The Mother-to-Child Transmission of Hepatitis C Infections - Literature review Example

Running Head: Literature Review for 7 Original Articles in Epidemiology and Research Design Subject Student’s Name: Instructor’s Name: Course Name and Code: Institution: Date Submitted: Literature Review for 7 Original Articles in Epidemiology and Research Design Subject Introduction Hepatitis C (HCV) is a clinical infection that is important, affecting about 170 million people all over the world, that is, about 3% of the world population. The infection is a health concern among public health authorities worldwide. The disease has been indicated as a significant cause of chronic and acute hepatitis, hepatocellular carcinoma and liver cirrhosis. The primary mode of transmission among adults is through intravenous drug injection in cases where needs are shared. Before screening for hepatitis C was introduced in the form of a standard blood transfusion measure, blood transfusion was a major route for transmission for children and infants. Antenatal HCV infection rates vary the world over, with figures ranging between 1% and 2.5% in most European countries and above 10% in the majority of sub-Saharan Africa. Studies have shown that prevalence rates in some parts of Egypt could be as high as 40%. Today, infection rates depend on the number of mothers who are infected. This paper analyzes seven studies that investigate mother-to-child transmission of HCV infections. Summary of seven researches 1. A Significant Sex—but Not Elective Cesarean Section—Effect on Mother-to-Child Transmission of Hepatitis C Virus Infection HCV infection remains a major public health problem in society and especially during pregnancy. Risk transmission factors should be identified in order for the appropriate interventions to be put in place. It is against this backdrop that European Pediatric Hepatitis C Virus Network (2005) carried out a study of Hepatitis C Virus (HCV) mother-to-child transmission. The study, according to European Paediatric Hepatitis C Virus Network, was motivated by poor quantification of various risk factors that contribute to the spread of this disease. The research took the form of a multicenter prospective study whereby HCV-infected mothers as well as their infants were tested. Those children who had a polymerase chain reaction of HCV RNA that is equal to or greater than 2 and/or any anti-HCV antibodies within the 18-month duration since birth were considered to have been infected. The researchers found out that the vertical transmission rate of HCV was 6.2 per cent while the confidence level was 95 %. The likelihood of girls being infected was twice as much as that of boys. Caesarian section did not have any significant effect on the rate of infection for both boys and girls. For HCV vertical transmission, elective cesarean section (CS) did not have a protective effect. Women with a co-infection of HCV and HIV transmitted HCV readily compared to women with an infection of HCV only. However, this difference was not statistically significant. Maternal history of the patients’ injection drug use, breastfeeding and prematurity did not have a significant association with transmission. Transmission was very frequent among viremic women, although it was also noted to occur among a few nonviremic women as well. From this study, it was concluded that women should not be discouraged from breastfeeding or being exposed to an elective CS solely on the basis of HCV infection. The sex-association finding was very intriguing and it is probably a reflection of biological differences in response and susceptibility to infection. The finding that elective CS delivery has no protective effect on the risk HCV transmission risk is very significant and it is poised to affect the approach that is taken in dealing with mother-to-child transmission. However, for mothers of infected children, the duration of ROM was noted to be significantly longer than that of mothers of uninfected children. Through multivariate analysis, the finding relating to co-infected women being more likely to transmit the virus appeared to be not statistically significant. In a world where 3% of the entire world’s population is infected with the HCV virus, the findings are very significant. Estimates of mother-to-child transmission risks range between 3% and 10%, something about which researchers have not been very enthusiastic about when it comes to research work. In fact, majority of researchers have been focusing on only infant feeding and mode of feeding as the expense of statistical analyses. Focus on the former areas is motivated by the widely held notion that they are very amenable to intervention. Little attention is given to retrospective studies and analyses, a situation that makes the available findings on vertical transmissions lack sufficient statistical power. Maternal HCV load seems like a predominant risk factor of HCV mother-to-child transmission. This, though, has not yet been fully quantified in in-depth studies. However, it is supported by consistent findings that indicate an increase in risk among women who are co-infected with both HCV and HIV. For these women, it is thought that HCV loads are secondary to the immunosuppression that is HIV-driven. However, HIV positive women are today being treated using potent antiretroviral therapy (ART) which plays a crucial role of improving response to immunity as well as reducing HIV transmission. The issue of whether such a form of treatment has an impact on HCV transmission remains to be addressed by medical researchers. 2. Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus In a different study, the European Paediatric Hepatitis C Virus Network (2001) set out to find out the effects that infant feeding and the mode of delivery have on the risk of transmission of Hepatitis C virus transmission from mother to the child. Prospectively collected data was analyzed using pooled retrospective analysis. The findings of the research were such that both avoidance of breastfeeding and elective caesarian section could not be recommended for women with hepatitis C Virus infection only. However, in the case of HIV-infected women, both avoidance of breastfeeding and undergoing caesarian section delivery are strengthened in case they are also infected with HCV. The background of the study was described as manifesting itself in unclear research findings regarding vertical transmission. According to European Paediatric Hepatitis C Virus Network, (2001), the confirmation that vertical (mother-to-child) transmission of HCV occurs has heralded efforts aimed at identifying factors that are possibly associated with the risk of a child getting a HCV infection from the mother. Additionally, maternal HIV co-infection has also been noted to increase the risk of HCV vertical transmission. Additionally, Hepatitis C virus viraemia remains a risk factor for both HCV-infected patients and HCV/HIV-infected women. However, it is rare for transmission to take place from non-viraemic women. A suggestion has also been made to the effect that women with HCV virus that has been acquired through injecting drug use have a much higher likelihood of transmitting the HCV to their children. Interest in various effects of infant feeding and mode of delivery also remains high in the European Paediatric Hepatitis C Virus Network’s (2001) research. For instance, it has been noted that there is an increase in risk of transmission among children who are vaginally delivered compared to those who are born through Caesarian delivery. However, the statistical significance of these studies was highly questionable; many of these studies did not have the power to detect, in some cases, the infected children were less than 10, and the issue still remains unresolved (European Paediatric Hepatitis C Virus Network, 2001). The research was carried out in the form of a two-page questionnaire, which included two questions on the mode of delivery, maternal HIV infection and breastfeeding status. Definitions of the infection status were provided in all the four participating centers. One form was filled for every mother-child pair by local coordinators using data that had been prospectively collected in local databases and patient notes. Emphasis was put on mothers who had been born to mothers with HCV on or after the first day of the year 1992. Children with a history of blood transfusion were excluded from the study. Various factors were found to be associated with the infection status of the child. These factors included mode of delivery, infant feeding, and HIV co-infection. Fifty percent of all children did not have their breastfeeding status recorded, 10% of whom were found to suffer from HCV. Five hundred and three women (35.4%) were co-infected with HIV and HCV (European Paediatric Hepatitis C Virus Network, 2001).It was also confirmed that maternal HIV co-infection had a significant effect on increased risk of HCV infection. The multivariate analyses failed to provide any evidence of an association between type of infant feeding or mode of delivery and the risk of HCV infection among women who are infected with hepatitis C only. 3. Prevalence and Clinical Course of Chronic Hepatitis C Virus (HCV) Infection and Rate of HCV Vertical Transmission in a Cohort of 15,250 Pregnant Women Conte (2000) set out to investigate the prevalence and natural course of chronic hepatitis C infection by evaluating 15250 pregnant women from Northern Italy while at the same time assessing the HCV perinatal and vertical transmission. Conte (2000) note that many studies have been previously done on HCV infection before, with the anti-HCV positivity frequency being reported to range between 0.7% and 4.4 %, while the rate of viremia has been noted to range between 63% and 67%. However, Conte (2000) also indicates that there are only a few published studies that investigate the infection patterns of HCV during pregnancy. Evaluation of vertical transmission of HCV, according to Conte (2000) has been done through several studies whereby in one series, the transmission was noted to range between 0% and 20%, with the mean rating being 5%. An additional note was also provided relating to decline in the rate of sexual transmission of HCV and the drop in the posttransfusion hepatitis risk. In this case, Conte (2000) predicted that future interest in studies relating to mother-to-child HCV transmission would increase merely because of a decrease in other risk factors. The patients who were studied in Conte (2000) were recruited between 1995 and 1998. All the women were requested to undergo an aspartate transaminase (AST) test and then they were taken through clinical evaluations within the first months of pregnancy. All the participants had to give a written, informed consent before participating. In 259 cases (71%), the delivery was vaginal, whereas delivery by means of Cesarean section was reported in 106 (29%) cases. The research also involved screening of the participants for HCV-RNA positivity or negativity. It emerged that 72% of all the anti-HCV women who participated were viremic. This figure is comparable to the one that had been observed among blood donors as well as in the general population. The findings of the study were in line with those that had been obtained in some limited number of cases in the past (Conte). 4. Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission Gibb et al (2000) carried out a study on mother-to-child transmission of HCV whereby in the background to study, it was noted that there exists little information on the topic of investigation. Additionally, no interventions had been done to decrease the transmission rates of the disease (Gibb et al, 2000). Using data from HCV-infected women as well as their infants, Gibb et al (2000) embarked on a probabilistic model to estimate the diagnostic accuracy of PCR tests in three Ireland hospitals and in the British Paediatric Surveillance Unit. The time to HCV-antibody loss in infants who were not infected was also determined. The findings were that by eight months, about 50% of all uninfected infants were noted to become HCV-negative. By 13 months, this figure had risen to 95%. Out of the 441 mother-child pairs that were studied, sensitivity was represented by only 22% while estimated specificity of PCR in the case of HCV RNA was 97%. Most significantly, vertical transmission rate was noted to be 6.7%, about 3 times higher than those pairs who were HIV co-infected. The HIV figure took into consideration adjustments made in order to accommodate other intervening variables. However, delivery through caesarean section was associated with a lower transmission risk when it was done before membrane rupture. According to Gibb et al (2000), the study revealed, among other things, that HCV transmission takes place predominantly around delivery time. This is indicated by low sensitivity of HCV RNA immediately after birth. If these findings relating to caesarean section are confirmed in future studies, then it will be necessary for medical practitioners to reconsider the conventional medical procedures relating to antenatal HCV testing (Gibb et al, 2000). The findings relating to vertical transmission risks among HCV-infected women who had no HIV infection were consistent with the results of previous studies. However, Gibb et al (2000) notes that in one of the previous studies, there was no summary estimate due to lack of heterogeneity across various small studies. The study by Gibb et al (2000) was larger in size and scope compared to these smaller, inconclusive studies. Just like in previous studies, the current study showed HCV/HIV co-infection rates to be three times higher compared to that of HIV-negative women. As it had been previously suggested, this difference could be due to a high HCV viral load that is associated with immunodeficiency (Gibb et al, 2000). 5. Increased Risk of Mother-to-Infant Transmission of Hepatitis C Virus by Intrapartum Infantile Exposure to Maternal Blood High maternal viremia, intrapartum exposure to marternal blood that is virus-contaminated and infantile hypoxia increases the risk of HCV transmission in the process of vaginal deliveries (Steininger et al, 2003). In a study of risk of mother-to-infant transmission of HCV, Steininger et al (2003) found out that caesarean section can reduce the HCV transmission risk only in selected cases. The study was done using clinical and virological data from 73 pregnant women who were infected with HCV. The mothers had given birth to 74 children. The data from these two sources were merged retrospectively through logistic regression analysis, in order to investigate various risk factors for HCV vertical transmission. In the study, 82% of the mothers who turned out to be HCV-RNA–positive were HCV-infected. Ten percent of the women were co-infected with the HIV virus. Nine children were infected with HCV, one was HIV-infected but none was found to be HIV-HCV co-infected (Steininger et al, 2003). Among all vaginal deliveries, a higher mean HCV load of mothers who had transmitted HCV to their infants was recorded in comparison to that of those who did not transmit the virus. The risk of virus-contamination was increased by reduction of the pH of the umbilical cord blood or the incidences of vaginal or perineal laceration during delivery. In an introduction to the study, Steininger et al (2003) noted that in developed countries, majority of new infections of HCV are acquired in the process of injection drug use (IDU). Although vertical transmission from the mother to the infant still remains rare during delivery, with all reported average transmission rates ranging between 5% and 10%, it remains the predominant mode through which infants acquire HCV (Steininger et al, 2003). Steininger et al (2003) also report the controversy that exists on the issue of the threat of the high maternal virus load that is supposedly poses a high transmission risk. Furthermore, the timing of perinatal transmission also remains uncertain. Additionally there is limited understanding of all the obstetrical factors influencing HCV vertical transmission (Steininger et al, 2003). The uncertainty about risk factors influencing vertical transmission is said to stand in contrast to that of HCV-1, where all the risk factors have been clearly identified, that is, vaginal delivery, RNA level and plasma HIV-1 level. In the study carried out by Steininger et al (2003), the study population consisted of HCV-infected women who had been put under study at the University of Vienna, Vienna, and who had had given birth in between the years 1994 and 1999. In the virological investigation, HCV antibodies were determined while during the clinical investigation, questionnaires were used to assess clinical data provided by HCV-infected mothers. The questionnaires were sent to mothers and their respective gynecologists soon after delivery as well as through reviews of case obstetric notes and case histories. The effects of various risk factors relating to HCV perinatal transmission should be evaluated using unconditional logistic regression analysis. According to Steininger et al (2003), this is because HCV load may change with time, meaning that only qualitative and quantitative HCV-PCR results that have been obtained in samples can only be taken within a period of 150 days both before and after the delivery period. This is often done in order to be used for the estimation of risk of mother-to-child transmission of HCV. 6. When does mother to child transmission of hepatitis C virus occur? According to Mok et al (2005), at least one third of infants get HCV during the intrauterine period. The research that that led them to this conclusion was based on a prospective cohort approach and was done on 54 children with HCV, who had been tested less than three days after birth. Seventeen children (31%) of the children were positive during the first days of life and were assumed to have gotten the infection in utero. A sex association was not noted in testing positive for PCR. It was noted that children who had evidence of intrauterine infection had a high probability of being of a low birth weight. However, children who were born to HCV/HIV co-infected women were noted to be PCR positive within the first 3 days since birth. However, this difference failed to reach a level of statistical significance (Mok et al, 2005). According to Mok et al (2005), the role that genotypes play in mechanism and timing of infections needs to be explored even further. Mok et al (2005) says that the rate of HCV mother-to-child transmission infection ranges between 4% and 10%. Maternal HIV/HCV co-infection has been closely linked with a four-fold increase in transmission of HCV infection. Mok et al (2005) indicates that women with HCV have a higher likelihood of transmitting the virus compared to non-viraemic women. Although transmission through breastfeeding is considered to be rare, it cannot be excluded. The study by Mok et al (2005) was based on the need to determine the exact time when vertical transmission of HCV takes place. The determination of such a time would be very helpful in the development of successful strategies of preventing mother-to-child transmission as well as other HCV-associated factors. Just like in Steininger et al (2003), the study by Mok et al (2005) involved use of clinical and virological characteristics, only that this time round, the data being considered is one relating to the first three days of the infants’ lives. Two groups of infants were formed: those who were PCR-positive and those who were PCR-negative. The sex and the mode of delivery are not associated with the condition of being PCR positive in an infant’s first three days of life (Mok et al, 2005). In each group, medial gestation was 39 weeks; in the first group, the range was between 33and 41 weeks while in the second group, the range was between 34 and 41 weeks. In this research, a multivariate analysis was not done since it was impossible to do so with only 54 children. Meanwhile, bivariate odd ratios calculations were made whereby one factor was adjusted for at a time, whenever this was possible. The odd ratio for maternal HIV infection effects increased within a range of 2.42 to 7.50 (97%). In a discussion of the study, it was highlighted that one of the 37 infants who turned out to be HCV-negative within three days after birth was considered to be infected because of the positive results of antibody tests done within 18 months. After the initial result that revealed that 37 infants were PCR-negative, other tests were done three months later, whereby 27 of these infants were PCR-positive. For the remaining infants, the second tests were done after 6 and seven months respectively. By seven months of age, 33 out of 36 infants were PCR positive. The remaining three infants had turned positive by 12, 13, and 15 month respectively. One of these three infants had been breastfed for 12 weeks while the other two had not been breastfed. It was difficult to determine the timing of the infection 12 infants in group 2 who turned positive for PCR tests later in life. These infants either had been breastfed or they had late negative PCR test results generated (Mok et al, 2005). 7. Obstetric management of hepatitis C-positive mothers: analysis of vertical transmission in 559 mother-infant pairs The objective of this study by McMenamin et al (2008) was to assess vertical transmission rates of HCV in the 2 tertiary level maternity units. The study was conducted in the form of a retrospective review of hepatitis C positive mothers vis-à-vis their pregnancy outcomes. The rate of HCV infection in the 74.649 deliveries that produced 559 liveborn infants born to 545 HCV-infected mothers was 0.7%. During the neonatal period, the number infants who tested negative for HCV were 423, whereas 18 (3.2%) were positive. Follow-ups for 21.1% of the infants were not possible and therefore, their outcomes were not accounted for in the research. Among HCV-negative mothers, no single case of vertical transmission was noted. McMenamin et al (2008) concluded that the vertical transmission rate for HCV was 4.1%. The findings were contrary to the recommendation that a planned caesarean be organized for purposes of reducing vertical transmission of HCV. Discussion Research on mother-to-child transmission of HCV infection has been going on for a very long time. Zuccotti & Ribero (1995) evaluated vertical transmission among 37 pregnant women. Twenty of these women had both HCV and HIV antibodies. HIV-positive women had the HCV sub-types 3a and 1a. Infection with the ribonucleic acid of HCV and the antibody of HIV were noted in 30.7% of 13 women as well as 25 % of the women who had HCV RNA alone. The research’s findings resembled those that had been arrived at by Kurauchi (1993) only that in the latter case, emphasis was in the perinatal period alone, with specific attention being put on breast milk, contamination with maternal blood and vaginal discharge. Weiner & Thaler (1993) found out a unique, predominant variant of hepatitis C virus in infants born to mothers with multiple variants. According to Lam & McOmish (1993), a human immunodeficiency virus infection with is not a significant co-factor in transmission of mother-to child infection of HCV. All these are results of early researches on various factors that were thought to affect mother-to-child transmission of Hepatitic C virus. The results of some of these researches have been proven to be wrong by subsequent researches. For instance, Riva (2005) noted that HIV was an important factor in transmission of HCV infection from the mother to the child. Multivariate analysis is the most commonly used method of analysis in epidemiology research on HCV mother-to-child transmission (European Pediatric Hepatitis C Virus Network (2005), Steininger et al, 2003), Mok et al (2005), Novati et al (1992), Zanetti (1999), Resti (1998), Okamoto (2000), Lin (1994). In other researches, clinical and virological data were analyzed in order for various factors, including HCV/HIV co-infection, breast feeding, caesarian section, contamination in maternal blood and vaginal delivery issues to be studied (Schröter (2000), Ferrero (2003), Polywka & Feucht (1997), Yeung (2001). Earlier researches whereby clinical and virological data were used seemed to yield different results compared to those ones where unconditional logistic regression analysis and prospective cohort methods were used. The use of unconditional logistic regression analysis in studying HCV perinatal transmission and other related factors was recommended, especially in small samples, where multivariate or bivariate regression analyses could not be used Inoue, Y. & Takeuchi, K. (1992), (Ruiz-Extremera, 2000), (Paccagnini & Principi, 1995), (Matsubara, Sumazaki & Takita, 1995). Conclusion Transmission of HCV infection from mother to child remains a very nagging issue in today’s HCV research. Recent researches have resulted in the various significant findings relating to transmission patterns, duration of transmission, and prenatal risk factors. The methodologies used have ranged from multivariate analysis to unconditional logistic regression analysis. When clinical and virological data sources are used, the outcomes seem to differ slightly depending on the methodological approaches used to analyze it. There is a need for various vertical transmission risk factors to be identified in the case of HCV just as it has been done previously in the case of HCV-1. Today, the most significant findings relate to the effect of elective CS, breast feeding, HCV-contamination in maternal blood and HIV/HCV co-infection. References Conte, D., Fraquelli, M., Prati, M., Colucci, A. & Minola, E. (2000). 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