The Effect of Anti-viral Drugs Used in Late Pregnancy on Long-term Development of Children

The Effect of Anti-viral Drugs Used in Late Pregnancy in Mothers With Hepatitis B Virus Infection on Long-term Development of Children

Mother to child transmission(MTCT) is the main route of hepatitis B virus(HBV) transmission.High HBV DNA level of pregnant women is the main risk factor of MTCT. Many literatures demonstrate that using nucleoside (acid) analogs in late pregnancy can significantly reduce HBV DNA level and effectively blocking MTCT. Therefore, treatment guidelines of hepatitis B in Europe and the Asia Pacific region clearly pointed out: Nucleoside (acid) analogs can be used in pregnant women after 28 weeks of gestation for blocking MTCT in mothers with high HBV DNA level. At present, the drugs used in late pregnancy including lamivudine (LAM) ,telbivudine(LdT) and tenofovir(TDF).

The safety of nucleoside (acid) analogues used in late pregnancy on children is not clear.In most of the related researches,the observation termination was 7-12 months after birth, and most were concentrated on the blocking effect of MTCT.The long-term impact of Nucleoside (acid) analogues on children's development has not been reported in the literatures. The aim of this study is to make clear of the effect of nucleoside (acid) analogues used in late pregnancy on long-term impact of children's development.

The one year old children born in Beijing Ditan hospital and whose mothers had taken LAM,LdT or TDF during late pregnancy will be enrolled as study group, and eligible children whose mothers untreated will be enrolled as control group. The children's height, weight, nutritional status, developmental quotient and immune response to hepatitis B vaccine etc will be evaluated at baseline and at 3 years old. By comparing the children's development in different groups as well as in self-control of different ages, we will discuss the effect of Nucleoside (acid) analogues on children's long-term development.

Study Overview

• Status: Unknown
• Conditions: the Safety of Anti-viral Drugs Used in Late Pregnancy
• Intervention / Treatment: Drug: Lamivudine; Drug: Telbivudine; Drug: Tenofovir

• Study Type: Observational
• Enrollment (Anticipated): 400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The one year old children born in BeiJing DiTan Hospital and whose mothers had taken Lamivudine, Telbivudine or Tenofovir and untreated in late pregnancy with HBV DNA level over 6.0 log10 IU/ml

Description

Inclusion Criteria:

• The one year old children whose mothers had taken Lamivudine,Telbivudine or Tenofovir in late pregnancy(28-30 weeks of gestation);
• The one year old children whose mothers untreated in late pregnancy;
• Children had completed standard hepatitis B vaccine and hepatitis B immune globulin combined active and passive prophylaxis;
• HBV DNA level of the children's mothers were over 6.0 log10 IU/ml before 28 weeks of gestation.

Exclusion Criteria:

• Children whose mothers over 35 years old at delivery;
• The couple having family hereditary disease or abnormal malformation has been found at fetal screening before 28 weeks gestation;
• History of amniocentesis during pregnancy;
• Co-infection with either hepatitis C virus, hepatitis D virus, human immunodeficiency virus, syphilis, toxoplasmosis, rubella or cytomegalovirus.
• Complications of pregnancy-induced hypertension, premature rupture of membranes, preterm birth, placenta previa or placental abruption; asphyxia at birth.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
group A; The one year old children born in Beijing Ditan hospital and whose mothers had taken Lamivudine in late pregnancy	Drug: Lamivudine; mothers use Lamivudine in late pregnancy; Other Names: 3-TC; CAS: 134678-17-4
group B; The one year old children born in Beijing Ditan hospital and whose mothers had taken Telbivudine in late pregnancy	Drug: Telbivudine; mothers use Telbivudine in late pregnancy; Other Names: CAS: 3424-98-4
group C; The one year old children born in Beijing Ditan hospital and whose mothers had taken Tenofovir in late pregnancy	Drug: Tenofovir; mothers use Tenofovir in late pregnancy; Other Names: Tenofovir Disoprox; CAS: 147127-20-6
group D; The one year old children born in Beijing Ditan hospital and whose mothers untreated in late pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of abnormal development	The children' development will be measured by Gesell Developmental Scales, including adaptability, mobility, fine motion skills, language ability and social skills.The children will be considered normal if the score is ≥86, score between 76-85 is suspicious, and score≤75 is abnormal.	6 months

Collaborators and Investigators

• Sponsor: Beijing Ditan Hospital
• Investigators: Principal Investigator: Wei Yi, Beijing Ditan Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: November 12, 2014
• First Submitted That Met QC Criteria: November 22, 2014
• First Posted (Estimate): November 26, 2014

Study Record Updates

• Last Update Posted (Estimate): November 26, 2014
• Last Update Submitted That Met QC Criteria: November 22, 2014
• Last Verified: November 1, 2014

More Information

Terms related to this study

• Keywords: safety; children; pregnancy; Hepatitis B virus; nucleoside (acid) analogs
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Lamivudine; Telbivudine
• Other Study ID Numbers: Z141107002514131