Seroepidemiologic Study of Spermatozoal Transmission of Hepatitis B Virus (HBV)

• ClinicalTrials.gov Identifier: NCT01574521
• Recruitment Status: Completed
• First Posted: April 10, 2012
• Last Update Posted: April 10, 2012
• Sponsor: YiYang Zhu
• Information provided by (Responsible Party): YiYang Zhu, Taizhou Hospital

Study Description

Brief Summary:

Animal experiments demonstrated that father might transmit HBV vertically via male germ line, however, whether it is really existed in human remains to be determined. Since HBV is a blood-borne virus, the unvaccinated pregnant women would be at risk for HBV exposure if their fetuses carried the virus from fathers. If women had been vaccinated for HBV before conception, what would happen to a maternal immune system if her fetus carried HBV from spermatozoa? However, the literature on transmission of HBV by spermatozoa in vivo is rare, the viral replicating status and fetal immune response in uterus are unknown. The aim of study was to detect father-to-fetus transmission of hepatitis B virus (HBV) in uterus.

Condition or disease
Hepatitis B

Detailed Description:

Transmission of hepatitis B virus (HBV) from mother-to-infant is the predominant route in most high prevalence areas such as China. However, father-to-child transmission also plays another important role in the prevalence of hepatitis B. Children infected with HBV from their carrier fathers would be horizontally by postnatal intimate contact or vertically via male germ line. The latter is considered an intrauterine infection, however, whether it is really existed in human remains to be determined.

In past decades, several experiments reported there presences of integrated HBV DNA in human spermatozoal chromosomes. Studies on embryos hybridized with mammalian ova and human spermatozoa were also confirmed that sperm-integrated HBV DNA can replicate and express the HBV protein in two-cell' hybrid embryos. All above findings demonstrated that father might transmit HBV to fetus by spermatozoa in theory.

Since HBV is a blood-borne virus, the unvaccinated pregnant women would be at risk for HBV exposure if their fetuses carried the virus from fathers. On other hand, maternal antibodies can pass through the placenta and enter the fetal circulation freely. If women had been vaccinated for HBV before conception, thus some attractive questions are raised that what would happen to a maternal immune system if her fetus carried HBV from spermatozoa? Would the fetus be passive immunized by hepatitis B immunoglobulin leaked from maternal circulation? However, the literature on transmission of HBV by spermatozoa in vivo is rare, the viral replicating status and fetal immune response in uterus are unknown. Only one study had detected HBV DNA and serological makers on eight aborted fetuses suspected with HBV transmission via spermatozoa, but it is a small sample study and the maternal serological status is uncertain.

Specimens applied for evaluating intrauterine infection include amniotic fluids, placental tissue and neonatal peripheral blood. Because postnatal sample is inevitably to be contaminated by maternal blood during delivery, it would be useless to determine the time when the infection was occurred (before or during the partum). A better alternative is detecting fetal infection before the partum by prenatal diagnostic technique. Comparing to the postnatal specimens, intrauterine specimens obtained from amniocentesis or cordocentesis can minimize the contamination of maternal blood. It is also a safety technique and the risk of nosocomial infection caused by invasive procedures is very low. The aim of this study was to investigate the fetal hepatitis B seroepidemiology by prenatal diagnostic technique and to find the evidence of HBV vertical transmission via spermatozoa.

Study Design

• Study Type: Observational
• Actual Enrollment: 407 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: A Fetal Seroepidemiologic Study in Hepatitis B Virus Transmitted Via Male Germ Line
• Study Start Date: January 2008
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: December 2011

Groups and Cohorts

Group/Cohort
Only father carrier; fetuses whose fathers were HBV carriers whereas mothers negatively.
only mother carrier; fetuses whose mothers were HBV carriers whereas fathers negatively.
both parents carriers; fetuses whose both parents were HBV carriers

Outcome Measures

Primary Outcome Measures :

1. positive rate of HBV in uterus [ Time Frame: one year ]
   HBV infection confirmed by serological makers(HBsAg, HBeAg, anti-HBs, anti-HBe anti-HBc)and HBVDNA. Samples were assessed by enzyme immunoassays and FQ-PCR

Secondary Outcome Measures :

1. response rate of postnatal vaccination [ Time Frame: half a year after immunization series ]
   neonates received three doses of recombinant vaccines were given on a 0-, 1-, and 6-month schedule, and other 100 IU of HBIG was administrated within 24 hours after birth. Post-vaccination testing for efficacy evaluation was performed at one-year old (half a year after immunization series).

Biospecimen Retention:   Samples With DNA

whole blood, serum,amniotic fluid

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 45 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

The research consisted of the pregnant women who visited for prenatal diagnosis during the January 2008 and June 2010.

Criteria

Inclusion Criteria:

• one or both of pregnant Woman and her husband were HBV carriers
• indicated for amniocentesis or cordocentesis

Exclusion Criteria:

• indicated for chorionic villous sampling

Contacts and Locations

Locations

China, Zhejiang

Taizhou Hospital of Zhejiang Province

LinHai, Zhejiang, China, 317000

Sponsors and Collaborators

YiYang Zhu

Investigators

• Study Director: Yi-Yang Zhu, MD; Taizhou Hospital of Zhejiang Province

More Information

• Responsible Party: YiYang Zhu, Center for Prenatal Diagnosis, Taizhou Hospital
• ClinicalTrials.gov Identifier: NCT01574521
• Other Study ID Numbers: tz2008032
• First Posted: April 10, 2012
• Last Update Posted: April 10, 2012
• Last Verified: April 2012

Additional relevant MeSH terms:

Hepatitis A; Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepadnaviridae Infections; DNA Virus Infections