Scolaris Content Display Scolaris Content Display

Vacunación de la hepatitis B durante el embarazo para la prevención de la infección en lactantes

Contraer todo Desplegar todo

Antecedentes

La infección de la hepatitis B en los lactantes aumenta el riesgo de infección crónica, cirrosis o cáncer de hígado (carcinoma hepatocelular) en el adulto. La transmisión perinatal es una vía común de la infección.

Objetivos

Evaluar la efectividad y los efectos adversos de la vacuna de la hepatitis B administrada a las embarazadas para prevenir la infección por el virus de la hepatitis B en lactantes.

Métodos de búsqueda

Se realizaron búsquedas en el Registro de Ensayos del Grupo Cochrane de Embarazo y Parto (Cochrane Pregnancy and Childbirth Group (31 de agosto 2014).

Criterios de selección

Ensayos controlados aleatorizados (ECA) que evalúan la vacunación de la hepatitis B comparada con placebo o ningún tratamiento durante el embarazo para la prevención de la infección en lactantes. Los cuasi ECA y los estudios cruzados (cross‐over) no fueron elegibles para su inclusión.

Obtención y análisis de los datos

Dos autores de la revisión de forma independiente evaluaron los ensayos para inclusión. Si se había incluido algún estudio, se planeó evaluar el riesgo de sesgo, extraer los datos y comprobar la exactitud de los datos de todos los estudios incluidos.

Resultados principales

No se identificaron estudios para la inclusión.

Conclusiones de los autores

No se encontraron ECA que evaluaran los efectos de la vacuna de la hepatitis B durante el embarazo para la prevención de la infección en lactantes. Por lo tanto, esta revisión no puede proporcionar orientación para la práctica clínica en esta área. Sin embargo, identifica la necesidad de realizar ensayos clínicos aleatorizados bien diseñados para evaluar el efecto de la vacuna contra la hepatitis B durante el embarazo en la incidencia de la infección infantil y para determinar cualquier efecto adverso.

PICO

Population
Intervention
Comparison
Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Vacunación de la hepatitis B durante el embarazo para la prevención de la infección en lactantes

La hepatitis B es una infección causada por el virus de la hepatitis B y ocurre en todo el mundo. En los lactantes y los niños, las dos fuentes principales de infección son la transmisión de una madre con infección por el HBV o vivir en una vivienda donde existan pacientes con infección. La transmisión perinatal es frecuente en áreas sumamente endémicas. Las vacunas de la hepatitis B están disponibles y requieren una serie de tres dosis en seis meses. Los efectos secundarios más frecuentes son dolor en el sitio de la vacunación y fiebre leve a moderada. La inmunización materna con la vacuna de la hepatitis B puede ser una forma de prevenir la infección por hepatitis B en los lactantes, antes de que se les pueda administrar la vacuna de la hepatitis B, y de brindarle protección al lactante. Los lactantes con infección por el virus de la hepatitis B tienen mayores probabilidades de desarrollar complicaciones como infección crónica, cirrosis o cáncer hepático (carcinoma hepatocelular). Esta revisión no encontró evidencia de ensayos controlados aleatorizados con respecto a los efectos de la vacuna de la hepatitis B para la prevención de la infección en lactantes.

Authors' conclusions

Implications for practice

This review found that there were no randomized controlled trials (RCTs) assessing the effects of hepatitis B vaccine during pregnancy for preventing infant infection. Consequently, this review cannot provide guidance for clinical practice in this area.

Implications for research

This systematic review has identified the need for well‐designed RCTs to assess the benefits and adverse effects of hepatitis B vaccine during pregnancy compared with placebo or no treatment for preventing infant infection. The trials should include clinical outcomes of the incidence of hepatitis B virus infection in infants.

There were many studies of using hepatitis B immunoglobulin (HBIG) during pregnancy to prevent neonatal infection. Further meta‐analyses are needed to determine the effectiveness and adverse effects of HBIG administered to pregnant women for preventing HBV infection in infants.

Background

Description of the condition

Hepatitis B virus (HBV) is an enveloped, double‐stranded DNA virus. Hepatitis B is an infection caused by the HBV and it occurs worldwide. The highest rates of HBV carriers are found in developing countries with limited medical facilities. In highly endemic areas of Asia, Africa and the Pacific, approximately 75% of hepatitis B carriers usually acquire the virus perinatally or in childhood (Safary 2000). In western and northern European countries and in North America, HBV infection is relatively rare and acquired primarily in adulthood. HBV infections result in 500,000 to 1.2 million deaths per year caused by chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) (Lavanchy 2004). Globally, HBV causes 60% to 80% of the world's primary liver cancers (Parkin 2001).

Diagnosis of hepatitis is made by biochemical assessment of liver function and coagulation studies (Hollinger 2001). Diagnosis is confirmed by demonstration of specific antigens and/or antibodies. Three clinically useful antigen antibody systems have been identified for hepatitis B: (1) hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti‐HBs IgG); (2) antibody (anti‐HBc IgM) and anti‐HBc IgG) to hepatitis B core antigen (HBcAg); and (3) hepatitis B e antigen (HBeAg) and antibody to HBeAg (anti‐HBe) to determine infectivity.

For infants and children, the two primary sources of HBV infection are perinatal transmission from infected mothers and horizontal transmission from infected household contacts. Perinatal transmission is common in hyperendemic areas, especially when HBsAg carrier mothers are also HBeAg positive (Hollinger 2001; Mahoney 1999). For a newborn infant whose mother is positive for both HBsAg and HBeAg, the risk for chronic HBV infection is 70% to 90% by six months postpartum in the absence of postexposure immunoprophylaxis (Wong 1984). By comparison, the infant risk for chronic infection is less than 10% in the mother who is HBeAg negative (Stevens 1985). Of those persons who are infected with HBV as infants or young children, 25% to 90% become chronic carriers, and approximately 25% of those with chronic infection die prematurely from cirrhosis or liver cancer (hepatocellular carcinoma) (Gitlin 1997; McMahon 1990). Development of chronic HBV infection at an early age increases the risk of HCC more than infection at older age (Hsieh 1992). Nearly 100% of children with HCC were hepatitis B surface antigen seropositive (Chang 1998). Breastfeeding by an HBsAg positive mother does not increase the risk for acquisition of HBV infection in the infant (Beasley 1975).

Description of the intervention

Hepatitis B vaccines are composed of the surface antigen of HBV (HBsAg), and are produced by two different methods: plasma‐derived or recombinant DNA (Assad 1999). Plasma‐derived vaccines, derived from the plasma of HBsAg‐positive donors, consist of highly purified, formalin‐inactivated and/or heat‐inactivated, alum‐adsorbed, hepatitis B subvirion particles (22 nm) of HBsAg that are free of detectable nucleic acid, and, therefore, noninfectious. Recombinant DNA yeast‐derived or mammalian cell‐derived vaccines, the S gene (pre‐S1, pre‐S2, S), is cloned and isolated, inserted into an expression plasmid and introduced into yeast or mammalian cells. The desired protein is expressed and assembled into 22 nm antigenic particles. As on natural HBsAg particles, the epitope that elicits the most important immune response is exposed on the surface of artificial particles. Vaccines used for primary prevention have effectively reduced the risk of infection in most populations (Mahoney 1993). Completion of hepatitis B vaccine programs induces protection in about 95% of recipients (Jackson 2007). Vaccination during pregnancy is safe and provides passive transfer of antibodies to the newborn (Anonymous 1991; Gupta 2003; Levy 1991).There are no known side effects from vaccination, in either pregnant women or their offspring (Grosheide 1993). The most common side effects from hepatitis B vaccination are pain at the injection site and mild to moderate fever (Andre 1989; Greenberg 1993).

Hepatitis B vaccine is given into the deltoid muscle by injection in a series of three doses (De Lalla 1988; Krugman 1981). The first shot is given at the elected date; the second dose a month later; and the third dose six months after the first dose. Vaccine batches should be stored at 2° to 8°C. Freezing destroys the potency of the vaccine. Factors that may reduce the immunogenicity of hepatitis vaccines include age (greater than 40 years), weight, genetics, hemodialysis, HIV infection, immunosuppression, tobacco smoking, subcutaneous injection, injection into the buttocks, and accelerated schedule (Ingardia 1999).

How the intervention might work

The mechanism of hepatitis B vaccination during pregnancy for preventing neonatal infection is the production of maternal antibodies that can be transferred across the placenta and provide the neonate with high antibody titers. This could protect the neonate from horizontal infection until active immunization after birth is protective (Reddy 1994).

Why it is important to do this review

Complex HBV epidemiology makes it difficult to evaluate and compare the effectiveness of different immunization policies. HBV infection rates vary in different parts of the world according to the pattern of hepatitis B transmission. In high endemic populations, transmission during delivery is considered for the main mode of perinatal transmission such as close contact with a caregiver who had HBV infection (Ghendon 1987). Many countries have implemented universal hepatitis B immunization at birth, which provides long‐term protection against infection in more than 90% of healthy people (Shepard 2006). Despite this, some infants who are born to HBV sero‐positive mothers have become infected by HBV despite having received passive‐active immunoprophylaxis (Ngui 1998). A prevention program by maternal hepatitis B vaccine immunization may be a way of preventing hepatitis B infection in infants before hepatitis B vaccine can be administered and provide protection. However, the ideal plan for hepatitis B vaccine administration during pregnancy, taking into consideration risk factors (high risk of HBV infection or the general population); endemic populations (high or low); and cost effectiveness, is not known.

Objectives

To assess the effectiveness and adverse effects of hepatitis B vaccine administered to pregnant women for preventing HBV infection in infants.

Methods

Criteria for considering studies for this review

Types of studies

We considered randomized controlled trials (RCTs) of hepatitis B vaccination during pregnancy for preventing infant infection. The randomized units could be individual or clustered (e.g. hospitals). Cross‐over trials and quasi‐randomized trials were not eligible for inclusion.

Types of participants

.All pregnant women who had negative test results of hepatitis B virus serology.

Types of interventions

Hepatitis B vaccine compared with placebo or no treatment.

Types of outcome measures

Primary outcomes

  • Incidence of hepatitis B virus infection in infants.

Secondary outcomes

  • Hepatitis B antibody for hepatitis B virus (HBs Ab) in newborns up to six months after birth.

  • Maternal antibody for hepatitis B virus (HBs Ab).

  • Adverse maternal effects such as local reactions at injection site (soreness, swelling, erythema); fatigue; fever; headache.

Search methods for identification of studies

The following methods section of this review is based on a standard template used by the Cochrane Pregnancy and Childbirth Group.

Electronic searches

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Trials Search Co‐ordinator (31 August 2014).

The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

  2. weekly searches of MEDLINE;

  3. weekly searches of Embase;

  4. handsearches of 30 journals and the proceedings of major conferences;

  5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Details of the search strategies for CENTRAL, MEDLINE and Embase, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group.

Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co‐ordinator searches the register for each review using the topic list rather than keywords.

We did not apply any language restrictions.

Data collection and analysis

For methods used in the previous version of this review, seeSangkomkamhang 2011.

For the 2014 update, two review authors independently assessed for inclusion the one report identified as a result of the search strategy and excluded it (Wang 2008) (see Characteristics of excluded studies). If future searches identify trials for inclusion, we will use the methods described in Appendix 1.

Results

Description of studies

Results of the search

The search of the Cochrane Pregnancy and Childbirth Group's Trials Register retrieved 13 studies. Eleven studies did not involve hepatitis B vaccine and were excluded. We sought full reports of the remaining two studies for detailed assessment. We identified only one full report of randomized controlled comparison between two doses and three doses of hepatitis B vaccine in pregnancy. The other study was only in abstract form.

Included studies

There are no included trials in this review.

Excluded studies

We excluded 13 studies, mostly because they assessed hepatitis B immunoglobulin (HBIG) for preventing infant hepatitis B infection, or they were not RCTs. One RCT compared two doses versus three doses of hepatitis B vaccine. For details, seeCharacteristics of excluded studies.

Risk of bias in included studies

Not applicable as there are no included studies.

Allocation

Not applicable as there are no included studies.

Blinding

Not applicable as there are no included studies.

Incomplete outcome data

Not applicable as there are no included studies.

Selective reporting

Not applicable as there are no included studies.

Other potential sources of bias

Not applicable as there are no included studies.

Effects of interventions

Not applicable as there are no included studies.

Discussion

Summary of main results

We found no studies to evaluate the effectiveness of hepatitis B virus during pregnancy in preventing neonatal infection.

Overall completeness and applicability of evidence

There are no studies that met our inclusion criteria.

Quality of the evidence

There are no studies that met our inclusion criteria.

Potential biases in the review process

We followed the process of review as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). There were no conflicts of interest with the review authors.

Agreements and disagreements with other studies or reviews

There are no other reviews and studies related to the efficacy and side effects of hepatitis B vaccine during pregnancy for preventing infant infection.