xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06023056</url>
    </required_header>
    <id_info>
      <org_study_id>chcmuzhb20221114</org_study_id>
      <nct_id>NCT06023056</nct_id>
    </id_info>
    <brief_title>Hepatitis B Vaccination After Neonatal Surgery</brief_title>
    <official_title>Influence of Delayed Vaccination of Hepatitis B Vaccine on Vaccination Safety and Immune Response of Newborns After Gastrointestinal Surgery</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Children's Hospital of Chongqing Medical University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Children's Hospital of Chongqing Medical University</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        At present, whether the hepatitis B vaccine (HBV) can be vaccinated on time after neonatal&#xD;
        surgery has become a common problem for children's families, neonatal surgeons, and&#xD;
        vaccination departments, but there are few relevant studies at home and abroad, and there is&#xD;
        no corresponding guide or consensus. In the early stage, our research team investigated the&#xD;
        vaccination plans of the vaccination units in the main urban areas of Chongqing for such&#xD;
        children through telephone follow-up, and found that the practices of each unit were&#xD;
        different, all based on their own experience, and there was no clear evidence to support the&#xD;
        vaccination or should not be vaccinated, which may cause some children to miss the best&#xD;
        vaccination time or increase the risk of vaccination. The center is a relatively large&#xD;
        neonatal surgery center in southwest China. The diagnosis and treatment of neonatal digestive&#xD;
        tract malformations is at the leading level in China. It can carry out various neonatal&#xD;
        operations such as neonatal necrotizing enterocolitis, congenital anorectal malformations,&#xD;
        and congenital megacolon. On average, it carries out more than 30 third and fourth grade&#xD;
        neonatal gastrointestinal operations every month. It has accumulated a lot of experience in&#xD;
        the follow-up of newborns, There is a large amount of clinical data support for children who&#xD;
        need to be vaccinated after surgery, so it is planned to follow up the second and third doses&#xD;
        of hepatitis B vaccine and whether there are adverse reactions related to vaccination for&#xD;
        children who need to be vaccinated after gastrointestinal surgery in the neonatal period, and&#xD;
        at the same time check the production of HBsAb after vaccination, The immune response and&#xD;
        adverse reactions of hepatitis B vaccine at different time points after surgery were studied&#xD;
        to increase clinical evidence for the determination of hepatitis B vaccine vaccination&#xD;
        program for newborns after surgery.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Research design&#xD;
  &#xD;
        1. Selection of research objects (research population)&#xD;
  &#xD;
        Newborns who were screened in the department and met all of the following criteria were&#xD;
        included in this study: 1) term infants and the first dose of hepatitis B vaccine had been&#xD;
        vaccinated on time; 2) Children with indications for staged gastrointestinal surgery, and the&#xD;
        first operation should be performed within 28 days after birth; 3) The child has no immune&#xD;
        system disease or serious development defect or dysfunction of heart, brain, liver, kidney&#xD;
        and other organs; 4) HBsAg - before initial operation; 5) Prenatal HBsAg - detection of the&#xD;
        mother or father of the child; 6) The guardian signed the informed consent form and agreed to&#xD;
        participate in the study. Exclusion criteria: 1) premature infants; 2) The first operation&#xD;
        time exceeds 28 days after birth; 3) There are serious developmental malformations or&#xD;
        dysfunction of heart, brain, liver, kidney and other organs or immune system diseases; 4) The&#xD;
        patient or one of his parents is HBsAg+; 5) Children who are allergic to hepatitis B vaccine&#xD;
        or have other serious adverse reactions; 6) Children interviewed by vector.&#xD;
  &#xD;
        The end point of the study is 6 years after joining the group. Two mid-term evaluations will&#xD;
        be conducted one year and two years after the start of the study. This project will apply for&#xD;
        funding until the mid-term evaluation of the first year. The follow-up research funds will be&#xD;
        supported by the follow-up projects or self raised funds. The criteria for withdrawal from&#xD;
        the cohort were: during the study period, the children were infected with hepatitis B virus&#xD;
        due to other reasons such as &quot;surgery, blood transfusion, trauma&quot;, or diagnosed with immune&#xD;
        related diseases during the follow-up period.&#xD;
  &#xD;
        2. Patient grouping&#xD;
  &#xD;
          1. Newborns who need to undergo gastrointestinal staging surgery as the research object can&#xD;
             be included in this study after meeting the inclusion criteria and obtaining the consent&#xD;
             of the guardian;&#xD;
  &#xD;
          2. The children included in this study were divided into &quot;delayed vaccination group after&#xD;
             surgery&quot; and &quot;standard vaccination group after surgery&quot; according to the evaluation of&#xD;
             the community vaccination department. At the same time, 1-year-old and 2-year-old&#xD;
             children with indirect inguinal hernia who were vaccinated according to the standard&#xD;
             immunization program and had no other diseases were taken as the &quot;control group&quot;;&#xD;
  &#xD;
          3. Collect the general information of the &quot;delayed vaccination group after operation&quot; and&#xD;
             the &quot;standard vaccination group after operation&quot;, the mother's prenatal hepatitis B&#xD;
             two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of&#xD;
             hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each&#xD;
             hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface&#xD;
             antibody in delayed vaccination group, standard vaccination group and control group was&#xD;
             compared;&#xD;
  &#xD;
          4. Collect the remaining serum of &quot;Postoperative Delayed Inoculation Group&quot; and&#xD;
             &quot;Postoperative Standard Inoculation Group&quot; for HBV DNA detection;&#xD;
  &#xD;
          5. The definition of bias refers to ROBINS-I standard, including bias caused by confusion,&#xD;
             bias in the selection of research objects, bias in the classification of intervention&#xD;
             measures, bias deviating from the expected intervention measures, bias caused by missing&#xD;
             data in the outcome measurement and bias in selective reporting of results. Bias is&#xD;
             divided into four levels: mild, moderate, severe and extremely severe.&#xD;
  &#xD;
        3. Interventions&#xD;
  &#xD;
        All the operated children were treated in Liangjiang Neonatal Surgery Department of&#xD;
        Children's Hospital Affiliated to Chongqing Medical University. Before operation, they were&#xD;
        examined for hepatitis B and HBV DNA.&#xD;
  &#xD;
        4. Follow up plan&#xD;
  &#xD;
        Collect the general information of the &quot;delayed vaccination group after operation&quot; and the&#xD;
        &quot;standard vaccination group after operation&quot;, the mother's prenatal hepatitis B&#xD;
        two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of&#xD;
        hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each&#xD;
        hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface&#xD;
        antibody in delayed vaccination group, standard vaccination group and control group was&#xD;
        compared; Collect the remaining serum of &quot;Postoperative Delayed Inoculation Group&quot; and&#xD;
        &quot;Postoperative Standard Inoculation Group&quot; for HBV DNA detection;&#xD;
  &#xD;
        5. Main measurement indexes&#xD;
  &#xD;
        Collect the general information of the enrolled children, the mother's two pairs and a half&#xD;
        of hepatitis B before delivery, the children's hepatitis B vaccination time, the adverse&#xD;
        reactions of hepatitis B vaccination, and the children's two pairs and a half of hepatitis B&#xD;
        before each hospitalization operation and at the age of 1 and 2; The level of hepatitis B&#xD;
        surface antibody in the delayed vaccination group, the standard vaccination group and the&#xD;
        control group were compared.&#xD;
  &#xD;
        6. Sample size calculation&#xD;
  &#xD;
        According to the previous statistics, the average value of HBsAb of 992 neonates in our&#xD;
        outpatient department was 349.5 IU/L, the standard deviation was 420.59 IU/L, and the average&#xD;
        value of HBsAb of 1317 1-year-old children was 575.5 IU/L. Therefore, it is estimated that&#xD;
        HBsAb will increase by 226 IU/L during the 1-year follow-up α= 0.05， β= 0.1, calculated&#xD;
        according to the following formula.&#xD;
  &#xD;
        Data management&#xD;
  &#xD;
          1. Data entry&#xD;
  &#xD;
             This project uses EpiData to establish the database. The database designer determines&#xD;
             the database creation requirements and database structure according to the case report&#xD;
             form (CRF form) to ensure that the database content and structure are consistent with&#xD;
             the CRF form, and the specified data can be properly entered into the database. The xx&#xD;
             database is strictly password protected, and only the personnel directly involved in the&#xD;
             research can obtain the password/account. According to the original observation records&#xD;
             of the subjects, the researchers timely, completely, correctly and clearly loaded the&#xD;
             data into the CRF table. The CRF form reviewed and signed by the investigator shall be&#xD;
             submitted to the clinical research data administrator in time. The research data are&#xD;
             entered into the EpiData database by authorized researchers. The database system of&#xD;
             EpiData is used for double person and double computer input, and then the database is&#xD;
             compared twice. Data changes due to input errors or other reasons will be recorded in&#xD;
             detail and confirmed by the researcher. The questions and answers between the data&#xD;
             administrator and the researcher are in the form of question table, which is kept for&#xD;
             future reference.&#xD;
  &#xD;
          2. Contents and methods of data verification and management&#xD;
  &#xD;
             Key points and process of data verification, as well as requirements for data locking.&#xD;
             For example, when all case report forms have been entered in duplicate and checked&#xD;
             without error, data cleaning has been completed, all queries have been answered or&#xD;
             explained, and data quality control has been completed, the data administrator will&#xD;
             write a database inspection report, which includes the completion of the study&#xD;
             (including the list of dropped subjects), inclusion/exclusion criteria, integrity check,&#xD;
             logic consistency check, outlier data check, time window check, drug combination check&#xD;
             Adverse event inspection, etc. The researcher confirmed that the database will be&#xD;
             locked.&#xD;
  &#xD;
          3. Safety evaluation&#xD;
  &#xD;
             All adverse events were recorded. In particular, incidents that resulted in&#xD;
             hospitalization, prolonged hospitalization, additional surgical or medical treatment, or&#xD;
             death were reported.&#xD;
  &#xD;
          4. Quality control and quality management&#xD;
  &#xD;
        Before the start of the study, patients were enrolled in strict accordance with the inclusion&#xD;
        and exclusion criteria, standardized case report forms (CRF) were developed, and ethical&#xD;
        review and clinical study registration were confirmed; During the research, ensure the&#xD;
        integrity of CRF table data records, the consistency of original data and CRF data, the&#xD;
        security of data archiving, review the completion progress and queue interruption, and&#xD;
        analyze the preciseness of data; After the study, confirm the integrity of statistical data,&#xD;
        the standardization of statistical methods, the standardization of paper writing, and update&#xD;
        the clinical study registration data.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">November 1, 2022</start_date>
    <completion_date type="Anticipated">November 1, 2030</completion_date>
    <primary_completion_date type="Anticipated">November 1, 2030</primary_completion_date>
    <study_type>Observational [Patient Registry]</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <target_duration>2 Years</target_duration>
    <primary_outcome>
      <measure>Prenatal hepatitis B surface markers</measure>
      <time_frame>1 month</time_frame>
      <description>Prenatal hepatitis B surface makers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) of mothers and childrens. Measurement of relevant indicators using Roche chemiluminescence method.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Newborn condition</measure>
      <time_frame>1 month</time_frame>
      <description>Surface markers of hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) in newborn.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Vaccination time</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Time for subjects to receive three doses of hepatitis B vaccine</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Adverse reactions</measure>
      <time_frame>2 years</time_frame>
      <description>Whether there are vaccine related adverse reactions after vaccination: fever, urticaria, local pain, erythema, induration, atc.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Immune effect of vaccine</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Results of hepatitis B surface markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) at the age of 1 and 2</description>
    </primary_outcome>
    <number_of_groups>3</number_of_groups>
    <enrollment type="Anticipated">180</enrollment>
    <condition>Vaccination Reaction</condition>
    <condition>Hepatitis B Virus Infection</condition>
    <condition>Digestive System Disorders of Fetus and Newborn</condition>
    <condition>Blood Transfusion Complication</condition>
    <condition>Hepatitis B Vaccine Adverse Reaction</condition>
    <arm_group>
      <arm_group_label>Delayed vaccination group after gastrointestinal surgery</arm_group_label>
      <description>Newborns undergoing gastrointestinal surgery are delayed from receiving hepatitis B vaccination in the vaccination institutions due to the impact of surgery.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>The group of vaccination on time after gastrointestinal surgery</arm_group_label>
      <description>Newborns undergoing gastrointestinal surgery shall be vaccinated with hepatitis B vaccine on time by vaccination institutions.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <description>Children who are free of disease and have vaccination and physical examination on time.</description>
    </arm_group>
    <eligibility>
      <study_pop>
        <textblock>
          Follow up the neonates who live in the medical institution and meet the inclusion criteria.&#xD;
          The end point of the study is 6 years after enrollment. Two mid-term evaluations will be&#xD;
          conducted one year and two years after the start of the study. This project applies for&#xD;
          funding until the mid-term evaluation of the first year. The follow-up research funds will&#xD;
          be supported by the follow-up projects or self raised funds. The criteria for withdrawal&#xD;
          from the cohort were: during the study period, the children were infected with hepatitis B&#xD;
          virus due to other reasons such as &quot;surgery, blood transfusion, trauma&quot;, or diagnosed with&#xD;
          immune related diseases during the follow-up period.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          1. Term neonates; 2. Underwent staged gastrointestinal surgery; 3. HBsAg-; 4. No immune&#xD;
          system disease; 5.no serious defect of heart, brain, liver, kidney and other organs.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          1. Premature; 2. HBsAg+; 3. Having immune system diseases; 4. Having serious defect of&#xD;
          heart, brain, liver, kidney and other organs; 5. Lost patients.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>N/A</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hanbin Zhao, Doctor</last_name>
      <role>Principal Investigator</role>
      <affiliation>Children's Hospital of Chongqing Medical University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hanbin Zhao, Doctor</last_name>
      <phone>18883370996</phone>
      <email>ddxek1994@outlook.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>yi wang, Doctor</last_name>
      <phone>17338332901</phone>
      <email>wy757311@hotmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Children's Hospital of Chongqing Medical University</name>
        <address>
          <city>Chongqing</city>
          <state>Chongqing</state>
          <zip>400014</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Hanbin Zhao</last_name>
        <phone>18883370996</phone>
        <email>ddxek1994@outlook.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <reference>
      <citation>National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(2):1-64. Erratum In: MMWR Recomm Rep. 2011 Jul 29;60:993.</citation>
      <PMID>21293327</PMID>
    </reference>
    <reference>
      <citation>Szilagyi PG, Rodewald LE. Missed opportunities for immunizations: a review of the evidence. J Public Health Manag Pract. 1996 Winter;2(1):18-25. doi: 10.1097/00124784-199600210-00005.</citation>
      <PMID>10186652</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>November 29, 2022</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 5, 2023</study_first_posted>
    <last_update_submitted>September 7, 2023</last_update_submitted>
    <last_update_submitted_qc>September 7, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Children's Hospital of Chongqing Medical University</investigator_affiliation>
      <investigator_full_name>Hanbin Zhao</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Hepatitis B Vaccination Reaction</keyword>
    <keyword>Hepatitis B Vaccine Adverse Reaction</keyword>
    <keyword>Neonatal surgery</keyword>
    <keyword>Gastrointestinal Surgery</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Hepatitis A</mesh_term>
      <mesh_term>Hepatitis B</mesh_term>
      <mesh_term>Herpesviridae Infections</mesh_term>
      <mesh_term>Hepatitis</mesh_term>
      <mesh_term>Digestive System Diseases</mesh_term>
      <mesh_term>Gastrointestinal Diseases</mesh_term>
      <mesh_term>Fetal Diseases</mesh_term>
      <mesh_term>Transfusion Reaction</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>We will decide whether to open the case according to the willingness to finally include the case.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06023056
  org study id: chcmuzhb20221114
  nct id: NCT06023056
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  At present, whether the hepatitis B vaccine (HBV) can be vaccinated on time after neonatal
        surgery has become a common problem for children's families, neonatal surgeons, and
        vaccination departments, but there are few relevant studies at home and abroad, and there is
        no corresponding guide or consensus. In the early stage, our research team investigated the
        vaccination plans of the vaccination units in the main urban areas of Chongqing for such
        children through telephone follow-up, and found that the practices of each unit were
        different, all based on their own experience, and there was no clear evidence to support the
        vaccination or should not be vaccinated, which may cause some children to miss the best
        vaccination time or increase the risk of vaccination. The center is a relatively large
        neonatal surgery center in southwest China. The diagnosis and treatment of neonatal digestive
        tract malformations is at the leading level in China. It can carry out various neonatal
        operations such as neonatal necrotizing enterocolitis, congenital anorectal malformations,
        and congenital megacolon. On average, it carries out more than 30 third and fourth grade
        neonatal gastrointestinal operations every month. It has accumulated a lot of experience in
        the follow-up of newborns, There is a large amount of clinical data support for children who
        need to be vaccinated after surgery, so it is planned to follow up the second and third doses
        of hepatitis B vaccine and whether there are adverse reactions related to vaccination for
        children who need to be vaccinated after gastrointestinal surgery in the neonatal period, and
        at the same time check the production of HBsAb after vaccination, The immune response and
        adverse reactions of hepatitis B vaccine at different time points after surgery were studied
        to increase clinical evidence for the determination of hepatitis B vaccine vaccination
        program for newborns after surgery.
  Research design
  
        1. Selection of research objects (research population)
  
        Newborns who were screened in the department and met all of the following criteria were
        included in this study: 1) term infants and the first dose of hepatitis B vaccine had been
        vaccinated on time; 2) Children with indications for staged gastrointestinal surgery, and the
        first operation should be performed within 28 days after birth; 3) The child has no immune
        system disease or serious development defect or dysfunction of heart, brain, liver, kidney
        and other organs; 4) HBsAg - before initial operation; 5) Prenatal HBsAg - detection of the
        mother or father of the child; 6) The guardian signed the informed consent form and agreed to
        participate in the study. Exclusion criteria: 1) premature infants; 2) The first operation
        time exceeds 28 days after birth; 3) There are serious developmental malformations or
        dysfunction of heart, brain, liver, kidney and other organs or immune system diseases; 4) The
        patient or one of his parents is HBsAg+; 5) Children who are allergic to hepatitis B vaccine
        or have other serious adverse reactions; 6) Children interviewed by vector.
  
        The end point of the study is 6 years after joining the group. Two mid-term evaluations will
        be conducted one year and two years after the start of the study. This project will apply for
        funding until the mid-term evaluation of the first year. The follow-up research funds will be
        supported by the follow-up projects or self raised funds. The criteria for withdrawal from
        the cohort were: during the study period, the children were infected with hepatitis B virus
        due to other reasons such as "surgery, blood transfusion, trauma", or diagnosed with immune
        related diseases during the follow-up period.
  
        2. Patient grouping
  
          1. Newborns who need to undergo gastrointestinal staging surgery as the research object can
             be included in this study after meeting the inclusion criteria and obtaining the consent
             of the guardian;
  
          2. The children included in this study were divided into "delayed vaccination group after
             surgery" and "standard vaccination group after surgery" according to the evaluation of
             the community vaccination department. At the same time, 1-year-old and 2-year-old
             children with indirect inguinal hernia who were vaccinated according to the standard
             immunization program and had no other diseases were taken as the "control group";
  
          3. Collect the general information of the "delayed vaccination group after operation" and
             the "standard vaccination group after operation", the mother's prenatal hepatitis B
             two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of
             hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each
             hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface
             antibody in delayed vaccination group, standard vaccination group and control group was
             compared;
  
          4. Collect the remaining serum of "Postoperative Delayed Inoculation Group" and
             "Postoperative Standard Inoculation Group" for HBV DNA detection;
  
          5. The definition of bias refers to ROBINS-I standard, including bias caused by confusion,
             bias in the selection of research objects, bias in the classification of intervention
             measures, bias deviating from the expected intervention measures, bias caused by missing
             data in the outcome measurement and bias in selective reporting of results. Bias is
             divided into four levels: mild, moderate, severe and extremely severe.
  
        3. Interventions
  
        All the operated children were treated in Liangjiang Neonatal Surgery Department of
        Children's Hospital Affiliated to Chongqing Medical University. Before operation, they were
        examined for hepatitis B and HBV DNA.
  
        4. Follow up plan
  
        Collect the general information of the "delayed vaccination group after operation" and the
        "standard vaccination group after operation", the mother's prenatal hepatitis B
        two-and-a-half, the children's hepatitis B vaccination time, the adverse reactions of
        hepatitis B vaccination, and the children's hepatitis B two-and-a-half before each
        hospitalization operation and at the age of 1 and 2; The level of hepatitis B surface
        antibody in delayed vaccination group, standard vaccination group and control group was
        compared; Collect the remaining serum of "Postoperative Delayed Inoculation Group" and
        "Postoperative Standard Inoculation Group" for HBV DNA detection;
  
        5. Main measurement indexes
  
        Collect the general information of the enrolled children, the mother's two pairs and a half
        of hepatitis B before delivery, the children's hepatitis B vaccination time, the adverse
        reactions of hepatitis B vaccination, and the children's two pairs and a half of hepatitis B
        before each hospitalization operation and at the age of 1 and 2; The level of hepatitis B
        surface antibody in the delayed vaccination group, the standard vaccination group and the
        control group were compared.
  
        6. Sample size calculation
  
        According to the previous statistics, the average value of HBsAb of 992 neonates in our
        outpatient department was 349.5 IU/L, the standard deviation was 420.59 IU/L, and the average
        value of HBsAb of 1317 1-year-old children was 575.5 IU/L. Therefore, it is estimated that
        HBsAb will increase by 226 IU/L during the 1-year follow-up α= 0.05， β= 0.1, calculated
        according to the following formula.
  
        Data management
  
          1. Data entry
  
             This project uses EpiData to establish the database. The database designer determines
             the database creation requirements and database structure according to the case report
             form (CRF form) to ensure that the database content and structure are consistent with
             the CRF form, and the specified data can be properly entered into the database. The xx
             database is strictly password protected, and only the personnel directly involved in the
             research can obtain the password/account. According to the original observation records
             of the subjects, the researchers timely, completely, correctly and clearly loaded the
             data into the CRF table. The CRF form reviewed and signed by the investigator shall be
             submitted to the clinical research data administrator in time. The research data are
             entered into the EpiData database by authorized researchers. The database system of
             EpiData is used for double person and double computer input, and then the database is
             compared twice. Data changes due to input errors or other reasons will be recorded in
             detail and confirmed by the researcher. The questions and answers between the data
             administrator and the researcher are in the form of question table, which is kept for
             future reference.
  
          2. Contents and methods of data verification and management
  
             Key points and process of data verification, as well as requirements for data locking.
             For example, when all case report forms have been entered in duplicate and checked
             without error, data cleaning has been completed, all queries have been answered or
             explained, and data quality control has been completed, the data administrator will
             write a database inspection report, which includes the completion of the study
             (including the list of dropped subjects), inclusion/exclusion criteria, integrity check,
             logic consistency check, outlier data check, time window check, drug combination check
             Adverse event inspection, etc. The researcher confirmed that the database will be
             locked.
  
          3. Safety evaluation
  
             All adverse events were recorded. In particular, incidents that resulted in
             hospitalization, prolonged hospitalization, additional surgical or medical treatment, or
             death were reported.
  
          4. Quality control and quality management
  
        Before the start of the study, patients were enrolled in strict accordance with the inclusion
        and exclusion criteria, standardized case report forms (CRF) were developed, and ethical
        review and clinical study registration were confirmed; During the research, ensure the
        integrity of CRF table data records, the consistency of original data and CRF data, the
        security of data archiving, review the completion progress and queue interruption, and
        analyze the preciseness of data; After the study, confirm the integrity of statistical data,
        the standardization of statistical methods, the standardization of paper writing, and update
        the clinical study registration data.
  observational model: Cohort
  time perspective: Prospective
  measure: Prenatal hepatitis B surface markers
  time frame: 1 month
  description: Prenatal hepatitis B surface makers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) of mothers and childrens. Measurement of relevant indicators using Roche chemiluminescence method.
  measure: Newborn condition
  time frame: 1 month
  description: Surface markers of hepatitis B (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) in newborn.
  measure: Vaccination time
  time frame: up to 2 years
  description: Time for subjects to receive three doses of hepatitis B vaccine
  measure: Adverse reactions
  time frame: 2 years
  description: Whether there are vaccine related adverse reactions after vaccination: fever, urticaria, local pain, erythema, induration, atc.
  measure: Immune effect of vaccine
  time frame: up to 2 years
  description: Results of hepatitis B surface markers (HBsAg, HBsAb, HBeAg, HBeAb, HBcAb) at the age of 1 and 2
  arm group label: Delayed vaccination group after gastrointestinal surgery
  description: Newborns undergoing gastrointestinal surgery are delayed from receiving hepatitis B vaccination in the vaccination institutions due to the impact of surgery.
  arm group label: The group of vaccination on time after gastrointestinal surgery
  description: Newborns undergoing gastrointestinal surgery shall be vaccinated with hepatitis B vaccine on time by vaccination institutions.
  arm group label: Control group
  description: Children who are free of disease and have vaccination and physical examination on time.
  study pop: 
  sampling method: Probability Sample
  criteria: 
  gender: All
  minimum age: N/A
  maximum age: N/A
  healthy volunteers: Accepts Healthy Volunteers
  last name: Hanbin Zhao, Doctor
  role: Principal Investigator
  affiliation: Children's Hospital of Chongqing Medical University
  last name: Hanbin Zhao, Doctor
  phone: 18883370996
  email: ddxek1994@outlook.com
  last name: yi wang, Doctor
  phone: 17338332901
  email: wy757311@hotmail.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  citation: National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 28;60(2):1-64. Erratum In: MMWR Recomm Rep. 2011 Jul 29;60:993.
  PMID: 21293327
  citation: Szilagyi PG, Rodewald LE. Missed opportunities for immunizations: a review of the evidence. J Public Health Manag Pract. 1996 Winter;2(1):18-25. doi: 10.1097/00124784-199600210-00005.
  PMID: 10186652
  responsible party type: Principal Investigator
  investigator affiliation: Children's Hospital of Chongqing Medical University
  investigator full name: Hanbin Zhao
  investigator title: Principal Investigator
  mesh term: Hepatitis A
  mesh term: Hepatitis B
  mesh term: Herpesviridae Infections
  mesh term: Hepatitis
  mesh term: Digestive System Diseases
  mesh term: Gastrointestinal Diseases
  mesh term: Fetal Diseases
  mesh term: Transfusion Reaction
  sharing ipd: Undecided
  ipd description: We will decide whether to open the case according to the willingness to finally include the case.