Hepatitis B, Perinatal Infection

Reporting Information

Class B

Report a case, suspected case, and/or positive laboratory result to the local public health department in which the patient resides by the close of the next business day. If patient residence is unknown, report to the local public health department in which the reporting healthcare provider or laboratory is located.

Reporting Form(s) and/or Mechanism

The Ohio Disease Reporting System (ODRS) should be used to report cases and lab findings to the Ohio Department of Health (ODH). For healthcare providers without access to ODRS, the Ohio Confidential Reportable Disease Form (HEA 3334) may be used.

The Positive Laboratory Findings for Reportable Disease Form (HEA 3333) may be used for laboratories without access to ODRS or electronic laboratory reporting (ELR) to report positive results.

The Viral Hepatitis Case Report (CDC OMB 0920-0728) is available for use by the local public health department when following up with cases. Do not send this form to ODH unless otherwise requested; information collected from the form should be entered into ODRS where fields are available.

Special Notes on Reporting

Local health departments should report all new pregnancies for women identified with acute or chronic hepatitis B infection, even if the case was reported prior to the pregnancy or during a previous pregnancy.

Agent

Hepatitis B virus (HBV) is classified in the Hepadnaviridae family, and is a member of the Orthohepadnavirus genus. The hepatitis B virus is a partially double-stranded DNA virus, 40-48 nm in diameter.

Case Definition

Clinical Criteria

Perinatal HBV infection in a child ≤24 months of age may range from asymptomatic to fulminant hepatitis.

Laboratory Criteria for Diagnosis

Laboratory evidence of HBV infection in a child consists of one or more of the following:

• Positive hepatitis B surface antigen (HBsAg) test (only if at least 4 weeks after the last dose of hepatitis B vaccine),
• Positive hepatitis B e antigen (HBeAg) test, or
• Detectable HBV DNA.

Epidemiologic Linkage

Born to a HBV-infected mother.

Case Classification

Suspected

Child 1-24 months of age born in the US to an HBV-infected mother or mother with unknown HBV infection status.

Probable

Child born in the US to an HBV-infected mother or mother with unknown HBV infection status and positive for HBsAg at ≥1 month of age and ≤24 months of age OR positive for HBeAg or HBV DNA ≥9 months of age and ≤24 months of age, but whose mother's hepatitis B status is unknown (i.e., epidemiologic linkage not present).

Confirmed

Child born in the US to a HBV-infected mother or mother of unknown status and positive for HBsAg at ≥1 month of age and ≤24 months of age OR positive for HBeAg or HBV DNA ≥9 months of age and ≤24 months of age.

Test Name Abbreviations

Public Health Management

I. Background

Great progress has been made in identifying hepatitis B surface antigen (HBsAg)-positive pregnant women and immunizing their infants with hepatitis B (Hep B) vaccine and hepatitis B immune globulin (HBIG) to prevent vertical infection, but there are still infants who acquire hepatitis B virus (HBV) infection. This occurs because either their mothers are not recognized as infected and the infant does not receive HBIG and the full hepatitis B vaccine series or the intervention does not prevent infection. Without post-exposure prophylaxis with HBIG and hep B vaccine, approximately 45% of infants born to HBV-infected mothers will become infected and up to 90% of those infected will develop chronic, life-long infection. Among infants who develop infection, 25% will die prematurely of liver cirrhosis or cancer. During 2020, a total 10 cases of perinatal hepatitis B that met the classification criteria for a confirmed case were reported to CDC (6); approximately 300 infants are exposed annually in Ohio (2). Although treatment of HBV infection is now possible and can attenuate the impact of infection, hepatitis B cannot yet be cured (3).

It is important to assure adequate immunity in infants of HBV-infected mothers and to determine if infection of the infant occurred with or without post-exposure prophylaxis. The Centers for Disease Control and Prevention (CDC) and the Advisory Committee on Immunization Practices (ACIP) recommend universal testing of pregnant women for HBsAg, post-exposure prophylaxis within 12 hours of birth with HBIG and the first dose of hepatitis B vaccine for infants born to HBV-infected mothers, universal birth dose administration within 24 hours of birth to all infants regardless of the mother's HBsAg status (4), completion of a valid three dose vaccine series in all infants, and post-vaccination serologic testing (PVST) for HBsAg and anti-HBs at 9-12 months for infants born to HBV-infected mothers or infants born in regions of high and intermediate HBV endemicity (3). The CDC Perinatal Hepatitis B Prevention Program helps promote these recommendations and provides case management of HBV-infected mothers and their infants. Evaluation of the program depends on the follow-up of exposed infants.

II. Fundamentals of Perinatal Hepatitis B Prevention

A. Serologic Screening of Pregnant Females

1. All pregnant females should be screened for hepatitis B infection (i.e., HBsAg) during each pregnancy as a part of routine prenatal care. All HBV-infected women must be reported to the local health department according to Ohio Administrative Code.
   • This screening should be done on all pregnant females during an early prenatal visit (e.g., first trimester) in each pregnancy, even if they have been vaccinated or tested previously (5).
   • Pregnant women without evidence of immunity who are identified as being at risk for HBV infection during pregnancy (e.g., having more than one sex partner during the previous 6 months, been evaluated or treated for an STI, recent or current injection-drug use, or having had an HBsAg-positive sex partner) should be vaccinated (5).
   • Screening should be repeated later in the pregnancy when admitted for delivery in those females who are at high risk for the acquisition of hepatitis B during pregnancy (e.g., recent or current injection-drug use, having had more than one sex partner in the previous 6 months or an HBsAg-positive sex partner, having been evaluated or treated for a STI) (5).
   • If a pregnant female is found to be HBsAg positive, a nucleic acid test for hepatitis B virus DNA (HBV-DNA), including qualitative, quantitative and genotype testing, is recommended to guide the use of maternal antiviral therapy during pregnancy for the prevention of perinatal HBV transmission.
2. Report pregnancy status along with test results for women who are positive for any one of the following three laboratory tests:
   • Hepatitis B surface antigen (HBsAg).
   • Hepatitis B e antigen (HBeAg).
   • Nucleic acid test for hepatitis B virus DNA (HBV-DNA) (including qualitative, quantitative, and genotype testing).
3. Immediately determine HBsAg status on all pregnant women presenting for labor and delivery without documentation of HBsAg test results for current pregnancy and those with risk factors regardless of previous HBsAg test results.
4. Infants born to women for whom HBsAg testing results during pregnancy are not available but other evidence suggestive of maternal HBV infection exists (e.g., presence of HBV DNA, HBeAg-positive, or mother known to be chronically infected with HBV) should be managed as if born to an HBsAg-positive mother.
5. For common hepatitis B serological profiles, see Table 1.

Table 1: Common Hepatitis B Serological Profiles

B. Hepatitis B Vaccine and HBIG Usage in Term Infants Born to HBsAg-Positive Mothers

1. At birth (within 12 hours of birth): Give first dose of vaccine plus HBIG.
2. At 1-2 months of age: Give second dose of vaccine (if using single-antigen vaccine).
3. At 6 months of age: Give third dose of vaccine (if using single-antigen vaccine).
4. For doses, see Table 2.
5. For immunoprophylaxis of preterm and low birth weight infants, see Table 3.
6. See Table 4 for schedule by vaccine type, which includes the use of combination vaccines.

Table 2: Recommended Dosages of Hepatitis B Vaccine
[Adapted from the Red Book: 2021 Report of the Committee on Infectious Diseases*]

* American Academy of Pediatrics. Hepatitis B. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, IL: American Academy of Pediatrics; 2021: 381-399

** For other hepatitis B-containing vaccines and multiple antigen vaccines such as Pediarix and Vaxelis, which cannot be used for the birth dose, see the Red Book, 2021.

Table 3: Hepatitis B Immunoprophylaxis by Birthweight for Infants Born to HBsAg-Positive or HBsAg-Unknown Mothers (including abandoned and safe haven babies)
[Adapted from the Red Book: 2021 Report of the Committee on Infectious Diseases*]

* American Academy of Pediatrics. Hepatitis B. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, IL: American Academy of Pediatrics; 2021: 381-399

** The rationale for giving HBIG within 12 hours (unless HBsAg is determined to be negative within 12 hours) is that the ODH Perinatal Hepatitis B Prevention Program has seen cases where HBIG was held pending the HBsAg determination (which proved to be positive); the patient was discharged and lost to follow-up, and, therefore, did not receive HBIG.

Table 4: Hepatitis B Vaccine Schedules for Infants ≥ 2000 g* by Maternal Hepatitis B Surface Antigen (HBsAg) Status
[Adapted from the Red Book: 2021 Report of the Committee on Infectious Diseases**]

* For infants weighing <2000g, the birth dose of hepatitis B vaccine should NOT be counted toward completion of the hepatitis B vaccine series. See the Red Book, 2021 for further information.

** American Academy of Pediatrics. Hepatitis B. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, IL: American Academy of Pediatrics; 2021: 381-399.

*** Combination vaccines should not be used for birth dose (or any dose through 6 weeks of age).

C. Hepatitis B Vaccine and HBIG Usage in Term Infants Born to Mothers of Unknown HBsAg Status (including abandoned and safe haven babies)

1. At birth (within 12 hours): Give first dose of vaccine. Draw maternal blood for HBsAg.
2. Give HBIG within 12 hours of birth (strongly preferred by the ODH Perinatal Hepatitis B Prevention Program [PHBPP] Bureau of Infectious Diseases) or await HBsAg result and, if positive, give HBIG as soon as possible but in less than seven days (American Academy of Pediatrics Red Book recommendation).
3. At 1-2 months of age: Give second dose of vaccine (if using single-antigen vaccine).
4. At 6 months of age: Give third dose of vaccine (if mother is found to be positive). If mother is found to be negative, give third dose of vaccine at 6-18 months of age. (If using single-antigen vaccine).
5. For doses, see Table 2.
6. For preterm and low birth weight infants, see Table 3.
7. For vaccination schedule by vaccine type, see Table 4.

D. Post-Vaccination Serological Testing Among Infants Born to HBsAg-Positive Mothers (and mothers whose serostatus remains unknown)

1. After the completion of the vaccine series, infants should be tested for HBsAg (to determine whether immunoprophylaxis failed) and anti-HBs (to determine whether the immune response was sufficient to ensure continuing protection).
2. Testing should be done at least 4 weeks after completion of the primary vaccination series, preferably at 9-12 months of age, but before 18 months of age (three to nine months after the completion of the series, but never earlier than nine months of age).

E. Additional Vaccination

1. Infants who test HBsAg-negative and anti-HBs-negative (anti-HBs <10 mIU/mL) should be revaccinated with a single dose of hepatitis B vaccine and receive post-vaccination serologic testing (PVST) 1-2 months later. Infants whose anti-HBs remains (<10 mIU/mL) following single dose revaccination should receive two additional doses of hepatitis B vaccine to complete the second series, followed by PVST 1–2 months after the final dose, or, based on clinical circumstances or family preference, HBsAg-negative infants with anti-HBs <10 mIU/mL may instead be revaccinated with a second, complete 3-dose series, followed by PVST performed 1-2 months after the final dose of vaccine. Combination vaccines may not be used for the second series.
2. If after the sixth dose, the child does not seroconvert, no more doses are indicated, and the child should be considered still susceptible to disease.

F. Screening of Household and Sexual Contacts of Pregnant HBsAg-Positive Females

Please see the Hepatitis B Infectious Disease Control Manual (IDCM) chapter.

G. Hepatitis B Vaccine and HBIG Usage Among Household and Sexual Contacts of Pregnant HBsAg-Positive Females

Please see the Hepatitis B Infectious Disease Control Manual (IDCM) chapter.

III. Identification and Reporting of HBsAg-Positive Pregnant Females: Recommendations for Local Health Departments

A. All Pregnant Females Should be Screened for HBsAg During Each Pregnancy

B. All Positive Laboratory Test Results

1. All positive laboratory test results of Class B reportable diseases, such as acute, chronic, and perinatal hepatitis B, are required to be reported to the local health department (LHD) within the jurisdiction the individual resides per Ohio Administrative Code (OAC) 3701-3-02.
2. This means that any physician, healthcare agency, or laboratory that detects a positive result for one or more hepatitis B serological markers (except anti-HBs) is required to report it to the appropriate LHD. (The presence of anti-HBs indicates immunity from either previous vaccination or resolved infection.)

C. All Females of Childbearing Age

All females of childbearing age (i.e., 10-50 years of age) and both male and female children (age 15 years and below) with one or more positive hepatitis B markers should be entered into the electronic Ohio Disease Reporting System (ODRS) regardless of clinical status as acute or chronic hepatitis B.

1. The pregnancy status of all females of childbearing age should be entered into ODRS.
2. If the pregnancy status is unknown for a female of childbearing age who has one or more positive serological markers for hepatitis B (e.g., HBsAg, HBeAg, HBV-DNA, hepatitis B genotype testing), the female's physician should be contacted to determine the pregnancy status; the status should then be entered into ODRS.
   • If the physician does not know the pregnancy status, the female should be contacted directly.
   • If the female has recently delivered, the LHD should collect clinical, diagnostic, and serological marker data that allows a determination of the status of hepatitis B (e.g., acute, chronic). This information should be entered into ODRS.

IV. Case Management of HBsAg-Positive Pregnant Females: Recommendations for Local Health Departments

A. The Pregnant Female Should be Interviewed by the LHD

The pregnant female should be interviewed by the LHD within five business days of report to identify all household and current sexual contact(s). If the pregnant female has been followed by the ODH PHBPP during a previous pregnancy, she should be asked if there have been new household and/or sexual contact(s).

This information should be entered into ODRS as it is acquired.

V. Management of Infants Born to HBsAg-Positive Mothers or Mothers of Unknown Serostatus (including abandoned and safe haven babies)

A. Ensure/Facilitate the Receipt of the Full Series of Hepatitis B Vaccination and HBIG Administration as Needed

1. Birth information will be sent to the LHD from the ODH PHBPP, if ODH receives the information from the delivery facility.
2. If notification of delivery is not received within three weeks of estimated date of delivery, the LHD should contact the prenatal care provider or delivery facility to determine pregnancy/delivery status.

B. Ensure/Facilitate the Determination of Post-Vaccination Serology

1. Upon completion of the full vaccination series, the LHD should ensure that post-vaccination serology testing is performed by following up as needed with the infant’s medical provider and/or the mother.

C. Determine Whether Additional Vaccination is Needed

1. If post-vaccination serology results are not received from the medical provider, the LHD should contact the infant's medical provider for the results.
2. If post-vaccination serology results indicate hepatitis B infection in the infant, the LHD should:
   • Contact the ODH PHBPP.
   • Report the infected infant as a confirmed or probable case in ODRS per ODH guidelines.
   • Refer the infant for further medical follow-up.
3. If post-vaccination serology indicates that the infant has had an insufficient immune response, the LHD should ensure/facilitate a second three-dose vaccine series, followed one month after the last dose by repeat testing.

D. ODRS Should be Used to Record and Track the Entire Management and Follow-Up of the Infant

All data should be entered into ODRS as it is acquired during management and follow-up.

VI. Management of Household and Sexual Contacts

Please see the Hepatitis B Infectious Disease Control Manual (IDCM) chapter.

VII. Case Closure

A. Upon Both Completion of the Infant's Three-Dose Series (or Six Doses if Indicated) and Documentation of Seroconversion with Post-Vaccination Serology (i.e., anti-HBs 10 mU/mL or More), as Well as a Negative HBsAg Test Result, the Infant Case in ODRS Should be Closed

1. As noted above, if seroconversion does not occur after six doses, the infant case in ODRS may still be closed because no further vaccination is recommended.
2. HBsAg should be drawn simultaneously with anti-HBs.

B. By the Time the Infant is 18 Months of Age, the LHD Should Make at Least Three Contacts with the Infant's Parents, Guardians, or Physician

1. Contacts can be via phone, mail, and/or in person.
2. Documentation of each contact attempt should be made in ODRS.

C. If a Pregnant HBsAg-Positive Female and/or an Exposed Infant Transfer Out of the Jurisdiction

If a pregnant HBsAg-positive female and/or an exposed infant transfer out of the jurisdiction, the LHD will update the ODRS record with the most current address available. To transfer a case, the LHD must provide a street address, city, and state. The LHD will transfer the case within Ohio. If the case transfers out-of-state, the ODH PHBPP staff will transfer the case to another state PHBPP coordinator and update the ODRS record.

D. Case Status in the Clinical Module Must be Changed from "Active Follow Up" to the Appropriate Closure Status.

References

1. A Comprehensive Immunization Strategy to Eliminate Transmission of Hepatitis B Virus Infection in the United States. Recommendations of the Advisory Committee on Immunization Practices (ACIP) Part 1: Immunization of Infants, Children, and Adolescents. MMWR December 23, 2005; 54 (RR16); 1-23.
2. ODH Perinatal Hepatitis B Prevention Program, 2018.
3. American Academy of Pediatrics. Hepatitis B. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, IL: American Academy of Pediatrics; 2021: 381-399.
4. Robinson CL, Romero JR, Kempe A, Pellegrini C. Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2017. MMWR Morb Mortal Wkly Rep 2017;66:134–135. DOI.
5. Schillie S, Vellozzi C, Reingold A, et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 2018;67(No. RR-1):1–31.
6. Centers for Disease Control and Prevention. (2022, August 18.) 2020 newly reported cases of perinatal hepatitis B. Centers for Disease Control and Prevention.