Caesarean section versus vaginal delivery for preventing mother to infant hepatitis C virus transmission
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the available evidence from randomised controlled trials that a policy of elective caesarean delivery versus vaginal delivery reduces the incidence of perinatal transmission of the hepatitis C virus.
Background
Most infants who acquire hepatitis C virus (HCV) infection do so in utero or in the peripartum period (Mok 2005; Resti 1998). Specifically, breastfeeding is not thought to be an important mode of transmission (Conte 2000; Resti 1998; Ruiz‐Extremera 2000). Infants who acquire HCV in utero or at birth do not develop clinically apparent liver problems in early childhood but most do develop chronic HCV infection and are likely to be at risk of longer‐term problems related to chronic liver disease, including hepatic fibrosis, cirrhosis, and hepatocellular carcinoma (Rerksuppaphol 2004; Resti 2003; Tovo 2000). There is no available vaccine for preventing HCV infection. Pharmacological treatment regimens are successful in eradicating infection in more than half of the treated individuals but these are not used in pregnancy (Gluud 2002).
The rate of mother to infant transmission of HCV is about 5% (Schwimmer 2000; Thomas 1998). Observational studies indicate that mother to infant transmission occurs predominantly in those women who have HCV ribonucleic acid detectable in their blood and that the risk of transmission is highest in those mothers who have a high hepatitis C viral load at the time of birth (Ceci 2001; Dal Molin 2002; Dore 1997; Resti 1998). Co‐infection with the human immunodeficiency virus (HIV) may also be a risk factor for transmission (Tovo 1997). The HCV genotype does not appear to affect the rate of perinatal HCV transmission (Resti 1998).
The overall prevalence of HCV infection among pregnant women in Europe and North America ranges from about 0.2% to 3% (Ades 2000; Conte 2000; Kim 2002). HCV seroprevalence is higher among pregnant women who live in economically deprived areas because of the high prevalence of specific major risk factors for transmission, especially injecting drug misuse (Goldberg 2001; Hutchinson 2002; Hutchinson 2004; McIntyre 2001). The HCV seroprevalence rate is also very high (more than 10%) in some developing countries where the practice of re‐use of unsterilised injecting equipment in healthcare settings is common (Ahmad 2004; Kumar 1997).
Observational studies have generally not provided evidence that the mode of delivery (caesarean section versus vaginal delivery) affects the risk of mother to infant HCV transmission (Ceci 2001; Conte 2000; Dal Molin 2002; EPHCVN 2001; Granovsky 1998; Resti 1998; Resti 2002; Spencer 1997; Tajiri 2001; Thomas 1998; Tovo 1997). Consensus statements and guidelines have concluded that elective caesarean section does not afford the infant protection from HCV infection and that routine screening for HCV in pregnancy is not warranted (NICE 2004; Seeff 2003). However, in these observational studies some of the caesarean sections occurred in labour following rupture of amniotic membranes. Uterine contractions may facilitate perinatal transmission of blood borne viruses by causing placental breaks that allow maternal blood to be passed to the fetus. The duration of membrane rupture has been shown to correlate with the incidence of mother to infant HCV transmission (Spencer 1997). Data from other observational studies have suggested that the rate of perinatal HCV infection might be reduced if infants are delivered by caesarean section prior to rupture of membranes (Gibb 2000; Paccagnini 1995).
Given the uncertainty of findings from observational studies, we aim to determine if there is any evidence from randomised controlled trials that offering elective caesarean section to mothers who are infected with HCV affects the risk of mother to infant HCV transmission. We recognise that a policy of offering delivery by elective caesarean section for women infected with HCV may have other consequences for mothers and infants in addition to the possible prevention of HCV transmission (Lilford 1990; Morrison 1995). These are important to consider given that the absolute risk of perinatal HCV transmission is low. These issues are also to be explored in a Cochrane review of caesarean section for non‐medical reasons at term (Lavender 2004).
Objectives
To evaluate the available evidence from randomised controlled trials that a policy of elective caesarean delivery versus vaginal delivery reduces the incidence of perinatal transmission of the hepatitis C virus.
Methods
Criteria for considering studies for this review
Types of studies
Controlled trials using random or quasi‐random participant allocation. Unpublished studies and studies published only as abstracts will be included only if assessment of study quality is possible and if other criteria for inclusion are fulfilled. We will contact authors of studies published as abstracts for further information.
Types of participants
Pregnant women with serological evidence of hepatitis C virus (HCV) infection. We plan separate comparisons of studies in which only women who had HCV detectable by ribonucleic acid (RNA) polymerase chain reaction (PCR) in blood participated and in which women co‐infected with HIV and HCV participated.
Types of interventions
Planned delivery by elective caesarean section (that is, planned to take place before rupture of membranes, or onset of labour or both) versus planned vaginal delivery. Data should be available for intention‐to‐treat analyses.
Types of outcome measures
Primary outcomes (HCV transmission‐related)
(1) Hepatitis C infection: positive HCV‐RNA PCR in blood on two separate occasions (including one at more than three months after birth), or positive anti‐HCV serology at age 18 months or more (Dunn 2001; Gibb 2000).
(2) Liver disease: clinical, biochemical, or histological evidence of chronic hepatitis, hepatic fibrosis, cirrhosis, or hepato‐cellular carcinoma.
(3) Need for treatment for chronic HCV infection or chronic liver disease.
Secondary outcomes (morbidities related to the actual method of delivery)
(1) Maternal morbidity: admission to an intensive care unit; postpartum haemorrhage and/or anaemia requiring blood transfusion; deep venous thrombosis and/or pulmonary embolism; postpartum infection (wound‐site, genito‐urinary tract, chest); postpartum haematoma (wound‐site, perineal); women's negative views of their birth experience assessed using a validated tool; postnatal depression or post traumatic stress syndrome assessed using a validated tool; other urogynaecological complications (for example, dyspareunia; uterovaginal prolapse; urinary, flatus, or faecal incontinence); subsequent pregnancy complications (ectopic pregnancy, abruption, sub‐fertility, miscarriage, hysterectomy, major obstetric haemorrhage).
(2) Infant morbidity: neonatal intensive care unit admission; respiratory distress syndrome requiring mechanical ventilation and/or surfactant replacement therapy; transient tachypnoea of the newborn requiring supplemental oxygen therapy; neonatal encephalopathy (as defined by trial authors).
Search methods for identification of studies
We will contact the Trials Search Co‐ordinator to search the Cochrane Pregnancy and Childbirth Group Trials Register.
The Cochrane Pregnancy and Childbirth Group's Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from:
1. quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
2. monthly searches of MEDLINE;
3. handsearches of 30 journals and the proceedings of major conferences;
4. weekly current awareness search of a further 37 journals.
Details of the search strategies for CENTRAL and MEDLINE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the 'Search strategies for identification of studies' section within the editorial information about the Cochrane Pregnancy and Childbirth Group.
Trials identified through the searching activities described above are given a code (or codes) depending on the topic. The codes are linked to review topics. The Trials Search Co‐ordinator searches the register for each review using these codes rather than keywords.
In addition, we will search the Cochrane Central Register of Controlled Trials (The Cochrane Library) using the following search strategy:
#1 hepatitis (all fields)
#2 Hepatitis (explode MeSH)
#3 cesarean or caesarean or cesarian or caesarian or cesarien or caesarien (all fields)
#4 Delivery,Obstetric (explode MeSH)
#5 (#1 OR #2) AND (#3 OR #4)
We will not apply any language restriction in searching and including papers. Trials that have been reported only as abstracts will be eligible if sufficient information is available from the report, or from contact with the authors, to fulfil the inclusion criteria.
Data collection and analysis
(1) Two authors will screen the title and abstract of all studies identified by the above search strategy and obtain the full articles for all potentially relevant trials. Both authors will re‐assess independently the full text of these reports using an eligibility form based on the prespecified inclusion criteria. We will exclude those studies that do not meet all of the inclusion criteria and will state the reasons for exclusion. We will request additional information from the trial author to clarify methodology. Where it will not be possible to evaluate the study because of language problems or missing information, we will classify the study as a 'study awaiting assessment' until a translation or further information can be obtained. The authors will resolve any disagreements by discussion until consensus is achieved.
(2) Two authors will assess the studies independently for selection bias (allocation concealment), performance bias (although it is unlikely that women or clinicians will be blind to the nature of the intervention), and attrition bias (completeness of assessment in all randomised individuals) (Alderson 2004).
(3) Two authors will use a data collection form to aid extraction of relevant information and data from each included study. Each author will extract the data separately, compare data, and resolve differences by discussion until consensus is achieved. If data from the trial reports are insufficient, we will contact the trial authors for information. We will include individual outcome data in the analysis if they meet the prestated criteria in 'Types of outcome measures'.
(4) We will process included trial data as described in the Cochrane Reviewers' Handbook (Alderson 2004). We will present outcomes for categorical data as relative risk, risk difference, and number needed to treat, with respective 95% confidence intervals. For continuous data, we will use the weighted mean difference with 95% confidence intervals.
(5) We will estimate the treatment effects of individual trials and examine heterogeneity between trial results by inspecting the forest plots and quantifying the impact of heterogeneity in any meta‐analysis using a measure of the degree of inconsistency in the studies' results (I² statistic). If we detect statistical heterogeneity, we will explore the possible causes (for example, differences in study quality, participants, intervention regimens, or outcome assessments) using post hoc subgroup analyses. We plan to use a fixed‐effect model for meta‐analyses. We will examine publication bias using a funnel plot, and a regression approach to assess funnel plot asymmetry (Egger 1997).
