Document text
Hepatitis B Birth Dose Vaccination
CDC Advisory Committee for Immunization Practices Meeting
September 18, 2025
1U.S. Centers for Disease Control and Prevention
Perinatal HBV transmission, which accounts for most infections globally,
results in severe health consequences.
HBV = hepatitis B virus. Schillie S. MMWR Recomm Rep. 2018
*Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tra nsformed into an image via text prompts 2
Hepatitis B in the U.S. — a Tale of two Epidemiologies
▪Up to 2.4 million persons estimated to have hepatitis B in
the United States1
-50% unaware of their infection2
▪Persons born outside the U.S.1,3
-Chronic infection since childhood
-Account for ~70% of all chronic infections
▪14,400 estimated acute hepatitis B cases in the U.S. in 20234
-Unvaccinated persons with behavioral risk factors
-Highest rates among adults aged 40 -59 years
-Adults have higher clearance rates and lower risk for chronic infection5
1.Wong et al. Hepatology 2021; 2. Bixler et al. Hepatol Commun. 2023; 3. Razavi -Shearer D, et al. The Lancet Regional Health Americas 2023; 4.
https://www.cdc.gov/hepatitis -surveillance -2023/about/index.html ; 5. Chapter 10: Hepatitis B | Pink Book | CDC
Source: Razavi -Shearer D, et al. The Lancet Regional Health Americas 2023.
Chronic HBV infection results in high lifetime healthcare costs.
4Annual costs of treating a patient with less severe hepatitis B: $25,308 –$93,935 (2025 USD)
Annual cost of treating a patient requiring a liver transplant: $174,282─$324,849 (2025 USD)
HBV = hepatitis B virus
Nguyen MH, Burak Ozbay A, Liou I, Meyer N, Gordon SC, Dusheiko G, Lim JK. Healthcare resource utilization and costs by disease severity in an insured national sample of US patients with ch ronic
hepatitis B. J Hepatol. 2019 Jan;70(1):24 -32
Original estimates converted from 2015 USD to 2025 USD using https://www.bls.gov/data/inflation_calculator.htm
Hepatitis B birth dose vaccination and immune globulin (HBIG)
substantially reduce the risk of mother -to-child transmission.
5Schillie S. MMWR Recomm Rep. 2018; Beasley RP et al. Lancet. 1983; Lee C et al. 2006; Beasley RP et al. 1977; Armstrong GL. Pediatrics. 2001;
Mahoney. Pac Hth Dialog 1996; Ruff TA. The Journal of Infectious Diseases. 1995
*Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tra nsformed into an image via text promptsEARLIER BIRTH DOSE VACCINATION HAS
GREATER EFF ECTIVENESS
Setting Time after birth
vaccinatedNumber of
Children%
HBsAg+
Palau> 3 days
≤ 3 days30
3236.7%
0.6%
Micronesia> 3 days
≤ 3 days78
2172.6%
0.0%
Indonesia> 7 days
≤ 7 days656
17173.0%
1.4%
Hepatitis B vaccines
•Two single -antigen hepatitis B vaccines are FDA -approved for use from
birth through adulthood; dosing varies by age group1
-Recombivax HB (1986)
-Engerix -B (1989)
•Safety
-The Institute of Medicine's Immunization Safety Review and the WHO's Global Advisory
Committee on Vaccine Safety concluded that hepatitis B vaccine is both safe and effective.1,2,3
1.Poland GA et al, NEJM, 2004. 2. Stratton K et al, Immunization Safety Review , National Academies Press, 2002. 3. Global Advisory Committee on Vaccine Safety, Wkly Epidemiol Rec, 2002.
6
Hepatitis B vaccination is a multidose series, with
increasing seroprotection among infants after each dose.
7
•Hepatitis B vaccination recommendations on child and adolescent immunization schedule – United States, 2025
•In addition to the immediate benefit of providing postexposure prophylaxis to the newborn, the
hepatitis B birth dose serves as the first dose of the infant vaccination series.*
•Among healthy infants, the 3 -dose hepatitis B vaccine series produces a protective antibody response
(anti -HBs ≥10 mIU /mL) in approximately:
•~25% of infants after the first dose,
•~63% of infants after the second dose, and
•~95% of infants after the third dose.
https://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.html (accessed 8/18/25);
*Except for pre -term infants weighing <2,000 grams born to women known to be HBsAg positive.
Schillie, S. et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep 67, 1 -31 (2018).
8For decades, ACIP has recommended universal hepatitis B screening for pregnant women and
birth dose vaccination for infants born to women who are HBsAg(+) or HBsAg status unknown.
ACIP hepatitis B screening recommendations for pregnant women and
perinatal postexposure recommendations for infants, United States
Modified from Bixler PHR 2023, Suppl Table 2. ACIP = Advisory Committee on Immunization Practices; HBIG = hepatitis B immune globulin; HepB , hepatitis B vaccine.
*Only single -antigen HepB vaccine should be used for the birth dose. Note: All hepatitis B birth dose vaccinations are considered to be the first dose of the infant series except among pre -term infants
weighing <2,000 grams who are born to mothers who are HBsAg positive.
1.CDC. MMWR Morb Mortal Wkly Rep 37, 341 -346, 351 (1988). 2.CDC. MMWR Morb Mortal Wkly Rep 33, 285 -290 (1984). 3. CDC. Update on hepatitis B prevention. MMWR Morb Mortal Wkly Rep 36, 353 -
360, 366 (1987). 4.CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 40, 1 -25 (1991). 5. Schillie , S. et al. MMWR Recomm Rep 67, 1 -31 (2018).
6. Mast, E. E. et al. MMWR Recomm Rep 54, 1 -31 (2005). 7. Bixler D, et al. Public Health Rep. 2023 Jun 9
9For decades, ACIP has recommended that the first dose of universal infant hepatitis B
vaccination among infants born to HBsAg( -) women occur close to birth.
ACIP hepatitis B infant vaccination recommendations, United States
Modified from Bixler PHR 2023, Suppl Table 2.
ACIP = Advisory Committee on Immunization Practices; HBIG = hepatitis B immune globulin; HepB , hepatitis B vaccine.
*Only single -antigen HepB vaccine should be used for the birth dose.
Note: All hepatitis B birth dose vaccinations are considered to be the first dose of the infant series except among pre -term infants weighing <2,000 grams who are born to mothers who are HBsAg p ositive.
1.CDC. MMWR Morb Mortal Wkly Rep 37, 341 -346, 351 (1988). 2.CDC. MMWR Morb Mortal Wkly Rep 33, 285 -290 (1984). 3. CDC. Update on hepatitis B prevention. MMWR Morb Mortal Wkly Rep 36, 353 -
360, 366 (1987). 4.CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep 40, 1 -25 (1991). 5. Schillie , S. et al. MMWR Recomm Rep 67, 1 -31 (2018). 6.
Mast, E. E. et al. MMWR Recomm Rep 54, 1 -31 (2005). 7. Bixler D et al. Public Health Rep. 2023 Jun 9
HBV infections are missed among some pregnant women and
can result in catastrophic outcomes.
10HBV = hepatitis B virus; PEP = post -exposure prophylaxis.
Schillie et al. MMWR Recomm Rep. 2018 Jan 12;67(1):1 -31.
Willis, B.C., et al., Pediatrics, 2010. 125(4): p. 704 -11.
CDC. MMWR Morb Mortal Wkly Rep. 2001 Feb 16;50(6):94 -7.
Nolt D, et al. Pediatrics. 2022 Feb 1;149(2)
Michigan, 1999
“On December 14, 1999, a previously healthy 3 -month -old infant was admitted to a hospital with
diarrhea and jaundice, and acute hepatic failure attributed to HBV infection was diagnosed. The
infant died on December 17, 1999. The infant had not received her first dose of hepatitis B vaccine
until age 2.5 months.
The infant's mother was found to be HBsAg -positive at the first of 10 prenatal visits.
However, the prenatal -care record provided to the birth hospital indicated that the mother
was hepatitis -negative . Neither the provider nor the laboratory reported the mother's test results to
MDCH as required by law.”
The Immunization Action Coalition documented
more than 500 transmissions of HBV in these
types of situations from 1999 to 2002
Hepatitis B birth dose vaccination serves as a critical safety net against
gaps in protection against perinatal HBV infection.
11
The National Perinatal Hepatitis B Prevention
Program identifies less than half of infants
estimated to be born to HBV infected mothers
Koneru et al. Pediatrics. 2021 Mar;147(3):e20201823.
Pham et al. Am J Prev Med. 2023 Jul;65(1):52 -59.
Kolasa et al . Pediatr Infect Dis J. 2017 Jul;36(7):e175 -e180.
Martin JA, Osterman MJK. Natl Vital Stat Rep. 2023 May;72(4):1 -14. PMID: 37252688.
Koneru A, et al. Pediatrics. 2021 Mar;147(3):e20201823.
Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tran sformed into an image via text prompts
Unvaccinated infants remain at risk of non -perinatal HBV acquisition.
•HBV transmission occurs through percutaneous or mucosal exposure to infectious blood or body
fluids
•HBV can remain viable for over 7 days on environmental surfaces at room temperature.1
•Household and Community Transmission: Unvaccinated children living with a person with
chronic HBV infection in a household or community setting are at risk for becoming infected.
-Prior to HepB BD, some U.S. -born children born to immigrant mothers without HBV infection had hepatitis
B prevalences of 7 –11%2,3 attributable to community or household exposures.
•In the United States, up to 2.4 M people are estimated to have hepatitis B4, and about 50% of
people with hepatitis B are unaware of their infection5.
•Children who receive HepB BD have higher rates of hepatitis B childhood vaccine series
completion and had a positive impact on rates of being up to date for other age -appropriate
vaccines 6,7,8
12HBV = hepatitis B virus. HepB BD = hepatitis B birth dose vaccination.
1. Bond et al, Lancet. 1981; 2. Franks et al, N Engl J Med. 1989; 3. Hurie et al, Pediatrics. 1992; 4. Wong et al, Hepatology. 2021; 5. Bixler et al, Hepatol ogy Communications; 2023. 6. Yusuf HR, et al, JAMA. 2000
Aug 23 -30;284(8):978 -83 8; 7. Mast, E. E. et al, MMWR Recomm Rep 54, 1-31 (2005). 8. Mennito SH, Darden PM.. J Pediatr. 2010 Apr;156(4):618 -22.
Hepatitis B vaccination has been the cornerstone of hepatitis B control
for decades and has brought the U.S. within reach of elimination.
05,00010,00015,00020,00025,00030,000
1991
Universal infant
hepatitis B
vaccination
1982
Risk -based
hepatitis B
vaccination2005
Universal infant
vaccination prior to
hospital discharge2018
Universal
infant hepatitis B
vaccination
within 24 hours
of birth
1991
Hepatitis B
vaccination
within 12 hours
of birth for
infants born to
women with
unknown
HBsAg status 2018 Hepatitis B vaccination and HBIG within 12 hours of
birth for infants born to women with unknown HBsAg status1988
Hepatitis B
vaccination and
HBIG within 12
hours of birth for
infants born to
HBsAg (+) womenReported cases of acute hepatitis B and key ACIP vaccination recommendations among infants, United States, 1980 -2023
HBIG = Hepatitis B immune globulin; CDC NNDSS Viral Hepatitis Surveillance (https://www.cdc.gov/hepatitis/php/statistics -surveillance/index.html );
†From 1991‒2010 all case classifications included (i.e., confirmed, probable, suspect, unknown); from 2011‒2023 only confirme d cases included
Bixler D, Roberts H, Panagiotakopoulos L, Nelson NP, Spradling PR, Teshale EH. Public Health Rep. 2023 Jun 9
Rescinding Universal HepB BD vaccination recommendations among infants born to HBsAg ( -) women
may result in more cases of perinatal HBV infection.
14Potential Benefits of Rescinding
Universal HepB BD RecommendationsPotential Risks of Rescinding
Universal HepB BD Recommendations
Reductions in rare cases of hepatitis B birth dose
vaccination adverse eventsIncreased cases of perinatal HBV transmission
Increased administrative complexity and failure points
for providers and health systems
Lack of safety net given gaps in access to prenatal care,
HBV screening, and HBIG access
Disproportionate harm to patients without insurance or
low healthcare engagement
Lower rates of hepatitis B childhood vaccine series
completion
Higher lifetime healthcare costs from missed
opportunities to prevent and eliminate hepatitis B
HepB BD = hepatitis B birth dose vaccination; adverse events listed in the section ‘Vaccine Safety’ in Schillie S. MMWR Recom m Rep. 2018 (page 11)
Request to CDC from ACIP Chair
•Survey of HepB vaccine recommendations in developed countries, including
the United States, Canada, all EU countries, UK, Norway, Switzerland,
Iceland, Australia, New Zealand, South Korea and Japan. Specifically,
-At what age is the first dose recommended for:
(i) children to HepB positive mothers, and for
(ii) other children?
-Also, in these countries, what is the prevalence of HepB infection in pregnant
women?
15
Global hepatitis B birth dose vaccination policies
16Hepatitis B vaccine birth dose vaccination policy by country, 20251
Universal HepB -BD:
Hepatitis B vaccine recommended for all
newborns.
Selective HepB -BD:
Hepatitis B vaccine recommended only to
newborns born to HBsAg(+) women.
Partially -Introduced Universal HepB -BD:
Hepatitis B vaccine recommendations among
newborns varies by geographic location within
the country (at least one jurisdiction
recommends universal HepB -BD).
HepB -BD = hepatitis B birth dose vaccination.
1. Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - Canada.ca ; Hepatitis B vaccine – NHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health
New Zealand | Te Whatu Ora ; Introduction of Hepatitis B vaccine ; Hepatitis B | The Australian Immunisation Handbook ; 20240220_Immunization_Schedule_english.pdf ; National Immunization
Program for children | Policy&Services : KDCA ; Hepatitis B
Hepatitis B first dose vaccination schedule in selected countries*
17Sources: Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - Canada.ca ; Hepatitis B vaccine –
NHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health New Zealand | Te Whatu Ora ; The Australian Immunisation Handbook ;
20240220_Immunization_Schedule_english.pdf ; National Immunization Program for children | Policy&Services : KDCA ; Hepatitis B* United States, Canada, all EU/EEA countries, UK, Norway, Switzerland,
Iceland, Australia, New Zealand, South Korea and Japan. Age at first dose Number of countries
At what age is the first dose recommended for children born to HBsAg (+) women? (N=38)
Before discharge from the hospital, or within 24 hours of birth 36
Ideally within 24 hours of birth but no later than 7 days after birth 1 (Ireland)
Within 48 hours of birth (majority of newborns are vaccinated within 24 hours) 1 (Denmark)
At what age is the first dose recommended for children born to HBsAg ( -) women?
Countries that provide a universal HepB -BD (N=8)
Same schedule as children born to HBsAg (+) women 7
Ideally within 24 hours but no later than 7 days after birth 1 (Australia)
Countries that provide selective HepB -BD and universal infant hepatitis B vaccination policy (N=26)
At the age of 2 months 18
At the age of 3 months 6
At the age of 12 -13 years 1 (Hungary)
Varies by province (2 months; 11 or 12 years) 1 (Canada)
Prevalence of hepatitis B among pregnant women in selected countries*
18Hepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian Perspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal immunoprophylaxis for
infants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; Updated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening and Management of
HBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMC* United States, Canada, all EU/EEA countries, UK, Norway, Switzerland, Iceland, Australia, New Zealand, South Korea and Japa n. •Only 6 of 38 selected countries* have national registries to track hepatitis B screening in pregnant women and
estimate prevalence on an annual basis
•The remaining 32 countries (including the United States), do not have national registries to track hepatitis B
screening during pregnancy; when available, prevalence estimates from these countries are based on surveys or
studies.
EU, UK and other countries with selective hepatitis B birth dose vaccination
have higher hepatitis B prenatal screening coverage than in the United States
19EU = European Union; UK = United Kingdom.
*No universal healthcare coverage
≠2023 data except for the following countries: Lithuania, 2021; United States, 2015 -2019; France, Germany, and Poland, data >5 but <10 years old.
No data is publicly available for Austria, Belgium, Croatia, Cyprus, Greece, Iceland, Italy, Japan, Latvia, Lichtenstein, Lux emb ourg, Malta, New Zealand, Norway, Romania, South Korea, Spain,
or Sweden.
Hepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian Perspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal
immunoprophylaxis for infants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; Updated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening
and Management of HBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMCCoverage of antenatal screening for hepatitis B in selected countries≠
Request to CDC from ACIP Chair
•Results from randomized trials concerning the administration of the HepB
vaccine within 24 hours of birth, with all results stratified by the HepB
infection status of the mother. Include both efficacy data and adverse
events, including all -cause morbidity and mortality. For children whose
mothers are HepB negative, present results for all children combined as
well as stratified by pre -mature birth and birth weight. If randomized data
is lacking for any of the requested populations, please mention that.
20
Search Results
*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16. doi: 10.1016/j.vaccine.2012.12.012. Epub 2012 Dec 17. 21Ordered Full -Text
(n = 93)ESR Search
Jan 1987 -Dec 2011
(n = 833)Existing Systematic Review (ESR)*Updated Rapid Systematic Review (URSR)
Ordered Full -Text
(n = 316)URSR Search
Dec 2011 -Aug 2025
(n = 1390)
Duplicates
(n = 11)
Did not meet
inclusion
criteria
(n=221)
Unable to
retrieve full -
text (n = 85)HepB Vaccination Studies
(n = 47)
Included in Original Review
(n = 43)Not relevant/
Duplicates
(n = 740)
Not relevant
(n = 46)
Duplicate
subjects
(n = 4)
Included in Update Review
(n = 7)Did not meet
inclusion
criteria for
URSR
(n = 36)HepB Birth Dose Studies
(n = 10)Not relevant
(n = 1063)Titles and Abstracts
Screened
(n = 1379)
Total Studies Included
(n = 17)
Summary of Cochrane risk of bias assessments* for studies in
existing and updated rapid systematic reviews (n=17)
22
D1
−
−
−
+
−
−
−
+
+
+
x
+
−
x
x +
+
D2
−
x
x +
+
+
−
−
+
+
−
−
+
−
−
+
+
D3
x
+
+
+
+
+
+
+
+
+
+
x
+
+
+
+
+
D4
x
x +
+
+
x
x + +
+
+
x
+
+
+
+
+
D5
−
−
+
+
+
−
−
−
x
+
+
−
−
−
+
+
+
Overall
x
x
x +
−
x
x
x
x −
x
x −
−
x
+
− Study
Assateerawatt (1993)
Bassily (1995)
Gorar (2024)
Halliday (1992)
Hieu (2002)
Hieu (2015)
Kang (2015)
Lee (1995)
Pande (2013)
Safadi (2021)
Tulenko (2024)
Velu (2007)
Wang (2022)
Yang (2015)
Yerushalmi (1997)
Zhu (2016)
Zhu (2017)Domains:
D1: Bias due to randomization.
D2: Bias due to deviations from intended intervention.
D3: Bias due to missing data.
D4: Bias due to outcome measurement.
D5: Bias due to selection of reported result.High
Some concerns
LowJudgment of Risk of Bias
*Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H -Y, Corbett MS, Eldridge SM, Hernán MA, Hope well S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T,
Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revise d tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.
Intervention Characteristics (n=17)
Abbreviations: µg, micrograms; HBIG hepatitis B immune globulin
*Not mutually exclusive
23Characteristic # of Studies Reporting (%)
Intervention Study Type Efficacy trials 2 (11.8%)
Timing of vaccination 1 (5.9%)
Product or formulation differences 8 (47.1%)
Dose and schedule 4 (23.5%)
HBIG co -intervention 2 (11.8%)
Vaccine Administered* Engerix 7 (41.2%)
Recombivax 1 (5.9%)
Other 14 (82.3%)
Vaccine Dose* 10 µg 13 (76.4%)
20 µg 2 (5.9%)
Other 6 (35.2%)
Vaccination Schedule 0, 1, 6 months 11 (64.7%)
0, 1, 2, 12 months 1 (5.9%)
Other 5 (29.4%)
Efficacy Trials (n=2)
Hepatitis B vaccine series first administered at birth achieved high levels of seroprotection .
Abbreviations: HBeAg , hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms
Seroprotection : Anti-HBs ≥10 mIU /mL at least 1 -2 month after the final dose in the vaccine series or between 9 -12 months of age.
24Author (year)Comparison
ArmsMaternal
StatusSeroprotection
% Difference Risk of Bias Intervention Comparator
Hieu (2002) Hepavax vs.
EngerixHBsAg positive 49/52 (94.2%) 45/52 (86.5%) 7.7 pct pts Some concernAuthor (year)Comparison
ArmsMaternal
StatusSeroprotection
% Difference Risk of Bias
Intervention Comparator
Assateerawatt
(1993)20 mcg +
HBIG vs.
20mcgHBsAg positive and
HBeAg positive26/26 (100%) 22/23 (95.7%) 4.3 pct pts HighHepB vaccine
Comparative efficacy
Efficacy Trials (n=2)
Among infants born to HBsAg positive mothers, h epatitis B birth dose vaccine
demonstrated efficacy in the prevention of perinatal transmission.
Abbreviations: HBeAg , hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms
*Vaccine refusals 25Author (year)Comparison
ArmsMaternal
StatusInfant HBsAg Positive Cases
Risk Ratio (95% CI) Risk of Bias Intervention Comparator
Hieu (2002) Hepavax vs.
EngerixHBsAg positive 1/53 (1.9%) 2/52 (3.8%) 0.49 (0.05, 5.25) Some concernsAuthor (year)Comparison
ArmsMaternal
StatusInfant HBsAg Positive Cases
Risk Ratio (95% CI) Risk of Bias
Intervention Comparator
Assateerawatt
(1993)20 mcg vs.
no vaccine*HBsAg positive and
HBeAg positive3/22 (13.6%) 34/40 (85.0%) 0.16 (0.06, 0.46) High
Assateerawatt
(1993)20 mcg +
HBIG vs. no
vaccine*HBsAg positive and
HBeAg positive1/25 (4.0%) 34/40 (85.0%) 0.05 (0.01, 0.32) HighHepB vaccine vs. no vaccine*
Comparative efficacy
Efficacy Trial (n=1)
Hepatitis B birth dose resulted in few systemic adverse events .
Abbreviations: HBeAg, hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms
26Author (year)Comparison
ArmsMaternal StatusSystemic Adverse Events
Risk Ratio (95% CI) Risk of Bias Intervention Comparator
Hieu (2002) Hepavax vs.
EngerixHBsAg positive 2/53 (3.8%) 2/52 (3.9%) 0.98 (0.14, 6.71) Some
concernsComparative efficacy
Note: majority of adverse events were reported as mild fever
Timing of Vaccination Trial (n=1)*
Among infants born to HBsAg negative mothers, high level of seroprotection and no significant
difference in adverse events reported between the intervention and comparison groups.
•Intervention: received 2.5 µg Recombivax vaccine at birth, 2 months, and 6 months
•Comparator: received 3 doses of 2.5 µg Recombivax vaccine seroprotection at the end of the study, starting at 18
months
•Maternal status: HBsAg negative
•Risk of bias assessed: High
•Outcomes:
-Seroprotection :
•91.0% (162/178) of intervention group achieved seroprotection 1 month after the final dose of the vaccine series
-Adverse events :
•Localized symptoms: I: 5/178 (2.8%); C: 3/191 (1.6%) → RR = 1.77 (95% CI: 0.43, 7.29); RD = 1.2%
•Systemic symptoms: I: 10/178 (5.6%); C: 4/191 (2.1%) → RR = 2.59 (95% CI: 0.83, 8.12); RD = 3.5%
•Summary:
-Over 9 in 10 newborn infants in the intervention group achieve seroprotection .
-Among infants born to HBsAg negative mothers, there was no significant difference in adverse events reported between the
intervention and comparison groups.
Abbreviations: C, comparison group; HBsAg, hepatitis B surface antigen; I, intervention group; RR, risk ratio; RD, risk diffe rence (absolute)
*Bassily , S.,Kotkat , A.,Gray, G.,Hyams, K. C.,Brown, F. M.,Imam, I. Z.,Arthur, R.. Comparative study of the immunogenicity and safety of two dosing schedules of hepatitis B vaccine in neonates. Am J Trop Med Hyg. 1995. 53:419 -22. 27
Product or Formulation Trials
Hepatitis B vaccine series beginning at birth among infants born to HBsAg positive or negative women
•Seroprotection (n=7)
-Achieved high levels of seroprotection among infants in both intervention (89% -99%) and comparison groups (71% -98%).
•Efficacy (n=4)
-Among HBsAg positive women, demonstrated equivalent efficacy in the prevention of perinatal transmission between
intervention and comparison groups
•Adverse events (n=5)
-Hepatitis B birth dose resulted in few local or systemic adverse events among infants in intervention and comparison groups
28Seroprotection studies: Halliday, 1992; Hieu, 2015; Safadi, 2021; Velu, 2007; Yerulshami, 1997; Zhu, 2016; Zhu 2017.
Efficacy studies: Halliday, 1992; Velu, 2007; Safadi, 2021; Zhu 2017.
*Local symptoms may include injection site pain, soreness, redness, swelling in the arm where the shot was given; alternative ly, investigators may report under a general grouping of “local adverse events”.
Systemic symptoms may include fever, excessive crying, rash, irritability, vomiting, diarrhea, loss of appetite, drowsiness; alternatively, investigators may report under a general grouping of “systemic adverse events”.
Local Symptoms (n=5) Systemic Symptoms (n=4)
Dose and Schedule Trials (n=4)
Among infants born to HBsAg positive or negative women,
hepatitis B birth dose vaccine schedule is seroprotective
29Author (year) Comparison Arms Maternal StatusSeroprotection
Percent
differenceRisk of Bias Intervention Comparator
Lee (1995) 5 mcg vs. 2.5 mcg HBsAg negative 261/279 (94.0%) 271/308 (88.0) 6.0 pct pts High
Kang (2015) 10 mcg vs. 5 mcg All negatives +
positives169/177 (95.5%) 166/173 (96.0%) -0.5 pct pts High
Tulenko
(2024)4 doses vs. 3
dosesHBsAg negative 24/28 (85.7%) 26/28 (93.0%) -7.3 pct pts High
Gorar (2024) HepB BD vax vs.
standard schedule
(no BD)HBsAg negative 116/121 (96.0%) 57/97 (59.0%) 37.0 pct pts High
Dose and Schedule Trials (n=2)
Among infants born to HBsAg positive or negative women,
hepatitis B birth dose vaccine schedule has high efficacy
30Author (year)Comparison
ArmsMaternal
StatusInfant HBsAg Positive Cases
Risk Ratio (95% CI) Risk of Bias Intervention Comparator
Kang (2015) 10 mcg vs.
5 mcgAll negatives
+ positives4/90 (4.4%) 6/90 (6.7%) 0.67 (0.19, 2.28) High
Tulenko (2024) 4-dose
series vs. 3 -
dose seriesHBsAg
negative0/28 0/28 1.00 (0.02, 48.7) High
Dose and Schedule Trials: Safety Outcomes (n=1)
Among infants born to HBsAg positive or negative women,
hepatitis B birth dose vaccine schedule resulted in few local or systemic adverse events
31Author (year)Comparison
ArmsMaternal StatusLocal Adverse Events
Risk Ratio (95% CI) Risk of Bias Intervention Comparator
Kang (2015) 10 mcg vs. 5
mcgAll negatives +
positives1/253 (0.4%) 2/253 (0.8%) 0.50 (0.05, 5.48) High
Author (year)Comparison
ArmsMaternal StatusSystemic Adverse Events
Risk Ratio (95% CI) Risk of Bias Intervention Comparator
Kang (2015) 10 mcg vs. 5
mcgAll negatives +
positives8/253 (3.2%) 7/253 (2.8%) 1.14 (0.42, 3.10) High
Evidence Gap / Limitations
Evidence Gap:
•Lack of placebo -controlled trials assessing efficacy
-This is not surprising as it is unethical to withhold a proven, safe and effective intervention (i.e., hepatitis B
vaccination) simply to include a placebo group
•Paucity of evidence reporting outcomes for preterm/LBW/ELBW infants, as well as morbidity and
mortality for all infants
Limitations:
•Heterogeneous reporting of timepoints and definitions
•Many of the studies were done before the wide application of the CONSORT statement*, which seeks to
improve reporting of randomized controlled trials (RCTs)
•Most of the RCTs (59%) assessed had a high risk of overall bias primarily due to the randomization and
measurement of outcomes
Abbreviations: LBW, low birth weight; ELBW, extremely low birth weight.
*Hopewell S, Chan A, Collins GS, et al. CONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials. JAMA. 2025 ;333(22):1998 –2005. doi:10.1001/jama.2025.434732
Conclusion
•Based on the included body of evidence:
-Hepatitis B birth dose induces high seroprotection and efficacy
-Hepatitis B birth dose vaccine is safe
-Head -to-head comparisons of various hepatitis B recombinant vaccine products,
doses, and schedule show no meaningful differences in reported outcomes in
efficacy and safety
33
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1-800-CDC-INFO (232 -4636)
TTY: 1 -888-232-6348 cdc.gov
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The findings and conclusions in this report are those of the authors and do not necessarily represent the official position
of the U. S. Centers for Disease Control and Prevention.
34
Background Slides
35
Search for Evidence
•Identified an existing systematic review focused
on HepB vaccination among newborns*
-Used the Schillie review as a starting point
-Search period: 1/1/1987 – 12/16/2011
•Conducted an updated rapid systematic review
using a similar search strategy
-Search period: 12/17/2011 – 8/14/2025
•Electronic databases searched:
-Medline (OVID)
-Embase (OVID)
36
*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16.
Existing Systematic Review*
•Objective: To summarize seroprotection and immunogenicity of recombinant hepatitis B
vaccines administered within the first 30 days of life
•Search Period: January 1, 1987 to December 16, 2011
•Databases: Medline (via PubMed) and Embase (OVID)
•Key Inclusion Criteria: studies reporting seroprotective response to monovalent recombinant
HepB vaccine administered to infants within ≤30 days
•Key Exclusion Criteria:
-When seroprotection was assessed in conjunction with administration of other vaccines
-When a combination vaccine containing hepatitis B vaccine was administered
-When vaccine was not administered intramuscularly
-When seroprotection was not reported within 3 months of the final dose
37*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16.
Updated Rapid Systematic Review: Inclusion/Exclusion Criteria
38Inclusion Criteria Exclusion Criteria
• Newborn infants receiving a HepB vaccine at birth
(i.e., ≤24 hours old at dose 1)• Non -English language articles
• Animal studies
• Randomized controlled trial
• Monovalent HepB vaccine administered within ≤24 hours of birth;
co-administration of HepB immune globulin (HBIG) is permitted• Combination infant vaccines at birth, when the HepB component’s
contribution or timing cannot be isolated
• No extractable data on maternal status; for HBsAg( -) mothers, no
data for total group and none for prematurity/birth -weight strata
• No outcome of interest reported
• Results not stratified by intervention arm
• Provided comparative data regarding the safety and effectiveness of
Hep immunization strategies, such as delayed HepB vaccination
(>24 hrs. after birth) or no HepB vaccination; other vaccination
schedule• Nonrandomized/observational designs; RCTs where all arms initiate
vaccine >24 hours after birth without a ≤24 -hour comparator
•Outcomes include any of the following:
•HBV infection
•Chronic HBV infection
•Seroprotection
•Seroconversion
•Safety outcomes
•All-cause morbidity
•All-cause mortality• Preprints
• Conference abstracts
• Editorial/Commentary
• Letter to the Editor
List of Outcomes
*Local symptoms may include injection site pain, soreness, redness, swelling in the arm where the shot was given. Alternative ly, investigators may report under a
general grouping of “local adverse events”; systemic symptoms may include fever, excessive crying, rash, irritability, vomiti ng, diarrhea, loss of appetite, drowsiness.
Alternatively, investigators may report under a general grouping of “systemic adverse events.”
39Outcome Type Outcome Definition Included in ESR? Included in URSR?
Efficacy • HBsAg and/or HBV DNA positivity Yes Yes
Seroprotection • Anti-HBs ≥10 mIU/mL at least 1 -2
month after the final dose in the
vaccine series or between 9 -12
months of age.Yes Yes
Safety • Local/systemic adverse events* Yes Yes
Morbidity • Severe illness
• HospitalizationN/R Yes
Mortality • Death N/R Yes
Abbreviations: anti -HBs, antibody to hepatitis B surface antigen; ESR, existing systematic review; URSR, updated rapid systemati c review; HBsAg, hepatitis B
surface antigen; HBV DNA, hepatitis B virus deoxyribonucleic acid. N/R = not reported
Risk of Bias Assessment
•Cochrane Risk of Bias, version 2 (RoB 2) 1
-Used to assess risk of bias in RCTs
•Bias related to:
–randomization process
–Deviation from intended intervention
–Missing outcome data
–Measurement of outcome
–Selection of reported results
-RoB 2 overall judgement options: low risk, some concerns, high risk
40
1Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H -Y, Corbett MS, Eldridge SM, Hernán MA, Hope well S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T,
Li T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revise d tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.
Analyses and Presentation Decisions
41Factor Decision
Type of Analysis Proportions for seroprotection; risk ratios for efficacy and safety outcomes
Time Point UsedSeroprotection: first reported time point immediately following the last dose in
a series
Efficacy (against HBV infection) : latest available time point with ongoing
intervention
Safety outcomes: at birth or the closest time point immediately after the birth
dose
Outcome Measure Multiple outcome measures reported separately
Overall Effect Estimate Measure Pooled random effect meta -analysis where possible
Multiple Intervention Arms Intervention arms reported separately
Summary Qualitatively compare summary estimates
Abbreviations: HBV, hepatitis B virus
Search Strategy: Medline (OVID)
421.exp Hepatitis B Vaccines/
2.(((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax
HB OR Hepavax -Gene).ti,ab,kf.
3.1 OR 2
4.Exp Infant/
5.(Infant* OR newborn* OR new born * OR neonat* OR birth OR birth -dose*).ti,ab,kf.
6.4 OR 5
7.Hepatitis B/im OR Hepatitis B Antibodies/ OR Hepatitis B Surface Antigens/
8.(seroprotection OR sero -protection OR immunogeni* OR immune response OR antibod*).ti,ab,kf.
9.7 OR 8
10.Randomized Controlled Trials as Topic/
11.(random* OR RCT* OR clinical trial* OR clinical stud* OR controlled trial* OR double -blind* OR
single -blind* OR placebo* OR control group*).ti,ab,kf,hw.
12.10 OR 11
13.3 AND 6 AND 9 AND 12
14.exp animals/ NOT exp humans/
15.13 NOT 14
16.limit 15 to dt="20111217 -20250814"
17.limit 16 to English language
Search Strategy: Embase (OVID)
1.exp Hepatitis B Vaccine/
2.(((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB OR Hepavax -
Gene).ti,ab,kf.
3.1 OR 2
4.Exp Infant/
5.(Infant* OR newborn* OR new born * OR neonat* OR birth OR birth -dose*).ti,ab,kf.
6.4 OR 5
7.Hepatitis B Antibody/ OR Hepatitis B Surface Antigen/
8.(seroprotection OR sero -protection OR immunogeni* OR immune response OR antibod*).ti,ab,kf.
9.7 OR 8
10."randomized controlled trial (topic)"/
11.(random* OR RCT* OR clinical trial* OR clinical stud* OR controlled trial* OR double -blind* OR single -blind* OR placebo* OR
control group*).ti,ab,kf,hw.
12.10 OR 11
13.3 AND 6 AND 9 AND 12
14.exp animal/ NOT exp human/
15.13 NOT 14
16.limit 15 to dc="20111217 -20250814"
17.limit 16 to English language
43
List of Included Studies (n=17), Part I
44References Latest Follow -
up Period
(months)Sample
Size
• Assateerawatt , A.,Tanphaichitr , V. S., Suvatte , V.,Yodthong , S.. Immunogenicity and efficacy of a recombinant DNA hepatitis B vaccine,
GenHevac B Pasteur in high risk neonates, school children and healthy adults. Asian Pac J Allergy Immunol. 1993. 11:85 -91.12 100
• Bassily , S.,Kotkat , A.,Gray , G.,Hyams , K. C.,Brown , F. M.,Imam , I. Z.,Arthur , R.. Comparative study of the immunogenicity and safety of two
dosing schedules of hepatitis B vaccine in neonates. Am J Trop Med Hyg. 1995. 53:419 -22.18 590
• Gorar , Z. A.,Butt , Z. A.. Impact of hepatitis B birth dose on immune response in Pakistani children: an open -label, non -inferiority
randomized controlled trial, implications for achieving SDG target. Infectious Diseases. 2024. 56:1 -10 .5 296
• Halliday, M. L.,Kang , L. Y.,Rankin , J. G.,Coates , R. A.,Corey , P. N.,Hu , Z. H.,Zhou , T. K.,Yuan , G. J.,Yao , F. L.. An efficacy trial of a mammalian
cell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China. Int J Epidem iol. 1992.
21:564 -73.12 220
• Hieu, N. T.,Kim , K. H.,Janowicz , Z.,Timmermans , I.. Comparative efficacy, safety and immunogenicity of Hepavax -Gene and Engerix -B,
recombinant hepatitis B vaccines, in infants born to HBsAg and HBeAg positive mothers in Vietnam: an assessment at 2 years. Vaccine.
2002. 20:1803 -8.24 105
• Hieu, N. T.,Sarnecki , M., Tolboom , J.. The safety and immunogenicity of two hepatitis B vaccine formulations (thiomersal -free and
thiomersal -containing) in healthy vietnamese infants: a phase III, prospective, single -blinded, randomized, controlled trial. Pediatric
Infectious Disease Journal. 2015. 34:79 -83.7 408
• Kang, G.,Ma , F.,Chen , H.,Yang , Y.,Guo , S.,Wang , Z.,Liang , X.,Li, L.,Cui , F.,Zhang , L.. Efficacy of antigen dosage on the hepatitis B vaccine
response in infants born to hepatitis B -uninfected and hepatitis B -infected mothers. Vaccine. 2015. 33:4093 -9. 6 506
• Lee, S. S.,Lo , Y. C.,Young , B. W.,Wong , K. H.,Lim , W. L.. A reduced dose approach to hepatitis B vaccination for low -risk newborns and
preschool children. Vaccine. 1995. 13:373 -6.12 587
• Pande C, Sarin SK, Patra S, Kumar A, Mishra S, Srivastava S, et al. Hepatitis B vaccination with or without hepatitis B immun oglobulin at
birth to babies born of HBsAg -positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babie s: a
randomized controlled trial. J Viral Hepat . 2013 Nov;20(11):801 -10.24 259
List of Included Studies ( n=17), Part II
45References Latest Follow -up
Period (months)Sample Size
•Safadi, R.,Khoury , T.,Saed , N.,Hakim , M.,Jamalia , J.,Nijim , Y.,Farah , N.,Nuser , T.,Natur , N.,Mahamid , M.,Amer , J.,Roppert , P. L.,Gerlich ,
W. H.,Glebe , D.. Efficacy of Birth Dose Vaccination in Preventing Mother -to-Child Transmission of Hepatitis B: A Randomized
Controlled Trial Comparing Engerix -B and Sci -B-Vac. Vaccines. 2021. 9:01.12 171
•Tulenko, S. E.,Ngimbi , P.,Mwandagalirwa , K.,Tabala , M.,Matondo , J.,Ntambua , S.,Mbonze , N.,Mbendi , C.,Luhata , C.,Jhaveri ,
R.,Edwards , J. K.,Becker -Dreps, S.,Moormann , A. M.,Kaba , D.,Yotebieng , M.,Parr , J. B.,Gower , E. W.,Thompson , P.. Immunogenicity of
a Birth Dose of Hepatitis B Vaccine in Kinshasa, Democratic Republic of Congo: A Randomised , Controlled Trial. Journal of Viral
Hepatitis. 2024. 31:795 -807.12 231
•Velu, V.,Nandakumar , S.,Shanmugam , S.,Jadhav , S. S.,Kulkarni , P. S.,Thyagarajan , S. P.. Comparison of three different recombinant
hepatitis B vaccines: GeneVac -B, Engerix B and Shanvac B in high risk infants born to HBsAg positive mothers in India. World J
Gastroenterol. 2007. 13:3084 -9. 12 158
•Wang, H.,Fang , J. W.,Gu , Z. W.,Song , D. J.,Chen , Y.,Chen , G. D.,Zhao , B.,Sun , C.,Ma , Y.,Wang , K. X.,Shen , J. Q.,Yang , X. F.,Luo , Q..
Application of hepatitis B immunoglobulin in prevention of mother -to-child transmission of chronic hepatitis B in HBsAg - and HBeAg -
positive mother. Journal of Obstetrics & Gynaecology . 2022. 42:877 -882.6 331
•Yang, S.,Ma , X.,Ni , H.,Zhou , S.,Hu , D.,Shi , H.,Chen , X.,Dong , H.,Xu , G.. Safety, immunization coverage and determinants of a new kind
of Hepatitis B vaccine firstly applied in Ningbo, China. Human vaccines & Immunotherapeutics. 2015. 11:2819 -26.6 8556
•Yerushalmi, B.,Raz , R.,Blondheim , O.,Shumov , E.,Koren , R.,Dagan , R.. Safety and immunogenicity of a novel mammalian cell -derived
recombinant hepatitis B vaccine containing Pre -S1 and Pre -S2 antigens in neonates. Pediatr Infect Dis J. 1997. 16:587 -92.12 205
•Zhu, F. C.,Sun , K. X.,Pan , H. X.,Yang , Z. H.,Lu , Y.,Liang , Z. L.,Liang , X. F.,Wang , F. Z.,Zeng , Y.,Li, J.. The immunogenicity in healthy infants
and efficiency to prevent mother to child transmission of Hepatitis B virus of a 10mcg recombinant yeast -derived Hepatitis B vac cine
(Hep -KSC). Vaccine. 2016. 34:2656 -62.6 1731
•Zhu, F., Deckx , H.,Roten , R.,Michiels , B.,Sarnecki , M.. Comparative Efficacy, Safety and Immunogenicity of Hepavax -Gene TF and
Engerix -B Recombinant Hepatitis B Vaccines in Neonates in China. Pediatric Infectious Disease Journal. 2017. 36:94 -101.12 1739