, in studies that included>50 HIV-HCV—coinfected women (χ2 test for heterogeneity, 3.46; degrees of freedom, 4; P = .484). B, Odds of vertical transmission of HCV from HIV-HCV—coinfected mothers to children, compared with HCV-monoinfected mothers, excluding 1 study that had extreme OR outlier of 57 (χ2 test for heterogeneity, 13.32; degrees of freedom, 8; P = .10). EPHN, European Pediatric Hepatitis C Virus Network.

Table 1
View larger version:
Table 1

Characteristics of studies included in a meta-analysis.

The number of mother-infant pairs in each study ranged from 37 to 1479 pairs, and the proportion of HIV-HCV—coinfected women ranged from 13.7% to 85.7%. Although all studies used standard HCV diagnostic methods, tests were not always routinely applied to all women (table 2). In addition, the exact timing of HCV maternal testing (antenatal, intrapartum, or early postpartum testing) was not specified. Only 4 studies performed quantitative PCR for HCV RNA for all women [21–24]. No studies provided information on maternal HIV stage or HIV load, and only 2 reported partial information on HIV antiretroviral treatment, which may affect the HIV load but has an unclear impact on HCV load [10, 11].

Table 2
View larger version:
Table 2

Comparison of methods used for diagnosis of hepatitis C virus (HCV) infection in mothers among studies included in the meta-analysis.

A total of 287 HCV-infected infants were identified, but infant HCV diagnosis and follow-up intervals varied (table 1). Six studies conducted HCV EIA antibody testing on infants after they were 18 months of age [10, 17–19, 21, 23]. Three of these studies also performed 2 HCV RNA PCR tests at least 3 months apart [18, 19, 23]. One study did not use antibody testing and instead diagnosed infant HCV infection by performing 2 HCV RNA PCR tests ≥3 months apart [24]. Of the remaining 2 studies, one diagnosed infant HCV infection using HCV EIA antibody tests without confirmatory RIBA after the subjects were 18 months of age [20], and the other performed 2 PCR tests at unspecified times [22]. Where reported, the duration of infant follow-up ranged from 6 to 90 months. Given the wide variation in diagnostic methods, misclassification of infant HCV infection may have occurred, although we attempted to correct for potential misclassifications associated with blood transfusions.

Studies were of varied quality (table 3). Six studies [17, 18, 21–24] handled misclassification bias well by identifying the means of transmission and/or by using superior HCV diagnostic criteria, whereas 4 studies [10, 11, 19, 20] were less clear about the possibility of misclassification bias. One retrospective study [18] examined stored blood specimens obtained from pregnant women several years after collection, but poor storage conditions may have led to misclassification.

Table 3
View larger version:
Table 3

Summary of quality assessment criteria for studies included in a meta-analysis.

Only 1 study [17] attempted to make groups comparable by matching, so the potential for selection bias was generally high in these studies. Only 1 study [20] provided clear information on whether differential loss to follow-up was likely. Regarding the comparability of HIV-infected and HIV-uninfected women at baseline, 6 studies provided IDU data [10, 20–24], whereas fewer provided information on Cesarean delivery [21–24], breast-feeding [11, 22–24], serum alanine aminotransferase level [23, 24], premature birth [11, 21], or HIV antiretroviral use [10, 11]. Among the 6 studies that reported IDU according to HIV status, 61% of HIV-HCV—coinfected women reported IDU, whereas only 26% of HCV-only infected women reported IDU, resulting in substantial differences between potentially confounding characteristics of HIV-HCV—coinfected women and women with HCV infection alone. Although 6 studies mentioned HCV genotype [10, 17, 18, 22–24], information generally only confirmed that infant HCV genotype matched the mother's. Only 2 studies [17, 19] provided CD4 cell counts, and 1 study [17] provided information on HIV load. If loss to follow-up is associated with HIV status, which is theoretically conceivable, this also could have introduced bias.

Eight studies performed univariate analysis of risk factors associated with HCV transmission [10, 17–19, 21–24], and of these, 3 identified HIV coinfection as a significant risk factor for vertical HCV transmission [21–23]. Two studies performed multivariate analysis [11, 20]. The first [20] controlled for maternal IDU, maternal HIV infection, breast-feeding, and vaginal delivery but performed the analysis only for a subset of mothers with positive HCV PCR results. The authors concluded that maternal IDU alone was significant. The second multivariate analysis [11] included maternal HIV status, mode of delivery, sex of infant, prematurity, and breast-feeding and found that only the sex of infant was a significant factor. Neither analysis suggested that maternal HIV infection was a statistically significant predictor of HCV transmission.

Quantitative analysis. Of 4424 mother-infant pairs, 858 (19.39%) included HIV-HCV—coinfected women. A total of 278 HCV-infected infants were born. Analysis of these 10 observational studies (after excluding potentially misclassified information) in a random effects model revealed that HIV-HCV—coinfected women have a 2.75 greater odds of transmitting HCV, compared with women with HCV infection alone (OR, 2.75; 95% CI, 1.51–4.99). However, the I2 statistic was 60%, indicating that the study estimates were heterogeneous and ideally should not be pooled (table 4).

Table 4
View larger version:
Table 4

Comparison of overall results of meta-analysis with sensitivity analyses, random effects models.

We performed a subgroup analysis of 7 studies that reported data on mothers with HCV viremia [10, 17, 19, 20, 22, 24]. The pooled odds of vertical transmission were 2.82 (95% CI, 1.17–6.81) among HIV-HCV—coinfected mothers with HCV viremia, compared with HCV-monoinfected mothers with HCV viremia (figure 3). The I2 statistic was 64%, again indicating that the study estimates were heterogeneous and should not be pooled.

The removal of the retrospective study [18] did not change the OR substantially (OR, 3.02; 95% CI, 1.66–5.50), and the I2 statistic indicated significant heterogeneity.

When we restricted studies to the 5 that had sample sizes of ≥50 subjects [11, 17, 19–21], the risk of HCV vertical transmission was found to be 1.90 (95% CI, 1.36–2.67), and the I2 statistic for heterogeneity was ≤50% (I2, -15%).

The removal of the study that had no transmission events in the HCV monoinfection group (and, therefore, an unstable zero cell) [22] produced an OR of 2.31 (95% CI, 1.42–3.75). Furthermore, the I2 statistic decreased to 40%, indicating that this study was the major source of statistical heterogeneity.

Previous SectionNext Section

Discussion

The results of our meta-analysis found that, compared with maternal HCV infection alone, maternal HIV coinfection increases the vertical transmission risk of HCV. We suggest that our most reliable estimate comes from the pooled analysis that included studies with ≥50 HIV-HCV—coinfected mothers (OR, 1.9; 95% CI, 1.36–2.67). As a group, these larger studies did not differ drastically in quality, showed low heterogeneity, and were of better overall quality. We, therefore, have determined that the odds of vertical HCV transmission are ∼90% higher for women infected with HIV and HCV than for those infected with HCV alone.

This estimate is similar to Pappalardo's estimate (OR, 1.97) [9]. However, we reached these estimates using different methods and studies. Our article selection criteria excluded 3 studies included in Pappalardo's analysis (1 conference abstract [25], 1 study that included <20 coinfected women [13], and 1 study that did not meet our criteria on antibody testing [26]). In addition, our review includes 2 new studies [10, 11], one of which was the largest study conducted to date on this topic. We also included the 1995 study by Zanetti et al. [22], which was excluded from Pappalardo's graphical analysis and study table. Finally, our analysis also differs from Pappalardo's in that we excluded potentially misclassified information from the 1998 study by Granovsky et al. [17].

Because observational studies have a greater risk of bias, it is more difficult to confidently use statistical meta-analyses to generate a meaningful summary statistic. The lack of comparability between these studies generally resulted from a lack of standardized HCV diagnostic criteria and the inability to control for known confounders. By nature of the exposure, high-risk individuals must be targeted for enrollment, and this can introduce high rates of loss to follow-up and may limit generalizability to areas where IDU is not the main mode of HIV acquisition. Our findings are likely generalizable to populations in which most cases of HCV infection are related to IDU, but they should be applied with caution to areas such as the developing world, where nutritional status, HIV subtype, HCV genotype, and other differences may influence HCV transmission.

Little information exists on how known confounding factors influence the relationship between HIV-HCV coinfection and HCV transmission. Information on Cesarean delivery may be particularly relevant, because most of the studies were conducted in Italy, where the procedure is common [27]. If Cesarean deliveries are protective against HCV transmission but not considered in studies, researchers may underestimate transmission rates for HIV-HCV—coinfected mothers, because most HIV-infected mothers in the United States and Europe deliver via Cesarean section.

Some studies identify maternal HCV viremia as a risk factor for HCV transmission, but few studies have tested for viremia [28, 29]. In a comparison of analyses restricted to mothers with HCV viremia, our OR was higher than that in the study by Pappalardo [9] (2.82 vs. 1.97), probably because our meta-analysis included 2 additional studies in which a number of mothers were tested for HCV RNA [10, 11]. Misclassification may have occurred among HCV antibody—positive mothers, because ∼15% of women clear HCV. In addition, improvements in HCV testing over time may have led to decreased instances of misclassification in more recent studies. However, this bias should be nondifferential, because evidence suggests that there is no difference in HCV clearance based on HIV serostatus [5, 23]. Because of the persistence of maternal antibodies and HCV RNA positivity in the absence of antibodies, serial measurements of HCV RNA level should also be performed in infants to avoid misclassification [17, 21, 26].

Our analysis indicates that large studies that control for potential known confounders, use clear selection criteria, show minimal loss to follow-up, and employ standardized HCV testing of infants and mothers using qualitative tests are needed. In addition, better understanding of the underlying biological mechanisms of HCV transmission in relation to HIV infection in both mothers and infants is needed to improve the quality of future studies on this topic. Future research in this area is critical to the development of effective public health measures to reduce vertical transmission of HCV to infants from HIV-HCV—coinfected mothers.

Previous SectionNext Section

Acknowledgments

We thank Ye Mon Myint for his contribution to preliminary work on this review, Eliseo Guallar and Steven Goodman for their guidance in meta-analytical methods, and Shruti Mehta for her helpful comments on the manuscript.

Potential conflicts of interest. All authors: no conflicts.

  • Received October 16, 2006.
  • Accepted January 5, 2007.
Previous Section
 

References

  1. ↵
    Joint United Nations Programme on HIV/AIDS (UNAIDS). AIDS epidemic update. 2005. Available at: http://www.unaids.org. Accessed 17 September 2006.
  2. ↵
    World Health Organization. Global distribution of hepatitis A, B, and C. Wkly Epidemiol Rec 2001;77:45-7. Available at: http://www.who.int/docstore/wer/pdf/2002/wer7706.pdf. Accessed 17 September 2006.
  3. ↵
    1. Alter M
    . Epidemiology of viral hepatitis and HIV co-infection. J Hepatol 2006;44:6-9.
    CrossRef
  4. ↵
    1. Sulkowski MS,
    2. Mast EE,
    3. Seeff LB,
    4. Thomas DL
    . Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000;30(Suppl 1):77-84.
    CrossRef
  5. ↵
    1. England K,
    2. Thorne C,
    3. Newell ML
    . Vertically acquired paediatric coinfection with HIV and hepatitis C virus. Lancet Infect Dis 2006;6:83-90.
    CrossRefMedlineWeb of Science
  6. ↵
    European Pediatric Hepatitis C Virus Network (EPHN). Three broad modalities in the natural history of vertically acquired hepatitis C virus infection. Clin Infect Dis 2005;41:45-51.
    Abstract/FREE Full Text
  7. ↵
    1. Jhaveri R,
    2. Grant W,
    3. Kauf TL,
    4. McHutchison J
    . The burden of hepatitis C virus infection in children: estimated direct medical costs over a 10-year period. J Pediatr 2006;148:353-8.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Arends JE,
    2. Boucher CA,
    3. Hoepelman AI
    . Hepatitis C virus and human immunodeficiency virus coinfection: where do we stand? Neth J Med 2005;63:156-63.
    MedlineWeb of Science
  9. ↵
    1. Pappalardo BL
    . Influence of maternal human immunodeficiency virus (HIV) co-infection on vertical transmission of hepatitis C virus (HCV): a meta-analysis. Int J Epidemiol 2003;32:727-34.
    Abstract/FREE Full Text
  10. ↵
    1. Ferrero S,
    2. Lungaro P,
    3. Bruzzone BM,
    4. Gotta C,
    5. Bentivoglio G,
    6. Ragni N
    . Prospective study of mother-to-infant transmission of hepatitis C virus: a 10-year survey (1990–2000). Acta Obstet Gynecol Scand 2003;82:229-34.
    CrossRefMedlineWeb of Science
  11. ↵
    European Pediatric Hepatitis C Virus Network (EPHN). A significant sex—but not elective Cesarean section—effect on mother-to-child transmission of hepatitis C virus infection. J Infect Dis 2005;192:1872-9.
    Abstract/FREE Full Text
  12. ↵
    1. Thomas SL,
    2. Newell ML,
    3. Peckham CS,
    4. Ades AE,
    5. Hall AJ
    . Use of polymerase chain reaction and antibody tests in the diagnosis of vertically transmitted hepatitis C virus infection. Eur J Clin Microbiol Infect Dis 1997;16:711-9.
    CrossRefMedlineWeb of Science
  13. ↵
    1. Manzini P,
    2. Saracco G,
    3. Cerchier A,
    4. et al
    . Human immunodeficiency virus infection as risk factor for mother-to-child hepatitis C virus transmission: persistence of anti-hepatitis C virus in children is associated with the mother's anti-hepatitis C virus immunoblotting pattern. Hepatology 1995;21:328-32.
    CrossRefMedlineWeb of Science
  14. ↵
    1. DerSimonian R,
    2. Laird N
    . Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Higgins JP,
    2. Thompson SG,
    3. Deeks JJ,
    4. Altman DG
    . Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
    FREE Full Text
  16. ↵
    1. L'Abbe KA,
    2. Detsky AS,
    3. O'Rourke K
    . Meta-analysis in clinical research. Ann Intern Med 1987;107:224-33.
    Abstract/FREE Full Text
  17. ↵
    1. Granovsky MO,
    2. Minkoff HL,
    3. Tess BH,
    4. et al
    . Hepatitis C virus infection in the mothers and infants cohort study. Pediatrics 1998;102:355-9.
    Abstract/FREE Full Text
  18. ↵
    1. Lam JP,
    2. McOmish F,
    3. Burns SM,
    4. Yap PL,
    5. Mok JY,
    6. Simmonds P
    . Infrequent vertical transmission of hepatitis C virus. J Infect Dis 1993;167:572-6.
    Abstract/FREE Full Text
  19. ↵
    1. Paccagnini S,
    2. Principi N,
    3. Massironi E,
    4. et al
    . Perinatal transmission and manifestation of hepatitis C virus infection in a high risk population. Pediatr Infect Dis J 1995;14:195-9.
    MedlineWeb of Science
  20. ↵
    1. Resti M,
    2. Azzari C,
    3. Mannelli F,
    4. et al
    . Mother to child transmission of hepatitis C virus: prospective study of risk factors and timing of infection in children born to women seronegative for HIV-1. Tuscany Study Group on Hepatitis C Virus Infection. BMJ 1998;317:437-41.
    Abstract/FREE Full Text
  21. ↵
    1. Tovo PA,
    2. Palomba E,
    3. Ferraris G,
    4. et al
    . Increased risk of maternal-infant hepatitis C virus transmission for women coinfected with human immunodeficiency virus type 1. Italian Study Group for HCV Infection in Children. Clin Infect Dis 1997;25:1121-4.
    Abstract/FREE Full Text
  22. ↵
    1. Zanetti AR,
    2. Tanzi E,
    3. Paccagnini S,
    4. et al
    . Mother-to-infant transmission of hepatitis C virus. Lombardy Study Group on Vertical HCV Transmission. Lancet 1995;345:289-91.
    CrossRefMedlineWeb of Science
  23. ↵
    1. Zanetti AR,
    2. Tanzi E,
    3. Romano L,
    4. et al
    . A prospective study on mother-to-infant transmission of hepatitis C virus. Intervirology 1998;41:208-12.
    CrossRefMedlineWeb of Science
  24. ↵
    1. Zuccotti GV,
    2. Ribero ML,
    3. Giovannini M,
    4. et al
    . Effect of hepatitis C genotype on mother-to-infant transmission of virus. J Pediatr 1995;127:278-80.
    CrossRefMedlineWeb of Science
  25. ↵
    1. Bossi G,
    2. Maccabruni A,
    3. Caselli D,
    4. Arlandi L,
    5. Silini E,
    6. Mondelli M
    . Mother-to-child HCV transmission: role of maternal HIV infection [abstract TH B 4326]. Int Conf AIDS 1996;11:306.
  26. ↵
    1. Mazza C,
    2. Ravaggi A,
    3. Rodella A,
    4. et al
    . Prospective study of mother-to-infant transmission of hepatitis C virus (HCV) infection. Study Group for Vertical Transmission. J Med Virol 1998;54:12-9.
    CrossRefMedlineWeb of Science
  27. ↵
    1. Arsieri R,
    2. Formisano V,
    3. Publiese A,
    4. Saporito M,
    5. Triassi M
    . Bollettino Epidemiologico Nazionale. 2002. Prevalence of Cesarean section and its relation to type of delivery facility, Campania. Available at: http://www.epicentro.iss.it/ben/pre_2002/giugno02/2_en.htm. Accessed 17 September 2006.
  28. ↵
    1. Giacchino R,
    2. Tasso L,
    3. Timitilli A,
    4. et al
    . Vertical transmission of hepatitis C virus infection: usefulness of viremia detection in HIV-seronegative hepatitis C virus-seropositive mothers. J Pediatr 1998;132:167-9.
    CrossRefMedlineWeb of Science
  29. ↵
    1. Thomas DL,
    2. Villano SA,
    3. Riester KA,
    4. et al
    . Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers. Women and Infants Transmission Study. J Infect Dis 1998;177:1480-8.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (2007) 44 (8): 1123-1131. doi: 10.1086/512815
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most